What began as a family trip to Switzerland in 2008 ended up as a public health nightmare in California.
The family's 7-year-old boy, who was intentionally unvaccinated against measles, was exposed to the virus while traveling in Europe. When he returned home to San Diego, he unknowingly exposed a total of 839 people, and an additional 11 unvaccinated children contracted the disease.
Three of those infected were babies, too young to have yet received the measles vaccines, and one of the babies was hospitalized for three days with a 106-degree fever, according to a report to be published in the April issue of Pediatrics.
Measles is just a plane ride away, including places like Switzerland and the U.K., said one of the researchers, Dr. Jane Seward, deputy director of viral diseases at the National Center for Immunization and Respiratory Diseases at the U.S. Centers for Disease Control and Prevention.
This study serves as a reminder that measles can be a very serious disease that can lead to severe complications and death, and that the measles, mumps, rubella [MMR] vaccine is highly effective and the best way to prevent measles. It's also a reminder that people who choose not to vaccinate don't just put themselves and their children at risk, but also their communities, which includes infants who are too young to immunize, she said
This 2008 outbreak was the first in San Diego since 1991, according to the report. Before the introduction of the measles vaccine in 1963, as many as 500 children died each year from the measles, and nearly 50,000 were hospitalized annually in the United States because of the virus, according to background information in the report.
In recent years, however, the virus has resurged as many parents choose not to vaccinate their children, often because of fears about serious side effects. In fact, a recent study from the University of Michigan found that even among those who do vaccinate, more than half are concerned about serious side effects. Many of these fears stem a reported link between the MMR vaccine and autism. This link has been disproved in numerous studies, however.
There are several reasons why parents are choosing not to vaccinate, said study co-author Albert Barskey, a CDC epidemiologist. Some are afraid of adverse events, and a lot of these fears are unfounded. Others feel that if their child does get sick, the current health-care system can take care of any unfortunate events, and some just don't see measles as a risk. They don't think it's in this country any more and don't think of traveling to Europe as a place where they might contract measles.
The San Diego outbreak, which Seward said was quickly and aggressively contained by the public health department, cost about $177,000 to get under control. Those costs include direct medical charges, the cost of quarantining those exposed, plus the expense of state and county personnel involved in containing the outbreak.
At the charter school that the 7-year-old with measles attended, 11 percent of the children were unvaccinated for measles. While state, or even county-level vaccination numbers may be high, pockets of areas exist where much higher numbers of children are unvaccinated, Barskey said.
Parents who intentionally under-vaccinate tended to be white, college-educated and have an upper or middle-income level, the study found. Many believe that living a 'natural lifestyle' will protect their children against vaccine-preventable illness, according to the study.
There's definitely a lack of appreciation of measles and what it can do, said Dr. Paul Offit, director of the Vaccine Education Center and chief of infectious diseases at Children's Hospital of Philadelphia. He said that in a recent Indiana outbreak, a 17-year-old girl was infected with measles on a trip to Romania, and when she came home she went to a church picnic attended by about 500 people. Of that group, 35 were unvaccinated. Three people out of 465 vaccinated got measles, while 31 out of the 35 who were unvaccinated contracted the disease, Offit said.
That's how highly contagious measles is, he said, pointing out that these people were at an outdoor church picnic, likely without sustained exposure to the infected teenager.
Parents need to realize that a choice not to get a vaccine is not a risk-free choice, said Offit.
Seward recommended that parents who are concerned talk with their child's pediatrician about the risks and benefits of childhood vaccines, as well as the risks of childhood diseases.
On January 30, 2010, at just after 10 in the morning, groups of probably rather badly dressed people gathered outside various branches of Boots the chemists, opened Boots-branded medicaments that they had bought inside and took overdoses. As described in a new book, The Geek Manifesto, one chap took loads of sleeping pills, while another swallowed arsenic. And then they went away, completely unharmed.
What these citizens — members of what has come to be called the sceptic movement — had demonstrated was not a miracle, but that overdosing on homeopathic medicine can do you no harm and that the reason for this is the same reason that it can do you no good. It’s because homeopathy does nothing — it doesn’t work. Never has, never will. The “science” on which it is based is flawed (in fact, it’s ridiculous) and any benefit that people imagine they get from the treatment is a placebo effect.
The overdosing “geeks” were important for two reasons, as Mark Henderson, author of the book and former science editor of The Times, demonstrates. For a start there was now — almost for the first time — a group of people who were not content to see claims made for discredited treatments without making everyone aware of the science that disproved those claims. And second, what they were doing had implications for public policy. If homeopathy had no benefits, then why should the NHS spend several hundred million pounds on making it available? And which other areas of contention and decision would benefit from similar scrutiny?
The geeks represent, for me, one of the most encouraging recent developments in British public life. In towns and cities up and down the country, groups are being formed of scientists and others who meet (often in a pub) and discuss ideas, policy, books and campaigns. Broadly, the impulse is to bring the scientific method to bear on national debates — a method that has been lacking.
I first properly understood just how bad we had become at rational discussion during the MMR crisis. In essence a rogue doctor, Andrew Wakefield, managed to hijack a large part of the national media and many leading figures in politics and the arts for his entirely erroneous suggestion that autism was linked to the MMR vaccination. It took years before the scientific and policy community finally convinced most people that there was no evidence for Dr Wakefield’s scare. And by then we had lost our herd immunity to measles, and children were once again suffering from the disease and, in one or two inevitable cases, dying from it.
I watched TV dramas that turned Dr Wakefield into a whistleblowing angel, read health correspondents who seemed to be more interested in the headline than the science and saw BBC documentaries that, without knowing it, distorted the evidence. And it made me think about all those other situations in which, perhaps without such malign consequences, the same thing was happening.
It became clear to me that most of us prefer anecdote to evidence. After the MMR brouhaha had died down here in Britain, I visited a friend in Sweden. He is one of the most intelligent people I know. When the subject of MMR came up he became impatient. Measles, he told me, did no harm in any substantial way and, as in our childhoods, it was best to do what he and his wife had done, which was to let their children contract the disease and get over it. And, I said, give it to other children, who might not get over it. Because not everyone does and nor did they ever. The discussion became angry. The conventional wisdom of the middle class was being challenged.
So it is with daft diets that cannot possibly work in the way that is claimed for them; “surveys” that have no statistical validity but inform many opinions; complementary therapies from acupuncture to reflexology; and a host of other anecdotally validated processes (as in “it worked for my Aunt Dottie”). But so it is too, as Mr Henderson argues, for major decisions, many of which should be based on a scientific evaluation of the evidence, but just aren’t. Though we might expect politicians to take a more rigorous approach to big, expensive decisions, the fact is they often don’t. They may not even know how to.
Scientists are not super-people who are beyond the tug of ego and the capacity for error. But the scientific method — the process of evaluation and re-evaluation, of test and experiment — is a vital discipline. It is no disgrace in science (as it is politics and occasionally even in journalism) to be proved wrong. The new results are studied, validated and incorporated and the circus moves on.
Whether the issue is drugs policy or the introduction of phonics into schools, we don’t apply the methods that we could to help us to make better decisions. Rather, we rely on selective evidence, persuasion, rhetoric and crossing our fingers and hoping like hell. So why is that? One reason may be that scientists don’t get to be decision makers and lawyers do. Of 650 MPs there are 158 from business, 90 former political advisers, 86 lawyers and 38 journalists. Just one MP worked as a research scientist and two have science PhDs. In the US Senate there are no former research scientists, but 38 per cent of senators are lawyers. In President Sarkozy’s first 16-strong, cabinet, 9 members were lawyers or had law degrees.
Dogs Can Smell Cancer
A new study adds to the body of research suggesting that "man's best friend" may actually be able to smell cancer.
Researchers in Germany found that dogs were able to pick up on the scent of organic compounds linked to the presence of lung cancer in the human body, and that their keen sense of smell may be useful for the early detection of the disease.
Four family dogs - two German shepherds, one Australian shepherd and one Labrador retriever - smelled test tubes containing breath samples of 220 patients, both those with lung cancer and those without it. The dogs were trained to lie down in front of the test tubes where they smelled lung cancer and touch the vial with their noses. According to the study, the dogs successfully identified lung cancer in 71 out of 100 patients with the disease.
And that's not all. Researchers also tested patients with chronic obstructive pulmonary disease. "COPD is quite common in patients with lung cancer and we were not sure if the dogs could tell the difference between both diseases," explains Enole Boedeker, an author on the study who practices general thoracic surgery in Stuttgart, Germany. "The dogs could recognize the cancer sample as easily as between the breath samples of the healthy study participants," Boedeker says. The study is published in the European Respiratory Journal.
This isn't the first study to use dogs' heightened sense of smell to identify disease in humans. Over the years researchers have theorized that cancer may actually have a detectable scent - cancer cells may produce chemical compounds that circulate throughout the body and can be breathed out of the lungs in a gaseous form. The use of canine scent to detect these compounds has shown promise in sniffing out breast cancer, bowel cancer, colon cancer, COPD and lung cancer, and even type 1 diabetes.
"This is probably the most sophisticated study I've seen on this topic," says Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. Lichtenfeld has been following research on sniffer dogs and blogged about the topic for ACS. "More and more studies are reinforcing the possibility that this is very real," he says.
But don't expect to see Fido in the office the next time you visit the doctor; the future clinical implications remain unknown.
"We've seen this happen enough to suggest there are compounds in the breath of patients with cancer that could provide an early warning about he presence of cancer in the body, but we still do not know exactly what those compounds are," Lichtenfeld says. "We can't pick out what the dogs smell.
Researchers say sniffer dogs are a promising "detection device," but more studies are needed to help identify the specific detectable markers in order to create screening methods.
"Unfortunately," the study authors conclude, "dogs cannot communicate the biochemistry of the scent of cancer."
Reducing Hospital Infections
At any given time, one of every 20 hospital patients has a hospital-acquired infection, according to the U.S. Department of Health and Human Services.This leads to an estimated 99,000 deaths in the U.S. each year and up to $33 billion in preventable health care costs.
Now a new study by University of North Carolina at Chapel Hill researchers finds that adopting an inexpensive set of infection control measures could potentially save many thousands of lives and billions of dollars. The study appears in the September 2011 issue of Health Affairs.
"These two initiatives, targeting ventilator associated pneumonias and central line associated bloodstream infections, involved simple steps that lead to dramatic reductions in not only the targeted infections, but also mortality and costs," said Bradford D. Harris, MD, who led the study while serving as an associate professor of anesthesiology and pediatrics in the UNC School of Medicine. He is now a medical officer at the U.S. Food and Drug Administration in Washington.
The study was conducted in the Pediatric Intensive Care Unit at North Carolina Children's Hospital, which is one of the five University of North Carolina Hospitals. The study tested three interventions aimed at preventing and reducing hospital acquired infections.
The first intervention was strict enforcement of standard hand hygiene practices on the unit. All health care workers are expected to wash their hands with soap and running water or an alcohol-based rub on entering and leaving a patient's room, before putting on and after removing gloves, and before and after any task that involves touching potentially contaminated surfaces or body fluids.
The second intervention was implementing a bundle of measures aimed at preventing ventilator-associated pneumonia. Examples included elevating the head of the patient's bed while the patient is receiving breathing assistance from a ventilator, giving the patient daily breaks from sedation and then -- while the patient was unsedated -- assessing whether or not the patient is ready to come off the ventilator, and providing daily oral care (teeth brushing, mouth washes, etc.) with a long-lasting antiseptic.
The final intervention was ensuring compliance with guidelines for the use and maintenance of central-line catheters. Examples included using sponges impregnated with an antiseptic, using catheters impregnated with antibiotics whenever possible, and performing two assessments per day of whether patients with central-line catheters still needed them.
Results of the study showed that patients admitted after these interventions were fully implemented got out of the hospital an average of two days earlier, their hospital stay cost about $12,000 less and the number of patient deaths were reduced by two percentage points.
The costs for implementing these measures were modest. Examples include roughly $21 a day for oral care kits and about 60 cents a day for antiseptic patches and hand sanitizers. But adoption of the three interventions collectively could save this single hospital unit an estimated $12 million a year, the study found. If replicated nationwide, these measures potentially could save thousands of lives and billions of dollars each year.
The Future
Take a moment to imagine what it would be like to live robustly to the ripe old age of 100 or more. You wouldn't die of any particular illness, and you wouldn't gradually waste away under the spell of some awful, enfeebling disease that began years or decades earlier.
It may sound far-fetched, but it is possible to live a long, disease-free life. Most of the conditions that kill us, including cancer and heart disease, could be prevented or delayed by a new way of looking at and treating health. The end of illness is near.
Today, we mostly wait for the body to break before we treat it. When I picture what it will be like for my two children to stay in good health as independent adults in 10 or 20 years, I see a big shift from our current model.
I see them being able to monitor and adjust their health in real time with the help of smartphones, wearable gadgets - perhaps like small, invisible stickers - to track the inner workings of their cells, and virtual replicas of their bodies that they will play much like videogames, allowing them to know exactly what they can do to optimize every aspect of their health. What happens when I take drug x at dosage y? How can I change the expression of my genes to stop cancer? Would eating more salmon and dark chocolate boost my metabolism and burn fat? Can red wine really lower my risk of heart attack?
From a drop of their blood, they will be able to upload information onto a personal biochip that can help to create an individualized plan of action, including both preventive measures and therapies for identified ailments or signs of "unhealthiness." (Other body fluids - like tears and saliva - might be routinely tested, too.) They would be on the lookout for problems like imbalances in blood-sugar control, a risk factor for diabetes, and uncontrolled cell growth, which could signal cancer. Their doctors won't just examine them once a year; they will continually monitor the next generation of patients, offering advice along the way.
What is equally exciting is that this patient data will be added to a universal database that can be aggregated by powerful search engines like Google and constantly fed into new trials and experiments -speeding up our understanding of which drugs work best for which people. The database might show, for example, that people with a particular genetic profile respond to one type of cancer treatment but not another. As more people anonymously add their health data, this database would become more and more effective as a tool for preventive medicine.
Today, most people who are concerned about their health follow sweeping, general guidelines. If you want to lose weight, you are likely to pick a diet that advises eating more fibrous vegetables and cutting back on processed sugar. If you want to reduce your risk for cancer, you avoid tobacco smoke, exercise regularly and take early detection seriously.
Ari Meisel suffered from the symptoms of Crohn's Disease for years before he decided to overhaul his health-care regimen. He's part of a movement of citizen scientists who are turning their bodies - and their lives - into personal laboratories.
The problem with health care today is that we don't know enough about the body to practice preventive medicine actively. With limited knowledge, diagnostic medicine makes sense. If we don't know what we're trying to prevent or how best to do it, we have to wait for an obvious symptom to emerge in order to take action. At that point, we're usually treating a disease that has had ample opportunity to progress.
We can do better. To start, we need to appreciate the body for what it is: a very complex network, much of which we don't yet fully understand. When you look at the body from this systemic point of view, you begin to see that a lot of what we know about health is gravely misunderstood.
In 2009, my colleague Danny Hillis - a former Disney engineer who pioneered the development of so-called parallel supercomputers - and I set up a way to measure 100,000 different types of proteins from a single drop of blood. The goal is to evaluate and make sense of the body's intricate inner workings in a way that's much more dynamic and insightful than what DNA alone can provide. Proteins change in your body every minute, depending on what's going on internally. Our ultimate plan is to develop tests, based on protein levels, for illnesses like cancer. Such tests could take the place of invasive techniques like biopsies.
The new Telcare meter marks a significant step toward bringing consumer medical devices closer to the world of modern technology.
With each passing year, the technology necessary for this revolution in medicine is growing less expensive. Last week, Life Technologies of Carlsbad, Calif., announced that it will be able to map an individual's entire genetic sequence in one day, for $1,000. Similar tests today cost many thousands of dollars. The ability to follow day-to-day changes in your body's proteins and metabolites is not far behind.
So how do we get to this future?
It has to start with data collection. In 2004, Dell launched a company program called Well at Dell to encourage healthy lifestyles. Employees receive alerts and information customized to their health issues, incorporating their latest test results and treatments and allowing them to make more informed decisions. A newly diagnosed diabetic, for example, might get information about how to monitor blood sugar and watch out for the circulatory problems that often accompany the disease.
Not surprisingly, these corporate health-management tools have come under fire, with most critics worrying about privacy. But we can't expect the health-care industry to continue to innovate and grow if we continue to hoard health information.
The federal agency that administers Medicare pays over half of the medical bills in the U.S., but it doesn't retrieve, organize or mine that data. Imagine how much better the Medicare system could be if all this data were analyzed to improve public health. Or imagine databases from many different sources, private and public, coming together in a centralized network that would look for patterns and try to translate them into new ideas for anticipating and preventing health problems.
Personalized medicine isn't as far away as you might think. Consider what's already happening in genetic profiling for individuals, which is available today for several hundred dollars. I co-founded a genetic screening company and am a big proponent of the technology. It allows us to take a broad look at DNA variations and to assess your risk for certain ailments and what medications, at what dosages, might work best, based on your metabolism. Just because you have one or two markers of genetic risk does not mean that you will definitely develop a particular condition, but the outcome can be affected by changes in lifestyle, or in some cases, by taking medication.
As these and other technologies advance, it will become progressively easier to monitor and maintain our overall health. Then it will be up to us. The promise of personalized medicine depends, finally, not on the tools that become available but on our determination to be informed and willing patients.
Could a NOSH-Aspirin-A-Day Keep Cancer Away?
The humble aspirin may soon have a new role. Scientists from The City College of New York have developed a new aspirin compound that has great promise to be not only an extremely potent cancer-fighter, but even safer than the classic medicine cabinet staple.
The new designer aspirin curbed the growth of 11 different types of human cancer cells in culture without harming normal cells, reported a team from the Sophie Davis School of Biomedical Education of The City College of New York in a paper published this month in the journal ACS Medicinal Chemistry Letters. The cancers controlled included colon, pancreatic, lung, prostate, breast, and leukemia. "The key components of this new compound are that it is very, very potent and yet it has minimal toxicity to the cells," said Associate Professor Khosrow Kashfi, the principal investigator.
The aspirin compound also shrank human colon cancer tumors by 85 percent in live animals, again without adverse effects, according to a second paper in press by the City College researchers and colleague Kenneth Olson of Indiana University School of Medicine, South Bend. Their results will appear in the journal Biochemical and Biophysical Research Communications, now available online. "If what we have seen in animals can be translated to humans," said Professor Kashfi, "it could be used in conjunction with other drugs to shrink tumors before chemotherapy or surgery."
Long the go-to drug for minor aches and pains, aspirin and other so-called non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, are known primarily for their ability to calm inflammation. Studies in the 1980's resolved a decades-old debate on the utility of a daily dose of aspirin to cut the risk of heart attack and stroke.
More recent studies tracking regular use of the drug and other NSAIDs demonstrated their remarkable ability to inhibit the growth of cancer. "There's a lot of data on aspirin showing that when taken on a regular basis, on average it reduces the risk of development of colon cancer by about 50% compared to nonusers," noted Professor Kashfi.
The fly in the ointment has been that prolonged use of aspirin posed its own dangers: side effects ranging from bleeding ulcers to kidney failure. To resolve this, the researchers created a hybrid of two earlier formulations, which they have called "NOSH-aspirin." They used the aspirin as a scaffold to support two molecules that have been shown to increase the drug's safety and potency. One arm of the hybrid aspirin releases nitric oxide (NO), which helps protect the stomach lining. The other releases hydrogen sulfide (H2S), which the researchers have previously shown enhances aspirin's cancer-fighting ability. The researchers suspected that the hybrid would be more effective than either of the two components alone to boost aspirin's safety and power against cancer.
"The hybrid is more potent -- and it is more potent by orders of magnitude -- compared to aspirin," said Kashfi. Only 24 hours after treating a culture of cancer cells, the NOSH-aspirin demonstrated 100,000 times greater potency than aspirin alone. "At 72 hours it is about 250,000 times more potent in an in-vitro cell culture against human colon cancer," Kashfi added. "So you need a lower amount to get the same result."
The effect of the hybrid was also far greater than the sum of its parts. Its potency was as much as 15,000 times greater than existing NO-aspirins and 80-fold more than those that incorporate H2S. The upshot is that a drug based on this hybrid would require lower doses to be effective, minimizing or potentially eliminating its side effects.
In the second study, when mice bearing human colon cancer tumors on their flanks were given oral NOSH-aspirin, the compound caused cancer cells to self-destruct, inhibited the proliferation of the cells and significantly reduced tumor growth without any signs of toxicity in the mice.
The stage is set for the development of a drug based on NOSH-aspirin. Kashfi noted that any working therapy for humans is years away, but the next step would be toxicity testing, and then clinical trials.
Low social status is bad for your health
ONCE upon a time the overstressed executive bellowing orders into a telephone, cancelling meetings, staying late at the office and dying of a heart attack was a stereotype of modernity. That was before the Whitehall studies, a series of investigations of British civil servants begun in the 1960s. These studies found that the truth is precisely the opposite. Those at the top of the pecking order actually have the least stressful and most healthy lives. Cardiac arrest—and, indeed, early death from any cause—is the prerogative of underlings.
Such results have since been confirmed many times, both in human societies and in other primate species with strong social hierarchies. But whereas the pattern is well-understood, the biological mechanisms underlying it are not. A study just published in the Proceedings of the National Academy of Sciences, however, sheds some light on the matter.
In it, a group of researchers led by Jenny Tung and Yoav Gilad at the University of Chicago looked at the effects of status on rhesus macaques. Experience has shown that these monkeys display the simian equivalent of the Whitehall studies’ findings. The high risk of disease among those at the bottom of the heap in both cases suggests that biochemical responses to low status affect a creature’s immune system. Those responses must, in turn, depend on changes in the way the creatures’ genes are expressed. To investigate this phenomenon means manipulating social hierarchies, but that would be hard (and probably unethical) if it were done to human beings. You can, however, do it to monkeys, and the researchers did.
Unhappy minds in unhealthy bodies
Dr Tung and Dr Gilad took 49 middle-ranking female macaques (females were chosen because a lot of previous work on animal hierarchies has been done on female macaques) and split them into groups of four or five. The researchers were able to control where in a group an individual ranked by the order in which it was introduced into its group (newly introduced monkeys almost always adopt a role subordinate to existing group members). The hierarchies thus established, the team conducted tests on cells in the monkeys’ blood, in an attempt to determine the effect of a macaque’s rank on her biochemistry and, in particular, on how rank influences the activity of various genes.
The answer is, a lot. Dr Tung and Dr Gilad looked at the expression in each animal of 6,097 genes (30% of the total number in a monkey genome—or, for that matter, in a human one). They were searching for correlations between social rank and gene activity, and in 987 genes they found one. Some genes were more active in high-ranking individuals; others were more active in low-ranking ones. The relationship was robust enough to work the other way round, too. Given a blood sample and no other information, it was possible to predict an individual’s status within her group with an accuracy of 80%.
The next question was what all these genes actually do. Sure enough the answer, for a substantial fraction of them, was that they regulate aspects of the immune system. In particular, low-status individuals showed high levels of activity in genes associated with the production of various immune-related cells and chemical signalling factors, as well as those to do with inflammation (a general immune response that involves tissue swelling and increased immune-cell activity in the affected area). Although the researchers did not explicitly examine the health of their simian charges, chronic, generalised inflammation is a risk factor, in people, for a long list of ailments ranging from heart trouble to Alzheimer’s disease.
Finally, the team investigated the mechanisms behind these differences in gene expression. In keeping with previous work, they found that high- and low-rank individuals showed different levels of responsiveness to a class of hormones called glucocorticoids, which regulate immune-system activity and response to stress. They also found changes in the mix of cells within the animals’ immune system itself. But what is new, and intriguing, is that they discovered, for the first time, evidence that a phenomenon called epigenetic change is at work.
Epigenetics—currently one of molecular biology’s hottest topics—is a process by which genes are activated or deactivated by the presence or absence of chemical structures called methyl and acetyl groups. Dr Tung and Dr Gilad found that methylation patterns were systematically different in high- and low-ranking animals. Crucially, these changes are generally passed on to the daughter cells produced when a cell divides, and are thus perpetuated throughout an animal’s life. To the extent that epigenetic marking is involved in creating social status, then, status may be being maintained by the animal’s cells as they replicate.
Destiny’s child?
Those who believe in progress will, however, be pleased to know that epigenetics is not necessarily destiny. Methyl groups may help maintain the status quo, but if that status quo is interrupted by outside events they can be wiped away and a new lot put in place.
Dr Tung and Dr Gilad discovered this because a few of their monkeys did change status within their groups. When that happened, changes in gene expression appropriate to the new status quickly followed. Those who do break free from their lowly station, then, may begin to reap the health benefits almost immediately.
As with any animal study, this one cannot simply be mapped straight onto humans. But it does provide pointers that researchers who work on people can use. In particular, the experiment ensured that social rank was the only factor being changed, providing strong evidence that the chain of causality runs from low social status, through a disrupted immune system to worse health, and not the other way around. The best medicine, then, is promotion. Prosper, and live long.
Why Exercise Works
ONE sure giveaway of quack medicine is the claim that a product can treat any ailment. There are, sadly, no panaceas. But some things come close, and exercise is one of them. As doctors never tire of reminding people, exercise protects against a host of illnesses, from heart attacks and dementia to diabetes and infection.
How it does so, however, remains surprisingly mysterious. But a paper just published in Nature by Beth Levine of the University of Texas Southwestern Medical Centre and her colleagues sheds some light on the matter.
Dr Levine and her team were testing a theory that exercise works its magic, at least in part, by promoting autophagy. This process, whose name is derived from the Greek for “self-eating”, is a mechanism by which surplus, worn-out or malformed proteins and other cellular components are broken up for scrap and recycled.
To carry out the test, Dr Levine turned to those stalwarts of medical research, genetically modified mice. Her first batch of rodents were tweaked so that their autophagosomes—structures that form around components which have been marked for recycling—glowed green. After these mice had spent half an hour on a treadmill, she found that the number of autophagosomes in their muscles had increased, and it went on increasing until they had been running for 80 minutes.
To find out what, if anything, this exercise-boosted autophagy was doing for mice, the team engineered a second strain that was unable to respond this way. Exercise, in other words, failed to stimulate their recycling mechanism. When this second group of modified mice were tested alongside ordinary ones, they showed less endurance and had less ability to take up sugar from their bloodstreams.
There were longer-term effects, too. In mice, as in people, regular exercise helps prevent diabetes. But when the team fed their second group of modified mice a diet designed to induce diabetes, they found that exercise gave no protection at all.
Dr Levine and her team reckon their results suggest that manipulating autophagy may offer a new approach to treating diabetes. And their research is also suggestive in other ways. Autophagy is a hot topic in medicine, as biologists have come to realise that it helps protect the body from all kinds of ailments.
The virtues of recycling
Autophagy is an ancient mechanism, shared by all eukaryotic organisms (those which, unlike bacteria, keep their DNA in a membrane-bound nucleus within their cells). It probably arose as an adaptation to scarcity of nutrients. Critters that can recycle parts of themselves for fuel are better able to cope with lean times than those that cannot. But over the past couple of decades, autophagy has also been shown to be involved in things as diverse as fighting bacterial infections and slowing the onset of neurological conditions like Alzheimer’s and Huntington’s diseases.
Most intriguingly of all, it seems that it can slow the process of ageing. Biologists have known for decades that feeding animals near-starvation diets can boost their lifespans dramatically. Dr Levine was a member of the team which showed that an increased level of autophagy, brought on by the stress of living in a constant state of near-starvation, was the mechanism responsible for this life extension.
The theory is that what are being disposed of in particular are worn-out mitochondria. These structures are a cell’s power-packs. They are where glucose and oxygen react together to release energy. Such reactions, though, often create damaging oxygen-rich molecules called free radicals, which are thought to be one of the driving forces of ageing. Getting rid of wonky mitochondria would reduce free-radical production and might thus slow down ageing.
A few anti-ageing zealots already subsist on near-starvation diets, but Dr Levine’s results suggest a similar effect might be gained in a much more agreeable way, via vigorous exercise. The team’s next step is to test whether boosted autophagy can indeed explain the life-extending effects of exercise. That will take a while. Even in animals as short-lived as mice, she points out, studying ageing is a long-winded process. But she is sufficiently confident about the outcome that she has, in the meantime, bought herself a treadmill.
Statistical Prediction
Analyzing medical records from thousands of patients, statisticians have devised a statistical model for predicting what other medical problems a patient might encounter called a “hierarchical association rule model.”
Like how Netflix recommends movies and TV shows or how Amazon.com suggests products to buy, the algorithm makes predictions based on what a patient has already experienced as well as the experiences of other patients showing a similar medical history.
“This provides physicians with insights on what might be coming next for a patient, based on experiences of other patients. It also gives a predication that is interpretable by patients,” said Tyler McCormick, an assistant professor of statistics and sociology at the University of Washington.
McCormick said that this is one of the first times that this type of predictive algorithm has been used in a medical setting. What differentiates his model from others, he said, is that it shares information across patients who have similar health problems. This allows for better predictions when details of a patient’s medical history are sparse.
For example, new patients might lack a lengthy file listing ailments and drug prescriptions compiled from previous doctor visits. The algorithm can compare the patient’s current health complaints with other patients who have a more extensive medical record that includes similar symptoms and the timing of when they arise. Then the algorithm can point to what medical conditions might come next for the new patient.
“We’re looking at each sequence of symptoms to try to predict the rest of the sequence for a different patient,” McCormick said.If a patient has already had dyspepsia and epigastric pain, for instance, heartburn might be next.
The algorithm can also accommodate situations where it’s statistically difficult to predict a less common condition. For instance, most patients do not experience strokes, and accordingly most models could not predict one because they only factor in an individual patient’s medical history with a stroke. But McCormick’s model mines medical histories of patients who went on to have a stroke and uses that analysis to make a stroke prediction.
The statisticians used medical records obtained from a multiyear clinical drug trial involving tens of thousands of patients aged 40 and older. The records included other demographic details, such as gender and ethnicity, as well as patients’ histories of medical complaints and prescription medications.
They found that of the 1,800 medical conditions in the dataset, most of them occurred fewer than 10 times. McCormick and his co-authors had to come up with a statistical way to not overlook those 1,400 conditions, while alerting patients who might actually experience those rarer conditions.
They came up with a statistical modeling technique that is grounded in Bayesian methods, the backbone of many predictive algorithms. McCormick and his co-authors call their approach the Hierarchical Association Rule Model and are working toward making it available to patients and doctors.
“We hope that this model will provide a more patient-centered approach to medical care and to improve patient experiences,” McCormick said.
Personalized Genome
Genetics researchers at Washington University, one of the world’s leading centers for work on the human genome, were devastated. Dr. Lukas Wartman, a young, talented and beloved colleague, had the very cancer he had devoted his career to studying. He was deteriorating fast. No known treatment could save him. And no one, to their knowledge, had ever investigated the complete genetic makeup of a cancer like his.
So one day last July, Dr. Timothy Ley, associate director of the university’s genome institute, summoned his team. Why not throw everything we have at seeing if we can find a rogue gene spurring Dr. Wartman’s cancer, adult acute lymphoblastic leukemia, he asked? “It’s now or never,” he recalled telling them. “We will only get one shot.”
Dr. Ley’s team tried a type of analysis that they had never done before. They fully sequenced the genes of both his cancer cells and healthy cells for comparison, and at the same time analyzed his RNA, a close chemical cousin to DNA, for clues to what his genes were doing.
The researchers on the project put other work aside for weeks, running one of the university’s 26 sequencing machines and supercomputer around the clock. And they found a culprit — a normal gene that was in overdrive, churning out huge amounts of a protein that appeared to be spurring the cancer’s growth.
Even better, there was a promising new drug that might shut down the malfunctioning gene — a drug that had been tested and approved only for advanced kidney cancer. Dr. Wartman became the first person ever to take it for leukemia.
And now, against all odds, his cancer is in remission and has been since last fall.While no one can say that Dr. Wartman is cured, after facing certain death last fall, he is alive and doing well.
Dr. Wartman is a pioneer in a new approach to stopping cancer. What is important, medical researchers say, is the genes that drive a cancer, not the tissue or organ — liver or brain, bone marrow, blood or colon — where the cancer originates. One woman’s breast cancer may have different genetic drivers from another woman’s and, in fact, may have more in common with prostate cancer in a man or another patient’s lung cancer.
Under this new approach, researchers expect that treatment will be tailored to an individual tumor’s mutations, with drugs, eventually, that hit several key aberrant genes at once. The cocktails of medicines would be analogous to H.I.V. treatment, which uses several different drugs at once to strike the virus in a number of critical areas.
Researchers differ about how soon the method, known as whole genome sequencing, will be generally available and paid for by insurance — estimates range from a few years to a decade or so. But they believe that it has enormous promise, though it has not yet cured anyone.
With a steep drop in the costs of sequencing and an explosion of research on genes, medical experts expect that genetic analyses of cancers will become routine. Just as pathologists do blood cultures to decide which antibiotics will stop a patient’s bacterial infection, so will genome sequencing determine which drugs might stop a cancer.
“Until you know what is driving a patient’s cancer, you really don’t have any chance of getting it right,” Dr. Ley said. “For the past 40 years, we have been sending generals into battle without a map of the battlefield. What we are doing now is building the map.”
Large drug companies and small biotechs are jumping in, starting to test drugs that attack a gene rather than a tumor type.Leading cancer researchers are starting companies to find genes that might be causing an individual’s cancer to grow, to analyze genetic data and to find and test new drugs directed against these genetic targets. Leading venture capital firms are involved.
For now, whole genome sequencing is in its infancy and dauntingly complex. The gene sequences are only the start — they come in billions of small pieces, like a huge jigsaw puzzle. The arduous job is to figure out which mutations are important, a task that requires skill, experience and instincts.
So far, most who have chosen this path are wealthy and well connected. When Steve Jobs had exhausted other options to combat pancreatic cancer, he consulted doctors who coordinated his genetic sequencing and analysis. It cost him $100,000, according to his biographer. The writer Christopher Hitchens went to the head of the National Institutes of Health, Dr. Francis Collins, who advised him on where to get a genetic analysis of his esophageal cancer.
Harvard Medical School expects eventually to offer whole genome sequencing to help cancer patients identify treatments, said Heidi L. Rehm, who heads the molecular medicine laboratory at Harvard’s Partners Healthcare Center for Personalized Genetic Medicine. But later this year, Partners will take a more modest step, offering whole genome sequencing to patients with a suspected hereditary disorder in hopes of identifying mutations that might be causing the disease.
Whole genome sequencing of the type that Dr. Wartman had, Dr. Rehm added, “is a whole other level of complexity.”
Exercise - The Magic Pill
From dementia and diabetes to high blood pressure – no pill protects us against ill health like exercise does.
IT'S 9 am in the office - time for my daily medication. As usual, I slink off to the fire escape for my fix. Twenty minutes later, I'm back at my desk, brimming with vitality and raring to go.
I've taken this medicine regularly now for about eight years, after developing elevated blood pressure in my mid-40s. I'd heard it could help reduce blood pressure and improve circulation. Sure enough, the high blood pressure vanished long ago.
Amazingly, this drug is freely available to everyone on the planet. It's completely up to you when you take it, and how much. And as research is now revealing, the more of it you take, the healthier you will be.
What is this wonder drug? It is plain old physical activity of all sorts - from running marathons to simply walking around your sofa while watching television. We've all heard that exercise is good for us, but what is becoming increasingly clear is the sheer extent of its benefits and why it works.
A plethora of recent studies shows that exercise protects us from heart attacks, strokes, diabetes, obesity, cancer, Alzheimer's disease and depression. It even boosts memory. And it has the potential to prevent more premature deaths than any other single treatment, with none of the side effects of actual medication. "It's a wonder drug," says Erik Richter, a diabetes researcher at the University of Copenhagen, Denmark. "There's probably not a single organ in the body that's unaffected by it."
Throughout evolution, humans have been active. Our ancestors chased prey as hunter-gatherers and fled from predators. More recently, they laboured on farms and in factories. But the decline of agricultural and industrial labour, plus the invention of the car, a multitude of labour-saving devices and - most perniciously - TV, computers and video games, mean we've all ground to a sudden and catastrophic standstill.
"We were built to be active, but the way our environment has changed and the way we live our lives has led us to become inactive," says Christopher Hughes, senior lecturer in sport and exercise medicine at Queen Mary, University of London.
Now we're paying the price. In 2009 Steven Blair, an exercise researcher at the University of South Carolina in Columbia, published a study of more than 50,000 men and women showing that a lack of cardiorespiratory fitness was the most important risk factor for early death. It accounted for about 16 per cent of all deaths in men and women over the period of study, more than the combined contributions of obesity, diabetes and high cholesterol, and double the contribution of smoking (see graph).
In other words, physical inactivity is killing us. "Everyone knows too much booze or tobacco is bad for you, but if physical inactivity was packaged and sold as a product, it would need to carry a health warning label," says Hughes.
As we have become inactive, so once-rare diseases have mushroomed. A report from the organisation Diabetes UK reveals that in 1935, when the world's population was just over 2 billion, an estimated 15 million people globally had type 2 diabetes. By 2010 the world's population had more than trebled and the number with diabetes had shot up to 220 million, with 300 million predicted for 2025. Likewise, results published earlier this year in the Journal of the American Medical Association showed that over a third of US men and women are obese, as are about 17 per cent of US children.
Weekly dose
The good news is that we can do something about it. I started running up and down the fire escape for a few minutes each day in the hope of not having to take cholesterol-lowering statins or drugs for high blood pressure. Now I'm eager to know what my daily routine is doing to my body and, more importantly, how it might be protecting me from disease.
The most robust evidence so far comes from the Exercise is Medicine initiative pioneered by the American College of Sports Medicine in Indianapolis, Indiana. Researchers there have collated studies over the past decade or so of people who follow the US government's advice on physical activity. This prescribes 150 minutes per week of moderate-intensity aerobic activity, such as brisk walking, ballroom dancing or gardening, or 75 minutes of more vigorous activity such as cycling, running or swimming.
Flush your system
What the Exercise is Medicine findings show is that this weekly dose of moderate exercise reduces the risk of premature death through heart disease by 40 per cent, approximately the same as taking statins.
Chi Pang Wen of the National Health Research Institute in Zhunan, Taiwan, offers some insights into precisely how physical activity prevents cardiovascular diseases. "Exercise can stimulate circulation, flush out fatty deposits in the walls of blood vessels and dilate small vessels that could otherwise be the cause of a heart attack or stroke," he says. In April he presented results from a study of over 430,000 Taiwanese men and women, showing that exercise reduced the risk of heart attacks by 30 to 50 per cent.
Exercise also keeps blood vessels clear by helping to destroy the most dangerous fats. Research published in February reveals that it alters the structure of fatty triglyceride particles in the bloodstream, making it easier for enzymes to destroy them before they can gum up the works. Many risks to circulatory health come from such fatty particles, in the form of chylomicrons produced in the gut, or very low density lipoproteins (VLDLs) pumped out by the liver. The bigger the VLDL particles are, the easier they are for enzymes to break down, and the findings show exercise causes the particles to enlarge by about a quarter.
"A single 2-hour bout of exercise reduced triglyceride concentrations in the circulation by 25 per cent compared with no exercise," says Jason Gill, who led the study at the University of Glasgow, UK. His team found a decrease in both types of fat, but it was twice as large for the more insidious VLDL particles.
One of the most startling findings of the Exercise is Medicine initiative is that a modest weekly dose of exercise lowers the chances of developing type 2 diabetes by 58 per cent, twice the preventive power of the most widely prescribed anti-diabetes medication, metformin.
Type 2 diabetes affects adults when they stop responding efficiently to the hormone insulin, which orders muscle and fat cells to absorb surplus glucose from the bloodstream. When insulin loses its punch, glucose continues circulating and creates the potentially fatal sugar imbalances that are the hallmark of diabetes.
How does exercise reverse this? The story dates back to 1982, when Richter found that insulin activity is enhanced by physical activity - at least, in rats. Experiments showed that after the rats ran around for a couple of hours, their cells became up to 50 per cent more responsive to insulin compared with the cells of non-exercising rats. "We confirmed it later in humans," Richter says.
As cells reawaken to insulin, it seems that surplus glucose gets sponged from the circulation. Richter found that the effects lasted for a couple of hours after exercise in rats, and up to two days in humans.
Recently he and colleagues have unravelled more details about how exercise brings this about. They have discovered that both insulin and muscle contractions during exercise activate a molecule in muscle and fat cells called AS160, which helps them absorb glucose. Once activated, AS160 orders the cell to send molecules to the cell's surface to collect glucose and bring it inside. Without these transporter molecules, glucose cannot get through the fatty cell membrane.
That's not the only way exercise also helps cells burn off excess sugar. Muscle cells absorb glucose and fatty acids from the bloodstream to replenish adenosine triphosphate (ATP), the molecular fuel found in most living cells. As ATP is used up, it produces waste products that are sensed by another molecule, AMPK. AMPK then orders cells to recharge by absorbing and burning yet more fat and sugar. In the mid-1990s, Grahame Hardie at the University of Dundee, UK, found exercise accelerates this process because muscle contraction activates AMPK.
Hardie says exercise has the potential to reverse obesity and diabetes and prevent cancer. The findings of the Exercise is Medicine initiative show that taking the US government's recommended weekly dose of exercise halves the risk of breast cancer in women and lowers the risk of bowel cancer by around 60 per cent. This is about the same reduction seen with low daily doses of aspirin.
How exercise does this is not yet clear - not least because so many factors are involved in cancer's appearance and progression, including sex hormone imbalances, the ability of the immune system to clear cancer cells, and damage to genes and DNA generally. However, some clues are beginning to emerge. "Exercise reduces body weight, which is a known risk factor for postmenopausal breast cancer," says Lauren McCullough of the University of North Carolina at Chapel Hill.
She also thinks that reducing fat deposits in the body results in less exposure to circulating hormones, growth factors and inflammatory substances. "All have all been shown to raise breast cancer risk," she says.
Another clue comes from work by Anne McTiernan of the Fred Hutchinson Cancer Research Center in Seattle, who studies bowel cancer. Biopsies from 200 healthy volunteers showed that, compared with exercisers, non-exercisers had more telltale signs of abnormalities in colonic crypts - recesses in the lining of the colon that absorb water and nutrients. Crypts in idle participants had an increased number of dividing cells, and these also climbed higher up the crypt walls, where they had the potential to form pre-cancerous polyps.
Another potential protection against cancer might come back to the ability of exercise to stimulate AMPK. Recent research by Beth Levine of the University of Texas Southwestern Medical Center in Dallas showed that exercise stimulates cells craving extra energy to burn unwanted rubbish, including faulty or mutated DNA that could trigger cancer if it hangs around. More recently, in unpublished work, Levine has discovered the same processes in brain cells, suggesting that exercise might play a role in staving off dementias and neurodegeneration.
As well as potentially staving off dementia, pounding the stairs might even help boost my brainpower and memory. Back in 1999, Henriette van Praag of the US National Institute on Aging in Baltimore, Maryland, found that mice using a running wheel developed new neurons in the hippocampus, a part of the brain vital for memory. "We had a doubling or tripling of neurons after they'd been running daily for about a month," she says. Subsequently, van Praag and other groups found the most likely reason: a doubling in the level of a substance in the hippocampus called brain-derived neurotrophic factor, or BDNF, which may support growth of new neurons.
More than a decade on, a team led by Art Kramer of the University of Illinois at Urbana-Champaign demonstrated through a brain-imaging study of 120 older adults that exercise increased hippocampus volume by around 2 per cent. It also improved their memory, as measured by standard tests. "The volume increase we saw can make up for approximately two years of normal age-related decrease," says Kramer. "We found that even modest increases in fitness can lead to moderate, 15 to 20 per cent improvements in memory."
The benefits aren't just restricted to adults. Kramer and his colleagues have also found that pre-adolescent children who exercise develop larger hippocampuses.
So if exercise is so beneficial, why won't people take it? At least 56 per cent of US adults don't meet the government's exercise guidelines. "The most common excuse people give in polls is that they don't have time," says Blair. Perhaps that is not surprising when US citizens spend, on average, almost 8 hours a day watching TV, according to a 2008 study.
For those, like me, who don't want the fuss of joining a gym, there is plenty people can do at home or the workplace in their own time and at their own pace. Blair cites a study in which researchers asked half of a group of couch potatoes to walk round their sofa during each TV commercial break. "They burned 65 calories more per hour, and that is 260 calories in 4 hours," he says. Over a week, their exertions met the US government recommendations for exercise.
And overweight people can benefit massively from exercise even if they don't lose weight, Blair points out. One of his studies has shown that for fit fat people, the risk of dying prematurely is half that for unfit lean people.
Once a marathon runner, Blair now walks for an hour a day, and at the age of 73, he has set himself the goal of walking 5 million steps each year, tracking his progress with a pedometer. He is concerned that not enough doctors recognise that lack of fitness is effectively a disease. He wants them to use fitness as a gauge of health, perhaps making their patients do a treadmill test as a matter of routine, rather than considering it as an afterthought.
Figures published in The Lancet last month back up his assertion that no action, other than abstaining from smoking, is as good for health as being physically active. The study also reveals that physical inactivity effectively kills 5 million people a year worldwide, as many as smoking (see map).
As for me, the stair-run does seem to be working, although I don't have health data from eight years ago to confirm my progress. Scans and tests last month showed my blood pressure and bone density are normal, and I have 6 per cent less body fat than is average for my age. Also, only 20 per cent of my fat is the dangerous sort around organs in the abdomen, compared with 30 per cent in most of my peers. My heart fitness, measured on a treadmill, is above average and I have no chronic diseases that I know of. Now, imagine you were offered a pill that did all that. Wouldn't you take it?
Beneficial Micro Organisms
IT WAS a revelation. Germs cause disease. When Louis Pasteur and Robert Koch discovered and developed what would later be called the germ theory in the 1860s, this was a radical, then revolutionary idea - one so good it seems obvious in retrospect.
At the heart of their work was the notion that individual species cause disease by invading our bodies. Over the next century, the notion of "germs" changed our behaviour. It led us to scrub our hands and actively fight specific pathogens (as researchers came to call dangerous germs) and to cure the diseases they cause. These changes saved millions, maybe billions of lives. Every day you rub shoulders with the success of this theory. How could there be anything wrong with it?
New research, however, is beginning to question, if not germ theory itself, at least some of the actions we have taken on its behalf. These studies come from very different groups of scientists, largely working separately and apparently without much awareness of each other. But I believe that they are unwittingly part of the slow unravelling of a new, broader theory of disease, the ecological theory of disease.
Here's the thinking. In the late 1980s, microbiologists and public-health researchers began to notice differences between rural and urban kids. Rural kids seemed less likely to develop allergies. A new idea was floated - perhaps they had been exposed to more bacteria that had helped their immune systems to "balance" themselves. This idea, often called the hygiene hypothesis, has since found support in empirical studies worldwide.
Country kids whose fingers still plunge regularly into the rich bacteria of soil (and farm animals) have fewer allergies. But it isn't just farm living: sometimes the exposure to a wilder bacterial life can be subtle. For example, a recent study in Australia found that pregnant mothers living with dogs were less likely to have children with allergies. These studies note fundamental differences between the immune systems of dirty kids and clean kids. Conclusion: in some ways it is better to be dirty.
More recently, a new version of the hygiene hypothesis has suggested that it isn't just large numbers of bacteria that it is good to be exposed to but, rather, many kinds of bacteria. Our immune system needs to be exposed to many species in order to sort the good from the bad. Without such exposure, argues this "biodiversity" version, mistakes get made. The immune system, in not having seen enough of the world, doesn't know quite what to attack. It attacks pollen. It attacks us.
This made me sit up and take notice. There are, I realised, many separate fields of science in which the failure to be exposed to good species or even just a diversity of species is believed to make us sick.
The "worm hypothesis" argues that our bodies evolved with parasitic worms as a dependable presence and that for some individuals the absence of such worms causes the immune system to overreact, leading to autoimmune diseases such as Crohn's, MS and asthma. The nature deficit hypothesis, on the other hand, argues that lack of exposure to nature in our city environments causes psychological problems in children who then suffer from any of a variety of behavioural and other problems. This is country cousin to the biophilia hypothesis, which suggests an innate fondness for nature and biodiversity, which both bring us benefits and, in their absence, costs.
All of these relate to the much older and well-accepted "deficiency" model, which correctly states that diseases such as scurvy are caused by the absence of whole classes of species (and their nutrients) in our diets.
What seems to have gone pretty much unremarked is that these ideas all suggest ways in which the absence of beneficial or historically common species in our lives can make us sick. In a way, taken together these ideas make up the obverse of the germ theory of disease; if the germ theory is about bad species being present, these hypotheses are all about good species that have gone missing.
Bringing the pieces of the puzzle together seems to show what I call the ecological theory of disease. This is the idea that illness can arise from the presence of species that negatively affect our health or the absence of species that positively affect our health.
Of course, to ecologists and evolutionary biologists, such a theory is not exactly news. We can all hold up long lists of species that require other species, their partners and neighbours, to survive. Think corals, lichens, leaf-cutter ants, tube worms, bean plants. Now think humans. Take away the species we benefit from every day and we would die in many different ways.
The point is that public-health researchers, medical researchers and doctors don't think like ecologists. Hospitals only consider other species when they are "bad", when, that is, they are behaving as germs. With a couple of examples we tend to regard as freakish (the medical use of leeches or fly maggots), doctors almost never prescribe the apple, bacteria, worm or other sort of "nature" your body is "missing", though if you took just the right mix it would surely help keep the doctor away.
So what should we do? If the germ theory of disease tells us to hunt down, scrub off and otherwise avoid bad species, the ecological theory of disease suggests the same, but that we also need to figure out how to attract, farm and nurture beneficial species. Fine. But there is a big problem: while we have spent the last 200 years chasing down bad species, we have spent far less time hunting good ones. Worse, while there are hundreds of pathogens that affect our health and well-being (with a small handful being the really deadly monsters), the precise melange of beneficial species we need could involve hundreds of thousands of species - or more.
Those species do not always have names. Recently, I catalogued the species on my body and my house, finding more than 2000 species, most of which most experts could not identify. Which ones were good for me? Who knows? What is worse, no one could tell me which good species I might be missing.
More and more, we seem to "know" that we need nature. Many of its species benefit us, but we are not yet smart enough to know which ones. We are left to wait for the systematists - those cataloguers of life - to find and name the species on our behalf. And then we will have to wait some more for the ecologists and evolutionary biologists to study those species. Only then, finally, will medical researchers begin to weigh up which ones we need and which ones we don't. But it will take a while.
We have neglected the book of life for so long that at our current rate of research, that without investment in projects larger than any yet imagined, much less implemented, we won't catch up for hundreds of years. Meanwhile, some of the species we are losing from forests and wild lands (or just from our modern lives) could easily be the ones that help to make us whole.
If we only knew which ones.
Parkinson's Diagnosis By Phone
A speech-processing algorithm could use the sound of your voice to diagnose a range of diseases, and spell the end of invasive physical exams
THOUSANDS of people may soon be making a very important three-minute phone call - to a computer. It could tell them whether or not they have Parkinson's disease.
Technology has long promised a revolution in "smart medicine", allowing painful pokes and prods to be replaced with faster, more accurate and non-invasive ways of diagnosing a range of diseases. That vision took a big step forward last week, when Max Little of the Massachusetts Institute of Technology's Media Lab appealed for people worldwide to test a voice-based system he helped develop for diagnosing Parkinson's. The software uses a speech-processing algorithm to identify telltale changes in the voice of a person with the disease.
Parkinson's affects some 6 million people worldwide. Although surgery and drugs can hold back its progression, there is no cure. Diagnosing it and tracking its course usually relies on an assessment of someone's symptoms using the Unified Parkinson's Disease Rating Scale, which involves tests of motor skills, for example. The process is time-consuming, expensive and requires people to attend a clinic for the tests to be carried out. It is partly because of this that it is thought that around a fifth of cases of Parkinson's are never diagnosed.
But the disease often manifests early on in the voice, as it affects the ability to control the vocal cords and soft palate. Common signs include a quaver in the voice, softer speech and breathiness or hoarseness, though they can be subtle at first. This makes Parkinson's a perfect candidate for diagnosis over the phone.
At the TEDglobal conference in Edinburgh, UK, Little explained how he and colleagues used their speech algorithm to process 263 recordings of 43 people, who had been asked to sustain six or seven vowel "ah" sounds. After being trained on 10 impairments or "dysphonias" in these recordings, the algorithm managed to diagnose Parkinson's speech markers 99 per cent of the time in the lab.
Parkinson's is a good place for the telemedicine revolution to start in earnest. "This kind of non-invasive technology, which can be seamlessly integrated into people's lives, could give you data on their social life, daily patterns, and track them over time," Little says. "We end up with a giant database with far fewer risk factors, which will give researchers a way to streamline the hunt."
Little's Parkinson's Voice Initiative website lists phone numbers for people to call the computerised diagnostic system. At the time of writing, the system was a quarter of the way towards the target of 10,000 callers that Little and colleagues are hoping to achieve.
Speech algorithms are already being applied in other diagnostic tests. Spin-offs from other projects at MIT, for example, are being used to spot depression, anxiety and post-traumatic stress disorder to help soldiers returning from battle.
With "life-loggers" and "quantified-selfers" now tracking all aspects of their own lives online, Little expects that freely available data of potential use to healthcare will become increasingly available. That will help create huge data sets and baselines of healthy people that software systems can use to hone their diagnostic capability and identify those who are in need of care.
Why Haven't Harmful Mutations Been Selected Out
The genes responsible for inherited diseases are clearly bad for us, so why hasn't evolution, over time, weeded them out and eliminated them from the human genome altogether? Part of the reason seems to be that genes that can harm us at one stage of our lives are necessary and beneficial to us at other points in our development.
The idea that the same gene can be both beneficial and harmful, depending on the situation, is called antagonistic pleiotropy. The theory has been around since the 1950s and has been used to explain aging, cancer and genetic diseases.
But until now, no one has been able to determine just how common antagonistic pleiotropy is -- on a genome-wide scale -- in any organism. In a paper to be published online Oct. 25 in the journal Cell Reports, Jianzhi "George" Zhang of the University of Michigan and his coworkers report that antagonistic pleiotropy is very common in yeast, a single-celled organism used by scientists to provide insights about genetics and cell biology.
Zhang and his colleagues say the findings have broad biomedical and evolutionary implications.
"In any given environment, yeast expresses hundreds of genes that harm rather than benefit the organism, demonstrating widespread antagonistic pleiotropy. The surprising finding is the sheer number of such genes in the yeast genome that have such properties," said Zhang, a professor in the Department of Ecology and Evolutionary Biology.
"From our yeast data we can predict that humans should have even more antagonistic pleiotropy than yeast," he said. "This suggests that special cautions are needed when treating inherited diseases, because a treatment that removes a disease-causing genetic effect may lead to adverse effects in other aspects of life."
Yeast has about 6,000 genes, about 1,000 of which are essential - eliminate any of them and the organism dies. Zhang and his colleagues worked with a set of 5,000 laboratory strains of yeast in which one non-essential gene had been deleted from each strain. Each strain was tagged with a genetic "barcode" to allow researchers to identify it later.
Zhang and his coworkers grew all 5,000 strains together in a single test tube and compared the growth rates of each strain, under various environmental conditions, to the growth rates of "wild type" yeast strains without gene deletions.
This side-by-side comparison allowed them to determine which genes were beneficial (increased growth rate) and which ones were harmful (decreased growth rate) under the six environmental conditions. Different mixes of nutrients and chemical stressors, such as ethanol, were added to the yeasts' growth media to create the six environmental conditions.
The researchers found that for each of the six conditions, on average, the yeasts expressed about 300 genes that slowed their growth and were therefore classified as harmful. Deleting those genes resulted in more rapid growth.
But many of the genes that were harmful under one set of environmental conditions proved to be beneficial under another, demonstrating widespread antagonistic pleiotropy, Zhang said.
"There are a lot of theories - some of them relating to aging, cancer and genetic disease - that invoke antagonistic pleiotropy. But it's not easy to measure, and empirically we have not known much about it," Zhang said. "Now, in yeast, we have found that antagonistic pleiotropy is very common."
Salt In The Wound
I realise that "rubbing salt into the wound" was a way of preventing infection. But how did it work?
• Applying salt to a wound creates a highly saline environment, one in which it is difficult for microbes to grow. The high concentration gradient between the salt solution and the fluid inside bacterial cells makes it hard for the microbes to extract water from the solution without using a lot of energy. As a result, the bacteria become dehydrated and cannot function normally or proliferate.
Concentrated sugar solutions also have a dehydrating effect. This accounts for the extended shelf life of chutneys and preserves, and explains why honey can be used on wound dressings and, ironically, on bee stings as an antiseptic.
The Anti-Vaxxers
Let me be clear right off the bat: Vaccines don’t cause autism.
It’s really that simple. We know they don’t. There have been extensive studies comparing groups of children who have been vaccinated with, say, the measles, mumps, and rublella (MMR) vaccine versus those who have not, and it’s very clear that there is no elevated rate of autism in the vaccinated children.
This simple truth is denied vigorously and vociferously by antivaxxers (those who oppose, usually rabidly, the use of vaccinations that prevent diseases), but they may as well deny the Earth is round and the sky is blue. It’s rock solid fact. They try to blame mercury in vaccines, but we know that mercury has nothing to do with autism; when thimerosal (a mercury compound) was removed from vaccines there was absolutely no change in the increase in autism rates.
I could go on and on. Virtually every claim made by antivaxxers is wrong. And this is a critically important issue; vaccines have literally saved hundreds of millions of lives. They save infants from potentially fatal but preventable diseases like pertussis and the flu.
So why did Congress hold hearings this week promoting crackpot antivax views?
I’m not exaggerating. The Committee on Oversight and Government Reform held a hearing trying to look into the cause and prevention of autism. Rep. Dan Burton (R-Ind.) launched into a several-minute diatribe (beginning at 12:58 in the video above) that starts off in an Orwellian statement: He claims he’s not antivax. Then he launches into a five-minute speech that promotes long-debunked and clearly incorrect antivax claims, targeting mercury for the most part. Burton has long been an advocate for quackery; for at least a decade he has used Congressional situations like this to promote antiscience.
In the latest hearing, Burton sounds like a crackpot conspiracy theorist, to be honest, saying he knows—better than thousands of scientists who have spent their careers investigating these topics—that thimerosal causes neurological disorders (including autism). He goes on for some time about mercury (as does Rep. Dennis Kucinitch (D-Ohio) starting at 21:44 in the video), making it clear he doesn’t have a clue what he’s talking about. For example, very few vaccines still use mercury, and the ones that do use it in tiny amounts and in a form that does not accumulate in the body.
Talking about the danger of mercury in vaccines is like talking about the danger of having hydrogen—an explosive element!—in water. It’s nonsense.
I won’t go further into details, because this shameful travesty of truth and medical health goes on for an hour. On Forbes.com, Steven Salzberg wrote a fantastic article about this Congressional farce. I strongly urge you to read it, since Salzberg brings the hammer down on the Congresscritters who think they know more about science than the scientists who actually devote their lives to this topic.
If you get the sense I’m angry, you’re damn right I am. Vaccine save lives, and antivaxxers put those lives in grave danger. These lives include people who are immunocompromised (people on immunosuppressants, for example, recovering from cancer or who have autoimmune diseases like rheumatoid arthritis). It also includes infants too young to get vaccinated, who rely on the rest of us getting our shots to increase herd immunity, reducing reservoirs for the infectious diseases to live.
And if you don’t think this has an impact, I urge you—if your heart can stand it—to read the story of Dana McCaffery, a perfect little girl who, at the age of four weeks—four weeks—died of pertussis, a disease she was too young to be vaccinated against and that she might never have contracted if it weren’t for low immunization rates where she lived.
Pertussis. Whooping cough. A disease that for years has been on the decline but has come roaring back—along with measles and other preventable diseases—because people aren’t getting vaccinated in high-enough numbers. I am a parent myself, with a fully-vaccinated daughter, I’ll add, and it breaks my heart when I think of what Dana’s parents, Toni and David McCaffery, went through.
Kinect and Physical Therapy
The “Kinect Effect” is rippling out even further. Michael Peck of Defense News reports that Microsoft is working with the Armed Forces to leverage Kinect technology in the service of physical therapy.
By joining Kinect with certain software, Microsoft can create a package that enables injured soldiers and vets to do their P.T. at home. Peck reports that Redmond is teaming up with the Air Force to “define requirements for a Kinect therapy system”; it’s also talking about the tech with the Army’s Communications-Electronics Research, Development and Engineering Center (CERDEC, headquartered in Maryland).
The Army and Air Force are hardly the only ones interested in the Kinect’s potential to aid in physical therapy, actually. The San Diego-based West Health Institute has been looking into the matter, reported InformationWeek in October. “The biggest problem with physical therapy is patients not doing enough of it or not doing it properly,” said one of the project leaders. “We are building a tool to help physical therapists measure progress in a fun way that could potentially help patients heal faster.” Georgia Tech has been investigating whether the Kinect can help kids with cerebral palsy.
And physical therapy is hardly the only tool for which the Armed Forces might like to use the Kinect. Peck also reports that the Kinect could be of use for group treatment of PTSD. “They can use avatars, which allows anonymity, but also allows for representatives who are therapists or licensed psychiatrists to connect with them,” Phil West, Microsoft’s director of public sector solutions, told Peck. “Therapists can say, ‘I know who you are because I have your case file. No one else in the room has to see in your face.’ It gives a way to engage and talk through problems while preserving anonymity.”
DARPA, the Joint Improvised Explosive Device Defeat Organization, Army Medicine, and the Navy’s Bureau of Medicine have all taken a shine to the Kinect, according to one Microsoft exec. And Army Small Business Innovation Research recently asked for proposals of a Kinect system that could track pilots as they flew, thereby gauging whether or not the pilots were spending too much time looking at a single display. This piece of hardware, originally intended for gaming, is ending up in some decidedly non-playful contexts.
USA Health
WEALTHY it may be, but healthy it is not. The US population experiences poorer health at all stages of life than the populations of 16 other rich countries.
Despite leading the world in pioneering anti-smoking laws, cancer screening and controlling high blood pressure, the US trails its richer "peer" countries in almost all other measures of health and longevity, says a US National Research Council report published last week.
At 75 years, men in the US have the lowest life expectancy in the group, while women have a life expectancy of 81 years - higher only than Denmark.
In nine categories of ill health ranging from infant mortality rates to the prevalence of sexually transmitted disease, US citizens consistently came at or near the bottom of the table.
"I was stunned by how pervasive the disadvantages were across so many factors," says Steve Woolf of Virginia Commonwealth University in Richmond, who chaired the report panel.
Woolf and his colleagues say that the problem is less to do with faults in the US health system, and more to do with behaviours that put US citizens at greater risk. "They consume the most calories per person, have higher rates of drug abuse, are less likely to use seat belts, and are more likely to use firearms in acts of violence," says Woolf.
Booze Kills The Flu
There's a lot of nasty, virulent bugs going around this year. Colds and flus are putting people out of commission for weeks on end. This means that by now one of your friends has told you to drink some whiskey because that'll knock the cold right out.
Some people swear by it. But is there any scientific evidence to support that (admittedly fun) hypothesis? Let's see.
Knocking Out the Virus
First let's address the theory that after you're already getting sick, drinking whiskey (or brandy, or other spirits) will kill the virus and you'll wake up healthy. It's a beautiful idea, but unfortunately no study has ever shown that this is remotely true. Further, it doesn't make any logical sense at all. People think, "Hey, alcohol is used to sterilize stuff and kill viruses outside of my body, so why wouldn't it work inside by body?" The answer is has to do with concentrations.
Once you're already infected with a cold or flu virus, it's in your bloodstream. That means that if you want to kill it, you'd have to kill it in your blood. Yes, consuming alcohol does raise your blood-alcohol levels, but not nearly enough. According to the Center for Disease Control (CDC), "Ethyl alcohol, at concentrations of 60%–80%, is a potent virucidal agent inactivating all of the lipophilic viruses (e.g., herpes, vaccinia, and influenza virus) and many hydrophilic viruses..." In other words, your bloodstream would likely need to be 60 to 80 percent alcohol (more alcohol than blood!) in order to kill your virus. When you consider that a blood-alcohol level of 0.2 percent is enough to put most people in a stupor, and bringing it up to 0.5 can easily cause death by alcohol poisoning, this is not a reasonable solution. You'd kill yourself before you'd kill your cold.
Soothing a Savage Throat
Theory number two. "Oh, you got a sore throat, bro? Throw back some whiskey and/or 151! It'll kill that ish real quick!" Thanks, dudebro. At least this one make a little bit of sense, in theory. Alcohol is used to disinfect surfaces. The surface of your throat is a surface! Q.E.D.! Except not really. A) The spirit probably doesn't stay on your throat long enough to really sterilize it, it's washed away by saliva. B) Even if it did, it would only clear the top part of your throat. When swallowing, liquid is passed down from your pharynx, through your esophagus, and into your stomach. The thing is that most sore throats continue down your breathing pipe, not your food pipe, which is why they are so difficult to sooth. Trying to rinse the soreness away would lead to asphyxiation before relief.
So why does whiskey (and hot toddies and such) sometimes make your throat feel better? Mostly because it gets you drunk. One of the byproducts of even lower levels of intoxication is that you stop feeling pain so acutely. While this sounds nice, there are risks, aside from the usual drunken ones. First, alcohol is very drying. When you've got a sore throat or a cough, the last thing you want is your throat to be any drier. Dry tissues are far more susceptible to abrasions. Second, alcohol brings your blood vessels closer to the surface of your throat, which greatly increases the chance of damaging your delicate tissues. And third, you know how when you're sick everybody tells you to "push fluids"? Drinking alcohol is like "pulling fluids." It's a diuretic, which means you are likely to wake up dehydrated. No bueno.
An amusing anecdote. A certain family member of mine was in the Navy and stationed on a submarine. He woke up with a sore throat. He figured, "Hell, alcohol kills bacteria, I'll just gargle with some." In the Navy they had access to 99-point-something percent pure alcohol (for cleaning things, I assume). He tossed some into his mouth. It burned like hell. He immediately tried to spit it out, but the alcohol has sucked the water out of his cheeks and lips, puckering him so badly that he couldn't open his mouth, so it just kept burning him. Eventually he managed to get a couple fingers into his mouth, and was able to pry open his lips enough for the alcohol to dribble down his chin. My gene pool, ladies and gentlemen.
Prevention
Now, this is interesting. There have been two studies which indicate that regular consumption of alcohol may actually make you less susceptible to getting colds in the first place (with caveats). The first study was conducted by Carnegie Mellon University in 1993 to see the relation between smoking, drinking, and susceptibility to the common cold. 391 subjects were "intentionally exposed to one of five respiratory viruses and 26 subjects given saline." The study concluded that smokers got sick more often, people who were smokers and drinkers got sick a normal amount, and people who just drank got sick less than the others.
The other study found somewhat different results. Published in 2001, the study looked at 4,272 faculty and staff of five Spanish universities. It found that alcohol intake in the form of beer and spirits had no effect whatsoever on a persons susceptibility to the common cold. However, the study concluded that people who drank more than 14 glasses of wine per week were a whopping 60 percent less likely to get sick, even more so for drinkers of red wine. That is a huge number. It is suspected, however, that it isn't the alcohol directly, but rather the high levels of antioxidants which are in the wine. If that's the case then drinkers of Guinness and other dark beers (which are high in similar antioxidants) might net similar benefits. It must be said, though, that 14 glasses of wine per week is not an insignificant amount (two per night, on average), and of course, there may be health risks that outweigh the cold-fighting benefits for some people.
Conclusion
We can reasonably conclude that if you're already sick (or getting sick), boozing ain't going to help you. In fact it may make things worse. That said, if you have a penchant for red wine, there's some evidence that suggests it may significantly boost your cold-fighting abilities. You may be able to get achieve the same results from grape juice, however. The jury is out on that one.
All that said, have I ever drank whiskey when I've felt a cold coming on and woken up in the morning miraculously feeling better? Yes. Is that good science? No. (Was it good whiskey? Yes.) I have also repeated the same "experiment" and woken up feeling much worse that I probably otherwise would have. Again, bad science, but the point is that results are wildly inconsistant at best. So, next time you're trying to go home early because you're feeling sick, and your friend is trying to sell you on staying out and drinking whiskey instead, tell him that his theories have no scientific basis! Nerd zing. That won't shut him up, but it'll make you feel better about yourself for going to bed at 8:30.
The Health Benefits of Sex
That common bedroom excuse - a headache - needs to be turned upside down, sexologist Shelley Hiestand says, because headaches can be cured by sex.
It is just one of the many health benefits derived from frequent sexual activity, says Dr Hiestand, formerly from Dunedin.
The 46-year-old Las Vegas resident has made a career out of giving doctor's orders more agreeable than most.
"I definitely encourage people to have more sex."
Dr Hiestand said those aged under 25 should aim for more than once a day and those between 25 and 30 at least once daily.
Accordingly, those between 30 and 40 should have sex at least four times a week, and anyone over 40 at least thrice weekly.
"The anti-ageing benefits are amazing. It basically doubles your life span once you get to your 60s and 70s.
"I'm 46 and my husband is almost 64. We've been married almost 20 years and make sure we have sex at least once a day." Dr Hiestand said research - including her own - showed frequent sexual activity reduced the risk of breast and prostate cancer, helped cardiovascular health and eliminated stress.
"The more sex people have, the more energetic, less depressed and more able to cope with life they are. It is the best stress relief. It helps women go through menopause easier because it balances hormone levels, and it increases libido."
She encouraged women especially to change their attitude to sex, from thinking of it as a chore to focusing on its benefits.
Maggots
From ancient times until the advent of antibiotics, physicians used maggots to help clean injuries and prevent infection. Because the maggots feed solely on dead flesh, doctors did not have to worry about bugs feasting on healthy tissue. The arrival of antibiotics relegated medical maggots to an artifact of an earlier era.
Widespread antibiotic resistance, however, rekindled interest in the use of medical maggots, and in 2004 the fda approved them as a valid “medical device.” Today maggot providers raise the larvae from sterilized fly eggs and place them in tea bag–like packages that physicians apply directly to wounds. (The packages prevent the maggots from crawling off and completing their maturation into adult flies.) As more physicians have turned to the insects to treat wounds, scientists have uncovered the two-pronged process by which maggots work their magic.
One study published last year in the Archives of Dermatology showed that maggots placed on surgical incisions helped to clear more dead tissue from the sites than surgical debridement, the current standard of care in which doctors use a scalpel or scissors. “Maggot debridement takes out all the dead and infected tissue, which is necessary for the wound to close,” says lead author Anne Dompmartin-Blanchère, a dermatologist at the University Hospital Center of Caen in France. Surgical debridement is often lengthy and painful, something that maggot therapy eliminates, she adds.
A separate study published late last year in Wound Regeneration and Repair by Gwendolyn Cazander of Leiden University Medical Center in the Netherlands and her colleagues found that secretions from the maggots modulate the complement response, a part of the immune system that reacts to invading pathogens and is crucial to clearing infections. Some complement activation is necessary, but too much complement leads to chronic inflammation, which can keep injuries open and vulnerable to infection. Maggot secretions turned down complement activity in blood samples from healthy adults by inhibiting the production of several important complement proteins, and, the researchers found, reducing this overactive immune response speeds up healing. “About 50 to 80 percent of the wounds we see can be healed with maggots,” Cazander concludes.
Maggot therapy might sound medieval, but modern medicine seems to show that it works.
Antibiotics Curing (Some) Chronic Pain
Hundreds of thousands of people with chronic lower back pain could be cured by antibiotics, according to ground-breaking research that one expert said deserved a Nobel Prize.
The discovery that infections cause up to 40 per cent of cases of lower back pain has prompted calls for an overhaul of NHS treatment to avoid unnecessary surgery. If results from Denmark are confirmed, they could spare hundreds of thousands of people in Britain agony and turn doctors’ understanding of the condition on its head.
“For this group of patients it is revolutionary,” said Hanne Albert, of the University of Southern Denmark, who led the research.
The findings apply to people with microfractures of the vertebrae known as Modic changes, characterised by severe pain which persists at night and worsens with exercise. The condition must be confirmed by an MRI scan.
Dr Albert said identifying this group was the equivalent of singling out migraine sufferers among people with headaches. It is estimated that more than four million people in Britain suffer from chronic lower back pain and that about half a million with Modic changes could be cured by a three-month course of antibiotics.
The research was turned down by leading medical journals because it was deemed too radical. Dr Albert said it “takes guts” to publish such revolutionary conclusions.
In one study, she found that more than 40 per cent of 67 patients with Modic-related pain had a type of anaerobic bacteria in the discs between their vertebrae. A year later, 80 per cent of these patients had seen the damage worsen, compared with 44 per cent of those without any bacteria. The bacteria find their way into the spine as a result of a slipped disc, and produce acid that damages bone and nerve fibres.
Dr Albert then carried out a trial on 162 sufferers, with half given antibiotics for 100 days and half given a placebo. While the control group remained largely unchanged, 80 per cent of those given antibiotics improved, feeling much less pain and taking half the number of sick days. “Most of them said a sentence like, ‘I’ve got my life back’,” Dr Albert said. The results are presented in two papers published in the European Spine Journal.
She compared her research with the discovery that bacteria cause stomach ulcers, which were long believed to be the result of stress.
Doctors took more than a decade to accept those findings and Dr Albert has formed an educational group to try to spread her discovery more quickly. But she urged patients not to badger their GPs for antibiotics unless their pain was confirmed as Modic-related.Peter Hamlyn, a consultant spinal surgeon at University College London Hospitals, has used Dr Albert’s technique on 24 of his private patients and says the difference is dramatic; one who could barely complete physiotherapy is now training for a triathlon.
“The discoveries of Hanne Albert and her team require us to reconsider our understanding of chronic low back pain,” he said. “They have described a discrete clinical syndrome, Modic- related back pain, a specific diagnostic test (MRI scanning) and an effective and low risk therapy.
“Modic-related low back pain accounts for perhaps 40 per cent of all chronic low back pain. One of the commonest causes of disability in our communities... chronic low back pain is an international plague. More work needs to be done, others must replicate this work but make no mistake, this is a turning point, a point where we will have to rewrite the textbooks. It is the stuff of Nobel prizes.”
Replacement Ears
Researchers at Princeton and Johns Hopkins have taken the development of 3D-printed latticework, that can be seeded to grow human tissue, to the next level. They've added bionics to it.
It's now relatively commonplace to produce 3D-printed latticeworks to replace lost tissue. Those lattices can be seeded with real human cells, which then grow, and result in an implantable replacement organ. These researchers wanted to see if they could incorporate simultaneous emplacement of functional electronics at the same time. In this experiment (which did not involve a human subject), they created a coil at the same time as the lattice, and it grew into an ear with a coil biologically incorporated. The coil could be used to receive induction audio signals from a hearing aid, or even to receive radio signals. Imagine that, stereo audio with no headphones.
Sunlight
Students at Strathclyde University were making the most of the sunshine in Glasgow yesterday as a study revealed that the benefits of exposure to sunlight could outweigh the risk of developing skin cancer.
Scientists at the University of Edinburgh reached that conclusion after measuring the blood pressure of 24 people in two 20-minute sessions under tanning lamps. Other experts decried the idea as unproven — and urged people to take care in the sun.
The researchers found that blood pressure fell for an hour after exposure to the lamp, but not in “sham” sessions where the ultra violet (UV) rays were blocked, leaving only heat.
Blood pressure when the heart was at rest (diastolic) fell by an average of 2mmHg, according to results to be presented today at the International Investigative Dermatology Conference in Edinburgh. Normal blood pressure at rest is 80mmHg. Pressure when the heart was pumping (systolic) was unaffected.
The researchers found that UV light releases nitric oxide from the skin, which dilates the arteries and so reduces blood pressure. Vitamin D levels were unchanged.
Richard Weller, senior lecturer in dermatology at the University of Edinburgh, who led the study, argues that because heart disease and stroke kill 80 times as many people as skin cancer, the benefits of sunlight could outweigh the risk.
Much larger studies would be needed to confirm this, however.
Waist to Height Ratio
People whose waists measure more than half their height are more likely to die early, a study has found.
The waist-to-height ratio is a more reliable predictor of early death than the traditional measure of obesity, the body mass index, the research found. The scientists who carried out the study said that doctors should start telling people: “Keep your waist circumference to less than half your height.”
The team looked at two sets of data: from the Health and Lifestyle Survey, which has followed thousands of people since 1984, and the Health Survey for England, which studies 8,000 people in detail every year.
Death rates were low for the 10 per cent of people with the lowest waist-to-height ratios, and rose steadily up to the ten per cent with the highest waist-to-height ratios. Men whose waist measurements are 80 per cent of their height at the age of 30 lose an average of 20 years of life, according to results being presented at the European Congress on Obesity in Liverpool.
Margaret Ashwell, a nutritional consultant and visiting researcher at Oxford Brookes University, who led the study, said: “It’s a distinct upward trend with waist-to-height ratio. With BMI, it’s vaguely upward but with waist-to-height ratio it’s significantly stronger.”
Last year she found that waist-to-height measurement was better than BMI in predicting problems such as heart disease and diabetes. She compared Arnold Schwarzenegger and Danny DeVito to illustrate the problem with BMI. “When you look at Arnie and Danny, it’s obvious [who’s fitter] ... But they both come out with a BMI of 34-35.” Dr Ashwell estimates Schwarzenegger’s waist-to-height ratio at 0.47, compared with 0.71 for DeVito.
BMI falsely reassures some “apple-shaped” people who may be at risk, she said. “There’s more and more evidence that it’s that central fat wrapped around the vital organs that is much more reactive. It’s just geographically nearer to the heart and liver and there is evidence that hormones that come out of this fat are more dangerous than fat that is on the hips.”
Statins
Should I, or shouldn’t I take a statin? That is the question. And if you are somewhat confused by recent media coverage, rest assured you are far from alone. One week there are calls for the cholesterol-lowering drugs to be prescribed more widely. The next, doctors are being accused of dishing them out too readily, and underestimating the side-effects. So what is the public to make of it all?
As with most polarised debates, considered opinion falls twixt the two extremes. Statins are certainly no panacea for the ills of the western world, but neither are they the spawn of the Devil. Used appropriately, statins offer significant protection against an early heart attack or stroke, and are generally well tolerated by most people who take them. But herein lies the stumbling block— what is appropriate?
Currently in the UK, doctors deem it appropriate to offer statins to those otherwise healthy people who have more than a 20 per cent (1 in 5) chance of having a stroke or heart attack in the next ten years (see box below). The National Institute for Health and Care Excellence (Nice) is considering reducing that threshold to a 10 per cent chance, a move that could mean anything up to five million extra middle-aged people in the UK would become eligible. In America it is already even lower at just a 7.5 per cent chance.
It is all about balancing benefit against risk. Although there remains controversy over the link between fats in your diet, fats in your blood and fats clogging up your arteries, few dispute that statins work. Depending on which study you believe, research suggests they reduce the risk of stroke and heart attack by about 25 per cent. Yet while a quarter of quite a lot is impressive, a quarter of not very much isn’t. So the lower your risk of heart attack and stroke, the less significant the protection you are likely to get from taking a statin. The downsides remain the same whatever your underlying risk, so there comes a point where the drugs are likely to do more harm than good.
Using the current 20 per cent risk threshold it is estimated that about 35 people will need to take a statin for five years to prevent one of them developing cardiovascular disease. Over that same period 1 in 40 taking the drugs will develop a statin-induced cataract, about 1 in 100 will have liver problems, and 1 in 400 will develop kidney failure. Reducing the threshold to just 10 per cent will mean more people will have to be treated to save a life, but the odds of a serious side-effect like kidney failure remain exactly the same, shifting the risk benefit ratio towards risk.
My other concern with lowering the threshold is that too many people regard statins as a substitute for healthy diet and lifestyle modification, rather than as a supplement to such changes. I would far rather my patients lost weight, exercised more, ate healthily, stopped smoking and drank in moderation than took a statin. And studies show that self-help often works much better than the drugs.
So what would I do? It is a pertinent question because I am at higher than average risk thanks to a poor family history and deranged cholesterol levels. I have taken a statin in the past and experienced no side-effects, but I stopped because I didn’t feel my level of risk warranted continuing the drug (I remain well below the 20 per cent threshold). And, for me, that 20 per cent level remains a sensible cut-off despite the changes Nice is considering.
Still, it remains a matter of personal choice. No doctor is going to force you to take a statin but they may well offer you one, and you should make an informed decision as to whether it is right for you. In part that will depend on how lucky you feel. Do bear in mind that if you decide to take statins, the lower your risk of problems in the first place, the luckier you need to be.
What do statins do?
The protective effects of statins are attributed to a reduction in cholesterol but they probably work in other ways too — including reducing inflammation of the lining of the arteries and stabilising deposits on narrowed artery walls so they are less likely to tear or break off (the classic precipitating event for most heart attacks).
Common complaints from people taking statins include upset stomach, sleep disturbance and aching muscles. Some also complain of mental fogging and poor memory, although statins may not be to blame.
Visit qrisk.org to calculate your cardiovascular risk.
Friday Operations
Patients who have operations on a Friday are almost 50 per cent more likely to die than those who go under the knife on a Monday, a study has found.
About 1,600 patients a year die needlessly because surgery becomes steadily more dangerous throughout the working week, the analysis suggests.
While previous studies have found that patients admitted at the weekend are more likely to die, the latest study is the first to find a similar effect during the week.
The authors of the report said the root causes were likely to be the same, with patients undergoing surgery on Fridays forced to recuperate over the weekend when senior doctors are often unavailable, nursing staff are fewer and testing services are reduced.
The findings will place pressure on NHS bosses to intensify their efforts to offer a fuller range of hospital services seven days a week.
“If I were a patient being operated on on Friday, I would want to know that there were adequate services available at the weekend to be able to pick up any potential problems,” said Paul Aylin, the assistant director of the Dr Foster unit at Imperial College London, who led the study.
“Our hypothesis was that there is a period of time immediately following operations, the first 48 hours, which is the critical time when things can go wrong. You get bleeds, or the beginnings of an infection ... and the closer you get to the end of the week, the more that post-operative period overlaps with the weekend services and therefore the potential for some of these complications being less well picked up.
“I think it’s not just lack of senior experienced staff — in general we’re talking about fewer nursing staff, fewer diagnostic services; if you can’t order an X-ray or a blood test, that will have an impact.”
Dr Aylin’s team looked at more than four million operations across England, ranging from hip replacements to heart bypasses. On Mondays, there were 5.5 deaths per 1,000 operations, but this climbed to 8.2 per 1,000 on a Friday, they report in the British Medical Journal.
After adjusting for different types of procedures, and the ages and illnesses of patients, deaths were 44 per cent more likely on a Friday than a Monday. Planned operations at the weekend were 82 per cent more likely to be fatal.
Antony Narula, a member of the council of the Royal College of Surgeons, said: “It is not acceptable that there should be such a wide variation in the mortality rates following elective surgery, according to the day of the week the operation takes place. It has long been recognised that the 48-hour period after surgery is critical to a patient’s chances of recovery and today’s study rightly suggests that this is an area which needs further research.”
Skeptoid Rebuts Alternative Medicines
A topic sure to get under the skin of many of its often vocal proponents is alternative medicine. Believers in unproven treatments and opponents of commercialized medicine can often take their beliefs very seriously, almost to the level of religion, and sometimes react with great hostility whenever their beliefs are questioned. So this subject always results in some fiery feedback. Let's read a few.
The Skeptoid episode addressing the claims of products that say they can boost your immune system was especially inflammatory — pun somewhat intended. Many marketers claim that drinking their special juice or taking their special supplements will strengthen your immune system with their unique blend of nutrients. In fact, this is not at all the way the immune system works, but many customers of such products were outraged at the suggestion. Jacob from Melbourne, FL wrote in and said:
I'm sure we all know someone who gets sick more often than other people. It's often someone who is in the same places as you (like a dorm room in college, or an office building), and they seem to catch EVERY cold that comes around. And no I'm not talking about the people that play hookie. I very rarely get sick, so when I compare myself to those other people, I am led to believe that my immune system is superior to theirs in some way. According to your analysis, if I'm not catching their colds, then my body's immune system must be attacking my healthy cells, in some sort of low-level auto immune disease-like function.
No, not catching every cold doesn't mean that you have an auto-immune disease, and that was not my conclusion in the episode. More likely you're in a different risk group. There are many different risk groups for catching colds. New schoolchildren, for example, are young and haven't been exposed to many colds before, but suddenly they're exposed to many at school, so a lot of them get sick. They bring them home to young parents, who catch them too. Older parents, school teachers, and experienced family doctors have already been exposed to virtually every cold on the planet and are more likely than non-parents to have the antibodies to any given cold. People who shake a lot of hands in their job are likely to catch a lot of colds, but if they've been doing it for decades they may have already caught a lot of the colds. Once your adaptive immune system is challenged with a new pathogen, your body retains resistance to that particular pathogen for years, decades, often even for life.
Don't confuse your adaptive immune system — the part consisting of antibodies created as responses to exposure to pathogens through disease or vaccination — with the innate immune system, systems like the skin and saliva and all the immune responses that produce the familiar symptoms of inflammation, fever, running nose. When that person at your office comes in with the full-blown cold symptoms, you're seeing their immune system in action and doing its job. It makes no sense to conclude that your own immune system is somehow "boosted" because it's not currently reacting to anything.
Alan from Los Angeles raised a common straw-man argument against approved drugs, that we claim herbal medicines don't do anything:
For those of you who say alternative medicines don't work, you will agree with me that herbal medicines count as alternative right? Will you say then that salicylic acid, digitoxin, paclitaxel, colchicine, vinblastine, cocaine, morphine, caffeine, nicotine, and countless other NATURAL compounds derived from plants used in traditional medicine have NO effect on the human body?
No, you're confusing the two terms, alternative medicine and herbal medicine. As you note, the vast majority of drugs on the market are derived from compounds found in nature. The whole science of ethnobotany is about discovering useful compounds in nature, not just herbs but insects, roots, fungi, algae, just about anything. Every pharmaceutical company has research stations in jungles, oceans, everywhere. Remember, every herb is a chemical, and many of them can be pharmacologically active. The development stage is where we isolate, refine, and possibly synthesize the active molecules, determine proper dosages, and so on. Then we test them clinically to be sure they work as intended before putting them on the market.
Alternative medicine, on the other hand, refers specifically to treatments that are either not yet proven to work, or proven not to work. They're often those that have been abandoned during the research stage for failing to yield anything useful. Thus they're not allowed to be sold with claims that they treat any disease, thus they're classified as "alternative".
Note that some of the herbal alternative medicines available over the counter are pharmacologically active: St. John's Wort, for one; which if you've ever been in surgery, is one that the anesthesiologist might ask you if you've taken recently. The reason I'd recommend against using any over-the-counter herbal compounds is that they have not gone through the drug development stage required for FDA approval, and you're getting an unknown dosage of unknown purity.
Our episode on magic jewelry assessed the claims made by many marketers of jewelry products that claim to produce healthful effects or improved sports performance, usually with the contention that ions, magnetic fields, vibrations, or some other such nonsense are involved. But one listener, Astrid from San Francisco, made a suggestion that I hadn't heard before; that wearing special therapeutic jewelry is simply a topical application of a mineral supplement:
Actually, copper is an essential mineral of the body. The skin absorbs things topically. You can see this realization now in the modern pharmacutical industry, they now produce many topical medicines. Wearing a bracelet may not be a cracked up as people are inflamed to believe. Also, many different people have many different healing needs. Everyone's body is different. A bracelet may help some people and not others. It depends on the need. No need to get inflamed and freaked out over people who experience healing by less chemical means.
Astrid's assertion that taking metallic elements into your body is a "less chemical means" is difficult to defend, as metals are (quite obviously) among the most familiar of chemicals. Her main point is that copper jewelry constitutes copper supplementation. There is some truth to this. An adult normally needs 1.5-3mg of copper per day to maintain the body's total burden of some 100-150mg, and in testing, copper bracelets worn around the wrist have been found to lose about 1.8mg/day. Metallic copper is slightly soluble in human sweat, and the copper has been found to be perfused into the skin.
The point to be cognizant of is that nearly all such research has sought to determine whether such copper supplementation is an effective treatment for arthritis, and that result has been a resounding no. So really, all that wearing a copper bracelet might be useful for is if you have some highly unusual diet that, for some reason, doesn't provide the same amount of copper as a normal diet, and you're suffering from a deficiency acute enough to justify the expense.
The episode on detoxification has continued to produce lots of feedback, even years afterward. The pitch that we all live in a toxic modern environment is compelling to many people and easy to sell. Isabelle from Victoria, BC conflated these alleged environmental toxins with prescription drugs, suggesting that they are equally toxic:
Oh my, Looks like the skeptoid is not aware that the 2nd cause of death in America is prescriptions correctly prescribed by their doctors. That is a fact! Total Health can only be acheive by natural means (except for emergencies). We are overloaded by toxins and detoxing on a regular basis can extend one's life significantly. The examples are so stupid to discard the whole industry like that. How lame
It is a fact that most people who die in the United States are under medical care at the time. Cardiovascular diseases as a whole are the leading killer, including heart attacks, strokes, and so on; followed by all the many cancers; followed by respiratory infections, car accidents, etc. Depending on how you group them into categories and break down the categories you can make just about anything rise to the top of the list. But clearly, a majority of deaths are of people treating chronic illness with medical care. You can say that it's the medical care that killed them, but it's not as true as saying it was the disease that the care was attempting to treat. Contrary to popular belief, medicine is not magic, and we simply can't cure everything despite our best tries. Thus, most people die under medical care.
This episode also produced a lot of non-specific anti-pharmaceutical feedback, which is ironic since all the detoxification products I'm aware of are themselves pharmaceuticals; just unapproved and unproven. Nevertheless, the episode prompted Tove from Varberg to repeat one of the most familiar arguments against science-based medicine:
I've had a lot of healthproblems and I found most doctors didn't bother to even try to find what was causing them, they just wrote a bunch of prescriptions for meds to treat the symptoms, they made my problems worse, always.
The idea that medical science treats just symptoms while only alternative practitioners treat the cause of disease is simply wrong. Doctors who have addressed this claim, like Steven Novella and Harriet Hall, have pointed out numerous times that — with the exception of chronic pain management — there's really not a single example of a medical treatment that does not attempt to treat the cause. Antibiotics are to kill bacteria infections. Trauma management and critical care attempt to repair injuries. Oncology focuses on killing the cancer cells. Other than when we're trying to make a terminal patient comfortable, the entirety of medical science is directed at finding and treating the cause of disease.
The episode on reflexology generated a lot of straw-man feedback. Reflexology is the idea that certain points on the soles of the feet and palms of the hand correspond to all bodily organs, despite the glaring fact that no anatomy connects them. For example, if you have stomach cancer, massage the spot on the sole of the foot that allegedly corresponds to the stomach, and you can cure the cancer. It's pure pseudoscience, but its proponents adhere to it religiously. Dee from Canada wrote:
I have been teaching reflexology for some years now. Here is the definition "Reflexology is the pressure point massage on the feet, hands and ears to relax athe body so that the body can heal itself" There is NO mysticism involved. Science proves that there are over 7200 nerve endings in the feet alone. If we can relax the body by massaging the feet - what a concept. Does it work? After a foot massage are you relaxed? Well that answers that.
This is by far the most common feedback I get pertaining to reflexology. Of course foot massages feel great and are relaxing, and yes, relaxation does reduce stress and that can impact general health and wellbeing. Science doesn't deny that at all; in fact, therapeutic massage is often doctor-recommended. But massage is not reflexology. A reflexologist gives a foot massage — along with all the real benefits it confers — but then makes a further claim that the massage is treating a specific disease or condition in some specific part of the anatomy. If they don't, it's not reflexology; it's massage. I've no doubt that the majority of reflexologists are talented masseuses whose foot massages produce true relaxation and stress reduction. That's what massage therapy is. It's not what reflexology is.
The requirements to get a massage therapy license are pretty onerous in most states, usually requiring hundreds or even thousands of hours of work as a trainee. But reflexology is not a board certified medical profession; any Joe Blow can legally hang out a shingle and call himself a reflexologist with no training whatsoever, even though any of the various self-certifying reflexology authorities may not like it. This type of loophole tends to draw people who want to shortcut the system. Probably most reflexologists are honest practitioners with no such desire to game the system, but any reflexologists who claim that it's identical to ordinary massage therapy either don't understand their own profession or are lying.
Vitamin Tablets Are Bad For You
These are not friendly times for bankers. On Thursday the Financial Conduct Authority set up a nationwide scheme of redress to reimburse customers who had bought “useless” policies insuring them against identity theft. The insurance was useless because banks were in any case obliged to indemnify all account holders against identity theft: they were being sold something they already had, even if they didn’t realise it.
If you think such behaviour is peculiar to bankers, think again. Is not such a scam identical in spirit to that perpetrated by the vitamin supplement business?
In fact, that apparently innocent industry’s entire business model could be described as a skilful mystification preying on the same public neurosis: the need to feel insured against unquantifiable risks. This parallel was unwittingly suggested by Simon Bandy, general manager of a vitamin supplement business, Health Plus. He was responding to a report last week by the consumer group Which?.
Health Products You Don’t Need was a drily factual debunking of some of the claims made by companies selling multivitamins and glucosamine supplements — that they make your heart, limbs and even brain work better and last longer. Some of the firms named by Which? responded that they would “redesign the packaging” — that is, withdraw their more outlandish claims. Others took refuge in silence.
And then there was Mr Bandy. He told a newspaper following up the report: “People do take supplements because they want to make sure they’re getting the nutrients their bodies require. They act as an insurance policy to make sure your body’s getting the right number of nutrients.” Yet, just like the gulled purchasers of the banks’ identity theft policies, we don’t need that “insurance”. Except in rare cases — such as vegans or some expectant mothers — we get easily enough of the vitamins we need from the food we eat.
Bandy suggested that low-income people reliant (allegedly) on junk food did not get enough vitamins and therefore needed what he sold; but it would be especially scandalous if these firms targeted the gullible poor, just as it would be if the banks had concentrated on their least well-off customers for the identity theft insurance scam.
In fact, supplements are consumed for the most part by middle-class people with far too much concern for their health to be living on a diet of Coke and mega-fries. It’s the worried well we’re talking about here: you don’t see many people with malnutrition browsing the shelves at Holland & Barrett, either for themselves or for their pets (the firm’s exclusive brand of multivitamins for animals claims to be “purr-fect for cats and dogs alike!”).
It’s true that not so long ago it was quite common for doctors to recommend that their patients take a daily multivitamin pill, though I suspect much of that was to satisfy the desire of hypochondriacs for some sort of “cure”; and since the view was until quite recently that popping large quantities of these pills was harmless, why not let such patients spend their own money on placebos?
Over the past decade, however, medical science has moved to the view that the ingestion of multivitamins can be dangerous; that they can even reduce life expectancy. This is the main theme of a fascinating new book, Killing Us Softly: The Sense and Nonsense of Alternative Medicine, by Dr Paul Offit, the head of the infectious diseases unit at the Children’s Hospital of Philadelphia. The recent research cited by Offit (which I summarise) should alarm those — in Britain more than a third of the population, apparently — who are habitual multivitamin pill-poppers.
In October 2011 researchers from Minnesota University evaluated 39,000 older women and found that those who took supplemental megavitamins died earlier than those who didn’t. In 2004 researchers from Copenhagen University reviewed 14 randomised trials involving more than 170,000 people who took vitamins A, C and E and beta-carotene to see if these lauded antioxidants could prevent intestinal cancers.
They concluded: “We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality.” In 2008 a meta-survey of all existing studies involving more than 230,000 people who did or did not receive supplemental antioxidants found that those who did had an increased risk of cancer and heart disease.
This seems counterintuitive, to put it mildly. Doesn’t the word vitamin derive from the Latin for life? Offit’s explanation for this seeming paradox is that you can have too much of a good thing (an ancient medical truth, “the dose makes the poison”, comes from the 16th-century physician Paracelsus). So, as Offit writes: “If you go into a General Nutrition Center [GNC] you can get a preparation which contains 3,333% of the recommended daily dosage of vitamin E. In fact that’s a typical vitamin E preparation. If you open up the bottle and take out one capsule you’ll find it’s smaller than an almond . . . but to get to 33 times the daily recommended allowance, you would need to eat about 1,700 almonds. I think if people saw that one capsule as 1,700 almonds they would be hesitant to take it. But they don’t see it that way.”
Indeed they don’t; which is why, despite the results of recent medical research, the industry keeps on growing. Offit, in disgust, quotes the chief executive of GNC, America’s largest chain of vitamin supplement stores, as saying: “The thing to do with is just ride them out . . . We see no impact on our business.” And this is big business — worth in America about $30bn (£20bn) a year and about £400m a year in Britain. I suspect many of those taking supplements with cuddly names believe they are evading the clutches of “big pharma”. Yet as Offit points out, “two of the biggest players in the megavitamin business are Pfizer and Hoffman LaRoche”.
One reason such companies are moving into this field is that the regulatory burden is far less onerous than it is for bona fide medicines. They are classed as supplementary foods rather than drugs. In one way this is understandable: any side effects are much less strong than those of pharmaceutical products — not least because many of them are little more than cleverly branded placebos. Yet if a product makes claims for medical efficacy its marketers should be able to substantiate those assertions with as much rigour as is required for any drug.
Puzzlingly, Britain is more resistant to this idea than any other country in Europe: a letter of protest against proposed European legislation tightening up the regulation of vitamin supplements collected more than 1m signatures and was duly delivered to Downing Street, back in Tony Blair’s day. So perhaps we should shrug our shoulders and recall the words of the late law professor Jim Gower that “regulation should not be at a level set to achieve the impossible task of protecting fools from their own folly”.
Gower was speaking about financial regulation. Yet whatever you think about bankers, their latest mis-selling doesn’t feast on our greatest terrors: ill health and death.
Standing Up
WINSTON CHURCHILL knew it. Ernest Hemingway knew it. Leonardo da Vinci knew it. Every trendy office from Silicon Valley to Scandinavia now knows it too: there is virtue in working standing up. And not merely standing. The trendiest offices of all have treadmill desks, which encourage people to walk while working. It sounds like a fad. But it does have a basis in science.
Sloth is rampant in the rich world. A typical car-driving, television-watching cubicle slave would have to walk an extra 19km a day to match the physical-activity levels of the few remaining people who still live as hunter-gatherers. Though all organisms tend to conserve energy when possible, evidence is building up that doing it to the extent most Westerners do is bad for you - so bad that it can kill you.
That, by itself, may not surprise. Health ministries have been nagging people for decades to do more exercise. What is surprising is that prolonged periods of inactivity are bad regardless of how much time you also spend on officially approved high-impact stuff like jogging or pounding treadmills in the gym. What you need as well, the latest research suggests, is constant low-level activity. This can be so low-level that you might not think of it as activity at all. Even just standing up counts, for it invokes muscles that sitting does not.
Researchers in this field trace the history of the idea that standing up is good for you back to 1953, when a study published in the Lancet found that bus conductors, who spend their days standing, had a risk of heart attack half that of bus drivers, who spend their shifts on their backsides. But as the health benefits of exercise and vigorous physical activity began to become clear in the 1970s, says David Dunstan, a researcher at the Baker IDI Heart & Diabetes Institute in Melbourne, Australia, interest in the effects of low-intensity activity—like walking and standing—waned.
Over the past few years, however, interest has waxed again. A series of epidemiological studies, none big enough to be probative, but all pointing in the same direction, persuaded Emma Wilmot of the University of Leicester, in Britain, to carry out a meta-analysis. This is a technique that combines diverse studies in a statistically meaningful way. Dr Wilmot combined 18 of them, covering almost 800,000 people, in 2012 and concluded that those individuals who are least active in their normal daily lives are twice as likely to develop diabetes as those who are most active. She also found that the immobile are twice as likely to die from a heart attack and two-and-a-half times as likely to suffer cardiovascular disease as the most ambulatory. Crucially, all this seemed independent of the amount of vigorous, gym-style exercise that volunteers did.
Correlation is not, of course, causation. But there is other evidence suggesting inactivity really is to blame for these problems. One exhibit is the finding that sitting down and attending to a task—anything from watching television to playing video games to reading—serves to increase the amount of calories people eat without increasing the quantity that they burn. Why that should be is unclear—as is whether low-level exercise like standing would deal with the snacking.
A different set of studies suggests that simple inactivity by itself—without any distractions like TV or reading—causes harm by altering the metabolism. One experiment, in which rats were immobilised for a day (not easy; the researchers had to suspend the animals’ hind legs to keep them still) found big falls in the amount of fats called triglycerides taken up by their skeletal muscles. This meant the triglycerides were available to cause trouble elsewhere. The rats’ levels of high-density lipoprotein (HDL) fell dramatically as well. HDL is a way of packaging cholesterol, and low levels of it promote heart disease. Other studies have shown the activity of lipoprotein lipase—an enzyme that regulates levels of triglycerides and HDL—drops sharply after just a few hours of inactivity, and that sloth is accompanied by changes in the activity levels of over 100 genes.
Papers which focus on people rather than laboratory animals have found similar effects. Happily, this research also suggests the changes can be reversed by small amounts of fairly relaxed activity. A study published last year by Dr Dunstan found that breaking up prolonged periods of sitting with two minutes of walking every 20 minutes made a big difference. After feeding his volunteers a sugary meal, he discovered that people who had been walking in this way had blood-glucose levels almost 30% lower than those of people who had remained seated.
For some scientists, this combination of epidemiology, animal experiments and human trials suggests that light-to-moderate exercise—standing up, walking around and the like—is something qualitatively different from an energetic, high-intensity workout. But not everyone is convinced. Many of the human studies are small-scale. (Dr Dunstan’s paper, for example, involved just 19 participants.) And not every study that has gone looking for the ill effects of inactivity has found them.
Still, the potential size of the problem means not everyone is prepared to wait for definitive proof. Sellers of standing desks are, naturally, jumping on the latest research findings to advertise their wares. And it is surely only a matter of time before the first law suit from a sickly cubicle slave reaches court.
Clarification: This piece seems to have caused some confusion on the web, for which we apologise. The frequent, gentle activity recommended by some researchers to stave off the dangers of long periods of sloth is not intended as a replacement for regular, vigorous exercise, but as a complement to it. We have tweaked the paragraph that seemed likely to be the cause of the muddle.
The Hygiene Hypothesis
Two of the most monumental developments in the history of human civilization, likely the innovations that have saved more human lives than any other, are soap and sanitation. When large numbers of people congregate in a single location for prolonged periods of time, excrement and waste quickly rise to unimaginable levels and are capable of spreading disease incredibly quickly. As I mentioned in my first post here at Food Matters, many pathogens utilize the fecal-oral transmission route, in which poop from an infected individual makes its way into the water supply or onto food by serial contact (touching a contaminated surface then touching food). Lack of hygiene dramatically increases the likelihood of this sort of infection, as many infectious microbes can grow unchecked on filth outside the body, and many viruses can linger on unwashed surfaces for long periods of time.
Thankfully, In modern developed countries, we don’t have to worry about this much. Most of us live in places with sanitation infrastructure that carries away our waste and delivers fresh water, and we tend to have bottles of life-saving soap in every room with a sink. In the absence of soap and sinks, waterless hand sanitizers, sanitizing wipes and bleach-containing cleaning products promise to keep away the dreaded germs. Yet while there’s no doubt that sanitation and hygiene are critical in reducing the spread of infectious disease, it’s possible that we’ve gone too far in trying to live a sterile life.
In 1989, British physician David Strachan proposed the “Hygiene Hypothesis,” which sought to explain a puzzling series of observations: Children in cities in developed countries and had fewer siblings, those that lived more sanitary lives and presumably had less exposure to infectious diseases, were more likely to develop allergies, asthma and other atopic diseases than those that lived on farms or in developing countries, or that had many siblings. In the nearly 25 years since this was first proposed, a great deal of research has shown that exposure to diverse bacteria or even parasitic worms helps to train and regulate the immune system, preventing it from becoming over-active.
Many of the ideas put forward to explain how microbes might regulate the immune system are, in my opinion, problematic. I’ll spare you the details for now (if you ask in the comments, I may just have the motivation to write it up!), but basically, they boil down to suggestions that turning on certain types of immune responses take energy away from other types of immune responses that might cause disease*. But there’s also evidence that, even in the absence of a full-blown immune response, exposure to different populations of bacteria can have a significant impact on the way that our immune system responds to other threats.
Take, for instance, the relationship between the denizens of our intestines and diabetes. I’m not talking about the science showing that these gut microbes can affect obesity (though that’s pretty amazing), I’m talking about the fact that having different populations of bugs can influence your liklihood of developing diabetes, regardless of weight. In 2008, a group of researchers led by Alexander Chervonsky at the University of Chicago showed that, in a mouse model of diabetes, mice lacking gut microbes had more severe disease, while those with gut microbes were protected. Three years later, a lab here at Harvard reported that the presence of a single type of bacterium called segmented filamentous bacteria (SFB) in the gut was sufficient to provide protection (unfortunately, consuming SFB is not a really a viable prevention strategy, since many other autoimmune disorders are more prevalent in animals with SFB in their guts). Other research has shown that diabetic humans have very different microbial populations in their guts, though this is probably an effect of altered metabolism rather than the cause.
Joint Pain and Weather
Atmospheric conditions, including temperature, pressure, and humidity, do not affect the temperature, pressure, or humidity inside the human body. Thus, there is no plausible way that the weather could impact joint pain.
Like taking Vitamin C to cure a cold, this is another medical myth that is so deeply ingrained that it's really hard to shake. For most of my life I believed my bum knee could predict weather changes. I thought it worked like a barometer. I was unaware that simply riding in an elevator produces much greater shifts in atmospheric pressure than common weather fronts. And so I fell victim to confirmation bias. You see the weather is almost always changing one way or another, and whenever my knee happened to hurt, I'd take notice if the weather was indeed changing. If it didn't, I probably just attributed the knee pain to the bum knee. Confirmation bias causes us to assign undue significance to events that confirm our belief, and causes us to rationalize away any events that don't.
Changes in humidity are even less plausible. Human bodies have very specific hydration levels. Walking through a sprinkler dramatically shifts the relative humidity outside your body, but does not affect your body's internal hydration. Neither does a humid or a dry day. The synovial fluid inside your joint is the same whether you're in the desert or the bathtub. If you became dehydrated enough for your synovial fluid to be affected, you would experience many other more severe symptoms of dehydration first.
Ice packs and heat packs can, however, be used to alleviate joint pain. The difference is that these, when applied directly for a period of time, will change your deep tissue's temperature at the point of application. However, weather only affects your skin; so long as you are properly clothed and don't experience hypothermia or hyperthermia, your body temperature remains unaffected.
Crash Diet Beats Diabetes
BRITAIN’S 2.6m type 2 diabetics have been offered new hope after scientists found a short-term crash diet can reverse the disease and restore their natural insulin levels.
They found that putting overweight diabetics on a diet of just 800 calories a day cleared the disease and returned them to health in a few weeks.
So far the technique has been tested successfully on only 11 patients, but now it is to be the subject of a £2.4m medical trial involving 280 people with obesity-induced diabetes.
The hope is that the crash diet could provide a clinical treatment for GPs around Britain to use to tackle the epidemic of diabetes that costs the NHS about 10% of its entire budget.
Professor Roy Taylor, director of Newcastle University’s magnetic resonance imaging (MRI) centre, who led the initial study, said the early findings were “enormously exciting”.
“We demonstrated that by changing calorie intake we could change fat levels in the liver and pancreas and return insulin production to normal,” he said.
“The new study is to see whether GPs can use this approach to reverse diabetes in their patients and whether it will stay reversed. The evidence is that it will, but we need a large-scale trial to prove that it works.”
Type 2 diabetes, unlike type 1, is closely correlated with obesity. It occurs when the body cannot produce enough insulin, or the body’s cells do not react to insulin, a hormone secreted by the pancreas that moves glucose from the blood and into cells where it can be used for energy.
With insufficient insulin, blood sugar soars, with a raft of dangerous side effects. These include a sharply increased risk of heart attack and stroke, blindness, foot amputation and dementia.
Scientists already know that people who undergo weight-loss surgery such as gastric bypasses often see their type 2 diabetes go into remission, but such treatments are dangerous and seen as the last resort. The crash-diet approach is based on new evidence about the underlying cause of the disease, linking its onset to the depositing of fat around the liver and pancreas. In healthy people the liver should contain only about 2% fat, but in the obese this can exceed 40%, which, research shows, can suppress insulin production.
Taylor and his co-researcher Mike Lean, professor of human nutrition at Glasgow University, who will be jointly overseeing the new trial, used MRI scans to observe how crash dieting rapidly removes these particular fat deposits, potentially explaining why it gets such rapid results.
“The good news is that if you cut fat in the diet then the liver fat falls very rapidly — and that means the pancreas can start working again,” said Taylor.
Allan Tutty, aged 54, from Sunderland, saw his diabetes go into remission after starting the crash diet in November 2012. By January he had lost 2st 7lb and his diabetes was in remission.
He said: “The hunger went away after a few days, but the biggest issue was the boredom, because the diet is just milkshakes and vegetables. I also didn’t sit down with the family at meal times, and at Christmas all I had was a salad.”
For Tutty the effort was well worth it. “Being diagnosed with diabetes had a powerful psychological effect on me. I was told there was no cure and it would be with me for ever. I feel better now psychologically and physically.”
Taylor and Lean are encouraged by such success stories, but say far more data is needed to assess the potential.
In their new study 140 patients with obesity-related type 2 diabetes will be put on low-calorie liquid diets for 8-20 weeks. Another 140 will act as controls — getting the best modern treatments but without having to diet.
Once they have hit their target weight and come off the diet, the patients will be monitored for up to two years to see if they can avoid regaining the lost weight.
Lean said the crash diet would be tough for people to stick to. “We’re confident that some people with type 2 will be able to achieve remission because we’ve seen it happen before. But what we really want to know is: how many can do it and are we able to identify those for whom it is not worth making the effort?
“If our analysis shows this approach is both effective and cost-effective, our aim will be to produce a programme that can be implemented in the NHS as soon as possible.”
Anna Morris, head of research funding at the charity Diabetes UK, said the crash-diet approach was the most promising they had seen in years. “We are putting £2.4m into this new trial, making it the biggest study we have ever funded. If the results are positive then the impact would be huge, but we need to wait and see what the outcomes are.”
Cherry-Picking
It’s not only Tamiflu where inconvenient data goes unpublished. Try climate science and psychology too.
Perhaps it should be called Tamiflugate. Yet the doubts reported by the House of Commons Public Accounts Committee last week go well beyond the possible waste of nearly half a billion pounds on a flu drug that might not be much better than paracetamol. All sorts of science are contaminated with the problem of cherry-picked data.
The Tamiflu tale is that some years ago the pharmaceutical company Roche produced evidence that persuaded the World Health Organisation that Tamiflu was effective against flu, and governments such as ours began stockpiling the drug in readiness for a pandemic. But then a Japanese scientist pointed out that most of the clinical trials on the drug had not been published. It appears that the unpublished ones generally showed less impressive results than the published ones.
Roche has now ensured that all 77 trials are in the public domain, so a true assessment of whether Tamiflu works will be made by the Cochrane Collaboration, a non-profit research group. The person who did most to draw the world’s attention to this problem was Ben Goldacre, a doctor and writer, whose book Bad Pharma accused the industry of often omitting publication of clinical trials with negative results. Others took up the issue, notably the charity Sense About Science, the editor of the British Medical Journal , Fiona Godlee, and the Conservative MP Sarah Wollaston. The industry’s reaction, says Goldacre, began with “outright denials and reassurance, before a slow erosion to more serious engagement”.
The pressure these people exerted led to the hard-hitting PAC report last week, which found that discussions “have been hampered because important information about clinical trials is routinely and legally withheld from doctors and researchers by manufacturers”.
The problem seems to be widespread. A paper in the BMJ in 2012 reported that only one fifth of clinical trials financed by the US National Institutes of Health released summaries of their results within the required one year of completion and one third were still unpublished after 51 months.
The industry protests that it would never hide evidence that a drug is dangerous or completely useless, and this is probably so: that would risk commercial suicide. Goldacre’s riposte is that it is also vital to know if one drug is better than another, say, saving eight lives per hundred patients rather than six. He puts it this way: “If there are eight people tied to a railway track, with a very slow shunter crushing them one by one, and I only untie the first six before stopping and awarding myself a point, you would rightly think that I had harmed two people. Medicine is no different.”
Imbued as we are with an instinctive tendency to read meaning into nature, we find it counter-intuitive that many experiments get significant results by chance and that the way to check if this has happened is to repeat the experiment and publish the result. When the drug company Amgen tried to replicate 53 key studies of cancer, they got the same result in just six cases. All too often scientists publish chance results, or “false positives”, like gamblers or fund managers who tell you about winners they backed.
Outside medicine, we popular science authors are probably guilty of too often finding startling results in the scientific literature and drawing lessons from them without waiting for them to be replicated. Or as Christopher Chabris, of Union College in Schenectady, New York, harshly put it about the pop-psychology author Malcolm Gladwell: cherry-picking studies to back his just-so stories. Dr Chabris points out that a key 2007 experiment cited by Gladwell in his latest book, which found that people did better on a problem if it was written in hard-to-read script, had been later repeated in a much larger sample of students with negative results.
To illustrate how far this problem reaches, a few years ago there was a scientific scandal with remarkable similarities, in respect of the non-publishing of negative data, to the Tamiflu scandal. A relentless, independent scientific auditor in Canada named Stephen McIntyre grew suspicious of a graph being promoted by governments to portray today’s global temperatures as warming far faster than any in the past 1,400 years — the famous “hockey stick” graph. When he dug into the data behind the graph, to the fury of its authors, especially Michael Mann, he found not only problems with the data and the analysis of it but a whole directory of results labelled “CENSORED”.
This proved to contain five calculations of what the graph would have looked like without any tree-ring samples from bristlecone pine trees. None of the five graphs showed a hockey stick upturn in the late 20th century: “This shows about as vividly as one could imagine that the hockey stick is made out of bristlecone pine,” wrote Mr McIntyre drily. (The bristlecone pine was well known to have grown larger tree rings in recent years for non-climate reasons: goats tearing the bark, which regrew rapidly, and extra carbon dioxide making trees grow faster.)
Mr McIntyre later unearthed the same problem when the hockey stick graph was relaunched to overcome his critique, with Siberian larch trees instead of bristlecones. This time the lead author, Keith Briffa, of the University of East Anglia, had used only a small sample of 12 larch trees for recent years, ignoring a much larger data set of the same age from the same region. If the analysis was repeated with all the larch trees there was no hockey-stick shape to the graph. Explanations for the omission were unconvincing.
Given that these were the most prominent and recognisable graphs used to show evidence of unprecedented climate change in recent decades, and to justify unusual energy policies that hit poor people especially hard, this case of cherry-picked publication was just as potentially shocking and costly as Tamiflugate. Omission of inconvenient data is a sin in government science as well as in the private sector.
Norovirus
Passengers on Royal Caribbean’s Explorer of the Seas came home two days early this week after more than 600 people fell ill with suspected norovirus, also known as Norwalk disease. Norovirus loves a good cruise ship, with its tight quarters full of people from all over the world. There have been nearly 200 confirmed norovirus outbreaks on cruise ships in the past 20 years, plus many other suspected maritime norovirus outbreaks that couldn’t be definitively linked to the virus. But it isn’t an exclusively sea-going pathogen. It accounts for more foodborne illness in the United States than E. coli and salmonella combined. It lives on doorknobs, handrails, and even soft surfaces like couches and carpets. Norovirus is all around you. And it is sickening more people than ever. It is a wondrous pathogen that should fascinate, disgust, and frighten you in equal measure.
Most viruses are encased by a lipid envelope, which has a couple of vulnerabilities. First, it dries out when exposed to the elements, which is one of the reasons HIV, for example, dies almost immediately outside of a host. In addition, alcohol-based sanitizers easily penetrate a lipid envelope and destroy the virus. Norovirus has a protein shell with no such weaknesses. It can live in the open for weeks and possibly months, and it is resistant to hand sanitizer and soap, unless you scrub the heck out of it. When a cruise ship suffers an outbreak, the Centers for Disease Control and Prevention advises that virtually every inch of the vessel and everything on it be drenched in a 5-percent bleach solution. Since schools, concert halls, movie theaters, and private homes rarely undergo such a thorough scrub-down, it’s disturbing to imagine how often we encounter norovirus. (If you decide to bleach your house after your child falls ill, it’s better to go with a 10-percent solution, since bleach degrades rather quickly in a bucket.)
Members of a college football team infected members of the opposing team through contact with uniforms.
The situation is all the more worrying when you consider norovirus’ second neat trick—it takes an incredibly small number of viral particles to make you sick. Most pathogens, such as influenza, need to invade you with an army of thousands to cause symptoms. That’s one of the reasons we’re generally healthy in a world teeming with viruses. Mathematical modeling suggests that as few as 10 norovirus particles can make an adult sick. The average norovirus virion is around 35 nanometers across—one-third the size of most viruses—so the volume of an infectious dose is uniquely small. It can easily find its way into your mouth through your hands or a whiff of infected air.
You can contract norovirus in the most subtle and disgusting ways imaginable. In 1999, after one gentleman vomited in a concert hall and nearby bathroom in Wales, more than 300 people inhaled enough airborne norovirus to become ill. Many of the victims were school children who came on a field trip the following day. In another case, several members of a college football team from North Carolina came down with norovirus and managed to infect members of the opposing team from Florida through contact with their uniforms, which were contaminated with particles of feces and vomit.
Norovirus is also eerily persistent. People with colds, for example, are typically not contagious beyond a week after symptoms commence. By contrast, laboratory experiments on human volunteers suggest that people infected with norovirus continue to shed virions for up to three weeks, long after the vomiting and diarrhea have passed.
Why would researchers use human volunteers to study such a horrible bug? Researchers have thus far been unable to culture norovirus in a dish. Last year, microbiologist Christiane Wobus and her colleagues at the University of Michigan were able to grow norovirus in immunocompromised mice, and some progress has been made infecting pigs whose guts had been rid of other microbes, but those are baby steps toward understanding the virus. Until we can grow this stuff in a laboratory, there’s little hope of developing a vaccine or an effective treatment. (Wobus calls in vitro culturing “the holy grail” of norovirus research.) Most of what we currently know comes from deliberately infecting volunteers who submit themselves to three days of nausea, vomiting, and diarrhea for the good of science and around a thousand bucks.
Incidence of norovirus has increased in the past couple of decades, and researchers have proposed an intriguing explanation: It may be learning to infect more people.
Your blood type—A, B, AB, or O—is defined by certain sugars on your blood cells. Similarly, people differ in the types of sugars on the cells that line the intestine. Certain strains of norovirus bind specifically to certain sugars—but the strains that have been traveling the world recently bind to a wider range of sugars. That seems to mean the strains can sicken a wider range of victims.
Humans aren’t the only hosts for norovirus. When filter-feeding shellfish ingest norovirus particles, the virus can bind to sugars in their systems and accumulate without making them sick. A recent study found norovirus contamination in 9 percent of oysters on the French market. In some cases, epidemiologists have traced human norovirus outbreaks to specific storms, as heavy rainfall caused sewage overflow and contamination of the oysters’ water supply.
How freaked out should you be? Moderately. Norovirus can kill, but usually indirectly; most deaths are among children or the elderly who become dehydrated, particularly in the developing world. The average adult will experience three days of miserable gastrointestinal distress. If it happens to you, avoid concert halls, football games, and any other social interaction, bleach everything you touch—and drink constantly.
Prostate Pill
A once-a-day pill for men with advanced prostate cancer cuts the risk of death by a third, “exciting” research has shown.
Experts said that, in a study of 1,700 men, enzalutamide allowed an average of 17 extra healthy months before the need for chemotherapy. It could soon become the standard choice for thousands of men with Britain’s most common male cancer, if hormone treatment fails.
The drug is available in Britain, but last week the NHS treatments adviser provoked uproar from charities when it imposed unexpected restrictions on who should be offered it after chemotherapy. The National Institute for Health and Care Excellence (NICE) said that it should not be offered to men who had tried an alternative modern treatment, abiraterone.
Previously enzalutamide, which has few side effects, had been tested only in men who had had chemotherapy and exhausted most other options. In the latest study it was given to men with few symptoms who had tried hormone therapy but not chemotherapy.
Over three years, men on enzalutamide were on average 29 per cent less likely to die than those on a placebo, while the risk of the disease worsening was cut by 81 per cent. Men did not need chemotherapy for 28 months on average, compared with 10.8 months for the control group, according to data presented at the American Society of Clinical Oncology Genitourinary Symposium in San Francisco.
Heather Payne, Consultant in Clinical Oncology at University College Hospital, London, said that the results were “very exciting and represent a significant milestone for the future treatment of men with advanced prostate cancer in the UK”.
She said: “This is the first drug in that pre-chemotherapy stage to show a survival difference, and I think this trial should change things hugely for men with prostate cancer. [Enzalutamide] should be used at the first relapse because it improves survival and delays the need for chemotherapy by 17 months, which has a big impact on quality of life.
“We want to keep men well and living their lives to the full, and, when you think of what men can do in that time, it’s really significant.”
Every year 41,000 men are told that they have prostate cancer, and 11,000 die. Dr Payne said that the drug, which works by using three blocking mechanisms to stop male hormones from reaching a tumour and fuelling its growth, could be offered to 6,000-10,000 men a year.
The research comes only three months after scientists hailed a breakthrough in the testing of prostate cancers. The new test, expected to be available in five years, focuses on measuring the levels of a protein known to be associated with the disease, and a study found it to be far more effective than present methods at diagnosing whether a cancer is aggressive or benign.
Bertrand Tombal of the Université Catholique de Louvain, one of the study leaders, said: “What impressed me most about the results is that treatment with enzalutamide delays the time to initiation of chemotherapy, a key factor in maintaining quality of life in men with advanced prostate cancer.”
Mikis Euripides, Director of Policy at Prostate Cancer UK, said: “Men with advanced prostate cancer desperately need more treatment options, and these encouraging results suggest that enzalutamide could not only delay the need for men to go through the agony of chemotherapy but in fact increase overall survival.
“Enzalutamide is already licensed for those who’ve had chemotherapy, but this trial will hopefully establish a robust base of evidence to de- monstrate that it should be available beforehand.
“This is good news, but sadly won’t help the one man an hour who dies of prostate cancer at present. We need to see drugs like enzalutamide available sooner rather than later, and so it’s a cruel twist that this study comes just days after NICE ruled out the drug for men who have have already had chemotherapy and the only other drug available at this stage — abiraterone. Men deserve better.”
Sandy Tyndale-Biscoe, chairman of the patients’ campaign Tackle Prostate Cancer, said: “We are delighted (but not surprised) by these results. They demonstrate something that we have long believed, namely that these new therapies are even more effective when used as soon as a man’s cancer develops to the ‘hormone-relapsed’ stage, and before he is half-killed by chemotherapy.”
Killing Cancer With Fever
AFTER he lost his first patient to cancer in 1891, William Coley was desperate to find an alternative treatment to offer next time, not just surgery and morphine.
That desire must have led the US surgeon to the first published account of "fever therapy" – treating cancer with pathogenic bacteria. It was an 1868 paper by the German physician Wilhelm Busch, describing how he had deliberately infected a neck sarcoma patient with dangerous bacteria. The infection almost killed her, but her huge tumour softened and shrank.
Though the surgeon did not invent fever therapy, he was the first to do it systematically. After some of the first people he tested it on died from the infection, he started to use heat-sterilised bacterial extracts, with good results. From 1895 until his death in 1936, Coley and his contemporaries treated hundreds of people with cancer by injecting them with pathogenic extracts. The starting dose was small and increased over subsequent shots until the patients developed a fever above 39 °C. Though there were failures, he achieved many cures and the technique came to be known as "Coley's toxins".
Despite this, with the rise of chemotherapy and radiotherapy, the treatment fell out of favour. Recently, there has been renewed interest in using bacteria to treat cancer, but the approach faces a major hurdle. As you might expect, regulatory authorities do not readily approve drugs containing unspecified substances and where there is no clearly known biological mechanism of action. But this is where my recent work with colleagues could help: we have found that there might be a simple immunological explanation for Coley's successes.
Coley's case studies and publications have been reviewed several times. In a 1953 report in the journal Acta Medica Scandinavica, Coley's daughter Helen Coley-Nauts re-examined the clinical cases described by her father. It wasn't easy. His records were not comprehensive and the bacterial extracts had often been prepared in different ways. Coley-Nauts found that her father had used 15 different preparations, 11 of which she deemed "not potent enough".
Even so, there is no doubt that Coley achieved some spectacular cures. In a 2008 review, Alberto Mantovani of the University of Milan, Italy, wrote that Coley "documented cases of the long-term survival of individuals with malignancies that remain a major challenge to treat now" (Nature, vol 454, p 436). For example, he treated a group of sarcoma patients with fever-inducing injections two to three times per week for several months. Many were late-stage, inoperable cases. Yet their five-year survival rate was higher than 80 per cent, according to Coley-Nauts's analyses.
Why did such treatment work at all, especially given that around 20 per cent of all cancers are caused by chronic infections? And in drug testing, fever is seen as a toxic adverse event, according to the US Food and Drug Administration. In other words, the belief is that fever usually signifies harm, not benefit.
But does it? Some years ago, I stumbled across a 1951 paper reporting that among 300 cases of childhood leukaemia, 26 spontaneous remissions were observed. Of those, 21 were preceded by a feverish infection (The American Journal of Medicine, vol 10, p 238). Although this was a small study, an 80 per cent correlation of spontaneous regression with fever seemed too odd to be a coincidence. When I started to analyse case studies and reviews of spontaneous cancer remission, it turned out that in a surprisingly large fraction a preceding infection – of the type known to cause fever – was reported.
The fever and cancer regression could just have been a coincidence, but what if there was a causal link? To test this, I looked at analyses of cancer across large populations. To my surprise, I found more than 30 studies showing that people who developed fever-causing infections such as measles, herpes and mumps more frequently over their lifetimes had a lower risk both of developing cancer and of relapsing after standard treatment.
So what do Coley's treatments, spontaneous remissions and the epidemiological studies have in common? And what could be the molecular explanation?
The answer might be a diverse range of chemical danger signals known as "pathogen recognition receptor ligands". These PRRL are produced by invading pathogens such as bacteria, viruses and fungi and they can put our innate immune system on red alert within minutes. But could PRRL protect against cancer? To find out, we need to look more closely at the immune system.
For a long time it was assumed that cancer cells are more or less invisible to the immune system. Millions of people die from cancer each year and if the immune system could respond, we would expect to see a much larger proportion of spontaneous regressions – or so the argument went. However, we now know many tumours are infiltrated by immune cells, such as cytotoxic lymphocytes, indicating that there is an active anti-cancer response. So while tumours are not invisible to the immune system, it seems the reaction is usually too weak to stop the cancer. What if PRRL could lift this immune reaction above a threshold needed for tumour shrinkage?
To mount a vigorous attack against invaders such as bacteria, viruses or cancer, immune cells called T-cells need to be activated. A T-cell can recognise cancer cells, but if it has not been properly turned on, it will remain relatively harmless to the invader. Dendritic cells are responsible for activating T-cells, but they in turn require PRRL for their own activation. Our hypothesis is that PRRL-activated dendritic cells can turn on several types of T-cells at once. So the immune response to a pathogen could also trigger an immune response to cancer cells.
Last year I tested this hypothesis in mice, working with Claudia Maletzki and Michael Linnebacher of the University of Rostock and Rajkumar Savai of the Max Planck Institute for Heart and Lung Research, Bad Nauheim, both in Germany. We found preliminary evidence that treatment with a single type of PRRL can slow tumour growth in mice and that a mix of PRRL can cure them, provided the treatment is given at regular intervals over a long period (Cancer Immunology, Immunotherapy, vol 62, p 1283). In our case, this was every other day for three weeks; adjusted for human life expectancy, this is analogous to a treatment over months, as Coley preferred.
Coley also thought that higher fevers correlated with greater success, but is fever necessary for PRRL to work? We don't know, but when the mice in our experiment were given a single dose of PRRL, their body temperature went up by about 1°C for a day.
Coley's treatments fit within a wider story of beneficial effects from infections and fever.In 1927, Julius Wagner-Jauregg won the Nobel prize for demonstrating the therapeutic value of malaria inoculation for treating syphilis. Today a standard treatment for bladder cancer is the injection of live bacteria – in the form of the BCG vaccine – but the mechanism is not fully understood. PRRL could be the explanation.
We believe that a PRRL mix could replace bacterial extracts, avoiding many of the regulatory obstacles. However, we are clearly a long way from it becoming an approved cancer treatment. To begin with, to test PRRL, the patient's immune system should not be too badly damaged by prior chemotherapy or radiotherapy. Yet a way round this would be to test on cancers for which chemotherapy is not very effective, such as pancreatic or liver cancer, or slow-growing prostate cancer.
Usually drugs are tested in mice first and then in humans, but thanks to Coley, human trials for the treatment of cancer with bacteria were carried out a hundred years ago. Perhaps we can finally provide the molecular explanation for his remarkable results.
Breast Cancer Breath Test
A breath test for breast cancer could help women avoid unpleasant X-ray screening after preliminary tests showed it was highly accurate at ruling out the disease.
A US-Dutch study showed that the test was feasible to use in clinics, with results available in about six minutes. Further trials are now underway but it is likely to be several years before any test is routinely available for Britain’s most common female cancer, which affects 50,000 women a year and kills 12,000.
It has long been known that cancers produce volatile compounds that can be detected in the breath, and a series of trials have shown that dogs are able to sniff out a range of cancers quite accurately. The latest study used a cheap device to look for an array of such compounds in the breath of 244 women who had been tested for cancer using traditional methods.
Professor Philippe Lambin, of University Hospital Maastricht, who started the project, said: “If the inner surface of the lungs could be stretched out flat, they would cover an area of around 100 square metres – about the size of half of a tennis court. This surface produce volatile compounds and this give us an opportunity to detect disease and treatment complications non invasively.”
The test picked up around 80 per cent of tumours while a negative result made it 99.9 per cent certain that a woman did not have cancer, scientists report in the journal PLoS One.
“A negative result on the breath test was especially useful,” said Professor Lambin. “Most normal healthy woman will have a negative breath test result, and they would probably not need a routine screening mammogram.”
He hopes that ultimately the test will be the first step in screening, with only those with a positive result needing to go to mammography appointments now offered to all middle-aged women. “We hope that it will decrease the amount of mammography that needs to be done,” he said.
Dr Roy Lalisang, of the Maastricht University Medical Centre and leader of the study, said: “Mammograms are often uncomfortable, painful, and require a dose of potentially hazardous radiation. In contrast, a screening breath test is safe, painless, non-invasive and does not expose patients to any radiation. Overall test accuracy for breast cancer was around 80 per cent, so women with a positive breath test should have additional investigations, including a mammogram.”
Prof Lambin said it was too early to say whether the test would cut down on unnecessary treatment, which has made the NHS screening programme increasingly contentious. A review in 2012 concluded that for every 1,300 lives saved by screening, 4,000 women were needlessly given surgery or chemotherapy.
Hannah Bridges, of the charity Breakthrough Breast Cancer, said: “New insights in to ways to detect breast cancer are exciting as the earlier the disease is discovered the better the chance of survival. Whilst this study doesn’t prove a breath test is better than mammography it does show that it’s a technique worth exploring further.”
Urine Test For Prostate Cancer
A new licence announced today between the University of Surrey and Randox, will bring to market a new test that will help with the early detection of prostate and bladder cancers.
Scientists at the University of Surrey have developed a more reliable way of detecting prostate and bladder cancers, by testing a small urine sample. The team focused on the EN2 protein produced by these types of cancers, and which is secreted into urine. Clinical trials in both Europe and the United States have found that the EN2 biomarker test is twice as effective as the 30-year-old PSA blood test currently used to detect prostate cancer.
The University of Surrey will supply key materials to Randox to manufacture and market products. It is hoped that a test could be made available in GP surgeries around the world, by 2015.
Hardev Pandha, Professor of Medical Oncology at the University of Surrey, said: "We are looking forward to working with Randox on this product. This new test could lead to faster detection that could save hundreds of lives, and also offers the potential for huge cost savings.
"Unlike in previous tests that require invasive procedures to produce a trigger, our studies show that the EN2 test immediately shows up and that levels of the protein correlate strongly with how far the disease has spread. This may then help a doctor assess whether the disease may be safely and actively monitored, or whether it has spread more widely and requires treatment."
Dr Peter FitzGerald, Randox Laboratories Founder and Managing Director, said: "With prostate and bladder cancers being among the top ten common causes of cancer death, accurate diagnosis is incredibly important to inform the type of treatment. We are therefore delighted to be working with the University of Surrey to develop and commercialise an EN2 biomarker. The concept of personalised medicine will shape the future of diagnostics and healthcare in general. Building relationships between academics, clinicians, industry and, of course, patients demonstrates how basic science discoveries made at the laboratory bench can be translated into clinical products that have real tangible impact for patients, the economy and society in general."
Nudge
Paying people small sums of money to be healthy can change their lifestyles even over the long term, an overview of research has concluded.
As little as £3 in cash or vouchers made people much more likely to quit smoking, take more exercise or get vaccinated, according to analysis which tells the Government that payments “may be a useful addition to the behavioural change toolkit”.
Ministers have in the past appeared keen on paying people to change their lifestyles, arguing that such “nudges” could be a cost effective way of relieving pressure on the NHS. The Department of Health has endorsed a scheme that pays children in shopping vouchers if they walk to school, while pregnant women have been paid to stop smoking. But few have moved into widespread use and last month a pilot study into giving women shopping vouchers as an inducement to breastfeed was criticised by doctors and midwives.
To assess whether such methods actually worked, a team from Newcastle University trawled scientific literature, finding 16 randomised trials of health-promoting payments involving 30,000 people.
Ten of the studies involved stopping smoking and short-term success rates were two and half times higher among people who were paid. Even more than six months later, smokers were still 50 per cent more likely to off cigarettes if they had been paid, they report in the journal PLoS One.
Five studies found that payments doubled the chances that people would come in for vaccination and screening while one study found that people who were paid to exercise were active for 16 minutes a day longer than those who were not.
Emma Giles, lead author of the study, said: “We were surprised at just how strong the effect was. People who took part in these reward or penalty schemes were much more likely to adopt healthy behaviours, and if they continued they would have more chance of remaining healthy for longer. Many studies used vouchers for supermarkets or similar things rather than actual cash. This might be a more acceptable way of implementing this.”
While the benefits of living healthily are uncertain and far in the future, the costs are immediate and obvious, and payments could provide a concrete compensation for this, the researchers say. They point out that the studies did not suggest that payments were any less effective for long term, complex changes such as giving up smoking than they were for short-term, simple things like getting a one-off jab.
Jean Adams, senior author of the study, said: “At this stage we don’t know the right level that incentives should be at, so it is not clear if this sort of scheme would save the NHS and country money. We try all kinds of techniques to try to help people to quit smoking or otherwise live healthy lives, so why not try this? It is about nudging people to healthier behaviours. There is a chance this could save the tax payer money in the long run.”
Circumcision
A new medical review published by Mayo Clinic makes the strongest case yet for cirumcision. Is it time to take the decision out of parents’ hands and make the procedure mandatory?
The choice of whether to circumcise one’s son—a decision both aided and hindered by a deluge of readily available information on the Internet—is an increasingly fraught one for parents. A quick Google search for “Should I circumcise my baby?” retrieves millions of articles, blogs, and academic papers all weighing in on the risks and rewards associated with the surgical removal of a newborn’s foreskin. Now, a new review published in the journal Mayo Clinic Proceedings claims the health benefits of circumcision exceed any risks by at least 100 to 1.
The review’s outspoken lead author, Brian J. Morris, a circumcision advocate and Professor Emeritus at The University of Sydney, Australia, hopes this new data will silence the debate once and for all. It’s Morris’ provocative position that infant circumcision contributes to overall public health in the same way that vaccines do, and should be equivalent to childhood vaccinations. And as such, he says, it’s unethical for doctors not to routinely offer it to parents.
“Each have a major population level benefit, but carry a risk that affects a very small proportion of individuals who receive the intervention. There are also extremely rarely deaths from each,” he told The Daily Beast via email. Moreover, “a vaccine is highly specific, whereas the protective effects of circumcision cover a wide array of medical conditions.”
The health benefits of circumcision are numerous. According to a mountain of research, documented in Morris’ review and noted by the APA in its recently updated policy statement, the benefits of circumcision include “prevention of urinary tract infections, penile cancer, and transmission of some sexually transmitted infections, including HIV.” These statistics can be misleading, however. For instance, the actual or absolute risk of penile cancer is so small (about 1 in 100,000) that an increased risk is still hardly any risk at all.
Many doctors, along with the American Academy of Pediatrics (AAP), agree that while health benefits of circumcision outweigh the risks, the decision is ultimately the parents’ to make. In 2012, the AAP changed its policy statement, discarding its neutral stance to weigh in heavily on the side of circumcision.
Still, some parents and healthcare providers argue that newborn circumcision is not only painful, but also unnecessary, and medical ethicists in the U.S. and abroad continue to debate its moral permissibility. Thirty-eight European physicians formally replied to the “cultural bias” in AAP’s policy change in the journal Pediatrics, noting its “conclusions are different from those reached by physicians in other parts of the Western world.”
The loudest among the opposition are people who’ve branded themselves “intactivists.” These groups say circumcision is “genital mutilation” and argue it needlessly violates a child’s autonomy and, according to one website, can cause “serious health risks, including infection, hemorrhage, surgical mishap, and death.” (Problems like these, it should be noted, are extremely rare. For infants, complication rates are approximately 0.2% and even those are usually minor and easily managed symptoms like bleeding or infection.)
Morris said that the “intact movement” also has something to do with declining rates, and likens the debate over circumcision to the one raging over vaccines. “The anti-circers and the anti-vaxers are very similar, and often the same people,” he said.
Using data from the National Hospital Discharge Survey (which doesn’t include out-of-hospital circumcisions, e.g. brit milah in the Jewish faith) with parsed data from adult circumcisions from the National Health and Nutrition Examination Surveys, Morris and his colleagues find that infant circumcisions have declined from 83 percent in the 1960s to 77 percent by 2010. The findings contradict a 2013 report from The Centers for Disease Control showing a slight increase in circumcisions over the last decade. In fact, Morris finds rates had decreased six percentage points during that time.
Both Morris and the CDC cite changing demographics and cost cutting as the reasons behind declining circumcision rates. Since Hispanic children are less likely to be circumcised, the climbing birth rate within the Hispanic population is largely responsible for the West’s significantly lower circumcision rates. Additionally, circumcision rates are 24 percent lower in the 18 states where Medicaid doesn’t pay for elective circumcisions.
Morris’s analysis further notes that half of uncircumcised boys and men will require treatment for a medical condition associated with his retained foreskin. Still, while noting the positive health effects of circumcision, could the comparison of the uncircumcised to the unvaccinated be alarmist, and a stretch? Morris doesn’t think so.
“Just as vaccination, failure to circumcise will put your son at serious risk of adverse medical conditions and he could indeed die from some of them,” he said. “What’s more he will harm others, from sexually transmitted infections which include oncogenic HPV types that cause cervical cancer, a potentially lethal cancer.”
Morris’ impassioned stance, while perhaps medically sound, may alienate the very parents he hopes to persuade. Despite headlines to the contrary, and geographical pockets of dissent, national vaccine coverage meets target levels at or above 91 percent. In other words, vaccines are widely accepted. It’s not so for circumcisions. And, as Morris concedes, the hands of millions of moms and dads who choose to forgo the scalpel can’t be forced.
“Whereas parents can be coerced into vaccination by denying access to childcare for their son, there are fewer inducements to do the right thing and have him circumcised,” he said.
Still, he acknowledges parental choice, and hopes that this risk benefit analysis along with the AAP’s affirmative policy statement will have a positive effect on future rates.
“Denial of infant male circumcision is denial of his rights to good health, something that all responsible parents should consider carefully,” he said.
Y-chromosome and Male Cancer
A simple blood test that can predict the risk of cancer in older men has been developed by scientists.
The test is based on the discovery that men with a common defect in their white blood cells are nearly four times as likely to die from cancer as those without the defect.
Scientists said that the technology could be available in clinics within five years and could allow high-risk men to be targeted with frequent screening and preventative treatments.
The discovery came as new analysis showed that half of people diagnosed with cancer now survive at least ten years, compared with just a quarter in the 1970s. Cancer Research UK said the big improvement in survival rates showed that cancer was on its way to becoming a chronic condition that people could live with for decades.
The latest study of more than 1,000 Swedish men suggests that white blood cells that lack the male Y-chromosome could be less efficient at detecting genetic mutations in the body that have the potential to turn cancerous.
Men who had the defect in 5 per cent to 10 per cent of their white blood cells were more than twice as likely to receive a diagnosis of cancer and lived half as long as those with undetectable levels of the defect.
The discovery could partly explain why men are more likely to get cancer than women and are more likely to die from it, scientists said.
Lars Forsberg, a geneticist at the University of Uppsala in Sweden who led the research, said that the team aimed to have a clinical test on the market within five to ten years.
“We can take a drop of blood from a man, maybe even a younger man, to identify these early signals that a person is at risk,” he added.
Marco Gerlinger, an oncologist and cancer geneticist at the Institute of Cancer Research in London, said that the finding was a rare example of a risk factor that affected lots of people — about one fifth of 70-year-olds — and substantially increased risk.
“Generally we find markers that have a very high risk, but are incredibly rare or common ones that only increase risk by a small amount,” he said. “This seems to be affecting quite a few men and it’s a strong effect, which makes it clinically very relevant.”
The study, published in the journal Nature Genetics, involved 1,153 Swedish men who were enrolled between the ages of 70 and 80 and followed for up to 20 years.
At the outset, blood samples from the men were analysed to test what proportion of their white blood cells were missing a Y-chromosome. Only men with no history of cancer took part.
Men with a detectable loss of Y-chromosome, equivalent to 5 per cent to 10 per cent of white blood cells, lived for 5.5 years on average compared to 11 years for men with no sign of loss of Y-chromosome in their blood.
When the causes of death were investigated in detail, the high-risk group were found to be 2.5 times as likely to be diagnosed with cancer and 3.6 times as likely to die from non-blood cancers.
Dr Forsberg believes that the loss of the Y-chromosome weakens the ability of the immune system to spot potentially dangerous mutations that are continually occuring in the body.
“When you lose the Y, that’s when the cancer grows,” he said.
Normally cells that lacked an entire chromosome would simply die, but blood cells appear to function fairly normally without the Y-chromosome, which is short and stumpy and contains far fewer genes than the X-chromosome.
Men have one X and one Y chromosome and women have two Xs, and there is no evidence for a similar effect in women.
Vitamin D
We’re told to stay out of the sun but a new study shows that a lack of vitamin D may leave us prone to other diseases.
It used to be a given that when the sun came out we would slap on the sunscreen and soak up the rays. Now a sunny day presents a conundrum. Should we limit our time outdoors to avoid damage from the sun’s harmful rays or should we ditch the SPF and allow our bodies to absorb the most potent supply of vitamin D available? This week a study added to the confusion by concluding that women who avoid sunbathing in the belief that they are lowering the risk of skin cancer might be more likely to get the disease than those who lie in the sun every day. The study is part of an ongoing “women’s lifestyle and health study” at the Karolinska Institute in Stockholm, looking at numerous different factors and diseases.
According to the Swedish researchers, guidelines telling people to stay out of the sun to reduce exposure to the ultraviolet radiation that is strongly linked to skin melanoma, may backfire. After following 30,000 women over 20 years, their findings, published in the Journal of Internal Medicine, suggest that avoiding the sun leads to an increased risk not only of melanoma but also of premature death from any cause, including other forms of cancer. After two decades they recorded 2,545 deaths with 1.5 women in a 100 who had the highest exposure to UV reported to have died compared with 3 in 100 for women who had avoided sunbathing. Indeed, Dr Pelle Lindqvist, the author, says the results “clearly showed that mortality was about double in women who avoided sun exposure compared to the highest exposure group”.
It is almost certain, say the researchers, that a lack of vitamin D from too little sunlight is to blame for the adverse health effects seen in their trial.
It’s not the first time levels of vitamin D have been held up as a barometer of wellbeing. Indeed, if there is a vitamin of the moment, it is this one. Last month, two studies, both published in the BMJ, showed that people with low levels of vitamin D are more likely to die from cancer and heart disease and to suffer from other illnesses. Others have suggested that good intakes appear to reduce the levels of bad cholesterol, and that too little elevates the risk of high blood pressure, osteoarthritis, and autoimmune disorders such as multiple sclerosis and arthritis.
For all its importance, however, how much we need and how we should obtain vitamin D remains shrouded in confusion. As a result, many of us fall woefully short of getting anywhere near enough to boost our health. It’s thought that around half the white population, up to 90 per cent of the multi-ethnic population and as many as a quarter of British children display deficiencies in the vitamin. “How to get enough vitamin D is simply not that straightforward,” says Professor Dorothy Bennett, a leading vitamin D researcher and head of the molecular cell sciences research centre at St George’s University of London. “We can get it from food up to a point, but it is hard to get enough from the diet. So we need other sources and that is where it becomes controversial.”
Dr Emma Williams, a nutrition scientist at the British Nutrition Foundation, says that, on average, we need around 10 mcg of vitamin D a day, mainly from food (children under the age of four need 7-8.5 mcg) but while fortified breakfast cereals, dairy products, egg yolks and oily fish will provide some of that intake, the vitamin is not as widely available in the diet as other nutrients. In total, Oliver Gillie, author of Sunlight Robbery and a leading vitamin D campaigner, says: “We should aim for at least 2,000 IU [50mcg] based on what studies have found, although many experts believe 4,000 IU per day [100mcg] from all sources — sun, diet, supplements — is best for optimum health.”
Gillie wears no sunscreen as often as possible and takes up to 4,000 IU as a supplement. With no clear symptoms of deficiency, the only way to tell if you are getting enough is through a blood test. But steps to increase your intake will undoubtedly help. Toxicity is rare, but possible, so ideally it should be taken under medical supervision or as prescribed by a nutritionist and Dr Graeme Close at Liverpool John Moores University says that “taking self-prescribed mega high doses” is certainly not recommended.
Nicknamed the sunshine vitamin, the most efficient source is the sun as it is synthesised when chemicals in the skin react to ultraviolet rays. But a lack of direct sunlight, fuelled by growing concerns for its adverse effects, and overuse of high-factor sunscreen combined with our increasingly indoor lifestyles are largely to blame for diminishing levels. Computer games and TV mean that many children are getting so little sunlight that their vitamin D levels have plummeted to the point that they develop bone deformities, an extreme side-effect of deficiency. At Southampton General Hospital, experts have evidence to suggest a resurgence of rickets, a problem previously linked to Victorian poverty. Latest NHS statistics show that there were 833 hospital admissions for children suffering from the condition in the year 2012-13, a rise from 190 cases ten years ago. “It is no myth that more of us are deficient,” Bennett says. “Equally it is no real surprise as nobody is arguing with the fact that the sun’s rays are the main cause of skin cancer. It’s a real dilemma for many people.”
So where should we start? Experts remain cautious about advocating sun exposure. Professor Kevin Cashman, head of the vitamin D research group at the University College Cork, says that researchers still need to pinpoint the precise levels of safe sun exposure that causes minimal skin damage but allows for vitamin D production — if, indeed, it exists. “With the current lack of such data it is clear why sun awareness campaigns are in place,” Cashman says. “It may well be that there is no such safe level and so there may be a zero tolerance public health policy in the future.” As things stand, the time spent in the sun without sunscreen should be minimal but regular. Sun bingeing, Gillie says, could cause more problems than short bouts of regular exposure.
On its website, Cancer Research UK recommends “only a few minutes in the summer sun in the middle of the day without sun protection” between April and September as sufficient to ensure you boost vitamin D. “Photobiologists say 15 minutes of UK sun is about right and that exposure to your face and arms is all that’s needed,” Bennett says. “Children generally need less time due to their smaller body size, so aim for 10-12 minutes without sunscreen for them.” People with darker skin will need to spend longer in the sun to produce the same amount of vitamin D. Without exception, all experts agree that the skin should never be allowed to redden or burn. “The larger the area of skin that is exposed to sunlight, the more chance there is of making enough vitamin D before this happens,” Gillie says. At all other times, wearing sunscreen is imperative.
For many adults, a safer option seems to be to pop a pill. Up to one in three people now take the sunshine vitamin in supplement form at some time during the year; its popularity buoyed by some evidence that higher levels offer greater protection against some diseases. Are they doing the right thing? As a fat-soluble vitamin (ie, one that is stored in the body, such as vitamins A, D and K, as opposed to water-soluble vitamins such as vitamins B and C, which are not stored in the body and so have to be replaced), there is potential for toxicity if too much vitamin D is consumed and several studies have raised concerns about risks of high-dose vitamins, including vitamin D. Although recent evidence suggests that even doses upwards of 10,000 IU a day of the vitamin aren’t toxic, experts recommend sticking to supplements containing 1,000 to 2,000 IU if you go down the supplement route. Children, unless at noted risk of deficiency, shouldn’t need a pill.
Not all experts think pills are the answer. A review of 462 studies involving more than a million adults carried out at the International Prevention Research Institute in Lyon last year concluded that a lack of vitamin D is not a trigger for many common illnesses and that taking supplements to boost your intake will make little difference to your health. And a team from the University of Auckland reported in the Lancet recently that there is little reason to prescribe vitamin D supplements to adults looking to reduce the risk of fractures or disease as they offer no significant protection against either.
As the debate rages on, Bennett prefers to err on the side of caution. Having been told too much sun is bad for us, we have avoided it to the point that we are missing out on its benefits. So what does she do? “I spend time outdoors, but I avoid the sun as much as I can and I take vitamin D supplements to boost my own levels,” she says. “It’s a simple strategy that I would recommend others take until we know more.”
Vitamin D Part 2
Boosting your vitamin D intake is not just good for your health, it can also boost your fitness. Scientists have discovered that getting enough of the sunshine vitamin can speed up your recovery from workouts and enhance your overall exercise performance. If you work out regularly — especially in a gym, yoga studio or indoor swimming pool — it could be that you not only need more vitamin D to sustain repeated physical demands on your body, but you are more likely to be deficient in it in the first place.
Dr Graeme Close, a researcher in sports nutrition and exercise metabolism at Liverpool John Moores University, says that many of our workout habits compound the lack of vitamin D available to our bodies. “It’s not just that a lot of people exercise indoors,” he says. “Even those who go outside often run or cycle early in the morning or late in the evening on a commute. Or they wear tight compression-type clothing and a sunscreen that prevents exposure to the sun.” Combined, these factors mean that “even using conservative guidelines” up to 70 per cent of the recreational and serious athletes tested by Close were found to have worryingly low vitamin D levels. Gwyneth Paltrow, known for her dedication to fitness almost as much as for her acting, is among those to have been diagnosed as vitamin D deficient a few years ago. And among the gym generation it is increasingly widespread.
There is an argument, Close says, that very active people are already prone to a shortfall in certain nutrients because they are gobbled up more quickly to cope with the stress and strain of workouts. Steve Simbler, a sports pharmacist who has worked with Olympians, says other factors might be at play. “Vitamin D is fat soluble and any that we take and don’t need is stored in body fat,” he says. “Gym-goers and athletes tend to have lower percentages of body fat than the average person, so it stands to reason that their ability to store it is compromised, despite the fact no clinical trials have yet proven this to be the case.”
What is clear is the impact that dwindling vitamin D has on many aspects of fitness. “It is more like a steroid hormone than a vitamin in the way it acts on the body and one side-effect of low values is diminished muscle function,” Close says. “It is needed by stem cells for muscle regeneration and recovery after a hard session and there is evidence it might protect immune functions during periods of intensive training.”
So, can boosting levels reverse these risks and help you to get more out of your workouts in the long term? To test this, Close and his team gave a group of footballers either a vitamin D supplement or a placebo and found that, after eight weeks of training, the nutrient group showed significant improvements in two out of six fitness assessments — 10m sprint times and vertical jumps — compared to no change among their placebo counterparts.
Perhaps the strongest evidence for workout devotees, though, comes in the form of the vitamin’s links with injury prevention and recovery. This year a team of exercise scientists from the University of Kentucky found that giving a group of swimmers, who trained predominantly indoors, a vitamin D supplement seemed to offer protection against muscle injuries compared with training partners who took a daily placebo. More than three quarters of the injuries recorded between September and March happened after a substantial drop in blood levels of vitamin D, leaving the authors to conclude that “supplementation could prove to be an easy and affordable method to preserve bone and decrease risk of injury”.
Simbler says that this is particularly relevant to people who cram much of their exercise into a weekend or who train for tough endurance events such as triathlons and marathons. “If you are doing that amount of work, then the stress on your muscles and joints is very high,” he explains. “Increasing vitamin D intake can help to lessen that damage so that you recover more quickly.”
Medical Studies Are Grossly Unreliable
Much of what medical researchers conclude in their studies is misleading, exaggerated, or flat-out wrong. So why are doctors—to a striking extent—still drawing upon misinformation in their everyday practice? Dr. John Ioannidis has spent his career challenging his peers by exposing their bad science.
IN 2001, RUMORS were circulating in Greek hospitals that surgery residents, eager to rack up scalpel time, were falsely diagnosing hapless Albanian immigrants with appendicitis. At the University of Ioannina medical school’s teaching hospital, a newly minted doctor named Athina Tatsioni was discussing the rumors with colleagues when a professor who had overheard asked her if she’d like to try to prove whether they were true—he seemed to be almost daring her. She accepted the challenge and, with the professor’s and other colleagues’ help, eventually produced a formal study showing that, for whatever reason, the appendices removed from patients with Albanian names in six Greek hospitals were more than three times as likely to be perfectly healthy as those removed from patients with Greek names. “It was hard to find a journal willing to publish it, but we did,” recalls Tatsioni. “I also discovered that I really liked research.” Good thing, because the study had actually been a sort of audition. The professor, it turned out, had been putting together a team of exceptionally brash and curious young clinicians and Ph.D.s to join him in tackling an unusual and controversial agenda.
Last spring, I sat in on one of the team’s weekly meetings on the medical school’s campus, which is plunked crazily across a series of sharp hills. The building in which we met, like most at the school, had the look of a barracks and was festooned with political graffiti. But the group convened in a spacious conference room that would have been at home at a Silicon Valley start-up. Sprawled around a large table were Tatsioni and eight other youngish Greek researchers and physicians who, in contrast to the pasty younger staff frequently seen in U.S. hospitals, looked like the casually glamorous cast of a television medical drama. The professor, a dapper and soft-spoken man named John Ioannidis, loosely presided.
One of the researchers, a biostatistician named Georgia Salanti, fired up a laptop and projector and started to take the group through a study she and a few colleagues were completing that asked this question: were drug companies manipulating published research to make their drugs look good? Salanti ticked off data that seemed to indicate they were, but the other team members almost immediately started interrupting. One noted that Salanti’s study didn’t address the fact that drug-company research wasn’t measuring critically important “hard” outcomes for patients, such as survival versus death, and instead tended to measure “softer” outcomes, such as self-reported symptoms (“my chest doesn’t hurt as much today”). Another pointed out that Salanti’s study ignored the fact that when drug-company data seemed to show patients’ health improving, the data often failed to show that the drug was responsible, or that the improvement was more than marginal.
Salanti remained poised, as if the grilling were par for the course, and gamely acknowledged that the suggestions were all good—but a single study can’t prove everything, she said. Just as I was getting the sense that the data in drug studies were endlessly malleable, Ioannidis, who had mostly been listening, delivered what felt like a coup de grâce: wasn’t it possible, he asked, that drug companies were carefully selecting the topics of their studies—for example, comparing their new drugs against those already known to be inferior to others on the market—so that they were ahead of the game even before the data juggling began? “Maybe sometimes it’s the questions that are biased, not the answers,” he said, flashing a friendly smile. Everyone nodded. Though the results of drug studies often make newspaper headlines, you have to wonder whether they prove anything at all. Indeed, given the breadth of the potential problems raised at the meeting, can any medical-research studies be trusted?
That question has been central to Ioannidis’s career. He’s what’s known as a meta-researcher, and he’s become one of the world’s foremost experts on the credibility of medical research. He and his team have shown, again and again, and in many different ways, that much of what biomedical researchers conclude in published studies—conclusions that doctors keep in mind when they prescribe antibiotics or blood-pressure medication, or when they advise us to consume more fiber or less meat, or when they recommend surgery for heart disease or back pain—is misleading, exaggerated, and often flat-out wrong. He charges that as much as 90 percent of the published medical information that doctors rely on is flawed. His work has been widely accepted by the medical community; it has been published in the field’s top journals, where it is heavily cited; and he is a big draw at conferences. Given this exposure, and the fact that his work broadly targets everyone else’s work in medicine, as well as everything that physicians do and all the health advice we get, Ioannidis may be one of the most influential scientists alive. Yet for all his influence, he worries that the field of medical research is so pervasively flawed, and so riddled with conflicts of interest, that it might be chronically resistant to change—or even to publicly admitting that there’s a problem.
THE CITY OF IOANNINA is a big college town a short drive from the ruins of a 20,000-seat amphitheater and a Zeusian sanctuary built at the site of the Dodona oracle. The oracle was said to have issued pronouncements to priests through the rustling of a sacred oak tree. Today, a different oak tree at the site provides visitors with a chance to try their own hands at extracting a prophecy. “I take all the researchers who visit me here, and almost every single one of them asks the tree the same question,” Ioannidis tells me, as we contemplate the tree the day after the team’s meeting. “‘Will my research grant be approved?’” He chuckles, but Ioannidis (pronounced yo-NEE-dees) tends to laugh not so much in mirth as to soften the sting of his attack. And sure enough, he goes on to suggest that an obsession with winning funding has gone a long way toward weakening the reliability of medical research.
He first stumbled on the sorts of problems plaguing the field, he explains, as a young physician-researcher in the early 1990s at Harvard. At the time, he was interested in diagnosing rare diseases, for which a lack of case data can leave doctors with little to go on other than intuition and rules of thumb. But he noticed that doctors seemed to proceed in much the same manner even when it came to cancer, heart disease, and other common ailments. Where were the hard data that would back up their treatment decisions? There was plenty of published research, but much of it was remarkably unscientific, based largely on observations of a small number of cases. A new “evidence-based medicine” movement was just starting to gather force, and Ioannidis decided to throw himself into it, working first with prominent researchers at Tufts University and then taking positions at Johns Hopkins University and the National Institutes of Health. He was unusually well armed: he had been a math prodigy of near-celebrity status in high school in Greece, and had followed his parents, who were both physician-researchers, into medicine. Now he’d have a chance to combine math and medicine by applying rigorous statistical analysis to what seemed a surprisingly sloppy field. “I assumed that everything we physicians did was basically right, but now I was going to help verify it,” he says. “All we’d have to do was systematically review the evidence, trust what it told us, and then everything would be perfect.”
It didn’t turn out that way. In poring over medical journals, he was struck by how many findings of all types were refuted by later findings. Of course, medical-science “never minds” are hardly secret. And they sometimes make headlines, as when in recent years large studies or growing consensuses of researchers concluded that mammograms, colonoscopies, and PSA tests are far less useful cancer-detection tools than we had been told; or when widely prescribed antidepressants such as Prozac, Zoloft, and Paxil were revealed to be no more effective than a placebo for most cases of depression; or when we learned that staying out of the sun entirely can actually increase cancer risks; or when we were told that the advice to drink lots of water during intense exercise was potentially fatal; or when, last April, we were informed that taking fish oil, exercising, and doing puzzles doesn’t really help fend off Alzheimer’s disease, as long claimed. Peer-reviewed studies have come to opposite conclusions on whether using cell phones can cause brain cancer, whether sleeping more than eight hours a night is healthful or dangerous, whether taking aspirin every day is more likely to save your life or cut it short, and whether routine angioplasty works better than pills to unclog heart arteries.
But beyond the headlines, Ioannidis was shocked at the range and reach of the reversals he was seeing in everyday medical research. “Randomized controlled trials,” which compare how one group responds to a treatment against how an identical group fares without the treatment, had long been considered nearly unshakable evidence, but they, too, ended up being wrong some of the time. “I realized even our gold-standard research had a lot of problems,” he says. Baffled, he started looking for the specific ways in which studies were going wrong. And before long he discovered that the range of errors being committed was astonishing: from what questions researchers posed, to how they set up the studies, to which patients they recruited for the studies, to which measurements they took, to how they analyzed the data, to how they presented their results, to how particular studies came to be published in medical journals.
This array suggested a bigger, underlying dysfunction, and Ioannidis thought he knew what it was. “The studies were biased,” he says. “Sometimes they were overtly biased. Sometimes it was difficult to see the bias, but it was there.” Researchers headed into their studies wanting certain results—and, lo and behold, they were getting them. We think of the scientific process as being objective, rigorous, and even ruthless in separating out what is true from what we merely wish to be true, but in fact it’s easy to manipulate results, even unintentionally or unconsciously. “At every step in the process, there is room to distort results, a way to make a stronger claim or to select what is going to be concluded,” says Ioannidis. “There is an intellectual conflict of interest that pressures researchers to find whatever it is that is most likely to get them funded.”
Perhaps only a minority of researchers were succumbing to this bias, but their distorted findings were having an outsize effect on published research. To get funding and tenured positions, and often merely to stay afloat, researchers have to get their work published in well-regarded journals, where rejection rates can climb above 90 percent. Not surprisingly, the studies that tend to make the grade are those with eye-catching findings. But while coming up with eye-catching theories is relatively easy, getting reality to bear them out is another matter. The great majority collapse under the weight of contradictory data when studied rigorously. Imagine, though, that five different research teams test an interesting theory that’s making the rounds, and four of the groups correctly prove the idea false, while the one less cautious group incorrectly “proves” it true through some combination of error, fluke, and clever selection of data. Guess whose findings your doctor ends up reading about in the journal, and you end up hearing about on the evening news? Researchers can sometimes win attention by refuting a prominent finding, which can help to at least raise doubts about results, but in general it is far more rewarding to add a new insight or exciting-sounding twist to existing research than to retest its basic premises—after all, simply re-proving someone else’s results is unlikely to get you published, and attempting to undermine the work of respected colleagues can have ugly professional repercussions.
In the late 1990s, Ioannidis set up a base at the University of Ioannina. He pulled together his team, which remains largely intact today, and started chipping away at the problem in a series of papers that pointed out specific ways certain studies were getting misleading results. Other meta-researchers were also starting to spotlight disturbingly high rates of error in the medical literature. But Ioannidis wanted to get the big picture across, and to do so with solid data, clear reasoning, and good statistical analysis. The project dragged on, until finally he retreated to the tiny island of Sikinos in the Aegean Sea, where he drew inspiration from the relatively primitive surroundings and the intellectual traditions they recalled. “A pervasive theme of ancient Greek literature is that you need to pursue the truth, no matter what the truth might be,” he says. In 2005, he unleashed two papers that challenged the foundations of medical research.
He chose to publish one paper, fittingly, in the online journal PLoS Medicine, which is committed to running any methodologically sound article without regard to how “interesting” the results may be. In the paper, Ioannidis laid out a detailed mathematical proof that, assuming modest levels of researcher bias, typically imperfect research techniques, and the well-known tendency to focus on exciting rather than highly plausible theories, researchers will come up with wrong findings most of the time. Simply put, if you’re attracted to ideas that have a good chance of being wrong, and if you’re motivated to prove them right, and if you have a little wiggle room in how you assemble the evidence, you’ll probably succeed in proving wrong theories right. His model predicted, in different fields of medical research, rates of wrongness roughly corresponding to the observed rates at which findings were later convincingly refuted: 80 percent of non-randomized studies (by far the most common type) turn out to be wrong, as do 25 percent of supposedly gold-standard randomized trials, and as much as 10 percent of the platinum-standard large randomized trials. The article spelled out his belief that researchers were frequently manipulating data analyses, chasing career-advancing findings rather than good science, and even using the peer-review process—in which journals ask researchers to help decide which studies to publish—to suppress opposing views. “You can question some of the details of John’s calculations, but it’s hard to argue that the essential ideas aren’t absolutely correct,” says Doug Altman, an Oxford University researcher who directs the Centre for Statistics in Medicine.
Still, Ioannidis anticipated that the community might shrug off his findings: sure, a lot of dubious research makes it into journals, but we researchers and physicians know to ignore it and focus on the good stuff, so what’s the big deal? The other paper headed off that claim. He zoomed in on 49 of the most highly regarded research findings in medicine over the previous 13 years, as judged by the science community’s two standard measures: the papers had appeared in the journals most widely cited in research articles, and the 49 articles themselves were the most widely cited articles in these journals. These were articles that helped lead to the widespread popularity of treatments such as the use of hormone-replacement therapy for menopausal women, vitamin E to reduce the risk of heart disease, coronary stents to ward off heart attacks, and daily low-dose aspirin to control blood pressure and prevent heart attacks and strokes. Ioannidis was putting his contentions to the test not against run-of-the-mill research, or even merely well-accepted research, but against the absolute tip of the research pyramid. Of the 49 articles, 45 claimed to have uncovered effective interventions. Thirty-four of these claims had been retested, and 14 of these, or 41 percent, had been convincingly shown to be wrong or significantly exaggerated. If between a third and a half of the most acclaimed research in medicine was proving untrustworthy, the scope and impact of the problem were undeniable. That article was published in the Journal of the American Medical Association.
DRIVING ME BACK to campus in his smallish SUV—after insisting, as he apparently does with all his visitors, on showing me a nearby lake and the six monasteries situated on an islet within it—Ioannidis apologized profusely for running a yellow light, explaining with a laugh that he didn’t trust the truck behind him to stop. Considering his willingness, even eagerness, to slap the face of the medical-research community, Ioannidis comes off as thoughtful, upbeat, and deeply civil. He’s a careful listener, and his frequent grin and semi-apologetic chuckle can make the sharp prodding of his arguments seem almost good-natured. He is as quick, if not quicker, to question his own motives and competence as anyone else’s. A neat and compact 45-year-old with a trim mustache, he presents as a sort of dashing nerd—Giancarlo Giannini with a bit of Mr. Bean.
The humility and graciousness seem to serve him well in getting across a message that is not easy to digest or, for that matter, believe: that even highly regarded researchers at prestigious institutions sometimes churn out attention-grabbing findings rather than findings likely to be right. But Ioannidis points out that obviously questionable findings cram the pages of top medical journals, not to mention the morning headlines. Consider, he says, the endless stream of results from nutritional studies in which researchers follow thousands of people for some number of years, tracking what they eat and what supplements they take, and how their health changes over the course of the study. “Then the researchers start asking, ‘What did vitamin E do? What did vitamin C or D or A do? What changed with calorie intake, or protein or fat intake? What happened to cholesterol levels? Who got what type of cancer?’” he says. “They run everything through the mill, one at a time, and they start finding associations, and eventually conclude that vitamin X lowers the risk of cancer Y, or this food helps with the risk of that disease.” In a single week this fall, Google’s news page offered these headlines: “More Omega-3 Fats Didn’t Aid Heart Patients”; “Fruits, Vegetables Cut Cancer Risk for Smokers”; “Soy May Ease Sleep Problems in Older Women”; and dozens of similar stories.
When a five-year study of 10,000 people finds that those who take more vitamin X are less likely to get cancer Y, you’d think you have pretty good reason to take more vitamin X, and physicians routinely pass these recommendations on to patients. But these studies often sharply conflict with one another. Studies have gone back and forth on the cancer-preventing powers of vitamins A, D, and E; on the heart-health benefits of eating fat and carbs; and even on the question of whether being overweight is more likely to extend or shorten your life. How should we choose among these dueling, high-profile nutritional findings? Ioannidis suggests a simple approach: ignore them all.
For starters, he explains, the odds are that in any large database of many nutritional and health factors, there will be a few apparent connections that are in fact merely flukes, not real health effects—it’s a bit like combing through long, random strings of letters and claiming there’s an important message in any words that happen to turn up. But even if a study managed to highlight a genuine health connection to some nutrient, you’re unlikely to benefit much from taking more of it, because we consume thousands of nutrients that act together as a sort of network, and changing intake of just one of them is bound to cause ripples throughout the network that are far too complex for these studies to detect, and that may be as likely to harm you as help you. Even if changing that one factor does bring on the claimed improvement, there’s still a good chance that it won’t do you much good in the long run, because these studies rarely go on long enough to track the decades-long course of disease and ultimately death. Instead, they track easily measurable health “markers” such as cholesterol levels, blood pressure, and blood-sugar levels, and meta-experts have shown that changes in these markers often don’t correlate as well with long-term health as we have been led to believe.
On the relatively rare occasions when a study does go on long enough to track mortality, the findings frequently upend those of the shorter studies. (For example, though the vast majority of studies of overweight individuals link excess weight to ill health, the longest of them haven’t convincingly shown that overweight people are likely to die sooner, and a few of them have seemingly demonstrated that moderately overweight people are likely to live longer.) And these problems are aside from ubiquitous measurement errors (for example, people habitually misreport their diets in studies), routine misanalysis (researchers rely on complex software capable of juggling results in ways they don’t always understand), and the less common, but serious, problem of outright fraud (which has been revealed, in confidential surveys, to be much more widespread than scientists like to acknowledge).
If a study somehow avoids every one of these problems and finds a real connection to long-term changes in health, you’re still not guaranteed to benefit, because studies report average results that typically represent a vast range of individual outcomes. Should you be among the lucky minority that stands to benefit, don’t expect a noticeable improvement in your health, because studies usually detect only modest effects that merely tend to whittle your chances of succumbing to a particular disease from small to somewhat smaller. “The odds that anything useful will survive from any of these studies are poor,” says Ioannidis—dismissing in a breath a good chunk of the research into which we sink about $100 billion a year in the United States alone.
And so it goes for all medical studies, he says. Indeed, nutritional studies aren’t the worst. Drug studies have the added corruptive force of financial conflict of interest. The exciting links between genes and various diseases and traits that are relentlessly hyped in the press for heralding miraculous around-the-corner treatments for everything from colon cancer to schizophrenia have in the past proved so vulnerable to error and distortion, Ioannidis has found, that in some cases you’d have done about as well by throwing darts at a chart of the genome. (These studies seem to have improved somewhat in recent years, but whether they will hold up or be useful in treatment are still open questions.) Vioxx, Zelnorm, and Baycol were among the widely prescribed drugs found to be safe and effective in large randomized controlled trials before the drugs were yanked from the market as unsafe or not so effective, or both.
“Often the claims made by studies are so extravagant that you can immediately cross them out without needing to know much about the specific problems with the studies,” Ioannidis says. But of course it’s that very extravagance of claim (one large randomized controlled trial even proved that secret prayer by unknown parties can save the lives of heart-surgery patients, while another proved that secret prayer can harm them) that helps gets these findings into journals and then into our treatments and lifestyles, especially when the claim builds on impressive-sounding evidence. “Even when the evidence shows that a particular research idea is wrong, if you have thousands of scientists who have invested their careers in it, they’ll continue to publish papers on it,” he says. “It’s like an epidemic, in the sense that they’re infected with these wrong ideas, and they’re spreading it to other researchers through journals.”
THOUGH SCIENTISTS AND science journalists are constantly talking up the value of the peer-review process, researchers admit among themselves that biased, erroneous, and even blatantly fraudulent studies easily slip through it. Nature, the grande dame of science journals, stated in a 2006 editorial, “Scientists understand that peer review per se provides only a minimal assurance of quality, and that the public conception of peer review as a stamp of authentication is far from the truth.” What’s more, the peer-review process often pressures researchers to shy away from striking out in genuinely new directions, and instead to build on the findings of their colleagues (that is, their potential reviewers) in ways that only seem like breakthroughs—as with the exciting-sounding gene linkages (autism genes identified!) and nutritional findings (olive oil lowers blood pressure!) that are really just dubious and conflicting variations on a theme.
Most journal editors don’t even claim to protect against the problems that plague these studies. University and government research overseers rarely step in to directly enforce research quality, and when they do, the science community goes ballistic over the outside interference. The ultimate protection against research error and bias is supposed to come from the way scientists constantly retest each other’s results—except they don’t. Only the most prominent findings are likely to be put to the test, because there’s likely to be publication payoff in firming up the proof, or contradicting it.
But even for medicine’s most influential studies, the evidence sometimes remains surprisingly narrow. Of those 45 super-cited studies that Ioannidis focused on, 11 had never been retested. Perhaps worse, Ioannidis found that even when a research error is outed, it typically persists for years or even decades. He looked at three prominent health studies from the 1980s and 1990s that were each later soundly refuted, and discovered that researchers continued to cite the original results as correct more often than as flawed—in one case for at least 12 years after the results were discredited.
Doctors may notice that their patients don’t seem to fare as well with certain treatments as the literature would lead them to expect, but the field is appropriately conditioned to subjugate such anecdotal evidence to study findings. Yet much, perhaps even most, of what doctors do has never been formally put to the test in credible studies, given that the need to do so became obvious to the field only in the 1990s, leaving it playing catch-up with a century or more of non-evidence-based medicine, and contributing to Ioannidis’s shockingly high estimate of the degree to which medical knowledge is flawed. That we’re not routinely made seriously ill by this shortfall, he argues, is due largely to the fact that most medical interventions and advice don’t address life-and-death situations, but rather aim to leave us marginally healthier or less unhealthy, so we usually neither gain nor risk all that much.
Medical research is not especially plagued with wrongness. Other meta-research experts have confirmed that similar issues distort research in all fields of science, from physics to economics (where the highly regarded economists J. Bradford DeLong and Kevin Lang once showed how a remarkably consistent paucity of strong evidence in published economics studies made it unlikely that any of them were right). And needless to say, things only get worse when it comes to the pop expertise that endlessly spews at us from diet, relationship, investment, and parenting gurus and pundits. But we expect more of scientists, and especially of medical scientists, given that we believe we are staking our lives on their results. The public hardly recognizes how bad a bet this is. The medical community itself might still be largely oblivious to the scope of the problem, if Ioannidis hadn’t forced a confrontation when he published his studies in 2005.
Ioannidis initially thought the community might come out fighting. Instead, it seemed relieved, as if it had been guiltily waiting for someone to blow the whistle, and eager to hear more. David Gorski, a surgeon and researcher at Detroit’s Barbara Ann Karmanos Cancer Institute, noted in his prominent medical blog that when he presented Ioannidis’s paper on highly cited research at a professional meeting, “not a single one of my surgical colleagues was the least bit surprised or disturbed by its findings.” Ioannidis offers a theory for the relatively calm reception. “I think that people didn’t feel I was only trying to provoke them, because I showed that it was a community problem, instead of pointing fingers at individual examples of bad research,” he says. In a sense, he gave scientists an opportunity to cluck about the wrongness without having to acknowledge that they themselves succumb to it—it was something everyone else did.
To say that Ioannidis’s work has been embraced would be an understatement. His PLoS Medicine paper is the most downloaded in the journal’s history, and it’s not even Ioannidis’s most-cited work—that would be a paper he published in Nature Genetics on the problems with gene-link studies. Other researchers are eager to work with him: he has published papers with 1,328 different co-authors at 538 institutions in 43 countries, he says. Last year he received, by his estimate, invitations to speak at 1,000 conferences and institutions around the world, and he was accepting an average of about five invitations a month until a case last year of excessive-travel-induced vertigo led him to cut back. Even so, in the weeks before I visited him he had addressed an AIDS conference in San Francisco, the European Society for Clinical Investigation, Harvard’s School of Public Health, and the medical schools at Stanford and Tufts.
The irony of his having achieved this sort of success by accusing the medical-research community of chasing after success is not lost on him, and he notes that it ought to raise the question of whether he himself might be pumping up his findings. “If I did a study and the results showed that in fact there wasn’t really much bias in research, would I be willing to publish it?” he asks. “That would create a real psychological conflict for me.” But his bigger worry, he says, is that while his fellow researchers seem to be getting the message, he hasn’t necessarily forced anyone to do a better job. He fears he won’t in the end have done much to improve anyone’s health. “There may not be fierce objections to what I’m saying,” he explains. “But it’s difficult to change the way that everyday doctors, patients, and healthy people think and behave.”
AS HELTER-SKELTER as the University of Ioannina Medical School campus looks, the hospital abutting it looks reassuringly stolid. Athina Tatsioni has offered to take me on a tour of the facility, but we make it only as far as the entrance when she is greeted—accosted, really—by a worried-looking older woman. Tatsioni, normally a bit reserved, is warm and animated with the woman, and the two have a brief but intense conversation before embracing and saying goodbye. Tatsioni explains to me that the woman and her husband were patients of hers years ago; now the husband has been admitted to the hospital with abdominal pains, and Tatsioni has promised she’ll stop by his room later to say hello. Recalling the appendicitis story, I prod a bit, and she confesses she plans to do her own exam. She needs to be circumspect, though, so she won’t appear to be second-guessing the other doctors.
Tatsioni doesn’t so much fear that someone will carve out the man’s healthy appendix. Rather, she’s concerned that, like many patients, he’ll end up with prescriptions for multiple drugs that will do little to help him, and may well harm him. “Usually what happens is that the doctor will ask for a suite of biochemical tests—liver fat, pancreas function, and so on,” she tells me. “The tests could turn up something, but they’re probably irrelevant. Just having a good talk with the patient and getting a close history is much more likely to tell me what’s wrong.” Of course, the doctors have all been trained to order these tests, she notes, and doing so is a lot quicker than a long bedside chat. They’re also trained to ply the patient with whatever drugs might help whack any errant test numbers back into line. What they’re not trained to do is to go back and look at the research papers that helped make these drugs the standard of care. “When you look the papers up, you often find the drugs didn’t even work better than a placebo. And no one tested how they worked in combination with the other drugs,” she says. “Just taking the patient off everything can improve their health right away.” But not only is checking out the research another time-consuming task, patients often don’t even like it when they’re taken off their drugs, she explains; they find their prescriptions reassuring.
Later, Ioannidis tells me he makes a point of having several clinicians on his team. “Researchers and physicians often don’t understand each other; they speak different languages,” he says. Knowing that some of his researchers are spending more than half their time seeing patients makes him feel the team is better positioned to bridge that gap; their experience informs the team’s research with firsthand knowledge, and helps the team shape its papers in a way more likely to hit home with physicians. It’s not that he envisions doctors making all their decisions based solely on solid evidence—there’s simply too much complexity in patient treatment to pin down every situation with a great study. “Doctors need to rely on instinct and judgment to make choices,” he says. “But these choices should be as informed as possible by the evidence. And if the evidence isn’t good, doctors should know that, too. And so should patients.”
In fact, the question of whether the problems with medical research should be broadcast to the public is a sticky one in the meta-research community. Already feeling that they’re fighting to keep patients from turning to alternative medical treatments such as homeopathy, or misdiagnosing themselves on the Internet, or simply neglecting medical treatment altogether, many researchers and physicians aren’t eager to provide even more reason to be skeptical of what doctors do—not to mention how public disenchantment with medicine could affect research funding. Ioannidis dismisses these concerns. “If we don’t tell the public about these problems, then we’re no better than nonscientists who falsely claim they can heal,” he says. “If the drugs don’t work and we’re not sure how to treat something, why should we claim differently? Some fear that there may be less funding because we stop claiming we can prove we have miraculous treatments. But if we can’t really provide those miracles, how long will we be able to fool the public anyway? The scientific enterprise is probably the most fantastic achievement in human history, but that doesn’t mean we have a right to overstate what we’re accomplishing.”
We could solve much of the wrongness problem, Ioannidis says, if the world simply stopped expecting scientists to be right. That’s because being wrong in science is fine, and even necessary—as long as scientists recognize that they blew it, report their mistake openly instead of disguising it as a success, and then move on to the next thing, until they come up with the very occasional genuine breakthrough. But as long as careers remain contingent on producing a stream of research that’s dressed up to seem more right than it is, scientists will keep delivering exactly that.
“Science is a noble endeavor, but it’s also a low-yield endeavor,” he says. “I’m not sure that more than a very small percentage of medical research is ever likely to lead to major improvements in clinical outcomes and quality of life. We should be very comfortable with that fact.”
Functional Medicine
Americans are sicker and taking more pills than ever, and our doctors are miserable. But not all is lost. Here’s how we can fix it.
If you happen to walk onto a medical ward and see a dead-eyed nursing assistant shoveling spoonfuls of pills into an elderly patient’s dry mouth, you might begin to get an idea of what’s wrong with our medical system. It’s a sight so commonplace that one young nurse turned to me recently and said, “I feel like they’re kept alive just to shove pills into them.”
But it’s not just the elderly. We’re all shoveling pills alarming rate. While Americans make up 5 percent of the population, we consume 75 percent of the world’s pharmaceuticals, The Daily Beast recently reported, and 7 out of 10 of us take prescription medicines. We take more pills than other industrialized countries, and yet we have worse health outcomes. With an approach like this, many people predict that health reform will fail simply because this medical model is so broken—expanding it will do nothing but explode the cost of care.
A lot of patients are fed up with being plied with pharmaceuticals and are turning to alternative practitioners. But many conventional doctors are also fed up and are jumping on the “alt med” bandwagon. Unfortunately, a lot of alternative medicine is indeed deeply unscientific, and deserves to be treated with skepticism. But there is a little known group of doctors who are taking a “functional” approach to the patient—by using basic science to seek out and correct the root cause of disease.
This kind of approach could revolutionize the way we treat some of the most common medical problems—and save money in the process. Take, for example, irritable bowel syndrome (IBS), a condition that affects some 15 percent of Americans. Instead of initiating the usual protocol of trying a series of medicines, functional practitioners would look for food triggers first. It seems logical, but shockingly this is not the standard-of-care. While much of the reasoning behind this “functional” medicine is sound, critics malign it as ”Quackademic medicine”.
Mark Hyman, MD, best-selling author, and current chair of the Institute of Functional Medicine, sees it as anything but quackery. “The outcomes in Functional Medicine are much more dramatic and much faster than conventional treatments, like days to weeks, and [it] gets to the root cause—it doesn’t just suppress symptoms,” Dr. Hyman, who also consults Bill and Hillary Clinton, told The Daily Beast. “That’s what we’re proving for inflammatory bowel disease, migraines, asthma, and things like autoimmune disease, gut issues, type 2 diabetes—all reverse very quickly… [for example], normal glucose in three days, whole body psoriasis gone in three weeks. Those results just don’t happen with drugs.”
Dr. Marcia Angell, after seeing the influence pharmaceutical money had on science during her two decades as the editor of the New England Journal of Medicine concluded, “It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines.” She’s not the only respected establishment voice sounding the alarm. Dr. John Ioannides concluded much the same thing, as was highlighted in The Atlantic article “Lies, Damn Lies and Medical Science.” Even the casual observer has to be aware of the pharmaceutical scandals involving recalls of pills like Vioxx.
Now, preventive protocols—like mammograms, colonoscopies, and Prostate-Specific Antigen tests—are being questioned. (And that’s the stuff we are supposed to be doing right!) But for years, many independent-minded doctors have been calling preventive protocols “disease mongering,” claiming the medical system has been doing little more than beating the bushes for business. Suffice it to say that many dedicated doctors feel there’s enough evidence that our entire approach is not only expensive but also corrupt—and we shouldn’t be expanding it, we should be dismantling it.
Of course, there will be formidable opposition from our own medical leadership who won’t be likely to reverse themselves on the protocols they’ve created. How can they? They call the guidelines they set in place “evidence based medicine” (EBM), even though, as we’ve seen in many cases, the evidence is pretty thin—and possibly even fraudulent. But it’s a brilliant strategy for controlling not just how practicing physicians think, but also what they do and say. After all, what doctor is willing to speak out against “evidence”?
Yet at its heart, all science begins with careful observation. You could say that science should begin in the exam room—not end there—because no one has a more vested interest in the patient getting well than a clinician and the patient. It was, after all, in the offices of Dr. Barry Marshall—an obscure Australian Internist who was desperate to understand why his stomach ulcer patients were failing to respond to conventional therapy—that the ulcer-causing bacterium H. pylori was discovered.
Marshall single-handedly reset our understanding of how ulcers are created, and won a Nobel Prize for his efforts. But now that it’s been decided that the only acceptable medical evidence comes out of a boardroom, observations and patients’ experiences are condemned as anecdote, and reasonable working theories dismissed as “woo.”
This has had an exceptionally negative effect on the practice of medicine and is particularly hard on our patients, who don’t feel listened to. It’s all exacerbated, of course, by the increasingly short doctor visit. Indeed, it was the embrace of evidence-based dogma that facilitated the creation of the 10-minute encounter. Why not? If we think we already know everything that is knowable, it shouldn’t take more than 10 minutes to deal with anyone.
Good science will always be relevant to the practice of medicine, but we’ve found we can’t trust “the science,” we can’t even trust the experts. The healing arts will be advanced not by the big science of pharmaceutical companies, but by the “little science” of the exam room—and through accepting that the patient will always be part mystery—beautiful and complicated—that a good physician will be alert and responsive to. It’s precisely this “little science” of the patient encounter that Dr. Hyman wants to capture. Today, he is working with the Cleveland Clinic to develop a Functional Medicine Institute to demonstrate how well the approach can work.
The healing arts will be advanced not by the big science of pharmaceutical companies, but by the “little science” of the exam room—and through accepting that the patient will always be part mystery
Critics of Functional Medicine claim that they too are interested in curing, not palliating disease. This may be true for infectious disease and cancer treatment, but it is demonstrably false for disorders like autoimmune disease that are on the upswing—and for which the conventional response is still, “We don’t know why patients have it.”
To be sure, Functional Medicine or related fields like Lifestyle Medicine may not have all the answers. But by addressing lifestyle issues first, physicians can help patients implement enduring low-cost fixes—and conventional medical leadership would do well to implement them into their protocols. In an era where we are pouring patients into the system, lowering physician pay, and increasing time pressures, without rethinking our entire approach we will do little to control costs or improve the nation’s health. (And I’m not just saying that to be provocative. Studies have shown that access to traditional care does little to improve population health.)
We’ll need to change the kind of medicine we practice to do that, and that will take some doing. Powerful forces—the pharmaceutical industry and an entrenched medical leadership come to mind—will want to keep things exactly as they are, while conveniently blaming individual physicians for the failure of the system they created—and calling anyone who steps out of line a “quack.”
Even with the backing of the Clintons, Dr. Hyman knows what he’s up against. But, in the face of all that, he thinks he can turn the tide. “If we can show that we have better outcomes and it’s cheaper to take a functional approach,” Dr. Hyman said, “in the end, the doctors who adopt this model—and their patients—they will be the ones who win.”
Apps: The First Step
There isn’t a thing about health care that isn’t costly. Clinical treatment of any kind costs patients an immense amount of money, an inordinate amount of time, and sometimes doesn’t even work the way we hoped it would. Given the huge level of investment it requires, it’s kind of remarkable that for much of the process, patients are kept in the dark. After all, our health care providers already know so much about us.
But what if that dynamic was reversed?
At the Northside Festival in Brooklyn on Thursday, a small panel convened to discuss the ways our data-driven tech scene can work to the advantage of every patient in health care--but hasn’t. Called “Empowering the Most Important Caregiver: The Patient,” members included Chris Bradley, CEO of Mana Health, Mario Schlosser of health insurance startup Oscar, Rachel Winokur of Aetna’s tech services division Healthagen, and Paul Wilder of The NY eHealth Collaborative.
“All of this data is being generated in health care,” said Chris Bradley, “but it’s not helping the people who need it most.”
Recent announcements from companies like Apple suggest that the next big push in tech is going to be for our health. But as tech enables us to take more control of wellness, it’s starting to bring a fresh load of inadequacies in the health care system to the surface.
During the launch of WellMatch, a service designed to provide price transparency in health care services, panelist Rachel Winokur came up against one of these head on. Winokur described a situation in which WellMatch had found a way to do the impossible: both make health care providers more money while saving patients significant cost.
“Providers have excess capacity that they probably want to monetize. So, Fridays at five o' clock the MRI machine is probably not being used, and that's a fixed cost. Let's figure out how we monetize that and offer discounts,” said Winokur. “We discovered, going down that route, that in order to offer a discount on the price, you've got to know what the price is. And nobody knew what the price was.”
It’s quite difficult to fix a system in which the particulars of its operation are even obscured from those in charge, you see.
However, even if we succeed in moving data about our health from the sole purview of our doctors and insurers, another challenge emerges: talking about it. According to Chris Bradley, making informed decisions about our health care implies a metric that we don’t actually have.
“We have no actual idea what we mean by quality. I think we're just starting to figure out what it means to be sick. Because until this year, we haven't actually had any unified view of a patient in the state of New York, or any of the United States,” said Bradley. “Only when we start to see a unified view over time, [will] we start actually figuring out, 'what does it mean to be well... How do we measure quality before we can improve it?”
As such, there’s a need for the new wave of health tech to build some form of wellness literacy. To Bradley, this means getting to work establishing two things necessary for any tech project to get off the ground: standards, and data--that unified view of what a healthy person looks like, in order to better determine what is wrong.
But even if the tech end of the bargain is held up, there are still two very real barriers towards patient empowerment. The first is a grim reality of the system: it’s in a patient’s interest to seek as little clinical help as possible. And it’s in an insurer’s interest to keep you coming back for more.
The ideal health care service of the future would cause some tension in this regard, by providing you with an app-based, online service that will fill a space that’s been covered poorly by our current model: the time between doctor appointments.
“When you think about the cost of the health care system, we also found that re-admits, post [pediatric hospital] discharge, went through the roof, because you go from 24 hour coverage to zero coverage,” said Rachel Winokur, citing analysis of clients whose children needed immediate medical attention.
That transition from nurses and doctors available to address any worrisome symptom at any time to an environment where no one is around at all is anxiety-inducing, and as co-panelists Chris Bradley and Mario Schlosser pointed out, something that could be absolved with better engagement and access to easily-interpreted medical information.
The other big problem is generational: using apps and other tech services to manage your health care is going to go over just fine with younger patients who are likely to be digital natives. They’re also the demographic that needs health care the least.
“The ‘Well’ of the world are going to do very well with data that they can access every day, the Fitbit type data,” said moderator Paul WIlder. “But if you look at the socioeconomics of this stuff, who is using it, it's not because we're worried about [our health].”
Those who need the health care system the most often mistrust it, and rightfully so. Prices are exorbitant, and, as panelist Rachel Winokour said at one point, physicians are often chosen out of convenience and insurance compatibility rather than quality—which the panel, as you’ll recall, holds that we aren’t really equipped to evaluate given our health care limitations. So how do we deal with a cynical population whose prejudices are probably justified?
“I think we're at a point in health care where there's enough people starting, that we're going to be able to show people, just through improvements, and through increased health, that it's worth doing these things,” said Chris Bradley, in a brief interview after the panel.
“Because now it's just kind of a black box, like, 'just trust me.' And I don't want to have to trust you, I want to see it, I want to see the proof and I want to see how it works for millions of other people.”
Three Tech Trends
Will technology and the Internet decimate the healthcare industry as they have done to the music and travel industries? Will nurses be replaced by robots? Will doctors be replaced by smartphone apps? A shift is surely occurring, but we still need medical professionals, real people with real compassion giving great care.
Three trends threaten to make much of today’s healthcare obsolete: the Internet has made patients more engaged in their own care, technology is advancing exponentially, and social media is a dominant force in daily life. Responding to these trends, has initiated a range of innovations: HereIsMyData, a service that consists of a personal health record, a community aspect, and an eHealth connector; AED4US, a crowdsourced database of locations of automatic electronic defibrillators; FaceTalk, a videoconference system that allows healthcare professionals to consult securely with patients and colleagues; AYA4, an online community for young adult cancer patients; and webcasted conferences — TEDxMaastricht, TEDxNijmegen, and 360andabove — to share ideas, dreams, and examples.
Location is becoming less important in healthcare. Mobile technology and cheaper testing methods are enabling us to monitor patients in their own homes. And procedures that required up to 15 days of hospitalization a decade ago only require three days today. In the last century, technology brought healthcare out of people’s homes and into centralized hospitals, but now technology is doing the opposite, bringing healthcare back into people’s homes.
Two-party research in a three-party world
Until now, health research has mainly been done by the pharmaceutical industry and researchers. Now, patients are doing their own medical research. MedCrowdFund, for example, is a social platform where patients can design and find funding for innovation and research.
Being a good doctor won’t be good enough anymore
People are no longer choosing healthcare providers based only on the quality of medical care they or their personal acquaintances have received. Patients now routinely research their physicians online and post reviews of their healthcare experiences. Fifty percent of U.S. smartphone users use their device to look up health information. Doctors can gain a competitive edge by providing both text-based and video web content.
Collaboration
Healthcare providers need to stop assuming they know what patients need, or, from an industry perspective, what healthcare professionals need. Listening is asking. The Radboud REshape & Innovation Center appointed a chief listening officer in 2009 to interview patients, family members, and caregivers about how the Center could help them. Feedback from these target groups has significantly benefited the Center’s healthcare projects. The Center also teams with innovators nationally and internationally, finding these likeminded collaborators through the Internet and particularly through social media.
Rules and regulations
Time-to-market for medical devices is much shorter today than it used to be, and many more devices are being released, leaving regulatory agencies to play catch-up. In addition to implementing regulatory requirements for digital healthcare innovations, policymakers should make open technical standards mandatory for information exchange and the reuse of existing and proven applications. And the financial system must be improved to ensure that the talented developers and producers of digital healthcare innovations are well compensated for their contributions.
Information systems
Huge amounts of data are being generated by information systems, medical records, tracking devices, lab results, and imaging resources. But all of this data currently resides in inaccessible silos where patients can’t make use of it. We need a central repository where individuals can access their own data in a comprehensive way, mine all of the different types of data, and understand their meanings, interrelationships, and interactions. We need open, transparent, user-friendly, and cooperative systems based on open technology standards that actively promote interoperability.
To speed the evolution of personal health data systems, the Radboud REshape & Innovation Center started a noncommercial service to set up these systems, validate them scientifically, and make them widely available. The Center recently introduced HereIsMyData, a service that provides a personal health record, as well as a platform for patients, caregivers, and families to talk about a specific disease, and connectivity tools for personal health devices, data visualization tools, and the Center’s own FaceTalk™ and MedCrowdFund™.
Aspartame
Discovered in 1965 at Searle (now Pfizer), aspartame is an artificial sweetener, aspartyl-phenylalanine-1-methyl ester. Chemistry types call it a methyl ester of the dipeptide of the amino acids aspartic acid and phenylalanine. It is 180 times as sweet as sugar, which is why it's such an effective low-calorie sweetener: It's needed in only miniscule amounts. Partly in response to all the anti-aspartame craziness out there, a group of scientists from the NutraSweet company published a 2002 review of dozens of studies and clinical trials performed worldwide in the journal Regulatory Toxicology and Pharmacology, which made the following conclusions:
Over 20 years have elapsed since aspartame was approved by regulatory agencies as a sweetener and flavor enhancer. The safety of aspartame and its metabolic constituents was established through extensive toxicology studies in laboratory animals, using much greater doses than people could possibly consume. ...Several scientific issues continued to be raised after approval, largely as a concern for theoretical toxicity from its metabolic components — the amino acids, aspartate and phenylalanine, and methanol — even though dietary exposure to these components is much greater than from aspartame. Nonetheless, additional research, including evaluations of possible associations between aspartame and headaches, seizures, behavior, cognition, and mood as well as allergic-type reactions and use by potentially sensitive subpopulations, has continued after approval. ...The safety testing of aspartame has gone well beyond that required to evaluate the safety of a food additive. When all the research on aspartame is examined as a whole, it is clear that aspartame is safe, and there are no unresolved questions regarding its safety under conditions of intended use.
And yet the claims persist unabated. Here are a few more, addressed point-by-point:
Claims that aspartame causes Multiple Sclerosis are entirely made up and have no evidence or plausible foundation. Search the Multiple Sclerosis Foundation's web site for "aspartame" to find more than enough information refuting this harmfully misleading claim.
The idea that aspartame causes "methanol toxicity" is based on the fact that when digested, aspartame does release a tiny amount of methanol. It's less than the amount you get from eating a piece of most any fruit. Tomato juice, for example, gives you four times the methanol of a can of diet soda. It's a common, naturally occuring environmental compound that is found in many foods. Nancy Markle, one of the most vocal aspartame conspiracy theorists, charges that the autoimmune disease lupus is actually misdiagnosed methanol toxicity caused by drinking 3-4 cans of diet soft drinks per day. If she's right, everyone who drinks a glass of tomato juice each day (or the equivalent in other fruits) is gravely ill with lupus. Time Magazine once devoted an entire article to debunking Nancy Markle's baseless claims about aspartame.
Much has been made of the claim that aspartame turns into formaldehyde in your system. This is true, because formaldehyde is a natural byproduct of digestion of methanol, and it happens whenever you eat almost anything. Formaldehyde is carcinogenic and is considered very dangerous in cases of occupational exposure, for example, when you get a dosage many orders of magnitude greater than the trace amounts produced during natural digestion. Again, aspartame does this in much smaller amounts than many common foods, so this has been a normal, healthy component of digestion for as long as humans have been eating fruits and vegetables.
Gulf War Syndrome is a weakly evidenced correlation between service in the Gulf War and incidences of chronic fatigue, chronic pain, and a range of vague neurological conditions. Anti-aspartame advocates blame aspartame for this, but there is no correlation between increased aspartame consumption and Gulf War service. In addition, aspartame is among the hypothesized causes that have been eliminated by the Research Advisory Committee on Gulf War Veterans' Illnesses.
What about Donald Rumsfeld's involvement with aspartame? He was the CEO of Searle at the time aspartame was approved as a sweetener. The reason he was hired was as a financial turnaround wizard, which he accomplished; he wasn't the guy in the lab designing artificial sweeteners. Even if you accept the conspiracy charges that he leveraged his cronies to force approval of a potentially dangerous product, that still says nothing about aspartame. It's a giant non-sequitur. To assess the safety of a product, we don't ask "Who was the CEO and who were his cronies?" we ask "What are the test results?" and so far, all of the test results show no association between aspartame and any of the diseases it is claimed to cause.
Some of the claims about aspartame breaking down into unwanted compounds are true at extreme levels of alkalinity or acidity, levels which would be fatal to a human being anyway. This is the case with many foods, by no means is this unique to aspartame. So if your body chemistry is such that aspartame would be a danger to you, you'd have to already be dead from some unrelated cause.
There is actually one known health risk associated with aspartame, but it only applies to people with a rare genetic disorder on chromosome 12 called phenylketonuria or PKU, which affects about 1 in 15,000 people. They can't metabolize phenylalanine, so they need to minimize not only aspartame but all phenylalanine products. Phenylalanine is an amino acid that's found in many, many foods, including breast milk; so it hardly makes sense to single out aspartame as the problem product.
It is true that you can't cook with aspartame, but not for any safety reasons. At cooking temperatures it breaks down and loses its flavor, like some other foods. For this reason aspartame is starting to lose ground in the market to Sucralose, another artificial sweetener that does retain its flavor when cooked.
When you hear claims that are supported only by a fringe minority that's in opposition to the scientific consensus, you have good reason to be skeptical right off the bat, but it doesn't mean it's not worth looking into. Aspartame has been looked into ad nauseum even after its approval, and found safe at every try; so at some point you have to depart from rationality to continue supporting the claims made against it. Enjoy your diet Dr. Pepper, it's not going to hurt you; if it was, I'd have been dead decades ago.
Blood Tests For Cancer
Globally, eight million people died of cancer in 2012.
The answers Bert Vogelstein needed and feared were in the blood sample.
Vogelstein is among the most highly cited scientists in the world. He was described, in the 1980s, as having broken into “the cockpit of cancer” after he and coworkers at Johns Hopkins University showed for the first time exactly how a series of DNA mutations, adding up silently over decades, turn cells cancerous. Damaged DNA, he helped prove, is the cause of cancer.
Now imagine you could see these mutations—see cancer itself—in a vial of blood. Nearly every type of cancer sheds DNA into the bloodstream, and Vogelstein’s laboratory at Johns Hopkins has developed a technique, called a “liquid biopsy,” that can find the telltale genetic material.
The technology is made possible by instruments that speedily sequence DNA in a blood sample so researchers can spot tumor DNA even when it’s present in trace amounts. The Hopkins scientists, working alongside doctors who treat patients in Baltimore’s largest oncology center, have now studied blood from more than a thousand people. They say liquid biopsies can find cancer long before symptoms of the disease arise.
This particular blood sample, though, was personal. It was from Vogelstein’s brother, an orthopedic surgeon one year younger. He was fighting skin cancer, and the disease was already spreading. There was hope he’d respond to a new type of drug, but the treatment causes swelling, and it’s difficult to tell from an x-ray or CT scan whether the cancer is melting away or not. So Vogelstein used his lab’s new technology. If the cancer DNA had disappeared from the blood, they might celebrate. If it was still there, maybe he could steer his brother to some last-ditch drug.
We’re not winning the war on cancer, and the death of Vogelstein’s brother shows why. Too many cancers are caught when they have become incurable. Each year, $91 billion is spent on cancer drugs worldwide, but most of those medicines are given to patients when it’s too late. The newest treatments, created at staggering expense, cost $10,000 a month and often extend life by only a few weeks. Pharmaceutical firms develop and test more drugs for late-stage cancer than for any other kind of disease.
“We as the public and as scientists have been entranced by this idea of curing advanced cancers,” says Vogelstein. “That is society’s Plan A. I don’t think that has to be the case.” There are other ways to reduce cancer deaths: wearing sunscreen, not smoking, and getting screened to catch cancer early. To Vogelstein, all these preventive steps represent “Plan B” because they receive so much less attention and funding. Yet when prevention works, it has better results than any drug. In the United States, the chance of dying from colorectal cancer is 40 percent lower than it was in 1975, a decrease mostly due to colonoscopy screening. Melanoma skin cancer, too, is treatable with surgery if caught early. “We think Plan B needs to be Plan A,” says Vogelstein.
The new blood tests could make that possible. For the first time, Hopkins researchers say, they are within reach of a general screening tool that could be used to scan broadly—perhaps at an annual physical—for molecular traces of cancer in people with no symptoms. “We think we’ve solved early detection,” says Victor Velculescu, a Hopkins researcher who runs a lab in the building next to Vogelstein’s.
Making such screening a routine practice in medicine will be challenging. One difficulty is that while the test may detect the presence of cancer DNA in the body, physicians might not know where the tumor is, how dangerous it is, or even whether it is worth treating. “We have to be cautious about how we talk about that,” says Daniel Haber, director of the Massachusetts General Hospital Cancer Center. He believes the DNA blood tests are “far from ready” and says very large studies will be needed to prove that they are useful. “There is a huge bar to get over,” he says.
Despite such skepticism, the technology is gaining attention. Tony Dickherber, head of the Innovative Molecular Analysis Technologies Program at the National Cancer Institute, says the idea of scanning blood for tumor DNA was “fringe at best” only three years ago. But now labs and companies from California to London are jumping in, producing a stream of improvements to the blood screening technology and new data supporting it. “People are starting to think that [Vogelstein] is right—this could be the best way to do early diagnosis,” he says. “[It] could be done much more widely than other screening technology we have, and you could screen for an incredible range of cancers.”
In February, doctors from Hopkins and 23 other institutions provided the largest survey yet of their findings. They studied the tumors of 846 patients with 15 different types of cancer. They found tumor DNA in the blood of more than 80 percent of patients with advanced cancers, the kind that have spread, and about 47 percent of those whose cancer was still localized and at the earliest stage. In advanced colorectal cancer, the DNA was always seen.
For the first time, Hopkins researchers say, they are within reach of a general screening tool that could be used to scan broadly—perhaps at an annual physical—for molecular traces of cancer in people with no symptoms.
The results might not at first appear impressive. A test that misses half the time? The benefit is that the tests are “exquisitely specific,” according to Velculescu. If you do have tumor DNA, it appears, so far, that you also have cancer. That could give DNA screening the edge over current tests for prostate and breast cancer, which frequently produce false positives. “It’s normal to have circulating DNA in the blood; it is not normal to have circulating DNA that matches a tumor,” says Stefanie Jeffrey, chief of surgical oncology research at Stanford University.
To Vogelstein, the blood tests mean it may be possible to catch more than half of cancers early on, and potentially cure them with surgery. “If there were a drug that cured half of cancer you’d have a ticker-tape parade in New York City,” he says.
Early Days
President Nixon’s War on Cancer was launched in 1971, when Vogelstein was in medical school. Years of frustration followed as drugs failed to make much of a dent in cancer deaths. What has changed is that now we know what causes cancer. Vogelstein’s work in the 1980s, carried out with colleague Kenneth Kinzler, helped demonstrate the crucial role of mutated genes in the disease. And scientists have now assembled a list of more than 150 genes that appear to be the key drivers. Even though cancer’s genetic landscape is complex, all the DNA mutations do one thing: they allow some cells to keep multiplying when normal cells would die. The resulting imbalance is cancer.
For pharmaceutical companies, this insight and the gene list have been the launching point for billion-dollar efforts to develop new drugs for advanced cancers. But to Vogelstein, the knowledge that DNA mutations cause cancer has always also meant something different: that it should be possible to spot the telltale changes early on, well before the disease is usually diagnosed. And in oncology, it’s a truism: the sooner you detect cancer, the better your chances.
Consider colorectal cancer, the type Vogelstein has studied most closely. It begins with a single mutation to a gene called APC. Yet it takes on average 30 years from that point for the cells to acquire several other DNA mutations they need in order to spread and kill. About 600,000 people die from colorectal cancer each year. “Nearly all of them will die only because their cancer was not detected in the first 27 years of the tumor’s existence,” Vogelstein says. “That is a huge window to intervene in this process.”
The problem has been that until the blood tests, there was no very easy way to look for these mutations. Vogelstein has been working on early-detection schemes since the 1990s, when he began looking for tumor DNA in urine and stool, using the laborious methods available at that time. He believes prevention and screening still receive too little attention, putting him, even now, in an “absolute minority” of researchers. He estimates that 100 times as many research dollars go toward drugs as toward these strategies.
This may explain why, despite his preëminence, Vogelstein seems to have a chip on his shoulder. The Hopkins research group, which includes several other well-known researchers, is quick to publish new ideas, but it often makes the effort to shoot down scientific concepts that are trendy elsewhere. Any young scientist who want to work there, according to the lab’s traditions, must first present his or her earlier scientific work while wearing a Burger King crown.
Luis Diaz
The lab’s work on the blood tests has been led by Luis Diaz, an oncologist who has become Vogelstein’s protégé. He hit on the idea of testing blood for cancer DNA in 2005, while researching whether a flesh-eating bacterium could be used to eradicate tumors. The work involved transplanting human cancers into mice, and Diaz recalls that he “needed a way to monitor the tumors in the mouse without killing it.” He and a colleague decided that they might be able to do that with a blood test. Soon they saw the level of human DNA bouncing down and up as the treatment worked or failed. If they could monitor DNA from a human tumor in mice, wouldn’t it work in humans, too?
The idea wasn’t entirely new. It’s been known since 1948 that free-floating DNA circulates in our veins and arteries. It’s normally a waste product of dead cells. But tumors also shed DNA into the blood. The portion of DNA in the blood that comes from tumors can be as high as 87 percent in a person dying from cancer, but often the amount is vanishingly small.
When Diaz began looking at the question, all this was not yet fact but muddy possibility. To develop the liquid biopsy, the Hopkins scientists first had to invent ways to pick out the tumor DNA from an overwhelming background of normal DNA. Working with blood donated by patients with colorectal cancer whom Diaz was treating in Baltimore, the researchers initially tracked only four cancer genes. Yet they could see that the tumor DNA in the blood would disappear quickly—even within a day—after these patients had surgery or drug treatments. Healthy control subjects never tested positive. “We realized this test can ask and answer the question ‘Do I have cancer?’” says Diaz.
Hopkins believes its test may be more sensitive than any tool doctors have now—at least for cancers that are too small to be seen with an imaging machine. Vogelstein estimates that a tumor has to contain at least 10 million cells, making it about as big as the head of a pin, to shed a detectable amount of DNA. To be visible on an MRI, by contrast, a tumor needs to be about 100 times that size, containing at least one billion cells.
The Hopkins physicians have begun using the DNA tests in an effort to determine whether malignant cells remain behind in patients whose tumors have been surgically removed. Working with Peter Gibbs, an Australian oncologist, they have scanned blood samples from 250 patients who have been operated on for early-stage colon cancer. Most of these people will turn out to be cured, but up to 30 percent are expected to suffer a relapse because not all the tumor cells were removed. The problem is that doctors don’t know which patients will relapse. “The surgeon will say, ‘Don’t worry - we got it all,’” says Diaz. “It’s frustrating to me, because then I have to tell the patient, ‘We don’t really know if you are cured.’” Survivors can get caught in a state of limbo, uncertain whether their disease is coming back, possibly in a more dangerous form. And the situation can drag on for years.
Patients could be frightened, doctors uncertain how to act. “The idea of screening healthy people and telling them ‘Oh, look, there is cancer somewhere but we don’t know where it is’ - well, that would be the death of the whole [idea],” says one oncologist.
The patients in Australia are checked for tumor DNA in their blood six weeks after surgery. So far, the researchers say, they have correctly identified about half the people who later relapsed. In the future, says Vogelstein, these patients could be flagged to receive chemotherapy, probably saving at least a third of them. Yet the limits of the test are also apparent, since it still missed half the patients whose cancer later reappeared.
Diaz says this may be because whatever cancer cells remain aren’t giving off enough DNA to detect. “We may have hit the biological limits,” he says. However, the cancer DNA could rise to detectable levels over time, and retesting patients periodically could pick that up. Even though Hopkins’s testing remains experimental, Diaz says he has enough confidence in it to tell some patients they are still sick and others that they are probably healed. “Six to eight weeks later, we can tell them if they are cured,” he says. “It’s very satisfying.”
Mass Screening
Vogelstein says his ultimate goal is to turn the blood tests into a way to routinely screen everyone for cancer. The Hopkins researchers believe they have a version of the test that can do that. Instead of tracking a few key cancer genes, they sequence a person’s entire genome using DNA from the blood sample. This lets them count how often chunks of genetic material are misplaced or appear scrambled. A large amount of rearranged DNA is a molecular side effect seen only on the chromosomes of cancer cells—a tip-off that cancer is present. But a full genome sequence is still expensive. “If a person has cancer, you don’t mind spending $5,000 on a DNA test. But you can’t have a test that costs $1,000 that you can do at an annual physical,” says Vogelstein. “The goal is to get the technology cheap enough to use in screening.”
That could take time. The cost of DNA sequencing has been falling very rapidly, yet a $100 genome—the price that might be low enough for a general screening test—could be 10 years away. In the meantime, Hopkins has begun several studies, mostly on individuals predisposed to cancer, to determine whether the techniques can catch tumors early in healthy people. One involves 800 people at risk for pancreatic cancer. In these unusual cases, people have cysts on the pancreas that sometimes turn into cancer but sometimes don’t. The clinical trial began following patients in 2012, and the researchers will get their first look at the results late this year.
Pancreatic cancer is a good test case for early screening. It’s not a very common cancer, but it’s the fourth-highest cause of cancer deaths in the United States, because it’s cured only 4 percent of the time. (Apple founder Steve Jobs died of it at age 56.) If detected very early, before it spreads, the survival rate rises to about 25 percent.
But extending the DNA tests to everyone is an enormous leap. Haber, the Mass. General oncologist, says the technology, as currently conceived, might tell a doctor if cancer is present. But unlike an imaging scan or a biopsy, it could leave you guessing where in the body it is. Patients would be frightened, doctors uncertain how to act. “The idea of screening healthy people and telling them ‘Oh, look, there is cancer somewhere but we don’t know where it is’—well, that would be the death of the whole [idea],” Haber says.
Medicine has a precedent of handling predictive tests poorly. Consider the PSA test, which detects a protein linked to prostate cancer. Not only does the test produce false positives a majority of the time, but some of the tumors it actually detects are so slow-growing that they aren’t worth treating. Millions of men have ended up getting treated for cancers that ultimately wouldn’t have affected them. By one estimate, for every 47 men who had their prostates removed, a single cancer death was avoided. Studies by researchers at Dartmouth College suggest that mammography also leads to overdiagnosis and overtreatment. About 25 percent of breast cancers discovered, and treated, would not have caused any symptoms. “You test everyone and end up treating people for diseases that would never have mattered, either because they wouldn’t have progressed or because people die of something else,” says Jonathan Skinner, a health economist at Dartmouth. “The downside of early screening can be very high.”
At Hopkins, however, Velculescu says he’s hopeful that mass DNA screening for cancer will become a reality. “If you can’t make a difference, then maybe you would want to remain ignorant,” he says. “But I can’t imagine that knowing about cancer wouldn’t help patients. Maybe we won’t dramatically act on every piece of information. Maybe we don’t do anything. But with these tests, it would be so easy to keep doing them and say to the patient, ‘Let’s see how it develops.’”
So far, companies aren’t talking loudly about broad screening for cancer in seemingly healthy patients. For now, Personal Genome Diagnostics, a diagnostic testing startup that Diaz and Velculescu founded, and several competitors, like Boreal Genomics and Guardant Health, offer liquid biopsies only to patients who are fighting late-stage cancer. For those patients, the tests might reveal whether a treatment is working in time to try something else if it’s not. Another valuable use of the technology is to track the specific DNA mutations driving a patient’s tumors. Since many new cancer medications are “targeted”—they block specific molecular processes—patients get them only if their tumor is the kind expected to respond. Doctors can already use DNA tests on chunks of tumor obtained through tissue biopsies. But the noninvasive blood tests could be easier and safer, allowing patients to be evaluated more frequently. Since cancer DNA is constantly mutating, that could help patients switch drugs when appropriate.
To Helmy Eltoukhy, the CEO of Guardant, liquid biopsies are “a huge idea” with many applications. For commercial and medical reasons, his company so far is marketing the tests only to people who have cancer. But he says early screening tests are on his company’s road map. “It’s obviously the Holy Grail,” he says. “Imagine the applications, and that is what we are working on.”
I asked both Vogelstein, who is 65, and Velculescu, who is 44, if they had ever tested themselves. Both said no. Yet overall, men in the United States have a 40 percent chance of developing cancer sometime, and the odds rise with age. If these researchers haven’t sought the screening, it seems questionable that the broader public will be eager to do it either. For a screening test to be performed widely as a public health measure, the entire medical community will have to participate, and that will take a great deal of time.
Vogelstein isn’t naïve. We’ll still need new drugs to treat people who develop cancer anyway. But he remains convinced that the best way to beat late-stage cancer is to prevent it from happening. When I offered my condolences to Vogelstein on the death of his brother, he waved them aside. “This is why we do the work,” he says. “A hundred years from now, when cancer and death from cancer is a lot less common, a lot of that is going to be due to early detection, not because we can cure a body riddled with tumors.”
Waist Size and Life Expectancy
THE key to a long life is having a waist no bigger than half your height, according to a new scientific study.
The report, to be published tomorrow, is based on 20 years of British medical records and is the first to quantify how many years you will lose to obesity as measured by your waist-to-height ratio.
Dr Margaret Ashwell, a co-author of the study, said the rule applied regardless of a person’s age, ethnicity or gender. She added that the evidence was so strong that it should provide the basis for a simple global health check, which anybody could perform with a piece of string if they did not have a tape measure: “Keep your waist circumference to less than half your height.”
The waist is the halfway point between the lowest rib and the hip bone, although researchers say it is good enough to measure the narrowest point — just do not breathe in.
The study by Ashwell and researchers from City University London’s Cass Business School is the first to analyse official health records and measure the impact on life expectancy of obesity, as measured by the ratio between your waist and height.
Mr Average, a 30-year-old man who is 5ft 10in tall, should have a waist of no more than 35in — but if that expands to 42in, or 60% of his height, he will lose 1.7 years. His female counterpart, who is 5ft 4 in tall, will die 1.4 years prematurely if she lets her waist expand from half her height, 32in, to 60% of her height, 38.4in.
The penalty in a reduced life span is much more severe for those who become seriously obese.
A man aged 30, of average height and a 56in waist, can expect to lose 20.2 years, while an obese woman of 30 with a waist of 51in will die 10.6 years early. However, only 0.2% to 0.3% of that age group are so excessively overweight.
The study also tracked the impact on 50 and 70-year-olds and found that they, too, sacrificed years from their lives by letting their waists exceed half their height. Fewer years will be lost, largely because their remaining life expectancy was lower to start with.
Ashwell, who in 1996 popularised the discovery that “apple-shaped” obesity is much more dangerous than “pear-shaped”, said the circumference of the waist is important because it indicates the amount of “central fat” in the body. This affects the vital organs, causing health problems from heart trouble to diabetes, unlike fat around the thighs, hips and bottom.
The findings will put pressure on the government to use waist-to-height ratio to assess the true threat of obesity. Ashwell said the proportion of adults at risk on this measure was 69% rather than the official estimate of 56%, which uses a ¬combination of waist circumference and body mass index (BMI).
She added: “People are living in false hope if they rely on their BMI figure. We have got to measure the right thing.”
Critics of BMI have long pointed out that it does not distinguish between fat and muscle. Arnold Schwarzenegger and Danny DeVito, co-stars of the 1988 movie Twins, had the same BMI, implying they would die 3.6 years early, whereas, if measured by their waist-to-height ratio, Schwarzenegger was in good health while DeVito’s excess fat meant he would lose 5.8 years.
The study demonstrates that BMI is particularly poor at predicting early death from obesity for women, while waist to height provides ¬accurate estimates for both sexes.
Cass examined morbidity and mortality figures as well as the Health and Lifestyle Survey, which has tracked a random sample of the population since 1985 on a range of measures including weight, height, waist measurement, diet and exercise. Researchers excluded smokers to avoid distorting the results.
Les Mayhew, professor of statistics at Cass, said: “There is now overwhelming evidence that government policy should place greater emphasis on waist-to-height ratio as a screening tool.”
The Institute and Faculty of Actuaries funded the early stages of the research, which will be published by the Public Library of Science.
The professional body representing GPs, which recently declared a state of emergency on childhood obesity, welcomed the findings but said it was unclear whether “worrying people about their weight actually motivates them to make a long-term commitment to lifestyle changes”.
Sense of Smell and Life Expectancy
PEOPLE whose hearts are failing, or who have had cancer or lung disease, have good reason to be concerned about their future. People who have merely lost their sense of smell might not be so worried. Actually, though, their prospects are worse. You are more likely to die within five years if you cannot recognise common smells than if you have ever been diagnosed with one of those more obviously deadly illnesses. That, at least, is the conclusion of a sobering study just published in PLOS ONE, by Martha McClintock and Jayant Pinto of the University of Chicago.
Dr McClintock and Dr Pinto were prompted to conduct their investigation because they knew olfactory problems can forewarn of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. They are also associated with abnormally shortened telomeres (the caps on the ends of chromosomes), and that shortening is, in turn, implicated in the process of ageing. Moreover, a good sense of smell helps keep people healthy by detecting pathogens and toxins in the air, stimulating appetite, and aiding memory, emotions and intimacy. The researchers therefore had good reason to wonder if measuring smell loss might predict mortality.
As part of the National Social Life, Health and Ageing Project, a survey organised by the University of Chicago that measures the health and well-being of older Americans, 3,005 participants aged between 57 and 85 completed a three-minute smell test devised by Drs McClintock and Pinto. The survey’s researchers prepared special felt-tipped pens scented with five common odours—fish, leather, orange, peppermint and rose—and presented them one by one to volunteers. After each presentation, the volunteer was shown pictures and names of four possible answers, and was asked to select the correct one. Getting one answer wrong was considered okay, or “normosmic”, but two or three errors labelled a person as “hyposmic”, or smell-deficient, and four or five counted them as “anosmic”, or unable to smell.
Five years later, 430 of the respondents were dead. The anosmic were particularly hard hit: 39% of them had perished, compared with 19% of the hyposmic and just 10% of the normosmic. After adjusting for age (older people are more likely to die), sex (women tend to live longer than men), socioeconomic status (richer, better-educated people enjoy greater longevity) and race (some ethnicities have longer lifespans than others), Dr McClintock and Dr Pinto found that the correlation still held true. Nutrition could not explain it. Nor could smoking or alcohol use. Even when they controlled for specific diseases, like heart failure, cancer, strokes and diabetes, the researchers found the relationship between not being able to smell and being more likely to die in the next half-decade remained robust. Only severe liver damage was a stronger predictor of death.
No one is suggesting that not being able to smell led directly to any of the deaths. Rather, the researchers think that smell may be the “canary in the coal mine of human health”. They note that olfaction relies on a turnover of stem cells (from which other sorts of cell develop) to maintain its functioning. Not being able to smell, they speculate, may signal a more general inability to regenerate and renew.
An Outline manifesto From The CEO of NHS
Our current debate on the future of NHS should start with two pleasing facts — and an inconvenient truth. Fact one: over the past 15 years the NHS has dramatically improved. Cancer survival is its highest ever level. Early deaths from heart disease are down by more than 40 per cent. About 160,000 more nurses, doctors and other clinicians are treating patients. And most long waits for operations have been slashed — down from 18 months to 18 weeks. In short, investment produced results. Public satisfaction with the NHS has nearly doubled.
Fact two: over the past five years, despite growing pressure, the NHS has been remarkably successful in weathering the recession. That’s despite a growing population, an ageing population and a sicker population, not to mention the addition of expensive new drugs and treatments, and the subtraction of swathes of local authority social care. Protected funding has helped, as has the shared sacrifice by staff through pay restraint.
We’re treating millions more patients than five years ago and, on one measure, the NHS has become some £20 billion more efficient. Transparency about quality has helped hospital care to improve. A world-leading genomes programme is harnessing the best of this country’s medical and scientific expertise. The Commonwealth Fund has just ranked us the highest performing health system of 11 industrialised countries.
Now for the inconvenient truth. Neither the NHS’s response to recent austerity, nor to the years before it, tell us much about how the health service will need to respond over the coming five years. On the one hand, recent methods of balancing the books are not going to be indefinitely repeatable and service pressures are building.
On the other, a tax-funded health service requires a healthy UK economy and, regardless of who forms the next government, the 6 or 7 per cent annual NHS funding increases of the pre-recession years are economically implausible. More probable is a phased return to sharing in the fruits of UK economic growth.
What’s more, even if there were no funding pressures, the NHS would still need to change. Fortunately, despite the Sturm und Drang of national debate, there is quite broad consensus on why that is necessary and what new-style health services should look like.
There is a recognition that frail older people with long-term health problems need far more personal and joined-up care. There is a determination to tackle the rising burden of preventable illness, which is further entrenching health inequalities; getting serious, for example, about the fact that a quarter of 11-year-old children are obese.
There is an acknowledgement that quality and efficiency of care is far from uniform and improvements are needed — for example on early cancer diagnosis or on mental health problems.
In other words, there is an acceptance that what’s great about the NHS can’t excuse what needs to change. That’s why we’ll shortly be publishing our NHS Five Year Forward View, which will make the case for some of the changes we’re going to need. It’s not a one-size-fits-all blueprint for every part of the country, let alone a detailed plan for everything that needs to happen. It is, however, a scene-setter for some of the bold action needed.
Care needs to be redesigned to erode the historical demarcations between primary, community and specialist care, between health and social care, and between physical and mental health services. Technology and new care models will unleash greater productivity.
We need to upgrade infrastructure and get serious about prevention, about patient power, about the role of employers, and about support for carers and the voluntary sector. The NHS is not just a “repair and care” service but a social movement.
So the NHS is up for change. We respect our history but can’t be hostage to it. We’re not naive about how difficult some of this will be. We’ll only succeed if governments and communities play their part. But, as the saying goes, “To will the end is to will the means”.
Simon Stevens is the chief executive of NHS England
More on Sunshine
Swedish study, published earlier this year, came to similar conclusions. This study, Avoidance of sun exposure is a risk factor for all-cause mortality, followed 29,500 women aged between 25 and 64 for more than 20 years. Those taking part had to fill in a detailed questionnaire. Among the questions, designed to separate sun avoiders from sun worshippers, were:
• Do you sunbathe during the summertime? (never or sometimes)
• Do you sunbathe during the winter, such as on holiday to the mountains? (never or sometimes)
• Do you use tanning beds? (never or sometimes)
• Do you go abroad on holiday to swim and sunbathe? (never or sometimes)
If you answered “no” to all these questions then you were a sun avoider. “Yes” to one or two questions made you a moderate exposer, while “yes” to three or four questions put you among the sun worshippers.
By the end of the study 2,545 women had died. Although the sun avoiders had developed fewer skin cancers, overall they were twice as likely to die as the sun worshippers from other causes. The conclusion was that “following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women’s health”.
Like all such studies the researchers tried to allow for the existence of confounding variables such as class, income and bad habits. Perhaps the sun avoiders were an unhealthy lot who spent their days in the dark drinking, smoking fags, eating burgers and tapping away on their computers? It appears that if anything the sun-avoiders were a more health-conscious bunch with more non-smokers and non-drinkers in their ranks. Yet despite this they were still dropping dead earlier. Why?
The researchers thought it might be because the sun avoiders weren’t getting enough vitamin D. This is known as “the sunshine vitamin” because most of what we get is generated in our skin by exposure to ultraviolet light. Once thought as being rather boring, important for the development of healthy bones and not much else, vitamin D in recent years has become a hot area of research, implicated in everything from brain development to the proper functioning of the immune system. Recent studies have shown that low levels of vitamin D are associated with increased risk of heart disease, stroke, schizophrenia, multiple sclerosis, asthma and at least a dozen cancers including, oddly enough, more aggressive forms of malignant melanoma.
It is something to bear in mind if you cover yourself in factor 60 at the first hint of sun, but over the next six months the debate will be largely theoretical. Few of us are going to be jetting off for a sunshine holiday to top up our tans and vitamin D levels. So what else can we do?
The easiest thing, of course, is to knock back the supplements. According to some studies, by the end of winter at least half of the UK’s white population and up to 90 per cent of the multi-ethnic population will lack sufficient vitamin D. With rickets on the rise the Department of Health recommends that all children between the ages of six months and five years get vitamin D drops and that you should also supplement if you are pregnant, breastfeeding or a 65-year-old who doesn’t get out much. There is, though, no consensus about what the rest of us should do. Too much vitamin D may be as bad for us as too little (see fact file).
You could, instead, try topping up your vitamin D levels through food, but this is easier said than done. Oily fish, for example, is recommended for its vitamin D content, but the amount of vitamin D you get varies hugely depending on the type of fish you eat and how it is cooked. Wild salmon is top of the vitamin D charts with more than twice the levels of farmed salmon or mackerel, but be aware that although baking it is fine, frying will destroy almost all the vitamin D content. Other natural sources of vitamin D include milk and eggs, two foodstuffs that we have unfortunately been warned off down the years because of a misplaced fear of their effect on cholesterol.
Apart from wild salmon, which is expensive, you would have to eat a lot of these foods to make much difference. In fact there is probably only one natural source of vitamin D that is cheap and reliable enough to boost blood levels through the long winter months. It is an old favourite but unfortunately an acquired taste. Cod liver oil, anyone?
Vitamin D levels may, however, only partly explain why sun worshippers seem to enjoy a longer life than sunshine avoiders. As part of the new series of the BBC Two programme Trust Me, I’m a Doctor, Gabriel Weston, a surgeon who spends a fair amount of her professional life cutting out skin cancers, interviewed the Edinburgh dermatologist Dr Richard Weller. You might expect Weller, as a dermatologist, to tell people to shun the sun. Instead, the studies he’s been making have made him wonder about current government guidelines. His doubts were raised by research he’s done that shows that sunshine lowers blood pressure. What he and others have discovered is that the UVA element of sunlight causes the release of nitric oxide into the bloodstream. The nitric oxide then makes arteries dilate, lowering blood pressure. The effect is not huge, but it is important.
“It’s a fall of about two millimetres of mercury,” Weller told Weston, “which doesn’t sound a lot, but if your blood pressure falls by two millimetres of mercury your risk of having a stroke drops by 10 per cent and of a heart attack by 7 per cent. And strokes and heart attack are the two biggest killers in Britain.” This may help to explain why deaths from heart disease soar during the winter months. Weller now thinks that for many people the benefits of sunshine may outweigh the risks and if further studies confirm these findings “we may need to reconsider our advice on sun exposure”.
Weller’s research certainly shook Weston, who told me that it has made her rethink what she now tells patients. If they are not at high risk of skin cancer — and most people in the UK are not — then she no longer recommends that they slather themselves with suntan lotion at all available opportunities.
As for me, well whether it’s raising my vitamin D or lowering my blood pressure, I look forward to the return of the sun. As the poet Walt Whitman put it: “Keep your face always toward the sunshine — and shadows will fall behind you.”
What Should You Worry About - Ebola or the Flu?
(New Yorker)
If you go by media coverage and public sentiment, the most important public-health problem in the United States right now is Ebola. Though the virus has infected only two people here, a recent poll found that forty per cent of Americans see Ebola as a “major or moderate threat” to public health, as Michael Specter points out in this week’s Comment. Meanwhile, over the past month, another infectious disease, Enterovirus D68, has made its way into the headlines. The virus causes respiratory problems, often severe, in children, and, in rare cases, kids infected with the virus have come down with muscle paralysis (it’s still not known whether the virus is actually causing the paralysis). So far, almost six hundred children, in forty-five states, have been infected by the virus, and though most have recovered quickly, five have died. Anxiety among parents has grown so much that some now wonder if we’ve been worrying too much about Ebola, and not enough about enterovirus.
In reality, we’re worrying too much about both Ebola and EV-D68, and too little about an infectious disease that is much more likely to inflict serious damage on the U.S. I’m talking, of course, about the flu. We know, based on past experience, that the upcoming flu season will kill thousands of Americans and send hundreds of thousands to the hospital. Yet the press seems relatively diffident about raising an alarm about this threat; its flu coverage has none of the high-pitched anxiety that suffuses writing about Ebola or EV-D68. EV-D68 has provoked headlines like “How Well is Sacramento Prepared for Ebola, Enterovirus Outbreak?” and “What Scares You More—Enterovirus D-68 or Ebola?” No one is asking “What Scares You More: Ebola or the Flu?”
They probably should. As we know, the flu can be deadly - according to the Centers for Disease Control and Prevention, the average annual death toll from influenza between 1976 and 2007 was more than twenty-three thousand. And unlike Ebola and EV-D68, for which there are no vaccines or real treatments, flu can almost always be prevented, or at least mitigated, if you get a flu shot. Stoking public concern about the flu could actually do some good, by encouraging people to get vaccinated. Instead, the media cover EV-D68 and Ebola as if they’re massive threats to our well-being even though they likely aren’t, and even though the average person can do little to prevent them anyway.
The reasons for this difference in coverage reveal how we think about risk and how our thinking shapes public-health outcomes. The Enterovirus isn’t new—it was first identified in 1962—but this strain is novel; we’ve never seen an outbreak of this size before (and that is, to be sure, something that should worry public-health officials). Novelty can make a problem scarier, and more newsworthy. And while Ebola has received more attention than EV-D68, the fact that the two diseases have appeared in the U.S. at the same time, and that we don’t have a vaccine for either one, has contributed to the sense that we’re being beset by new invaders. Finally, the fact that EV-D-68 affects children almost exclusively makes it seem more threatening. As Daniel Levitin writes in his new book, “The Organized Mind: Thinking Straight in the Age of Information Overload,” we have a “culturally universal and innate” impulse “to protect our young, even the young of those not related to us.”
The flu, by contrast, is all too familiar: many of us have had it. And, while we wouldn’t want to get it again, if we’re in good health we can feel confident that we would survive it. The fact that past flu crises (such as swine flu in the nineteen-seventies, or H1N1 in 2009) turned out to be less devastating than experts predicted has made us skeptical about flu-related warnings. The fact that most flu fatalities are adults (in particular, the elderly) somehow makes the disease less alarming, even though it’s almost certain that more children will die of the flu this year than of EV-D68. Paradoxically, knowing that we have good ways to combat the flu makes us less concerned about the damage it does. You might think it newsworthy that, even though we have an easily accessible flu shot, the disease still sends hundreds of thousands of people to the hospital and, in some years, tens of thousands of people to the morgue. Instead, we consider flu fatalities to be one of those unfortunate facts of life.
At work here is the curiously divergent and inconsistent way most of us think about risk. As a myriad of studies have shown, we tend to underestimate the risk of common perils and overestimate the risk of novel events. We fret about dying in a terrorist attack or a plane crash, but don’t spend much time worrying about dying in a car accident. We pay more attention to the danger of Ebola than to the far more relevant danger of flu, or of obesity or heart disease. It’s as if, in certain circumstances, the more frequently something kills, the less anxiety-producing we find it. We know that more than thirty thousand people are going to die on our roads this year, and we’ve accommodated ourselves to this number because it’s about the same every year. Control, too, matters: most of us think that whether we’re killed in a car accident or die of heart disease is under our control (as, to some degree, it is). As a result, we fear such outcomes less than those that can strike us out of the blue.
These attitudes toward risk are irrational, but they’re also understandable. The real problem is that irrational fears often shape public behavior and public policy. They lead us to over-invest in theatre (such as airport screenings for Ebola) and to neglect simple solutions (such as getting a flu shot). If Americans learned that we were facing the outbreak of a new disease that was going to do what the flu will do in the next few months, the press would be banging the drums about vaccination. Instead, it’s yesterday’s news.
Knockout Genes
Large DNA databases could speed the discovery of new drugs.
Ten years ago, scientists discovered that some people are naturally missing working copies of a gene known as PCSK9. The consequences of the mutation were extraordinary. These people, including a Texas fitness instructor, a woman from Zimbabwe, and a 49-year-old Frenchman, had almost no bad cholesterol in their blood. Otherwise, they were perfectly normal.
Drug companies pounced on the clue. To lower cholesterol, they would also try to block PCSK9. Now two separate drugs that disable the gene’s activity are nearing FDA approval. People taking the medications have seen their cholesterol levels plummet dramatically, sometimes by 75 percent.
Regeneron Pharmaceuticals, the company behind one of these drugs, now says it’s building a giant database of human DNA information in what amounts to a large-scale, systematic search for the next PCSK9. At a new genetic research facility that Regeneron completed last month in Tarrytown, New York, the company says it has begun a five-year effort to sequence the genomes of as many as 100,000 volunteers recruited from East Coast hospitals and identify rare genetic outliers among them.
So far, 13,000 people’s DNA has been partly decoded, and the company is using software to search for deleted genes. By checking against the volunteers’ medical records, or by calling them in for intensive testing, the company expects to learn if these missing genes cause illness or, perhaps, also have unusual protective effects.
By and large, it’s not good to be missing a gene. Yet missing a gene can sometimes provide powerful protection against disease.
People missing a particular gene are known as “knockouts” after a kind of laboratory mouse that’s been genetically engineered to lack a gene. Knocking out a gene from mice is a widely used technique that permits scientists to judge a gene’s function by its absence.
Rapidly expanding databases of human genomes mean researchers can now find knockout people instead. To scientists, that’s going to be a valuable shortcut to determine what human genes do. What effect does missing a gene have on a person’s body? To drug companies, these individuals promise living, breathing answers to some of the biggest questions they face, like whether their drugs will actually work, and whether blocking a given gene would be safe to do, or instead cause problems. “It’s a huge emphasis for us because these are incredibly informative natural human experiments,” says Aris Baras, director of R&D initiatives for the company.
At its Tarrytown, New York, genetics facility, Regeneron plans to sequence the genomes of 100,000 people using automated systems like this robot for preparing DNA.
By and large, it’s not good to be missing a gene. Such defects are the cause of diseases like cystic fibrosis and muscular dystrophy. Over time, scientists say, evolution has been working against these errors, which accounts for why they are relatively rare. Yet missing a gene can sometimes provide powerful protection against disease. People missing the SLC30A8 gene are half as likely to get diabetes as people with it. Those without working copies of a gene called CCR5 can’t get infected with HIV.
“This is going to be the major model of human disease research going forward,” predicts Sekar Kathiresan, a cardiovascular specialist at Massachusetts General Hospital who advises Regeneron. (This month Kathiresan reported another gene that, when missing, greatly cuts a person’s risk of heart disease.) Drug companies bet millions on drugs that cure animals or work in a lab dish. But 90 percent of drugs tested in human studies show no beneficial effect, or prove toxic. It’s guesswork at a staggering scale. “Animals don’t predict people. The concept now is to leverage the successes of the human genome, and develop medicines to mimic them,” he says.
Nobody’s Perfect
Most large-scale genetic research is a search for the causes of disease, not the nature of health. But in 2008, Daniel MacArthur, a computational geneticist now at the Massachusetts General Hospital, became interested in how frequently genes are completely dysfunctional in healthy people. Along with collaborators, he scrutinized the genomes of 185 people.
MacArthur’s analysis, completed in 2012, found that each of us has, on average, one entirely defective copy of about 80 genes, and another 20 genes for which neither copy works. In other words, everyone’s genome is a little dysfunctional. (Most genes are present in matching pairs—one inherited from your mother, and one from your father.)
At Regeneron, Baras says they have confirmed MacArthur’s estimates in 8,000 people they’ve sequenced. “We are all using common algorithms, and we’re seeing the same kinds of statistics,” he says. Not all the missing genes are interesting. Many code for trivial traits, like one of hundreds of odor receptors, or crop up so frequently that they’re unlikely to be important. Baras says Regeneron is setting those aside and focusing instead on rare cases where people are missing the same genes its drugs are designed to block or interfere with.
Already, two-thirds of the company’s R&D projects have human experiments to match them. “That is a very interesting and exciting statistic for us. Usually we find one or two people, but there are cases where we already have hundreds of individuals,” Baras says.
“We couldn’t scan for these mutations before for a very simple reason. Before, we did not have the data.”
As its next step, Regeneron plans to call some of these individuals in for detailed medical exams, to determine what’s different about them. In the case of PCSK9, the difference was much lower cholesterol. But that wasn’t the most important finding. Once enough examples of people missing that gene were found, researchers were able to compare them to tens of thousands of controls who did have the gene, and prove that their risk of dying from a heart attack was sharply lower. “Here you have definitive protection against cardiovascular disease, and it’s safe. This is the type of evidence that gives people a lot of confidence,” says Baras. “It’s a huge point. It tells you lifelong deficiency in this gene is good.”
Big Data
The ability to search systematically for genetic outliers among healthy people is relatively new. Previously, scientists relied on rougher gene maps that didn’t give them access to letter-by-letter DNA information as a complete genome sequence does. That is changing as DNA sequencing becomes cheaper. This year, some labs purchased a new type of sequencing machine, called the X-10, which costs $10 million to buy, but can decode 50 genomes each day, or about two per hour, for a price of between $1,000 and $2,000 each.
That means more labs are betting on the law of large numbers. They include Human Longevity Inc., a startup created by entrepreneur J. Craig Venter, which wants to decipher one million people’s genomes by 2020. Another effort, known as the Resilience Project, is looking for one million healthy volunteers over age 40 so they can be checked for any of 125 disease genes that should have caused debilitating childhood illnesses, but for some reason didn’t. Even Google, which made its own leap into genomics this year, said it would start decoding the DNA of healthy people, although its objectives aren’t known.
“We couldn’t scan for these mutations before for a very simple reason. Before, we did not have the data,” says Kari Stefansson, CEO of DeCode Genetics, an Icelandic genetics company owned by the U.S. biotechnology giant Amgen. He says his company bought an X-10 and will have sequenced the genomes of 25,000 Icelanders by the end of next year, augmenting gene maps it previously built.
In October, researchers with his company said it was well on its way toward building its own knockout catalog. They said the company would invite 8,000 people it had identified to undergo “deep phenotyping,” or a barrage of measurements involving scales, rulers, brain scans, IQ tests, and blood measurements to assess 500 traits.
Even so, Stefansson is skeptical that human knockouts will turn out to be the easy path to blockbuster drugs that some are hoping for. “It’s not an argument without virtues, but it’s also an incredible simplification. Most of these scenarios are more complicated,” he says.
Side Effects
To MacArthur, knockouts are interesting because they’re a way to document the function of genes, good or bad. He created something he calls the “Human Knockout Project” that is helping to study populations in Finland and London and whose aim, he says, is to take every gene in the genome and find a person missing it. But that’s only a manner of speaking. He expects that for many genes, a knockout will never be found. That’s because the majority of genes are essential to life. Without them, you’d never have been born.
That turns out to be a question of urgent importance to husband and wife scientists Eric Minikel and Sonia Vallabh, who have been working alongside MacArthur at Massachusetts General Hospital. Vallabh’s mother died of fatal familial insomnia, an extraordinarily rare disease in which a misfolded protein builds up in the brain, causing dementia and early death. Vallabh has inherited the gene mutation that causes FFI, and has a 100 percent chance of developing the illness, unless some kind of treatment is developed.
Before her diagnosis three years ago, Minikel was an urban planner and Vallabh had gone to law school. But they switched careers and became scientists in order to try to cure Vallabh before she falls ill.
Vallabh’s mutation is the opposite of a knockout—it adds an unwanted function, causing her prion protein to fold in a way that it shouldn’t. This month she switched to another Boston laboratory to explore whether an advanced form of gene therapy, called genome editing, might allow her to eliminate the prion gene from her brain cells altogether.
But would doing so be dangerous? Knockout mice that have been genetically engineered to lack the prion gene seem to be mostly normal, but that’s no guarantee that the same is true of humans. For instance, the knockout surveys carried out by MacArthur’s lab have found more than 40 healthy people with mutations known to prove fatal to mice. Vallabh says she worries that if she were to succeed in eliminating her prion gene it could cause another disease, perhaps equally grave.
In the compressed time frame Vallabh faces—she has perhaps 20 years to cure herself—finding a living person without the prion gene would be one important clue. This year, she and Minikel carried out such a search across DNA sequences of more than 60,000 people as part of MacArthur’s Knockout Project.
They turned up three individuals missing one copy of the prion gene—but, so far, no one who is missing both copies.
Minikel says it may mean that people can’t live without the gene. Or it could be that their database isn’t yet big enough. The gene is small and therefore less likely to be affected by mutations. Working quickly with a pad and paper, with Vallabh looking over his shoulder, Minikel roughly estimated it might take a database of a billion people to know for sure.
Electrically stimulating the tongue may help repair neural damage
A little-known fact: the tongue is directly connected to the brain stem. This anatomical feature is now being harnessed by scientists to improve rehabilitation.
A team at the University of Wisconsin–Madison recently found that electrically stimulating the tongue can help patients with multiple sclerosis (MS) improve their gait. MS is an incurable disease in which the insulation around the nerves becomes damaged, disrupting the communication between body and brain. One symptom is loss of muscle control.
In a study published in the Journal of Neuro-Engineering and Rehabilitation, Wisconsin neuroscientist Yuri Danilov and his team applied painless electrical impulses to the tip of the tongue of MS patients during physical therapy. Over a 14-week trial, patients who got tongue stimulation improved twice as much on variables such as balance and fluidity as did a control group who did the same regimen without stimulation.
The tongue has extensive motor and sensory integration with the brain, Danilov explains. The nerves on the tip of the tongue are directly connected to the brain stem, a crucial hub that directs basic bodily processes. Previous research showed that sending electrical pulses through the tongue activated the neural network for balance; such activation may shore up the circuitry weakened by MS.
The team is also using tongue stimulation to treat patients with vision loss, stroke damage and Parkinson's. “We have probably discovered a new way for the neurorehabilitation of many neurological disorders,” Danilov says.
Loss of Sense of Smell Linked to Early Mortality
PEOPLE whose hearts are failing, or who have had cancer or lung disease, have good reason to be concerned about their future. People who have merely lost their sense of smell might not be so worried. Actually, though, their prospects are worse. You are more likely to die within five years if you cannot recognise common smells than if you have ever been diagnosed with one of those more obviously deadly illnesses. That, at least, is the conclusion of a sobering study just published in PLOS ONE, by Martha McClintock and Jayant Pinto of the University of Chicago.
Dr McClintock and Dr Pinto were prompted to conduct their investigation because they knew olfactory problems can forewarn of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. They are also associated with abnormally shortened telomeres (the caps on the ends of chromosomes), and that shortening is, in turn, implicated in the process of ageing. Moreover, a good sense of smell helps keep people healthy by detecting pathogens and toxins in the air, stimulating appetite, and aiding memory, emotions and intimacy. The researchers therefore had good reason to wonder if measuring smell loss might predict mortality.
As part of the National Social Life, Health and Ageing Project, a survey organised by the University of Chicago that measures the health and well-being of older Americans, 3,005 participants aged between 57 and 85 completed a three-minute smell test devised by Drs McClintock and Pinto. The survey’s researchers prepared special felt-tipped pens scented with five common odours—fish, leather, orange, peppermint and rose—and presented them one by one to volunteers. After each presentation, the volunteer was shown pictures and names of four possible answers, and was asked to select the correct one. Getting one answer wrong was considered okay, or “normosmic”, but two or three errors labelled a person as “hyposmic”, or smell-deficient, and four or five counted them as “anosmic”, or unable to smell.
Five years later, 430 of the respondents were dead. The anosmic were particularly hard hit: 39% of them had perished, compared with 19% of the hyposmic and just 10% of the normosmic. After adjusting for age (older people are more likely to die), sex (women tend to live longer than men), socioeconomic status (richer, better-educated people enjoy greater longevity) and race (some ethnicities have longer lifespans than others), Dr McClintock and Dr Pinto found that the correlation still held true. Nutrition could not explain it. Nor could smoking or alcohol use. Even when they controlled for specific diseases, like heart failure, cancer, strokes and diabetes, the researchers found the relationship between not being able to smell and being more likely to die in the next half-decade remained robust. Only severe liver damage was a stronger predictor of death.
No one is suggesting that not being able to smell led directly to any of the deaths. Rather, the researchers think that smell may be the “canary in the coal mine of human health”. They note that olfaction relies on a turnover of stem cells (from which other sorts of cell develop) to maintain its functioning. Not being able to smell, they speculate, may signal a more general inability to regenerate and renew.
One weakness of their work, they concede, is that they do not know the causes of the deaths they recorded—as that was not asked in the original survey. Another is that the study was but a snapshot. It cannot show whether those at risk have always had poor smell, or have developed it recently. Nevertheless, Dr McClintock and Dr Pinto do seem to have found the makings of a simple test that could sniff out danger ahead, and thus possibly avert it.
Doubts About Prostate Studies
SCIENTIFIC data from clinical trials provides the foundation of medical decision making, from a doctor’s prescription pad to sweeping public health policies. Public trust that the data is accurate and unbiased is the glue that binds our $3 trillion health care system. I worry that this trust, particularly when it comes to American men and their physicians and screening programs for prostate cancer, is now at risk.
In 1970 I discovered the prostate-specific antigen, or PSA, which is now the most widely used tool in prostate screenings. But there has been a growing concern about whether the use of the PSA test has led to overdiagnosis and overtreatment, with millions of unnecessary surgeries, complications and deaths.
Nevertheless, the medical community has roundly embraced the results of a recent study finding that PSA screening reduced prostate cancer deaths by 20 percent. The study, the European Randomized Study of Screening for Prostate Cancer, joined another survey, the so-called Swedish Goteborg study (the results of which provided a basis for the European Randomized Study), which found an astounding 44 percent reduction.
But there’s a big problem with both of these studies: In March the Goteborg study’s authors announced in the British Medical Journal that their data “are not available to outside investigators.”
That the researchers would block access to government- and charity-supported research is bad enough. Even worse, it calls into question why, if the data was strong, the researchers wouldn’t open it up to independent scrutiny.
As it turns out, there are some major concerns about the methodology and results of the studies, first raised last fall in the Journal of the National Cancer Institute by two Australian researchers.
The European Randomized Study reported results from seven countries, while Goteborg was a single-site study in Sweden. In both, men were divided into two groups: One underwent regular PSA tests, while the other was not screened. The results were published in The New England Journal of Medicine and the journal Lancet Oncology, respectively.
As the Australian researchers, Ian E. Haines and George L. Gabor Miklos, noticed, there was something strange about the data sets: A large amount of the data in the European Randomized Study came from a separately reported Finnish study, which showed no significant lifesaving benefits of PSA screening.
They found further red flags in terms of biased patient treatment. Many of the men who developed prostate cancer received excessive amounts of a treatment called hormonal monotherapy, which some research now indicates can actually accelerate cancer. Depending on which groups — screened and not screened — those men were in, the results of the study could be significantly compromised. And yet that information was missing from the published reports. When Drs. Haines and Miklos requested the European data to undertake independent analyses, researchers in both studies were unwilling to release it.
Even more troubling was that the European Randomized Study investigators transferred an astounding 60 percent of the data from the Swedish Goteborg study into their own data pool. Since the Goteborg study was alone among country-specific studies in showing an almost 50 percent reduction in prostate cancer deaths for screening recipients, such an overweighting of the data obviously tipped the balance in favor of lives saved. This is a bright-line ethical breach: Without this biased transfer, the lifesaving claims of PSA screening vanish.
Further bias was highlighted by Otis Brawley, the chief medical and scientific officer of the American Cancer Society, and by Paul Goldberg, the editor of the Cancer Letter. They pointed out that the nonscreened Swedish men who contributed to the two studies were not even informed that they were in a clinical trial, which introduced an unacceptable variable between them and the PSA-screened men, who were informed.
Finally, several senior authors of the European trials, and their American supporters, have potential conflicts of interest that relate to payments from companies involved in marketing PSA tests, or in holding patents in the PSA and prostate cancer diagnostic space — relationships documented by the International Committee of Medical Journal Editors, in the forms that accompany the PSA-study publications and in disclosures found in CA: A Cancer Journal for Clinicians.
As a result, those physicians who have not examined the data in depth are now treating patients on the basis of deeply flawed data. How flawed? That’s the real issue: Because the authors won’t release their data, we don’t know.
It is imperative that, as part of America’s continuing efforts at health care reform, we develop a declaration of principles about the need for data transparency. Our regulatory bodies must insist that clinical trials, and especially taxpayer-funded ones, be open to scrutiny by independent investigators who have no ties to industry. Hoarding data, especially flawed data, is unacceptable when lives are at stake.
Ibuprofen as Life-Extender
Ibuprofen, a common over-the-counter drug used to relieve pain and fever, could hold the keys to a longer healthier life, according to a study by researchers at the Buck Institute for Research on Aging. Publishing in PLoS Genetics (open access) December 18, scientists showed that regular doses of ibuprofen extended the lifespan of yeast, worms and fruit flies.
Brian Kennedy, PhD, CEO of the Buck Institute, said treatments, given at doses comparable to those used in humans, extended lifespan an average of 15 percent in the model organisms. “Not only did all the species live longer, but the treated flies and worms appeared more healthy,” he said.
“The research shows that ibuprofen impacts a process not yet implicated in aging, giving us a new way to study and understand the aging process.” But most importantly, Kennedy said the study opens the door for a new exploration of “anti-aging medicines.”
The work was the result of a collaboration between the Buck Institute and Texas A & M’s Agrilife program. Michael Polymenis, PhD, an AgriLife Research biochemist started the work in baker’s yeast and then moved it into worms and flies. Polymenis, who also is a professor in the biochemistry and biophysics department at Texas A&M University, said the three-year project showed that ibuprofen interferes with the ability of yeast cells to pick up tryptophan, an amino acid found in every cell of every organism.
Tryptophan is essential for humans, who get it from protein sources in the diet. “We are not sure why this works, but it’s worth exploring further. This study was a proof of principle, to show that common, relatively safe drugs in humans can extend the lifespan of very diverse organisms,” he said. “Therefore, it should be possible to find others like ibuprofen with even better ability to extend lifespan, with the aim of adding healthy years of life in people.”
Chong He, PhD, a postdoctoral fellow at the Buck Institute and lead author on the paper, said the extended lifespan in the model organisms would be the equivalent to another dozen or so years of healthy living in humans. “Our preliminary data in the worms showed that ibuprofen also extended their healthspan,” she said. “Healthy worms tend to thrash a lot and the treated worms thrashed much longer than would be normally expected. As they aged, they also swallowed food much faster than expected.”
In C. elegans worms, ibuprofen has also been shown to suppress a phenotype associated with aging, inhibiting the deposition of amyloid β peptide, a marker for Alzheimer disease, the paper notes.
Ibuprofen is in the class of compounds known as NSAID’s — nonsteroidal anti-inflammatory drugs used for relieving pain, helping with fever and reducing inflammation. The World Health Organization includes ibuprofen on their “List of Essential Medications” needed in a basic health system. Although deemed relatively safe and commonly used, ibuprofen can have adverse side effects, particularly in the gastrointestinal tract and the liver at high doses.
Medical Errors
Thousands of patients are killed or seriously injured because of mistakes caused by the poor design of drugs packets and confusing medical equipment, according to a report for the head of the NHS.
Medical equipment with the “off” switch next to key controls, and medicines with similar names and packaging cause errors that would never occur in industries such as aviation which take safety more seriously, experts say. Temporary staff often fail to get to grips with machines in a way that standardisation should make impossible.
Simon Stevens, chief executive of NHS England, has been urged to use the buying power of the health service to insist that companies standardise equipment and drugs in a way that makes errors easier to avoid, as happened decades ago on aircraft.
Jeremy Hunt, the health secretary, has repeatedly said the health service must aspire to airline standards of safety.
Official figures show at least 8,000 patients a year are killed or severely harmed needlessly by drug errors. Jane Reid, a nursing academic, who has written the report on the human factors of safety for Mr Stevens, said many cases could be avoided with better design.
Professor Reid said: “Humans are fallible, they have attention blindness. We don’t see what we’re not expecting to see. At times of high stress, distraction is a real challenge. I think this has just been put in the too-difficult box. I find it staggering if you think about the purchasing power of the NHS.
“Staff should not use a piece of equipment unless they’ve been trained, but you have agency staff who move from one place to another and they may be working with one type of machine one day and another the next, so the potential for errors is quite significant.”
Martin Bromiley, who launched the Clinical Human Factors Group after his wife died after an avoidable error during an operation, said: “Hospitals are full of error-prone environments and opportunities for things to go wrong.”
He said that “look-alike, sound-alike medication” makes it much more likely that rushed staff will give patients the wrong drugs, particularly if there are no consistent rules about which types are stored where. “The NHS will buy drugs in similar packaging which do very different things, and just say to clinicians, ‘Be very careful not to make a mistake’.”
Doctors are often blamed for mistakes such as the death of 18-year-old Wayne Jowett, after a cancer drug was wrongly injected into his spine. Professor Reid said it made no sense that intravenous drips had not been redesigned to make this impossible, when even cash machines are standardised.
Last night it emerged that more than 300 consultants have written an open letter to Mr Stevens warning that patients with cancer, heart disease and other major conditions will suffer harm and avoidable deaths under NHS funding proposals.
Under the proposals, hospitals which provide specialist care to more patients than expected will be reimbursed only half the cost of every extra case in an attempt to make the service more cost effective and divert funds to long-term disease prevention.
Combining Multiple Genome Databases
A coalition of geneticists and computer programmers calling itself the Global Alliance for Genomics and Health is developing protocols for exchanging DNA information across the Internet. The researchers hope their work could be as important to medical science as HTTP, the protocol created by Tim Berners-Lee in 1989, was to the Web.
One of the group’s first demonstration projects is a simple search engine that combs through the DNA letters of thousands of human genomes stored at nine locations, including Google’s server farms and the University of Leicester, in the U.K. According to the group, which includes key players in the Human Genome Project, the search engine is the start of a kind of Internet of DNA that may eventually link millions of genomes together.
The technologies being developed are application program interfaces, or APIs, that let different gene databases communicate. Pooling information could speed discoveries about what genes do and help doctors diagnose rare birth defects by matching children with suspected gene mutations to others who are known to have them.
The alliance was conceived two years ago at a meeting in New York of 50 scientists who were concerned that genome data was trapped in private databases, tied down by legal consent agreements with patients, limited by privacy rules, or jealously controlled by scientists to further their own scientific work. It styles itself after the World Wide Web Consortium, or W3C, a body that oversees standards for the Web.
“It’s creating the Internet language to exchange genetic information,” says David Haussler, scientific director of the genome institute at the University of California, Santa Cruz, who is one of the group’s leaders.
The group began releasing software this year. Its hope—as yet largely unrealized—is that any scientist will be able to ask questions about genome data possessed by other laboratories, without running afoul of technical barriers or privacy rules.
The researchers felt they had to act because the falling cost of decoding a genome—then about $10,000, and now already closer to $2,000—was producing a flood of data they were not prepared for. They feared ending up like U.S. hospitals, with electronic systems that are mostly balkanized and unable to communicate.
The way genomic data is siloed is becoming a problem because geneticists need access to ever larger populations. They use DNA information from as many as 100,000 volunteers to search for genes related to schizophrenia, diabetes, and other common disease. Yet even these quantities of data are no longer seen as large enough to drive discovery. “You are going to need millions of genomes,” says David Altshuler, deputy director of the Broad Institute in Cambridge and chairman of the new organization. And no single database is that big.
The Global Alliance thinks the answer is a network that would open the various databases to limited digital searches by other scientists. Using that concept, says Heidi Rehm, a Harvard Medical School geneticist, the alliance is already working on linking together some of the world’s largest databases of information about the breast cancer genes BRCA1 and BRCA2, as well as nine currently isolated databases containing data about genes that cause rare childhood diseases.
In March, the group launched a test of whether scientific organizations would be willing to share data. A product called Beacon lets the owner of a database open it up for strictly limited searches.
“We are not trying to invent a technical feat; it’s breaking down this problem of people not sharing data,” says Marc Fiume, a computer science graduate student at the University of Toronto who built part of the interface. “This lets you probe, but without identifying anyone or violating patient privacy.”
So far, 15 databases are compatible with Beacon, which Fiume rates a reasonable success. Three are stores of public genomes that Google maintains a copy of, and one is at a software company called Curoverse in Boston (see “Google Wants to Store Your Genome”).
Haussler says a future protocol would offer access to progressively more data, but in a controlled way. Scientists would have to register, or even sign legal agreements. “If it’s ‘Give me the whole genome,’ you’d enter a contract for that,” he says.
One change the alliance is pushing is a new type of master consent form, the document that lays out volunteers’ rights when they hand over their genomes. The new consent is broader than most, giving permission for “controlled access” by “researchers around the world.” It promises that no researcher will identify a participant, although since DNA is a unique, like a fingerprint, there would be no guarantees.
Like the W3C, the Global Alliance has “host institutions” that pay its bills. So far, they are the Broad Institute, the Wellcome Trust Sanger Institute in the U.K., and the Ontario Institute for Cancer Research, according to Altshuler, who declined to say how much money each had contributed.
John Wilbanks, chief commons officer of the nonprofit Sage Bionetworks, is working with the alliance and is also a former member of the W3C. He says the alliance has a harder task than the W3C did. “The Web existed long before the Web Consortium did. That is the big difference,” he says. “The Web got traction, and the consortium was created to manage it. They didn’t have to create the Web.”
Aspirin and Anti-Inflammatories vs Skin Cancer
We all know the risks of with spending too much time in the sun. Ultraviolet rays can increase the risk of skin cancer, which is why we – or at least, the more cautious among us – put on sunscreen before we set off on an extended outing.
But it turns out there’s another preventative measure that can significantly reduce your risk of skin cancer, one you may already be taking. A new study reports that non-steroidal anti-inflammatory drugs (NSAIDs), which include such common drugs as ibuprofen and aspirin, can reduce a person’s likelihood of a certain type of skin cancer by 18 percent.
A Likely Link
Previous studies have found that NSAIDs can help prevent colon, breast, lung and prostate cancers. Researchers also suspected that the drugs might prove effective against a common type of skin cancer called squamous cell carcinoma, whose dark-colored tumors invade and damage surrounding skin tissue. NSAIDs have been shown to inhibit the action of an enzyme known as COX-2, which is released by skin cells in response to UV light exposure.
Catherine Olsen, Adèle Green and colleagues set out to test that hypothesis by re-examining previously published studies in what’s called a meta-analysis – a statistically rigorous way of mashing-up findings across a number of different studies. Although a 2012 study had tried a similar approach and hadn’t found any correlations between NSAID treatment and risk of squamous cell carcinoma, that study hadn’t had access to papers from the last two years – a difference the researchers thought might prove crucial.
Selective Searching
The team started by searching the PubMed database for a long list of keywords, then pared down the list to exclude duplicate papers, as well as studies with inconclusive results, insufficient data, and overly broad or irrelevant conclusions. This narrowed the list down to just nine papers. The studies included both individuals at a high risk of squamous cell carcinoma (because they’d been diagnosed with pre-cancerous or cancerous lesions) and members of the general population followed over a number of years. Over 6,000 cases of squamous cell carcinoma were compared to over 100,000 people who didn’t have or didn’t develop the cancer.
The team gathered the raw data and performed a series of statistical analyses on that dataset – looking not only for correlations between NSAID treatment and reduced risk of squamous cell carcinoma, but also for a high level of consistency in those correlations.
Causes and Questions
The results of the analysis were clear: the use of non-aspirin NSAIDs reduced individuals’ risk of developing squamous cell carcinoma by 15 percent. When aspirin was included in the data, the risk dropped even further, by a total of 18 percent. The findings appear in the Journal of Investigative Dermatology.
Researchers also found that NSAID treatment seemed to be of most benefit for patients who had a history of pre-cancerous growths known as actinic keratoses, or who had a history of skin cancer itself.
The scientists don’t know how it is, exactly, that NSAIDs stave off skin cancer, though the most likely mechanism is the one that’s already been demonstrated for other types of cancer: inhibition of the enzyme COX-2. This is another question that the researchers hope to explore more in the near future, with the goal of helping doctors prescribe NSAIDs in more effective ways. “We believe that NSAIDs have potential as part of a skin cancer-prevention strategy,” Olson says. “However, more information on dosages and duration of use of NSAIDs is required before strong and specific recommendations on skin cancer prevention can be made.”
The results provide further evidence of the usefulness of NSAIDs for staving off cancer, especially in people who’ve had skin cancer in the past. And that’s a sunny outcome for everyone.
Screening Often Bad Idea
Screening healthy people for diseases is almost always pointless and sometimes causes more harm than good, scientists have claimed.
Researchers reviewed the evidence for the efficacy of screening for 19 diseases, including breast and prostate cancer, and found that, except in rare cases, it does not save lives but often results in unnecessary and sometimes risky medical interventions. “We should not take for granted that screening is a good idea,” John Ioannidis, a professor from Stanford University, said. “With exceptions, screening is pointless, and even harmful.”
For the paper, published in the International Journal of Epidemiology, he and his colleagues examined 57 separate trials. In only a third of the diseases considered did screening result in a fall in mortality from that disease. When looking at mortality overall, that figure dropped to one in ten. The second measure was considered more relevant, because one of the criticisms of screening is that it can lead to harm in and of itself, causing extra deaths in other ways.
Professor Ioannidis said that screening was not always a good idea because “firstly, it requires that we have a very effective treatment for early cases. Sometimes we just don’t have these treatments. Secondly, no test is perfect. We may misdiagnose people with having a disease, when they don’t have it. They may then have procedures done to them, and even operations.”
He conceded that screening did seem to be effective for colorectal cancer and aortic aneurysms.
Beetroot Juice to Lower Blood Pressure
Drinking a glass of beetroot juice every day can significantly lower blood pressure, according to a study.
The vegetable juice has long been recommended for those with hypertension. Scientists at Queen Mary University of London found that many patients could bring high blood pressure back to normal with 250ml daily.
Beetroot contains “inorganic nitrate”, which is converted to nitrite in the body, and aids flow by widening blood vessels. The patients drinking the juice had an average decrease in blood pressure similar to the reduction achieved by taking a single antihypertensive drug. “This research has proven that a daily inorganic nitrate dose can be as effective as medical intervention,” said Amrita Ahluwalia, the lead author of the study. “For those looking to work dietary nitrate into their daily diets, the trick is not to boil the vegetables — as dietary nitrate is water soluble — but steaming, roasting or drinking in a juice all has a positive effect.”
The clinical trial, published in the journal Hypertension and funded by the British Heart Foundation, was carried out among 64 patients aged 18 to 85. Those who drank the juice saw improvements in blood pressure and blood vessel dilation capacity, and a reduction in arterial stiffness. When they stopped drinking it, their blood pressure returned to its high levels.
Simple device to lower BP
A simple implant the size of a paper clip can dramatically reduce high blood pressure in patients who are not responding to drugs, research has shown.
The device, called a “coupler”, is inserted between an artery and vein in the upper thigh during a 40-minute procedure under local anaesthetic.
It creates a passage between the two vessels that acts like a safety valve, reducing pressure in the arterial system by allowing blood to flow into the veins.
The effectiveness of the device was studied in 83 patients with uncontrolled hypertension, or high blood pressure. Forty-four were fitted with the coupler while the control group received conventional drug treatment. Those given the implant experienced a “significant and durable” reduction in blood pressure compared with the control group, the scientists said.
The patients also had fewer complications and hospital admissions linked to high blood pressure.
The device also worked well in patients who had failed to respond to renal denervation, a procedure that involves the removal of nerves.
Melvin Lobo, the lead researcher from Queen Mary University of London, said: “The coupler effectively targets the mechanical aspects of how blood circulation works so it’s a totally new approach to controlling blood pressure. [It] also highlights the importance of arterial stiffness as a major cause of resistant high blood pressure and it targets this issue both safely and successfully.”
The implant is made by Rox Medical, a US company that funded the study, which was published online by The Lancet.
Antibiotics To Fight Cancers
In most families, dinner table conversation is restricted to what happened at school or whether homework has been completed.
But Michael Lisanti asked his eight-year-old daughter how she would cure cancer, and it seems she may have got it right.
Camilla Lisanti suggested using antibiotics, ‘like when I have a sore throat’.
Her parents, a husband-wife cancer research team were sceptical at first but tested out her theory in their Manchester University lab. And to their surprise, several cheap and widely-used antibiotics killed the most dangerous cancer cells.
The antibiotics fought seven of the most common cancers – including breast, prostate, lung and hard-to-treat brain tumours.
One antibiotic, doxycycline, is widely used to treat acne and is thought to be particularly promising. It costs as little as 6p a day. In contrast, some of the latest cancer drugs cost several hundred pounds a day.
Cancer charities said the research shows that the answers to some of the biggest questions are right in front of our eyes.
Professor Lisanti and his wife, Federica Sotgia, were discussing their research over dinner one evening when they decided to ask their daughter for her opinion.
The professor said: ‘She has heard us talk about cancer a lot and we thought it would be fun to ask her what she thought about cancer therapy.
‘We asked her how she would cure cancer and she said “Mum and Dad, I would just use an antibiotic, like when I have a sore throat.’
Rather than completely dismissing the answer, the professor did a DIY experiment, rubbing an antibiotic cream on a small growth on his face.
When the growth disappeared, he did some reading that confirmed that Camilla may have been on to something.
Seven of the most common cancers, such as breast, prostate, and hard-to-treat brain tumours, were slowed by the drugs which stopped them producing mitochondria which they use to reproduce.
Unknown to Camilla, a bubbly bilingual child who wants to be a teacher, some antibiotics stop cell from making mitochondria, the tiny engine rooms that supply them with energy.
Camilla’s parents showed that cancer stem cells – the deadly ‘mother cells’ that give birth to tumours, keep them alive and ease their spread around the body – have particularly high numbers of mitochondria.
They also showed that four common antibiotics killed these stem cells in samples taken from breast, prostate, lung, ovarian, pancreatic, skin and brain cancers.
Importantly, healthy cells were not harmed.
The experiments on cells in a dish suggest that antibiotics could be used to stop cancer in its tracks and prevent it from spreading through the body – the main way it kills.
Researchers say the results are promising and Mr Lisanti is now seeking funding to try the treatment on humans
If they are shown to fight the disease, they could potentially also be used to prevent the cancer in those at high risk of developing it.
Several previous studies support Camilla’s idea.
This includes one in which lung cancer patients lived longer after being given an antibiotic to treat an infection they had.
Some 75 per cent lived for at least a year – up from the usual 45 per cent.In another study, tumours completely disappeared after just three weeks of taking doxycycline for an infection.
Cancer Research UK cautioned that Professor Lisanti’s work was done in the lab and doesn’t tell us whether antibiotics will work on people with cancer.
But Breakthrough Breast Cancer, which helped fund the research, is much more optimistic
Dr Matthew Lam, the charity’s senior research officer, said: ‘The conclusions the researchers have drawn, while just hypotheses at this stage, are certainly interesting.
‘Antibiotics are cheap and readily available and if in time the link between their use and the eradication of cancer stem cells can be proved, this work may be the first step towards a new avenue for cancer treatment. ‘This is a perfect example of why it is so important to continue to invest in scientific research.
‘Sometimes there are answers to some of the biggest questions right in front of us. But without ongoing commitment to the search for these answers, we’d never find them.’
Camilla’s parents have acknowledged her contribution to their research by naming her as an author of their study, which is published in the journal Oncotarget.
Cheap Drugs
WHEN Lu Yong, a Chinese businessman, was diagnosed with a chronic form of leukaemia in 2002, his doctor prescribed Glivec, a drug made by Novartis, the Swiss multinational.
The drug costs almost £2,400 a month, however — more than his insurance would pay — and after two years of footing the bill, Lu, 46, was close to bankruptcy.
Salvation came in the form of Veenat, a generic Indian-made drug, that can be bought for £20. Keen to help others in the same position, Lu began to buy and sell Veenat, at no profit, extending his network to more than 1,000 sufferers.
There was a catch: while Veenat can be used to treat leukaemia patients in India, it has not been approved for use in China.
Lu, who was arrested last summer and has since been bailed, faces trial on charges of credit card fraud and the sale of counterfeit drugs. If convicted, he is likely to face a jail sentence.
With hundreds of people signing a petition calling for Lu’s acquittal, his case is being seized on by campaigners across the world. It follows the arrest last year of another Chinese couple who sold Indian anti-cancer drugs through an online supermarket.
Lu’s story has drawn comparisons to the Oscarwinning film, The Dallas Buyers Club — itself based on a true story — in which Matthew McConaughey plays an Aids patient who smuggled unapproved drugs from Mexico into Texas in the mid-1980s to treat himself and other patients.
India is known as the “pharmacy of the developing world”; keen to keep down the price of life-saving drugs, the Indian government has angered pharmaceutical companies by allowing its firms to produce versions of patented drugs, such as Glivec, and sell them far more cheaply than the real thing.
The policy has prompted the creation of “buyers’ clubs”, similar to one set up by Lu, around the world. In Thailand and South Africa they have sprung up to import cheap antiretroviral medicines for HIV sufferers. Western doctors have also lobbied for prices to be brought down.
In Britain, it is not known how many people are buying cheap Indian drugs to treat illnesses such as cancer. It is not illegal to bring them into the country for personal use. Veenat can be shipped to the UK via online companies for less than £100.
Western public health campaigners also hope that pharmaceutical companies will lower their prices in America and Europe. Several companies have clashed with the Indian government over generics.
In 2013, Delhi ruled against an appeal by the pharmaceutical giant, Bayer, to block the generic version of Nexavar, a drug used to treat kidney, liver and thyroid cancer. The Indian copy is 97% cheaper than Nexavar.
Diarmaid McDonald, from the UK-based Stop Aids network, said earlier buyers’ clubs for HIV medicines had highlighted the “injustice of laws and systems” and acted as a catalyst for change.
Four Lies About the Measles Outbreak
The Disneyland measles outbreak hasn’t shown any signs of doing anything other than getting worse. As of right now, over 100 cases have been diagnosed in states across America. Most are situated in Southern California, and the vast majority are among people who aren’t vaccinated. Sadly, this is mostly children who never gave their consent to not be protected from preventable disease.
Nobody who follows the anti-vaccine movement, and deals with their arrogance, chemphobia, fecklessness and endless self-delusion should be surprised by any of this. And nobody should be surprised by the lies that have emerged around this measles outbreak. Because that’s inherently what the anti-vax movement is about — lies. Lies about coverups, lies about toxins, lies about the real causes of disease, lies about the danger, lies about who caused it, lies, lies and more lies.
Here are four of the worst lies, but by no means are these the only ones:
Measles isn’t that bad, so it’s okay that a bunch of kids have it – First, nobody has the right to be the Arbiter of Things That Are and Aren’t That Bad. Terms like “bad” are relative and have no real meaning from one person to the next. But beyond that, the measles absolutely can be “that bad.” While it’s true that the majority of cases are mild and clear up with rest (which can be “that bad” for a family that has to burn sick days at work or spend money putting their child in the hospital), that doesn’t mean they all are. And it certainly doesn’t mean that the worst can’t happen.
Measles is almost comically contagious, and is particularly horrific for babies less than a year old, patients on immuno-suppressant drugs and the elderly – all people who can’t vaccinate for one reason or another. And despite the ludicrous pontificating of anti-vaccine doctors who should know better, it can and does kill. According to World Health Organization statistics, there were 145,700 deaths from the measles in 2013.
Most of these were children from developing countries where the vaccine that’s eschewed by natural granola parents in America wasn’t available. One imagines these parents shaking their heads at the hubris of privileged moms and dads who cast aside the vaccine they so desperately needed because of vague fears about “toxins.”
Prior to the development of the MMR shot, the death toll from measles was catastrophic. Before 1980, measles caused an estimated 2.6 million deaths each year around the world. The fact that this awful number has been cut to something much less (though still) awful, is a cause for celebration – not for harangues to “do your research” and “get the real facts.” Statistically, measles has a mortality rate of about .3% in the developed world. So when the outbreak in the US hits 300 cases, we’ll be due for a measles-related death. It’ll probably be a child, and almost certainly someone whose parents chose not to vaccinate.
Does it have to come to a dead kid for the outbreak to be “that bad?”
Some people who were vaccinated got the measles anyway, so the vaccine doesn’t work! Nyer, nyer! – The first part of this statement is true. According to Wired, of the 52 measles cases known to have originated at Disneyland, about six were in patients who had been at least partially vaccinated. Four had gotten the recommended double shot of MMR, one at 12-16 months, the second at 4-6 years.
So if vaccinated people still get the measles, that means the measles vaccine is worthless, right?
Of course not. Let’s start with the assumption that almost nothing is 100% anything. No vaccine can be 100% effective or safe because 100% means it literally never fails. And virtually nothing never fails. Getting out of bed isn’t 100% safe. The most benign and well-studied medicine isn’t 100% effective. We can’t think in absolute always and never statements. We have to go with what we know works the majority of the time.
It’s clear that the MMR shot does – and the Disneyland outbreak proves it. Please note that all of this is utterly off the cuff math, but even with a lot of variables, it proves my point.
If you take the raw numbers of how many people visit Disneyland, it averages about 40,000 per day. Some days it’s more, some days it’s less. It’s hard to find good numbers for the national rate of vaccination, but a CDC study from 2013 gives it around 92% for children ages 1-3 (note this is right on the line of the herd immunity threshold of 83-94%). Let’s extrapolate that percentage to the people coming to Disneyland on a daily basis and say it’s 36,800 vaccinated people and 3,200 unvaccinated people. The measles exposures have been narrowed down to a five day period, but let’s just say all the infections happened on one day.
Using the numbers from Wired, there are 46 known unvaccinated people and 6 known vaccinated people who’ve contracted the measles. So 6 out of 36,800, which is .016%; and 46 out of 3,200, which is 1.4%.
I’m not a math whiz, but one of these numbers is way, way higher than the other. And it’s not the number of vaccinated people who still got the measles. Sometimes the vaccine doesn’t take for whatever reason, but the vast majority of the time it does – and 100% of the time more than not vaccinating.
Measles patients are coming into America via our open borders. Thanks, Obama! – Without getting into a pointless and decidedly non-scientific argument about immigration policy, this just isn’t factually correct. It wasn’t true for the EVD-68 outbreak from last fall, and it’s not true about measles.
Mexico’s vaccination rate against measles has dropped in the last year, but it’s still at 89% as of 2013. Honduras is the same, 89%. For the Dominican Republic, it’s 79%, which is low. El Salvador is 94%. None of these are numbers that suggest massive numbers of unvaccinated children are pouring over our Swiss cheese borders and infecting good old American kids. In fact, there aren’t any measles outbreaks going on in any of these countries, and the only known measles case in Mexico is someone almost certainly infected as part of the Disneyland outbreak. The United States’ vaccination rate against measles, incidentally, is 91%. This is a decrease from the last three years (thanks, anti-vaxxers!), but in line with the South American countries supposedly inundating us with disease carriers.
As of this writing, the “patient zero” for the measles outbreak hasn’t been identified. That is to say that we don’t know who the first person with measles was to walk through the gates of Disneyland during the five day infection period. It’s probably a person who traveled to the US after being infected with measles in another country – most likely somewhere in Europe, Africa or Asia, where measles vaccination rates are lower than the US. That person would only need to spread it to one or two unvaccinated Americans, who spread it to others, who spread it to others, and on and on.
No credible evidence exists the first measles case is from either an illegal immigrant, or a vaccinated child, as anti-vaccine advocate are claiming.
My child is so special he/she doesn’t need your toxic vaccines – This is the most maddening lie about the measles outbreak, because it’s entirely based on opinion. The other lies, while wrong, are at least somewhat plausible. But to claim that you don’t vaccinate your kid because your kid is somehow “better” than the other kids is the logical fallacy known as special pleading – and also unfathomably arrogant.
When parents say things like “vaccines aren’t for us” or “my kid has a strong immune system” or (and this one is my favorite) “my child is pure” what they’re saying is that their kid is above the rules and they’re better at parenting than those poor sheeple getting their toxic jabs. They believe science and nature don’t apply to them, because they’re “aware” and their kids are special snowflakes.
I hate to break it to these parents, but their kid isn’t special. Neither is mine. Neither is yours. Neither is anyone’s.
Not in that way. No person is above the rules when it comes to nature. Nobody gets a free pass.
Measles doesn’t care if you eat organic, are GMO-free, never go to the doctor, have a strong immune system or have more purity than the other children. Polio isn’t interested in your natural hygiene and ancient remedies. Rubella couldn’t care less that you’ve “done your research” and “woken up.” And if you think these are okay, wait till you get a good look at smallpox, who will end you without a second thought.
These diseases will do what they’ve evolved to do, which is fight to live and make more of themselves. The places they end up living will by and large be unvaccinated people – no matter how pure or special or granola they are. And these people who end up harboring these diseases might very well die.
Because that’s what happens in nature.
This is the greatest lie, not just of this measles outbreak, but of the anti-vaccination movement in general: that some children are so special that they don’t need vaccines to protect them – mom and dad will do it. And nature will vociferously disagree whenever it gets a chance.
So what will it take before there aren’t any more anti-vaccine lies? One measles death? Ten? A rubella outbreak? A smallpox outbreak? Polio to make a comeback? How high will the bodies have to stack up before the anti-vaccine advocates and their enablers in medicine and the media say that this has gone way too far?
What will it take for the lies to stop?
Anti-Vaxxers: They’re Raging Narcissists
“Who cares if a kid dies from measles, as long as I got to make my choice!”
With the measles outbreak bringing vaccination back into the spotlight, one question is rarely answered: Why do more people now choose not to vaccinate their children? In a word: Narcissism.
When the measles vaccine was introduced in 1963, American culture was very different. Children were not told they were special (at least not in a good way). The current mantras of “believe in yourself” and “just be yourself”—much less “I love me”—barely existed. College students were less likely to think they were superior to their peers than they are now. In short, individualism had yet to dominate American culture.
It does now, and individualism has crossed over into narcissism in many pockets of our culture. Narcissism is the perfect formula for choosing not to vaccinate your kids. No, not everyone who makes this choice is narcissistic, but the pervasive cultural narcissism in the U.S. makes these ideas possible and accepted even without individuals displaying the personality trait. Either way, it’s remarkable how many characteristics of narcissism map on to anti-vaccine ideas.
1. Narcissistic people believe they should be able to do what they want, no matter how it affects others. Parents sometimes state their belief that vaccines “are not the right choice for my child.” Because, apparently, their child is special, and should be able to opt out of something everyone else does. It’s the classic commons dilemma: We need everyone to do their part. If just a few people freeload, they can get the benefits without the risks. When too many people freeload, the system falls apart. That’s exactly what is happening right now with the measles outbreak.
2. Narcissistic people have less empathy. Those too young or medically vulnerable to be vaccinated are only protected if the vast majority of people get the vaccine, known as herd immunity. Because some parents exercise their “choice,” other people’s children can get sick or even die. But who cares, because I got to make a choice!
3. Narcissistic people have a hard time believing anyone knows better than they do. So unless they’ve done the vaccine testing themselves, why should they believe anyone who tells them vaccines are safe and effective? It doesn’t matter to them that study after study shows this and doctors and other authorities continuously say this.
Because some parents exercise their “choice,” other people’s children can get sick or even die. But who cares, because I got to make a choice!
Basically, the modern, narcissistic idea is not to trust anyone except yourself. In previous decades, Americans were more trusting, both of each other and of authorities such as doctors and the government. Recently, however, trust in others and in institutions have reached all-time lows. Apparently, Americans only trust themselves; everyone else is an idiot.
4. Narcissistic people are overconfident. In stock-market simulations, they take too many risks because they don’t expect to lose money. They’re special, so bad things won’t happen to them. Until they do—like children getting the measles because they weren’t vaccinated. This is also at the root of the argument that we should “let nature take its course,” that works until it’s you or your kid who gets sick and dies. But narcissism lets people believe it will never be them.
The science on vaccination is extremely clear: Vaccines save lives and are exceedingly safe. Characterizing the discussion around vaccines as a “debate” is misleading. It’s not a debate any more than evolution vs. creationism is a “debate.” There is no debate. Let’s move on to figuring out why people endanger their kids—and, more infuriatingly, ours—by not vaccinating their children.
Health Budget
The cost of almost all new drugs approved by the NHS kills more people through cuts to care elsewhere than the medicines themselves save, authoritative analysis shows.
The National Institute for Health and Care Excellence (Nice) does more harm than good by diverting NHS resources into expensive drugs from other areas such as radiotherapy, nursing staff and mental health services, according to academics who have advised the rationing body.
The government’s Cancer Drugs Fund is even more damaging, costing patients five years of good quality life for every one year it adds, the study published today finds.
Approving a drug that costs the health service £10 million will lead to 51 extra deaths in patients with cancer, heart and lung diseases, as well as worse quality of life for people with mental health problems, joint and muscle pain, or conditions such as Alzheimer’s and MS, the analysis suggests.
“These are real people who are dying as a consequence of additional costs,” said Karl Claxton of the University of York, who led the study. “We do face a pretty stark choice which is to say, ‘We simply cannot afford these drugs at this price’, and take that political hit, or we continue to accept [the price] but know that we will be damaging health overall.”
To decide whether drugs are value for money, Nice uses a formula to judge how much must be spent on them to give a patient one extra year of good quality life. Drugs are generally approved if they cost less than £20,000 to £30,000 for one quality adjusted life-year. Yet when Professor Claxton analysed data on the effect of changes in NHS budgets he concluded that overall it costs the NHS £13,000 to provide one year of good quality life through existing treatments. “That means that currently, Nice guidance is doing more harm than good overall and it also means we are paying too much, not too little, for branded pharmaceuticals.”
Nice has often been criticised for rejecting new drugs because they are too expensive, and it has relied on the principle that if it asks the NHS to pay for a new drug, the health service will have to find savings elsewhere. Professor Claxton’s analysis, published in the journal Health Technology Assessments, suggests that the costs of almost all new drugs are outweighed by the value of the radiotherapy machines, A&E staff or dementia services that have to be foregone to pay for them.
Amid controversy over Nice’s repeated rejections of expensive cancer drugs, the Tories set up the Cancer Drugs Fund to pay for these medicines, which now has a budget of £340 million. Professor Claxton said: “If you’re saying that for political reasons we have to have a cancer drugs fund, because we’re not brave enough or not honest enough to say we can’t afford it, that’s fine, but at least we should be confronted with the health consequences.”
Sir Andrew Dillon, chief executive of Nice, praised the study, urging critics who say Nice refuses too many drugs to consider the impact of paying for more.
“There aren’t back pockets stuffed with cash that the NHS reaches for,” he said. “There are consequences if you invest in cutting-edge technology. It’s about striking a balance which we think we’ve done at Nice.”
The £13,000 cut-off “would shut the door on pretty much all of the new technologies that Nice looks at”, Sir Andrew added.
End of Life Intervention
It's hard to talk about end-of-life care, partly because the concept of a "good death" is a weird and sad one to grasp, not only for the person dying, but for their caretakers and doctors as well. Research has shown, though, that the more doctors, social workers, and others in the health-care system discuss with patients what they want the end of their lives to look like, the more likely they are to die in a (relatively) comfortable manner.
One cruel aspect of this subject is that sometimes medical care itself can contribute to bad deaths, increasing a patient's discomfort without significantly extending their life — or, if it does significantly extend their life, greatly reducing its quality along the way. Cardiopulmonary resuscitation and intubation are two common examples. Being revived with CPR can lead a patient to face more pain and further complications, and one study noted that intubation — a tube being worked down a patient's air pipe to provide for the free flow of air to and from the lungs — "is uncomfortable at best and torturous in many circumstances and may lead to a lingering posttraumatic stress response." So in an ideal world, patients who are critically ill would have a chance to seriously consider whether they want to endure these procedures.
Often, though, patients don't really have these discussions with their doctors before a health setback forces the issue. Since medical staff are required to try to save a patient's life with all the standard available tools for doing so unless the patient has specifically indicated otherwise prior to falling unconscious — or has legally given a family member or friend the power to make these decisions on their behalf — this lack of communication, though understandable given how emotional end-of-life conversation can be, leads to a lot of unnecessary suffering (and, it should be said, it contributes to the United State's very high per-capita medical costs, a huge chunk of which goes to care for the very old and very sick).
That's where a new study in the Journal of General Internal Medicine comes in. A team of 16 researchers led by Dr. Areej El-Jawahri of Mass General Hospital and Harvard Medical School, a member of a group calling itself the Video Images of Disease for Ethical Outcomes (VIDEO) Consortium, wanted to see whether a short video about CPR and intubation could affect a patient's end-of-life preferences. They found 150 patients, 76 years old on average, at MGH and Newton-Wellesley Hospital (which is in the Boston suburbs) who had serious health conditions and who doctors said had a year or less to live. Half of them, the control group, were given normal end-of-life care, including discussions with their doctors about CPR and intubation, as per the hospitals' policies. The other half was shown a three-minute video about CPR and intubation that sought to explain to patients exactly what these procedures entail. (I've requested a copy and will include it if the researchers send it.)
The results were pretty stark. Prior to the experiment, 84 percent of the control group and 81 percent of the video group said they wanted CPR if it was necessary to keep them alive. After the experiment, the control group's preference remained about the same (81 percent still wanted to be resuscitated), while the video group's preference fell severely: Just 43 percent of patients said they wanted CPR after seeing the video. The numbers for intubation were similar: For the control group, once again 84 percent wanted it before the experiment and 81 percent after, and for the video group there was a shift from 77 percent all the way down to 36 percent. Members of the video group who were discharged and later readmitted to the same hospital were also much more likely to refuse CPR and intubation upon their readmission, as compared to members of the control group who were similarly readmitted.
"What is remarkable about the present study is the huge impact of such a simple intervention — showing a three minute video — on patients' understanding of treatment options, and their subsequent changes in preference for aggressive care," said Dr. Lauren Nicholas of John Hopkins Bloomberg School of Public Health, who has conducted her own research on end-of-life care and wasn't affiliated with this study.
The video clearly did a good job imparting some hard truths about the procedures in question: They could easily lead to further complications and a protracted stay in the ICU leading up to death. The second and fifth questions, in particular, show just how poorly informed many patients are about CPR and the prognoses of patients who undergo it — and these were patients at hospitals known to be good on the palliative-care front, where, as the authors put it, "admitting physicians are encouraged to discuss CPR and intubation preferences with patients at the time of admission to the hospital or when there is a change in the patients’ clinical status."
Nudges to Encourage Vaccination
Four years ago schools and day cares in western Washington embarked on an experiment. Too many kids in the state were going without needed vaccines that protect them against measles, whooping cough and other preventable diseases. Part of the problem, public health officials believed, was that parents lacked accurate medical information and held misguided beliefs that the vaccines were not necessary.
So they drafted some help—specifically, other parents who were trained by public health workers to answer common questions about vaccines’ risks and benefits. Armed with that knowledge and paid small stipends, these advocates went out to educate other parents. Many of the trained parents took to Facebook to spread the pro-vaccine word; others set up information booths at school and community events. “Over a period of three years we worked in a total of 21 sites including elementary schools, child care and preschools,” says Mackenzie Melton, immunization coordinator at WithinReach, a nonprofit that helped organize the program.
In the U.S. it was one of the only recent efforts to audition new methods for getting more parents to follow childhood vaccine recommendations. The majority of U.S. parents—83 percent—vaccinate with the recommended schedule but the gap in full vaccination has help set off the multistate measles outbreak that has gripped the U.S. since late last year. The spread only underscores how little researchers know about ways to boost vaccination rates among American communities. Scientific American interviewed nine experts studying or experimenting with ways to get parents to vaccinate their kids and analyzed the available peer-reviewed literature. The picture that has emerged elucidates a gap in public health knowledge and strategy when it comes to getting hesitant parents to accept vaccine recommendations for their kids. It also reveals that the sweet spot for intervention are parents that are on the fence, not those who have already decided against vaccines.
What works
Indeed, in the case of the Washington State peer educators program, researchers did not expect the vaccine-resistant parents to switch course—the hope was to inform parents who have not yet made up their minds. The program’s backers are still analyzing whether they achieved the short-term goals of raising awareness and affecting parental attitudes. Certainly, swaying more parents in low-vaccine communities to favor immunization would likely curb outbreaks, because so many vaccine-hesitant parents appear to live in clusters.
Recruiting community members to become pro-vaccine leaders is unique in North America but it is typical of what UNICEF (United Nations Children’s Fund) does with its partners in developing countries, notes Benjamin Hickler, a communication for development specialist at the fund. “Whether it’s breast-feeding, vaccinations or sanitation, we use peer networks and this kind of community-based approach, and it’s very effective.”
Yet in countries like the U.S. where vaccines are widely available, the science seems better at telling researchers what doesn’t work, rather than what does. One 2014 study from Dartmouth College researchers, for example, actually found that repeated pro-vaccine messages from public health agencies can actually backfire by creating more resistance to immunization among those with firmly held anti-vaccination beliefs. “This is an area where the science on the vaccines themselves is far ahead of the messaging and outreach,” says Brendan Nyhan, a professor at Dartmouth and author of that work.
One known way to improve vaccine coverage rates is for states to force compliance. Mississippi does not allow parents to exempt their children from receiving vaccines for personal reasons, and the state has the highest vaccination rates in the country. But eliminating exemptions for personal reasons is often politically unpalatable. Twenty states currently allow vaccination exemptions because of personal, moral or other beliefs, according to the National Conference of State Legislatures.
Money talks
But it may still be possible to achieve high vaccination rates and keep personal exemptions. In Australia parents can also choose to opt-out of vaccines, but measles vaccination coverage for one-year-olds is 94 percent, according to World Health Organization data. (The U.S. only has 91 percent coverage for measles vaccines at the same age.) So what’s different? One factor may be that the Australian government provides financial incentives for parents to get kids vaccinated—specifically, in the form of tax credits. Physicians, too, receive a small payment when children get vaccinations on schedule. Parents can still choose to forgo the inoculations and receive the tax credit, but their clinician would have to sign off on an exemption form (which some refuse to do).
The hassle of having to get that exemption “tends to sort out the hesitant from the more entrenched nonvaccinators,” says Julie Leask, a professor of public health at the University of Sydney. She believes the policy has been a major driver in helping to get kids vaccinated. The U.K., which has a measles vaccination rate of 95 percent, has also adopted its own financial approach. There, clinicians’ pay partly hinges on childhood immunization coverage.
Researchers, however, have yet to prove that financial incentives definitively boost the immunization rates. And even though something like the U.K. policy appears to work in that setting, “everything comes at a price,” says Daniel Salmon, deputy director at the Institute for Vaccine Safety at Johns Hopkins University. “A critic can argue that clinicians have a financial incentive to vaccinate” and are therefore not medically objective.
New strategies
Some researchers are still searching for approaches that can sidestep such critiques. Rutgers University psychology professor Gretchen Chapman studies what nudges push people to get seasonal flu vaccines. Her research has revealed that an effective way is to make it slightly more difficult to opt out of getting flu vaccines rather than to opt in. In one study she found that more individuals will accept a flu vaccination if they receive a message saying a flu shot appointment has already been scheduled (along with information on how to cancel it) than if they are told how to schedule an appointment.
The same default logic also appears to hold true with childhood immunizations. A 2013 study published in Pediatrics found that when parents were told that their child would receive a vaccine at their appointment instead of being asked which vaccines they wanted their kids to receive, more children ended up with their recommended shots. In fact, phrasing vaccine decisions as a choice rather than a decided course increased the odds that parents would refuse the recommended regime by almost 18-fold, says study author Douglas Opel, a professor of pediatrics at the University of Washington. That’s even after his team accounted for whether parents were known to be vaccine-hesitant and controlled for if the parent and clinician had a long-established relationship.
Rather than legislate opt-in rules, one community is trying a simpler approach that relies on the Internet, another top source of information used by parents. In Ashland, Ore., where the vaccine exemption rate was almost 30 percent last year and climbed as high as 66 percent in one private school (meaning that parents of 66 percent of kids had delayed or refused at least one recommended vaccine), public health workers and community members built a Web site (Ashlandchild.org) detailing the risks and benefits of vaccines. That site largely replaced the community education nights and peer-to-peer education projects that town had going for years. “We were just feeling like we weren’t getting much accomplished. Maybe we didn’t figure out the right way to break in but we felt as if our energies would be better served by trying to do this through the internet,” says Jim Shames, medical director for Jackson County Health and Human Services in Oregon.
Information delivered via a Web site may be effective but the science is perhaps clearest on one thing: In the U.S. what happens in the doctor’s office matters. Health care providers are one of the most important sources of information in decisions about childhood vaccines, according to surveys of parents. Unfortunately, physicians have no clear script for what to say. Parents that are hesitant to have their children receive inoculations are not all the same nor are there that many of them. Resistance to vaccination usually boils down to fears of long-term harm to their child or pain to children given so many shots.
Salmon, the Johns Hopkins researcher, hopes to move more people into the pro-vaccine camp by starting such conversations between health care workers and parents earlier—even before a baby is born. In November he and his colleagues kicked off a five-year, multimillion-dollar study with pregnant women. “We are focusing on obstetric providers and pregnant women. I think targeting pregnant woman is a really good idea—especially first-time moms, because they may not have made up their minds,” he says. Their tablet-based intervention hinges on women filling out a survey with demographic information and underlying attitudes, then they receive targeted videos and messages (for example, a Latina woman will get a video of a Latina woman talking to her about the safety and importance of getting her children vaccinated).
A generation of resistance
The need for new strategies to boost vaccination rates may come as no surprise considering that the current generation of parents may not have ever seen the first-hand dangers of measles and other preventable diseases. And without personally witnessing those diseases, parents may be more receptive to poor information, especially when readily delivered through social media or slick Web sites. “It’s become very difficult, especially because of how sophisticated anti-vaccination Web sites have become, to distinguish between the global scientific consensus of experts and these sites that, for a number of reasons, question that expertise, recast it as a conspiracy with Big Pharma or say this is about freedom versus the state,” Hickler says.
Modifying those Web sites to help dispel such misinformation is one approach that may provide a starting point for the U.S., he says.* In Australia, for example, the government used consumer protection laws to make at least one anti-vaccination network change its Web site name and more clearly state its vaccine position so parents would know what they are getting. Such an approach could be a lever that wouldn’t “impinge on individual freedom but help vaccine-hesitant parents navigate the conflicting advice out there,” he says.
Experts agree on at least one long-term approach: getting today’s kids onboard with vaccination. Once they learn about the safety and importance of childhood inoculation then perhaps anti-vaccination will not be as big of an issue when they have their own kids.
Robot Surgeons
SURGEONS will use robots to conduct kidney transplants for the first time in Britain this spring, as the machines take on an increasing number of medical procedures.
Some medics predict that, in the next five years, robots will make the decisions about where to cut into the patient.
From next month, surgeons at Guy’s and St Thomas’ NHS Foundation Trust in London will turn to robots to perform keyhole kidney transplants, because the machines can carry out the most crucial part of the operation more quickly than a human.
Keyhole surgery is less painful and allows the patient to recover more quickly. At the moment, however, many surgeons feel they are not able to sew the blood vessels attaching the donated kidney to the patient quickly enough during a keyhole procedure. If not done swiftly enough, the donor kidney becomes damaged because it does not have a blood supply from the patient.
Carefully attaching the blood vessels between the donor kidney and the patient is the most important element of a kidney transplant.
A transplant surgeon will control the robot, which should manage the sewing up, through the tiny keyhole-sized incision in the body, within 30 to 40 minutes.
Nizam Mamode, consultant transplant surgeon at Guy’s and St Thomas’, who will be doing the robotic transplants, said: “What the robot does is allow you to stitch much more quickly than you otherwise would be able to do.”
So far, about 300 such robotic transplants have been conducted in India. Smaller numbers have been carried out in America and Italy.
Initially, the da Vinci robot, already used for other types of surgery including bladder surgery, will be used for the transplants. Surgeons expect to soon have a robot designed specifically for transplants.
Mamode predicts that in future robots will not just be driven by surgeons but will make key decisions such as where to cut into the patient.
Mamode said: “I think, increasingly, the robots will be making those decisions ... about where to cut. So, if you just think about going through the abdominal wall, normally the way that we would do it is, take a knife, go through the skin, stop, seal all the bleeding vessels, cut a bit more, have a look to see if we are right down to the level we need to be, cut a bit more. We are very close to a stage where a robot could do that.”
Brian Davies, emeritus professor of medical robotics at Imperial College London, believes surgeons will still wish to take the final decision about where the series of cuts are made, but says robots will increasingly advise doctors.
Davies said: “What we will see more of in the next five years is the ability to advise the surgeon of the suggested location and sequence of cuts, together with alternative possibilities.”
Surgeons at the Royal Devon and Exeter NHS Foundation Trust are investigating whether imaging technology could be attached to the end of a robot arm so that during an operation to remove cancerous tissue, the machine could tell the surgeon where the cancer is and how much tissue should be removed.
John McGrath, consultant urological surgeon at Royal Devon and Exeter, says it is possible that in future robots could be programmed to perform such an operation on their own.
McGrath said: “If we knew on the MRI scan before surgery where the tumour was, you could you take the surgeon out completely and just program into the robot a series of co-ordinates, and it would remove the area we have identified on a scan and remove it safely.”
Davies believes the surgeon will be reluctant to let robots work entirely on their own, however. He said: “Such systems are not totally autonomous in deciding what is the target tissue in real time on the patient. The surgeon, in taking responsibility for her patients, will want to have the final say.”
Robots are now commonly used to remove prostate glands, bladders and wombs. It is estimated that 80% of prostate cancer patients now have the prostate removed by a robot.
Cold Caps
Hair loss is one of the most obvious side effects of cancer treatment. Now, a growing number of breast cancer patients are freezing their scalps as a way to preserve their hair during chemotherapy.
The hair-saving treatment, widely used in Europe, requires a specialized frozen cap worn tightly on the head before, during and for a couple hours after a chemotherapy session. The method can be time consuming, expensive and uncomfortable, but numerous women swear by the results.
“I had the wig ready, but I never had to use it,” said Eileen Bruno, 50, of Westwood, N.J., who last year completed chemotherapy and cold cap treatment while maintaining her full head of thick, blond hair.
After learning that she had early-stage breast cancer, Ms. Bruno said she worried about her health – and losing her hair.
“Knowing I was going to lose my hair was an awful thing for me,” Ms. Bruno said. “I was really struggling with the fact that not only was I sick, but I was going to have to look sick to myself and the rest of the world.”
Ms. Bruno learned of the cold-cap treatment through friends, and gained the support of her doctors at the Weill Cornell Breast Center in New York, one of only a few New York hospitals that accommodate cold-cap treatment. The hospital has made space for a special medical freezer that keeps the caps ready at the right temperature, donated by the Minneapolis nonprofit group The Rapunzel Project. Patients can also stay in the infusion area after chemotherapy ends to finish the cold-cap treatment.
Ms. Bruno used the Penguin Cold Cap, which is essentially an ice pack fitted tightly on the head like a swim cap. The cold caps, which are rented for about $600 a month for a set of caps, must be kept frozen and changed quickly every half-hour. Many women enlist friends or family members to help them quickly change and refreeze the caps as needed. Some patients hire “cappers” to help, paying $300 to $750 a day for the service.
Another scalp cooling system, called the DigniCap, is less labor intensive. It uses a small machine and tubes filled with a coolant to chill the cap.
Researchers at the University of California, San Francisco, and several other medical centers around the country recently completed a pilot study and clinical trial in 120 patients. U.C.S.F. also monitored about 100 women who used the Penguin cap. The results have not been published, but both studies showed that most women who used a scalp-cooling cap kept most of their hair, said Dr. Hope Rugo, the director of breast oncology at U.C.S.F., who led the research.
Losing your hair is a “declaration to the world” that you have cancer, Dr. Rugo says. “Hats are fine and good, but everyone knows you’ve lost your hair.”
Dr. Rugo said the DigniCap may soon become the first scalp-cooling device to be approved by the Food and Drug Administration, a move that would increase the likelihood of insurance reimbursement and make them more widely available. “It’s so important for people to know we may have an F.D.A.-approved device in the near future,” she said.
Cold cap treatment is not typically covered by insurance, although doctors tell stories of women winning reimbursement in lieu of wig costs. The cost varies depending on the duration of chemotherapy and the type of cap used, but doctors estimate that the average cost of a scalp-cooling treatment is about $2,000 a patient.
Wendy Brown, 59, was found to have breast cancer last year and learned of the DigniCap study from Dr. Rugo, her oncologist. She said using the cap created brief moments of discomfort, and it had to be worn for two additional hours after her chemotherapy ended. Other than that, she described the cap as “goofy” and a source of amusement among her friends, who manipulated photographs of her wearing the cap to make it look as if she were scuba diving or piloting a Red Baron-style airplane like the cartoon character Snoopy.
A surprising benefit of keeping her hair was privacy.
“One of the advantages is that you don’t walk around with people giving you that ‘Oh, you’ve got cancer,’ look,” Ms. Brown said. “It’s nice to be able to control who you tell and who knows.”
Women who have used the Penguin cold caps say they can be heavy and the first few minutes of freezing can be excruciating. They wrap themselves in electric blankets, socks and sweaters to endure the treatment, which is given concurrently with chemotherapy and generally adds a few hours of treatment to a chemo session.
“For the first few minutes, it’s painful, but I feel fine,” said Jane Cohn, 44, a nurse who had her first chemotherapy and cold-cap treatments last fall. “It’s very cold for two minutes, but I’m sitting under a warm blanket. I don’t even think about the chemo and I don’t worry about my hair. It has helped with my stress, because I know my hair is going to be here.”
The scalp-cooling treatment is believed to work in two ways. By reducing the temperature of the head, the cap slows down the metabolic activity of the follicular cells in the hair, reducing the effects of chemotherapy on scalp hair. “If you put the hair follicle to sleep a bit it won’t be as sensitive to the effect of chemotherapy,” Dr. Rugo said.
The cap may also have an effect by constricting blood vessels to limit the amount of chemotherapy that penetrates the scalp. This has led to some concern that cold-cap users could theoretically be at risk for their cancer to metastasize to the scalp. However, doctors say scalp metastasis is incredibly rare, and with the cold caps widely used in Europe, doctors there have not detected a rise in cancer spreading to the scalp area.
Women who use the caps say they know the caps are working because they begin to lose all their other body hair, but only have mild thinning of their scalp hair that is not noticeable to most people. During treatment, patients are advised to be gentle with their hair, avoiding blow drying and heat treatments, coloring or frequent washing.
Dr. Tessa Cigler, a Weill Cornell oncologist involved in the cold-cap studies, said she first learned about cold caps from a patient who had researched the treatment and learned about their use in Europe. After studying the European data on cold-cap treatment, she allowed her patient to use them and became interested in conducting her own research.
The success of a cold cap treatment often depends on the duration and type of chemotherapy regimen, so not every woman is a candidate, Dr. Cigler says. In addition, cold caps are typically used only on patients with solid tumors, like breast cancer, and are not suitable for patients with blood cancers.
“Cold cap therapy is really empowering to many patients,” Dr. Cigler said. “It has allowed many patients to protect their privacy, and allows women to maintain their self-esteem and their sense of well-being during a really difficult time.”
Paying For The NHS
Political parties are in denial over how to relieve the growing pressure on the health service. We need an honest debate about new means of paying for it.
“A&E won’t kiss it better,” say the bracing but necessary advertisements on London buses. Unfortunately, A&E won’t necessarily save your life either, not for want of expertise or compassion but because of a fundamental mismatch between supply and demand that afflicts the entire NHS.
The service is in the grip of a four-pronged vice of ageing patients, ever-costlier treatments, rising expectations and acute pressure on budgets. Everyone who debates health policy in parliament knows this. There is surprisingly little disagreement on the basic priorities for improving care, from better co-ordination between hospitals and care homes to the need for more resources. What no main party leader dares discuss is where those resources must be found.
The business model of the NHS is strained beyond repair. At a time when half of us will develop cancer sometime in our lives and cutting-edge drugs can cost £50,000 per patient a year, a worldclass health service free at the point of need, funded entirely from direct taxation, is not sustainable. If the next government is serious about preserving the NHSit must level with voters about the need to find new ways to fund it. The approach need not amount to privatisation. However, it will have to borrow from the best systems in other countries. Most deliver better outcomes, especially in the treatment of serious illness. All are insurance-based, with charges in some cases for hospital stays and doctors’ visits. As a result they are better able to keep up with demand. The NHS is a wheezing laggard by comparison.
Bleak new statistics from the nation’s ambulance services illustrate the point. Responses to freedom of information requests by The Times show that the number of patients with life-threatening conditions forced to wait more than an hour in an ambulance before A&E treatment doubled last year. The number who died before even being admitted to an A&E department tripled.
Ambulance queues caused by unnecessary callouts are one reason for this trend. Others include ill-advised referrals by the 111 health line, overstretched A&E staff, inadequate or non-existent out of hours care at GP surgeries and weekend bottlenecks when elderly patients with chronic conditions end up at accident and emergency for want of timely residential care.
Labour would have voters believe the NHS is on life-support and about to be sold off for scrap to the highest bidder. In fact sensible research by the King’s Fund think-tank has given the lie to the privatisation myth. Barely 5 per cent of NHS services have been outsourced to the private sector. Nor is money a panacea, yet there is no doubt that more of it is needed. Even Labour’s campaign promise of £2.5 billion a year more than the Tories falls far short of the extra £8 billion a year that Simon Stevens, the current NHS chief executive, says is needed.
Without funding on this scale the service will face a £30 billion shortfall by the end of the decade. To bridge it, brave thinking that shatters old taboos is needed. As Mr Stephens has written in this newspaper, the health service cannot be a hostage to its history. But that is what it will be unless politicians find the courage to stop worshipping the service and rethink it for the modern age. For five years David Cameron has himself been hostage to his three-letter health policy (“NHS”). Labour is so deeply in thrall to the status quo that this week it forced the Commons health select committee to scrap an NHS report for being too supportive of the coalition.
The health service consumes less as a share of GDP than comparable systems abroad, but it ranks poorly on keeping people alive, it is over-politicised and it is heading for insolvency. The prime minister who works out how to pay for it will go down in history as the one who saved it.
Approving New Drugs
“IF WE didn’t take any risks, we wouldn’t approve any drugs,” says Susan Ellenberg, a professor of biostatistics at the University of Pennsylvania. “Some people will always want a new drug sooner and say they’re willing to take a chance. Others will ask, why didn’t you study it longer and find out about this horrible side-effect?”
During her long career, Dr Ellenberg has used data to quantify and communicate those risks. Along the way she has helped to shape a discipline that owes as much to ethics and philosophy as it does to pure mathematics. Now medicine is entering a new digital age, one of Big Data and high-tech personalised treatments that are tailored to an individual’s genetic make-up. But more data does not necessarily mean better data, so amid the increasing complexity it will be as important as ever to measure correctly which treatments work and which do not.
It is a job Dr Ellenberg is well suited to. She has already played a big part in improving the data-monitoring committees that now oversee virtually all clinical trials; she has helped establish standard practices for tracking dangerous treatments; and she has encouraged patient lobbies to find a voice in clinical testing.
But Dr Ellenberg nearly missed becoming a statistician at all. As a high-school maths teacher in the 1970s, she took a summer job analysing clinical trial data. Luckily, she became so engrossed that she quit her job and returned to graduate school for a doctorate in statistics. The basics of randomising subjects into different groups and leaving the patient (and ideally health-care workers as well) unaware of the treatment each was receiving were well known. However, there were still plenty of mistakes being made.
“In the old days, people used to throw out some of their data,” says Dr Ellenberg. “If a patient didn’t comply with their treatment, the researchers would say, how can they possibly contribute to the question of how that treatment works? So they just dropped them.” In one case Dr Ellenberg worked on in the 1970s, doctors wanted to test whether chemotherapy could help people recovering from colon cancer surgery. The study required patients to start chemotherapy within six weeks of their operation for the best chance of catching any remaining cancer cells. Those who missed the deadline were automatically excluded from the analysis.
Dr Ellenberg realised that most reasons for starting treatment late, such as a slower recovery from surgery because of old age or a particularly large tumour, would probably mean a poorer prognosis regardless of any subsequent treatment. Excluding those people would leave the chemotherapy group with healthier members on average, making a drug look beneficial even if it did nothing. Dr Ellenberg insisted that the investigators track everyone who had been randomised into the study, even if they were treated late or not at all.
In 1988, Dr Ellenberg became the first chief of biostatistics for AIDS at the US National Institute of Allergy and Infectious Diseases. She arrived at a desperate time. HIV appeared to be a death sentence, patients were demanding treatments, however unproven, and doctors were struggling to catch up. With most infectious diseases, patients could be treated and followed up within weeks to see whether the pathogen had disappeared. With HIV/AIDS, they might have to monitor trial members for years to see who lived and who died.
Measuring surrogates
Dr Ellenberg championed a concept called surrogate endpoints that she had pioneered in cancer trials. These are biochemical measures that can indicate quickly whether a patient in a trial is likely to improve, remain stable or deteriorate in the long-term. For example, blood pressure can be a surrogate endpoint for cardiovascular mortality. The challenge with AIDS was working out which of dozens of biological markers had the best predictive value. Dr Ellenberg helped narrow these down to ones that were strongly associated with long-term survival, such as CD4 white-blood-cell counts. “I wish I could tell you that led to wonderful results and now we know how to do it,” she says, “But we’re still limping along.”
The problem is that a surrogate for one treatment may not work with another, either because the second treatment functions differently or has side-effects. But it was still a step forward, allowing investigators to screen potential drugs more quickly. Nothing could be fast enough for some activists, however, who wanted early access to anything that might slow the progression of AIDS. “The clinical leadership was unwilling to talk with activists at that point,” says Dr Ellenberg, “But I saw that the Act Up group in New York had a very carefully thought-out set of principles for doing AIDS trials.”
Dr Ellenberg welcomed Act Up to her statistical working group on AIDS, and changes began to trickle through. Until then, some studies had not allowed trial patients to take drugs other than the one being tested, even though many AIDS sufferers needed a cocktail of medications to fight opportunistic infections. Dr Ellenberg showed that a study could deliver useful results while allowing its members to continue with life-saving medicines. Patient groups are now routinely involved in planning clinical trials.
The role of placebos in clinical testing was a thornier problem. The most reliable results can always be obtained by comparing two identical groups, one of which receives a treatment and the other an inert placebo. Ethically, however, doctors are loth to withhold an effective treatment where one exists, so many trials simply compared a new drug to an existing one. In 1993 Dr Ellenberg moved to the US Food and Drug Administration (FDA). In a series of scientific papers, she and a colleague demonstrated that such trials can often fail to demonstrate the effectiveness of new treatments. In 2002, the World Medical Association changed its recommendations to permit placebo-controlled trials explicitly where patients would not suffer serious or irreversible harm.
Without the right analytical methods, more data just gives a more precise estimate of the wrong thing
The same year, Dr Ellenberg wrote a book about the importance (and the dangers) of analysing data as it accumulates during a clinical trial. Her ideas of how data-monitoring committees should function quickly became standard practice. It had long been realised, for example, that a trial might reveal one treatment to be much better than another. The only ethical thing to do in that case would be to stop the trial and give everyone the superior drug. In the past, statisticians keen to find such magic bullets would crunch their data every few weeks or months. “But if you look at your data often enough, sooner or later you’ll observe by chance that one arm of the test looks better,” says Dr Ellenberg. “There is now a mistrust of the whole concept of early termination.”
She also cautions against the temptation to set statistics aside when faced with something that appears to be urgent: “There are groups saying they would be opposed to doing randomised trials for drugs or vaccines for Ebola because it’s so serious. But we’re not doing anybody any favours if we don’t find out whether these drugs or vaccines actually work.”
Much of Dr Ellenberg’s work at the FDA focused on the safety of medicines, particularly vaccines, once they were on the market. No clinical trial can ever catch the rarest side-effects but tracking those down from sporadic reports, anecdotes and coincidences is incredibly difficult. She notes that most infants are vaccinated and sometimes children get very sick. But is it the vaccine or just coincidence? “I was trying to make something out of the worst, dirtiest kind of data that you could possibly imagine,” adds Dr Ellenberg.
The arrival of electronic medical records and the advent of Big Data promises massive statistical analyses that can uncover everything from uncommon side-effects to how peoples’ genes might affect their future well-being. The technology is likely to be particularly useful in detecting bad treatments, thinks Dr Ellenberg. While most reported problems may continue to be coincidences, at least biostatisticians will be able to compare reliable lists of who took a drug and who experienced unpleasant reactions. The problem, says Dr Ellenberg, is detecting the signal from the noise. “The more people you have the richer your database will be but also the more ways there are to be misled by the data.” Without the right analytical methods, she believes, more data just gives a more precise estimate of the wrong thing.
From the genes
Dr Ellenberg points out that services like 23andMe, which provide ancestral and medical interpretations of individuals’ genetic information, have not yet delivered the revolution in health that many had expected. In the early days of genomics, excited mathematicians thought they had discovered thousands of correlations, most of which were chance findings. Dr Ellenberg also worries that presenting people with links between particular genes and health outcomes might lead them to worry needlessly or seek out potentially harmful treatments for conditions they do not yet suffer from.
In his state-of-the-union address, Barack Obama lauded personalised medicines. But these are tricky to approve. When a disease affects millions, large clinical trials can reliably spot even small differences between drugs. But for personalised treatments, or ones targeting rare “orphan diseases” that affect only a few people, those differences become much harder to spot. Nevertheless, Dr Ellenberg believes statistics can help by integrating evidence from other trials.
Dr Ellenberg continues to work on surrogate endpoints and clinical trials, including a new study testing an innovative approach to attacking HIV. She also recently travelled to Botswana to help statisticians and clinicians there develop their own biostatistics programmes. Like most medical academics, Dr Ellenberg would like to see an end to the practice of some pharmaceutical companies quietly burying trial data that is inconvenient to them. Thousands of clinical trials have never been registered with oversight agencies and results from around half of all clinical trials (often those with unfavourable results) remain unpublished. Making that data available to statisticians would almost certainly lead to new discoveries and clinically useful findings.
However there could also be negative consequences. “Sharing raw data could promote inappropriate re-analyses,” warns Dr Ellenberg. She says there are many who would be ready to believe any analysis claiming to prove that vaccines caused harm.
That the dry world of statistics is becoming a battleground of ideas and commercial interests, affecting the future of medical care and the lives of people around the world, may shock some. For Dr Ellenberg, who has spent her professional life emphasising the life-saving importance of accuracy, it is no surprise at all. “We’ve got all this data,” she says. “The answer isn’t to ignore it. The answer is to figure out how to limit the number of mistakes we make.”
Smartphone Apps
BY SOME accounts, one in five Americans use health apps on their smartphones. The apps can also connect to sensors worn on the body to monitor vital signs, such as a runner’s heart rate. Others assist with diagnostics, for instance by using the phone’s camera to analyse the colour of test strips dipped in samples. Plug-in devices are also appearing to enable phones to take biological measurements directly. Two of the latest can detect exposure to HIV, the virus which causes AIDs, and diagnose other conditions.
Samuel Sia and his colleagues at Columbia University in New York have miniaturised a laboratory-based blood test called an ELISA (for enzyme-linked immunosorbent assay). It detects biological markers, such as antibodies made in response to an infection. A sample of blood from a finger prick is placed in a small disposable plastic cassette that contains reagents necessary for an ELISA. The cassette is inserted into the test-device itself, which is small enough to fit into the hand of the user and contains what is known as a “lab-on-a-chip”. This, in turn, is plugged into the phone. An app manages the test and after 15 minutes a negative or positive result is displayed on the phone’s screen.
The equipment was recently tried out by health-care workers in Rwanda testing pregnant women, from a single sample of blood, for HIV and syphilis. The results were encouraging and the team are now exploring how to bring their smartphone test to market. Dr Sia says he estimates the device itself would cost about $35 to manufacture. An ELISA machine in a laboratory could cost more than $18,000.
The other idea is from Descue Medical, a Salt Lake City-based startup founded by two brothers, Christopher and Andrew Pagels. They have come up with a product called iTest. The pair, both biomedical-engineering students, hope to have their first test-kit on sale in 2016 after obtaining clearance from America’s Food and Drug Administration. It can diagnose “strep throat”, a nasty infection by Streptococcus pyogenes, a bacterium. The condition needs treatment with antibiotics. It is most common in children and young teenagers and can cause complications, such as inflamed kidneys and rheumatic fever.
Their kit includes a swab that is rubbed against an infected patch of throat. This is placed into a vial containing a liquid, which washes the sample into solution. The vial is then fitted into the iTest device, which in turn is plugged into a phone. The brothers say the device uses a technique called voltammetry, which measures the current in a sample as a function of the voltage applied to it. Rapid strep tests are not new, but usually involve mixing solutions and looking for a visible reaction.
The strep test, though, is only the beginning of the brothers’ ambitions. The idea is to offer a variety of different test kits that can be used by the same iTest device to diagnose a range of conditions, says Andrew Pagels. The brothers say they have already developed tests for HIV and MRSA, a bacterial infection which is particularly difficult to treat, and are working on tests for the flu, sexually transmitted diseases and a combination test for dengue fever and malaria. Another test would allow a smartphone to detect troponin. Elevated levels of this protein in the blood can verify that someone has had a heart attack. The brothers anticipate the main iTest device would sell for about $150 with the test kits available separately.
By offering lab-type diagnostics to almost any population with access to a smartphone, such devices would be particularly useful in remote and resource-poor areas. But they are bound to give hypochondriacs yet another reason to fiddle with their handsets.
Young Blood
IT SOUNDS like the dark plot of a vampire movie. In October, people with Alzheimer's disease will be injected with the blood of young people in the hope that it will reverse some of the damage caused by the condition.
The scientists behind the experiment have evidence on their side. Work in animals has shown that a transfusion of young mouse blood can improve cognition and the health of several organs in older mice. It could even make those animals look younger. The ramifications for the cosmetics and pharmaceutical industries could be huge if the same thing happens in people.
Disregarding vampire legends, the idea of refreshing old blood with new harks back to the 1950s, when Clive McCay of Cornell University in Ithaca, New York, stitched together the circulatory systems of an old and young mouse – a technique called heterochronic parabiosis. He found that the cartilage of the old mice soon appeared younger than would be expected.
It wasn't until recently, however, that the mechanisms behind this experiment were more clearly understood. In 2005, Thomas Rando at Stanford University in California and his team found that young blood returned the liver and skeletal stem cells of old mice to a more youthful state during heterochronic parabiosis. The old mice were also able to repair injured muscles as well as young mice (Nature, doi.org/d4fkt5).
Spooky things seemed to happen in the opposite direction, too: young mice that received old blood appeared to age prematurely. In some cases, injured muscles did not heal as fast as would be expected.
Several other experiments have shown similar effects. In 2012, Amy Wagers at Harvard University showed that young blood can reverse heart decline in old mice. Her team paired healthy young mice with old mice that had cardiac hypertrophy – a condition which swells the size of their heart – and connected their circulatory systems. After four weeks, the old mouse's heart had shrunk to the same size as its younger partner. In this experiment, the young mouse was seemingly unaffected by the old blood, its heart not changing in size.
Once the researchers had ruled out the effect of reduced blood pressure on the older mice, they identified a protein in the blood plasma called growth differentiation factor 11 (GDF11) that appeared to fall with age. To see if it was linked to the rejuvenating effects, the team gave old mice with enlarged hearts daily injections of GDF11 for 30 days. Their hearts decreased in size almost as much as they had in the parabiosis experiments (Cell, doi.org/q2f).
A year later, the same team showed in mice that daily injections of GDF11 also increases the number of blood vessels and the number of stem cells in the brain – both factors known to improve brain function. A separate team led by Tony Wyss-Coray at Stanford performed similar experiments. His team injected blood plasma from young mice into old mice and showed an improvement in the old mice's physical endurance and cognitive function (Nature Medicine, DOI: 10.1038/nm.3569).
In both mice and humans, GDF11 falls with age. We don't know why it declines, but we know it is involved in several mechanisms that control growth. It is also thought to mediate some age-related effects on the brain, in part by activation of another protein that is involved in neuronal growth and long-term memory.
So the billion-dollar question is: would a GDF11 boost have the same effect in humans? Wyss-Coray thinks it will, having taken the next step of injecting young human blood plasma into old mice. His preliminary results suggest that human blood has similar rejuvenating benefits for old mice as young mouse blood does.
"We saw these astounding effects," he says. "The human blood had beneficial effects on every organ we've studied so far."
Now, the final step – giving young human blood plasma to older people with a medical condition – is about to begin. Getting approval to perform the experiment in humans has been relatively simple, says Wyss-Coray, thanks to the long safety record of blood transfusions. He warns against swapping blood at home because transfusions need to be screened for disease, matched for blood type and the plasma needs to be separated out. "Certainly you can't drink the blood," he says. "Although obviously we haven't tried that experiment."
So in early October, a team at Stanford School of Medicine will give a transfusion of blood plasma donated by people under 30 to older volunteers with mild to moderate Alzheimer's.
Following the impressive results in animal experiments, the team hopes to see immediate improvements in cognition, but Wyss-Coray cautions that it is still very experimental. "We will assess cognitive function immediately before and for several days after the transfusion, as well as tracking each person for a few months to see if any of their family or carers report any positive effects," he says. "The effects might be transient, but even if it's just for a day it is a proof of concept that is worth pursuing."
All researchers involved in the work agree that GDF11 is unlikely to be the only factor that keeps organs youthful. "It's too optimistic to think there would be just one factor," says Francesco Loffredo, who studies the effects of young blood in old animals at Harvard University. "It's much more likely to be several factors that exert these effects in combination."
Loffredo says the approach of testing the effects of young blood in people with Alzheimer's is fascinating, but reckons in the long-term it is best to continue to strive to identify the individual factors that are exerting the rejuvenating effects so that they can be translated to humans more easily. "Imagine if you had to be transfused with young blood all the time – it's hard to imagine as a therapy. Who is going to be donating all this blood?" he asks.
Wyss-Coray agrees. "It would be great if we could identify several factors that we could boost in older people," he says. "Then we might be able to make a drug that does the same thing. We also want to know what organ in the body produces these factors. If we knew that, maybe we could stimulate that tissue in older people."
Chemotherapy aid
Alessandro Laviano at the Sapienza University of Rome in Italy says that the research on diseases of ageing certainly holds promise, but he is more interested in the potential use of young blood in chronic disease. People with cancer who resist muscle loss have better chances of survival, he says. "So I'd like to consider the possibility of using these youthful factors in young blood to reduce the muscle wasting that occurs during chemotherapy."
Genetic Mutations and Prostate Cancer Treatment
Thousands of men with prostate cancer could be treated with drugs developed for other tumours, according to an “incredibly exciting” study that reshapes understanding of the disease.
Nine in ten men with advanced cancer have genetic mutations that could be targeted with drugs designed to treat other types of disease, suggest “game-changing” findings by British researchers. They say that the discovery could offer patients dozens of new therapies.
The findings move the NHS a step closer to routine DNA analysis of tumours to discover which drugs are likely to be most effective, as treatment becomes increasingly personalised by genetic type.
Scientists gathered samples from 150 patients of tumours that had spread to the bone, lymph nodes and soft tissues, before analysing their genetic code as well as those of the patients. Writing in the journal Cell, they say that the “comprehensive genetic map” of prostate cancer results shows that 89 per cent of men have targetable mutations.
Johann de Bono, of the Institute of Cancer Research in London, who led the research, said: “Our study shines new light on the genetic complexity of prostate cancer as it develops and spreads — revealing it to be not a single disease, but many diseases each driven by their own set of mutations.”
He said the findings could be “gamechanging”, arguing: “What’s hugely encouraging is that many of the key mutations we have identified are ones targeted by existing cancer drugs, meaning that we could be entering a new era of personalised cancer treatment.”
For example, a fifth of the men had mutations in the BRCA genes, which increase the risk of breast cancer, as in the case of the actress Angelina Jolie.
Trials are under way to test whether drugs designed to target these mutations will help men with prostate cancer, and Professor de Bono said that similar work must now be done for a string of other therapies. He said that this meant “certainly more than ten and hopefully in the future it will be more than 100” new drugs that could be used in prostate cancer.
“There have only been five or six drugs that have ever improved survival so if we get ten more in the next decade that would be amazing,” he said.
Every year 42,000 men are given a diagnosis of prostate cancer, a fifth at the most advanced stage when the disease has spread. Professor de Bono said that a wider range of drugs could help more men to survive the disease, which kills 11,000 a year.
He already routinely does genetic profiles of his patients at the Royal Marsden hospital in London and says that with the cost down to about £300, this should spread nationwide in less than five years.
“It’s not yet rolled out across the NHS but it soon will be. I have no doubt that in the very near future it will become the standard of care,” he said. “It will bring a huge opportunity for bringing lots of drugs in to these patients and treating them more precisely and better.”
Iain Frame, director of research at Prostate Cancer UK, said: “This is incredibly exciting and groundbreaking research. It suggests for the first time the list of genetic mutations to search for to build up a blueprint of a man’s prostate cancer once it has spread. This could provide the information about the best routes of attack in each individual case, which is crucial if we are to reduce the number of men dying needlessly from this disease.”
Paul Workman, chief executive of the ICR, said: “Cancer becomes lethal at the stage when it spreads round the body and stops responding to treatment but until now it has been incredibly difficult to find out exactly what is going on genetically at that critical point. This major new study opens up the black box of metastatic cancer, and has found inside a wealth of genetic information that I believe will change the way we think about and treat advanced disease.”
Virtual Reality Therapy For Stroke Victims
In virtual reality, an arm impaired by a stroke can seem strong again. And, according to new research, that illusion could be the key to give patients the confidence they need to practice using their weakened limbs in real life.
After a stroke, patients may compensate for losing the muscle strength in one limb by using the working limb more frequently. Eventually, a behavioural pattern of non-use can form, where the weak limb is totally ignored. This is called “learned non-use.” While it may initially result in making life a little easier, if a stroke patient doesn’t learns to properly use the arm with reduced strength, they may never get to.
Traditional therapy for this condition involved constraining the working limb and forcing the patient to use their impaired limb to complete tasks. But, according to researchers from the Laboratory of Synthetic, Perceptive, Emotive and Cognitive Systems at the Universitat Pompeu Fabra in Spain, the real key to getting people to use their affected limbs could be giving them a boost of confidence in VR.
In a pilot study involving 20 patients, the researchers got patients to reach for a target in a virtual world using their strong and weak arms; their movements were captured and digitized by an Xbox Kinect. The performance values for their “bad” arms—which controlled how fast and accurate they appeared in virtual reality—were then manipulated and enhanced. In subsequent tests, where their strength was unmodified, the patient's’ actual performance and the likelihood of using their bum limb was calculated.
"After enhancement of movement, patients started using their paretic limb more frequently,” Belén Rubio Ballester, the study’s lead author, said in a statement. “This suggests that changing patients' beliefs on their capabilities significantly improves the use of their paretic limb. Surprisingly, only ten minutes of enhancement was enough to induce significant changes in the amount of spontaneous use of the affected limb.”
Curiously, not one of the patients reported noticing the VR enhancements to their impaired limbs. However, “one of the patients commented that both virtual limbs moved faster during session 2, where only the paretic hand moved faster,” the researchers write. Apparently, the illusion was both subtle and convincing.
Virtual reality is finding more and more uses in therapy, precisely because you can test the impossible in the digital realm. For example, researchers can simulate triggering situations in order to treat PTSD in military veterans. When it comes to medical therapy, the principle is pretty much the same: if you you can simulate the right conditions, maybe you can improve patient responses.
Retina Diagnostics
WHETHER or not eyes are windows to the soul, they can provide a view of a person’s health. Eye problems are not the only things to show up; recent studies indicate that eyes can also reveal the presence of broader disorders like heart disease, stroke threats, diabetes, Alzheimer’s and multiple sclerosis. Frequent eye monitoring may help detect these ailments early, and now a new device promises to make that easier.
Retinal imaging is best left to professionals, not least because a doctor needs to get a patient’s eye in precisely the right position to see all the blood vessels inside. Even so, Tristan Swedish of Massachusetts Institute of Technology’s Media Lab, a place where diverse disciplines often collide in remarkable ways, speculated that it might be possible to create a device that would allow patients to take snapshots of their own retinas.
Working on the principle of “if you can see me, I can see you”, Mr Swedish describes his idea in an upcoming issue of the Association of Computing Machinery Transactions on Graphics. He generates a red light that shines through tiny holes to make it look as if there are four red lights in a diamond formation in his device. Patients initially see the lights as rather dim dots but, as they move their eyes around, they quickly notice that the dots become brighter when they look in a specific direction. When these dots become particularly bright, a second diamond of dim red lights becomes apparent inside the first four. The person then moves their eyes again until they can see all eight bright lights forming a diamond within a diamond.
The lights are a bit like optical archery, with a ninth light in the centre of the two diamonds as a bull’s eye of sorts. A patient’s retina must be perfectly aligned with the centre light for a clear photograph to be taken. The task is not easy, but with around ten minutes of practice most people are able to push a button at just the moment they see all nine lights and capture an image that can be analysed.
For the time being, eye doctors are the only ones qualified to scrutinise images produced by the device, but that could soon change. Mr Swedish says his colleagues at the Media Lab are already developing software capable of analysing colouration, blood-vessel shapes and other traits found in the retina that can help determine the health of patients, and plot that information over time. Such a system might make it possible for people to monitor themselves and, if there are any warning signs, to be advised to see a doctor for a closer look.
Dementia Detection
A digital pen with built-in sensors can diagnose signs of dementia and Parkinson’s disease more quickly and accurately than a doctor, research suggests. The £160 pen can analyse every stroke, angle and hesitation of a patient who has been asked to perform a series of drawing tasks by measuring the position of the tip 80 times per second.
The process has been developed by scientists in the US, who have been working to digitise a 50-year-old process used by GPs and neurologists known as the “clock-drawing test”.
The test asks a patient to draw from memory a clockface with hands set to a specific time and then asks them to copy a pre-drawn clockface — known as the “control clock” — with hands set at the same time. Doctors then judge the accuracy, neatness and completeness of the completed drawing by eye to assess whether the patient may be suffering from a memory impairment disorder such as Alzheimer’s or a motor skills disorder such as Parkinson’s.
Those with Alzheimer’s tend to perform poorly when trying to draw a clock from memory, tending to draw larger, more elliptical clock faces, omitting numbers and forgetting the time they were asked to draw. Those with Parkinson’s tend to draw much smaller, narrower and scruffier clock faces with signs of having struggled to control their hand movements. Researchers from Massachusetts Institute of Technology and other US universities said: “While there is a variety of well-regarded manual scoring systems, these often rely on the clinician’s subjective judgment of under-specified properties of the drawing.”
Rather than asking doctors to judge by eye whether there has been a “minor distortion” on the shape of the clock or whether the hour hand is “clearly shorter” than the minute hand, the Anoto Live Pen — available for $249 (£159) and commonly used to digitise sketches or signatures — can measure the exact length of the hands, the precise distortion of the clock face and the position of all the numbers.
It can also record “every stroke, pause or hesitation” from the patient, adding a new layer of analysis to the test.
Researchers used the pen in 2,600 tests over nine years and found that those with Alzheimer’s spent more time thinking about what they had to draw before putting pen to paper and also left a long gap between placing the numbers on the clock face and deciding where to place the hands. Those with Parkinson’s tended to take much longer over the process of drawing the clock and used a higher total number of strokes.
Cynthia Rudin, a professor at MIT, told MIT News: “We’ve improved the analysis so that it is automated and objective. With the right equipment, you can get results wherever you want, quickly and with higher accuracy.”
Eric Karran, a director at Alzheimer’s Research UK, said the clock-drawing test was only one in a series of methods used in diagnoses, but said: “Harnessing new technology to provide more accurate diagnoses is always welcome, although it will be important to test this device in a larger number of people and in multiple medical centres. Improving the accuracy and timeliness of a dementia diagnosis is crucial to help people receive the right support, access treatments and receive opportunities to take part in clinical research.”
Cardiac Repair
A potentially revolutionary treatment has been developed that promises to help cardiac muscles to heal after heart attacks.
Scientists have used a small patch to deliver a protein to the outside of mammalian hearts, aiding the growth of healthy muscle cells rather than forming the scar tissue that makes it less able to pump. If the research in pigs and mice is shown to be successful in humans, it could offer a way of returning people to health after heart attacks without leaving the scarring that forever degrades the ability of the heart.
After a heart attack, there can be significant damage to the muscles, which die owing to lack of blood flow. The body responds by creating scar tissue, which cannot pump and does not contract, leaving people considerably more vulnerable to fatal heart attacks in the future.
For the study, published in the journal Nature, scientists from Stanford University used a patch that secreted a protein called Fstl1. This protein is normally made in a layer of the heart called the epicardium, but is not made when the cells are damaged. Collagen patches were applied to the hearts of mice and a small number of pigs who had scarred hearts. Within a month, the hearts had markedly improved function. In some cases, hearts so damaged that in humans they would have been candidates for transplantation had been healed to the extent that they were no longer critically impaired.
“Current medicine is very good at saving lives,” said Pilar Ruiz-Lozano, from Stanford. “However, the injury that has been done with the heart attack remains.
“Current medicine preserves only the muscle that is left. This medicine, however, is killing the injury. Instead of the scar left after a heart attack, it will replace the scar with healthy tissue.”
Professor Ruiz-Lozano hopes to extend the research to humans, with plans to carry out the first clinical trials within the next two or three years.
One aspect they would be looking to test was whether the patch reduced the rate of follow-up heart attacks. Even if it does not, she thinks that it could still represent a significant advance.
“It would probably prevent a second attack. What it would do anyway is increase the quality of life of people who have had heart attacks.”
Christopher Allen, senior cardiac nurse at the British Heart Foundation, welcomed the research, but said that it was still in its early days and that more study was needed. “There is currently no cure for heart failure, and in its severest form the chances of surviving for more than five years are worse than many forms of cancer,” he said. He added that the research “potentially provides another piece of the puzzle that may lead to a cure for heart failure in years to come”.
US Drug Prices
What with a former peanut-company owner, Stewart Parnell, being sent to prison for knowingly selling salmonella-tainted peanut butter, and Volkswagen’s C.E.O., Martin Winterkorn, resigning after revelations about the cheat software in the firm’s diesel-powered cars, it took a special magnitude of corporate misbehavior to make the business-news headlines in the past couple of weeks. But Martin Shkreli, the C.E.O. of Turing Pharmaceuticals, managed it when his company said it was raising the price of a sixty-two-year-old lifesaving drug from $13.50 to seven hundred and fifty dollars a pill. The move quickly became a major scandal; Shkreli was called “the most hated man in America.” Yet the true scandal of Turing’s profiteering scheme was that it was entirely legal.
Daraprim—which is used to treat toxoplasmosis, a condition that afflicts AIDS patients, among others—first came on the market back in 1953, so it has long since gone off patent. But what Shkreli recognized was that, even with a generic drug, regulatory barriers and a lack of competition can make big price hikes possible. In Daraprim’s case, only one company had regulatory approval to sell the drug in the United States. So, in August, Turing bought those rights. Shkreli knew that, in principle, other companies could produce their own versions of Daraprim. But it seemed a fair bet that none of them would try. The market for Daraprim is small—eight to twelve thousand prescriptions a year in the U.S.—and any company that wanted to enter the market would have to go through the expensive and time-consuming process of getting F.D.A. approval. As it happens, several companies already make and sell a generic version of Daraprim abroad, but they weren’t a worry, either, because they, too, would have to jump through the F.D.A.’s hoops to sell it here. Turing loaded the deck even further in its own favor by insisting on a model of “closed distribution” for the drug, restricting access to patients, doctors, and a limited number of distributors and pharmacies. In the unlikely event that another company wanted to produce Daraprim, it would be hard to buy enough of the drug to reverse-engineer.
Essentially, Shkreli is exploiting rules devised to protect consumer safety in order to create a virtual monopoly and then charge whatever he wants. Monopolies are inherent to the drug industry in the U.S.: patents, in effect, are temporary monopolies. But we have patents because they give drug companies an incentive to invest in developing new drugs. There’s no such justification in the case of Daraprim. Turing’s price gouging does not reward innovation and it doesn’t reflect the cost of production. In the United Kingdom, Daraprim sells for less than a dollar a pill.
Turing’s business model is a quintessential example of rent seeking: increasing profits not by adding real value for customers but by exploiting loopholes. And, unfortunately, Turing is not alone. Last year, another company run by Shkreli acquired the rights to a kidney-disease drug called Thiola and raised the drug’s price twentyfold. In 2011, K-V Pharmaceutical got F.D.A. approval to market a synthetic hormone that had been used for decades to prevent preterm births. Once K-V got approval and exclusive rights, it raised the price from around fifteen dollars to fifteen hundred dollars an injection. There have also been alarming increases in the prices of common drugs like doxycycline. Generic-drug makers have been merging with each other, leaving fewer competitors. “Without price competition, the generic model fails,” Gerard Anderson, a professor of public health at Johns Hopkins, told me. “Without competition, there are no market forces that limit price increases.”
That doesn’t mean there’s nothing to be done. In place of closed distribution, the F.D.A. can require companies to make samples of their drugs available to competitors. The F.T.C., as Anderson argues, should be more aggressive in limiting mergers among generic-drug makers. And the U.S. and other developed countries should also adopt an arrangement known as regulatory reciprocity: if a drug maker has approval to sell a drug abroad, it should be able to sell that drug here, and vice versa. Safety concerns may rule out importing drugs from just anywhere, but there is no good reason for a company selling a drug in, say, Germany to have to spend time and money to get the right to sell it here. Foreign competition has played a central role in holding down retail prices in industries ranging from automobiles to consumer electronics. It’s time drug prices were subject to the same rules. Shkreli has said, since the backlash, that Turing will roll back the Daraprim price increase. But the fate of toxoplasmosis sufferers shouldn’t depend on the egomaniacal whims of a “pharma bro.”
Of course, these kinds of measures would make drug companies anxious, but they should be doing all they can to encourage competition, if only out of self-interest. If market forces and smarter regulations can’t limit price gouging, then drug makers could be subject to more drastic measures, like price controls or compulsory licensing—a system that compels companies to license drugs to other manufacturers. The Turing scandal has shown just how vulnerable drug pricing is to exploitative, rent-seeking behavior. It’s fair enough to excoriate Martin Shkreli for greed and indifference. The real problem, however, is not the man but the system that has let him thrive.
US Hypochondriacs
Hypochondria among Americans may be jeopardising the development of new medicines, as a study reveals that the placebo effect is becoming worryingly powerful in the US.
Huge American drugs trials are increasingly foundering on the unexplained scientific phenomenon, which does not appear to be happening anywhere else in the world.
The findings leave US drugs companies with a serious dilemma. As the difference between receiving a new painkiller and simply thinking that you are receiving a new painkiller evaporates, it is becoming ever harder to tell whether the drug works or not.
This may explain why more than nine out of ten new pain-relief drugs fail at the testing stage.
Researchers in Canada have found that it is becoming harder for US doctors to distinguish between the effects of experimental painkillers and sham capsules of white powder.
An analysis of 84 US trials to be published in the journal Pain showed that between 1996 and 2013 the gap in effectiveness between painkillers and placebos shrank from 27 per cent to 9 per cent. There was no such effect elsewhere.
Jeffrey Mogil, head of the pain genetics lab at McGill University in Montreal, who led the work, said the shock was not that the placebo response seemed to be getting stronger, but that it was happening only in America. He added: “It’s probably simply that American trials can be more expensive because US pharmaceutical companies are bigger and have more money to spend than their counterparts elsewhere. Or perhaps because the US FDA (Food and Drug Administration, the country’s main medicines watchdog) is more demanding than elsewhere. But curiously our data suggest that in other countries, size and length of trials were not related to placebo response, which may actually suggest that there really is something different about American trial participants.”Another explanation may be the country’s heavily medicalised culture. About one in 20 Americans suffers from hypochondria and even minor ailments are treated with drugs.
Dr Mogil believes that drugs companies may have to abandon placebo trials. “The problem is that [the placebo response] is getting bigger but responses in the drug groups are not, such that the treatment advantage — drug minus placebo — is getting smaller.
“Ironically, the solution implemented thus far has been to increase sample size, which we show is actually making matters worse.”
Pharma Companies Suppressing Data
Pharmaceutical companies are lobbying to block the public release of clinical trial data in a move that campaigners say puts patient safety at risk.
A European transparency initiative is proposed to ensure that when regulators approve new drugs the full data from the trials would be publicly released, rather than just a summary published in a medical journal. The proposal comes after high-profile cases in which independent researchers found that drugs such as Tamiflu or the antidepressant Seroxat were more dangerous or less effective than pharmaceutical companies had claimed.
In the case of Seroxat, a GlaxoSmithKline drug, the full study reports were restricted. When researchers accessed the papers, they found that the drug was linked to self-harm and suicide in teenagers — even though the drug company’s summary of the research had said that it was safe and effective.
Campaigners have said that while all companies are ostensibly on board wit the reforms, some are now asking to be allowed to redact so much data before the release that it would effectively lead to the removal of all useful information. The pharmaceutical companies say that they are doing this to ensure that details of patients involved in the trial remain confidential. Other scientists argue that the approach effectively renders the whole exercise pointless.
“Healthcare professionals cannot reliably inform patients of the potential benefits and potential harms of medicines when the underlying clinical trial data is kept secret,” said Peter Doshi, from the University of Maryland school of pharmacy, who has campaigned for the release of all data. “Without raw data, we are left vulnerable to trusting at face value journal articles that may, in truth, be little more than marketing dressed up as peer-reviewed science.”
Tom Jefferson, a British researcher based in Rome who works for the respected Cochrane Collaboration, a volunteer health organisation, said that there was a moral, as well as a practical, necessity to change the regulations. He said that the transparency initiative would be undermined if much of the data were redacted. “If you carry out an experiment on a human you have certain responsibilities,” Mr Jefferson said. “One of those is that you shouldn’t suppress data.” Both scientists said that it should be possible to make the patients anonymous without rendering the research useless. “Journals have articles ten to 15 pages long,” Mr Jefferson said. “The underlying data set is tens of thousands of pages long. This means they can present the product in the best possible light — which is what they’ve been doing. We’ve got abundant, overwhelming evidence this is the case.”
Research released this year showed that when industry sponsors medical trials of its own drugs they are backed 97 per cent of the time. This is why the European Medicines Agency, a London-based umbrella organisation for national regulators, is working to introduce a voluntary code for the release of all data as drugs come to market, so that other researchers can reassess it as necessary.
Researchers involved in the discussions have told The Times that several companies want a strict approach to make this data so anonymous that, when applied to real-world examples, such as the Tamiflu research, it removes virtually all the information.
A spokesman for the European Federation of Pharmaceutical Industries and Associations said it was working to “balance responsible reporting for public health benefit and safeguarding patient confidentiality”.
Professor Doshi said it was imperative that the data remained usable. “After years, we finally have a system that’s soon to go live and make trial data public,” he said. “But at the last minute, there’s a move that could render the system useless.”
Statins - A Doctor's Verdict
The push to prescribe statins to an extra 4.5 million people, under National Institute for Health and Care Excellence (Nice) guidelines has left me in a quandary. It is perplexing because not only have I started some of those people on the drugs, but I am eligible myself. So why am I not leading by example?
Until recently statins were prescribed only to those deemed to be at high risk of stroke or heart attack, either because they had already had one or because risk calculators (see below) predicted that they had a 20 per cent or more chance of “an event” over the next ten years. On the whole, doctors agreed. Yet last year Nice lowered the bar to 10 per cent to include nearly a third of the adult population over the age of 40. Do they all need medication?
Most GPs appear to think not, which prompted a report in The Times last week that said people could be dying prematurely. Nice predicts that its guidance could prevent 2,600 deaths yearly, so why are GPs reluctant? I can’t speak for colleagues but I can share my experiences as both GP and patient. Putting millions more on statins may make sense at a population level but what about the patient sitting in front of me? Are they going to be one of the few whose heart attack or stroke is delayed, or in the minority for whom side effects (from muscle aches to diabetes) make matters worse ?
In truth they are most likely to end up in the majority of those who take statins yet derive little or no benefit. Depending on which research you believe I would have to put at least 100 patients in the 10-20 per cent risk range on statins for five years or more to prevent one of them dying from a heart attack or stroke. Fine for that lucky one, but not so clever if you are one of the ten who end up with side effects. And I have no reliable way of predicting who is going to be lucky.
Because of a combination of poor family history and a high cholesterol level my risk is now above the new lower threshold. My GP’s calculator predicts that if I start a statin today it could delay my first stroke or heart attack by three years (from 77 to 80) — a benefit that diminishes the longer I procrastinate (1.7 extra years at 65).
Tempting, but not tempting enough given my concerns. First, statins work in a relatively crude fashion and lower cholesterol levels by throwing a spanner into an important metabolic system that has evolved to do far more than clog up my arteries. I am not convinced we yet fully understand all the ramifications. To be fair, I have tried statins and, other than vivid dreams and a few memory lapses, I didn’t notice any side effects. My struggle to remember the names of a few drugs may just have been a reflection of my workload during the time I was on them, yet my memory improved when I stopped taking them so I am reluctant to restart.
My second concern is the crudeness of the calculators. They may reflect what is likely to happen to 1,000 people like me, but that doesn’t mean it is accurate for me. And, crucially, they take no account of diet or exercise patterns. So I am treating the threshold as a wake-up call. I am going to exercise more frequently and giving my otherwise healthy patients in the 10-20 per cent category similar advice — opt for lifestyle changes and a Mediterranean diet first, pills second.
I’ll probably take statins one day, but not just yet. I hope I don’t regret it.
A Dust Pill
Millions of Britons who suffer from dust allergies could be offered a lasting cure within a year after successful trials of a pill made from mites.
The daily tablet, which builds up the body’s tolerance over several months, would supersede injections and could also relieve the symptoms of asthma.
As many as 12 million Britons are thought to struggle with ailments brought on by dust mites, with symptoms including wheezing, disturbed sleep and inflammation. At present, some sufferers are offered jabs to boost their immune systems against the allergy. Most have to make do with antihistamines that offer temporary relief.
A pill consisting of freeze-dried dust mites that dissolves under the tongue could prove to be a cheap alternative, a growing body of scientific evidence suggests. The treatment has been approved by the European drugs watchdog and experts believe it could appear in British pharmacies next year.
The pill, officially known as house dust mite sublingual immunotherapy, has been developed by the pharmaceutical companies Merck and ALK.
It acts like a vaccine, gradually making the immune system accustomed to dust mites. It begins to ease the symptoms within three to four months, according to a clinical trial released this year that involved almost 1,000 European adults.
The results from another trial, published last weekend in the Annals of Allergy, Asthma and Immunology, appear to show that it is safe for most teenagers, although many had minor irritation in their mouths and eyes. Two patients had life-threatening allergic reactions.
Other tests indicate that it could be a potent treatment for asthma, which affects 5.4 million people in Britain and is often closely linked to dust. The tablet seems to be a particularly effective treatment for those whose asthma cannot be controlled with inhalers.
Hendrik Nolte, a scientist at Merck who has played a leading role in developing the drug, said one study had shown that it cut the number of asthma attacks by a third. The pill won approval from the European Medicines Agency in August and will soon go on sale in 11 countries including France, Germany and Italy.
Sofia Grigoriadou, clinical secretary of the British Society for Immunology and a consultant immunologist at Barts Health NHS trust in London, said she expected British regulators to follow suit. “It’s definitely something that’s going to be coming forward,” she said. “This [latest] paper is a safety trial but there’s good evidence that this treatment is working for adults, it’s improving the symptoms of rhinitis [inflammation in the nose] and as a consequence works for asthma.”
Dr Grigoriadou said that the side effects experienced by many patients during the first fortnight of treatment, including swelling of the throat and mouth and itchy eyes, were a downside. For the significant minority whose quality of life was seriously spoiled by their allergy, however, the tablet provided a major improvement, she added.
Blood Test To Detect Prostate Cancer
A simple blood test could spare thousands of prostate cancer patients from unnecessary and risky surgery.
Prostate cancer is the most common cancer in British men, with more than 25,000 new cases of the disease and 10,000 deaths every year.
More than four out of five malign prostate tumours are graded as “low risk”, but each year several thousand men with these cancers opt to have the gland cut out in an operation that carries a significant risk of infertility, impotence or incontinence. Fewer than one in ten of these procedures is thought to be necessary, but it is very difficult to work out which patients would die if they were not treated.
Cancer researchers, led by the University of Copenhagen, have discovered a chemical that marks which lowgrade prostate tumours are likely to carry a significant risk of death if the gland is not removed. The scientists looked at the proteins in 28 samples of cancerous prostate tissue and noticed that one of these complex strings, known as pro-neuropeptide Y (pro-NPY) appears at much higher levels in aggressive tumours. When they measured the protein in biopsies from 750 Scandinavian men with “low-grade” prostate cancer, they found that those with high levels were more than twice as likely to die from the disease.
Amilcar Flores Morales, professor of molecular disease biology at Copenhagen, said this suggested that proNPY was a “biomarker” that doctors could use to pick out the minority of patients who would benefit from the prostate surgery. Because pro-NPY also circulates in the bloodstream, Professor Flores Morales believes his team could use it to develop a simple blood test to gauge the risk of death.
The study is published in the journal European Urology.
Prostate Cancer and Testosterone
A blood test could be used to determine how advanced prostate cancer is, giving men the choice of undergoing drastic surgery or letting the disease take its course.
By testing the levels of testosterone in the blood doctors have now discovered that they are able to see how aggressive the cancer is before performing surgery.
Many men with advanced stages of prostate cancer have operations to remove the prostate but, even after this, relapse is common and survival rates are poor. According to the Italian doctors behind the discovery, a blood test could be used before surgery to inform patients about the severity of their disease.
Aggressiveness of the cancer is measured by examining a tissue sample of the prostate, taken from a biopsy, to see how much of the sample has been taken over by cancer cells. This is known as the Gleason score, and can help to determine the best course of treatment and possible outcomes.
Researchers in Milan have now found that low levels of testosterone indicate that the patient will have a high Gleason score, which indicates a poor outcome after treatment.
A group led by Marco Moschini, a urology expert at San Raffaele hospital, retrospectively correlated hormone levels and Gleason scores in 1,017 patients who underwent radical surgery to remove their prostates. he results, presented at the European Association of Urology (EAU) in Munich, showed that 118 of these patients had a Gleason pattern 5 — the highest score.
Dr Moschini said: “This association will allow us to predict what the outcome will be before we decide to treat a patient with surgery. Potentially this can be helpful to identify patients with the most aggressive prostate cancer before surgery. There is an urgent need for new research to uncover the role which hormones play in prostate cancer development. “What we don’t yet know is if this is an association, or if hypogonadism [low levels of testosterone] in some way increases the risk of developing highgrade prostate cancer. If this is the case, then it may be that treating the hypogonadism can lessen this risk, but we need more work before we can be sure of that.”
Prostate cancer is the most common cancer in men and the second highest cause of cancer deaths, with 30 men dying from it each day, the majority of whom are over 65. More than 100 men are diagnosed with prostate cancer each day and rates of diagnosis have increased by 10 per cent in the past five years.
Alexandre de la Taille, a professor with the EAU scientific congress committee, said: “Several reports in the literature mention that low serum testosterone level is associated with prostate cancer aggressiveness.“This study highlights the fact that SHBG [sex hormone-binding globulin] is also linked to high Gleason score. These cancers, developed in this special hormonal environment, are probably due to different molecular pathways and represent a new field to explore.”
Malcolm Mason, a professor and prostate cancer expert at Cancer Research UK, said: “There is a need to develop better tests to identify men with aggressive prostate cancer. “This study is part of a bigger picture, with researchers exploring a number of different approaches to better predict aggressive forms of the disease, including imaging with MRIs, and other new tests.
Toxoplasma and Humans
Road rage and other acts involving a sudden loss of self-control could be linked to a parasite spread by cats.
Infection by Toxoplasma gondii doubles the chances of suffering bouts of uncontrollable anger, a study found.
People with intermittent explosive disorder (IED) are liable to display outbursts of violent rage which are disproportionate to the provocation received — for instance, when annoyed by another driver on the road.
Scientists who assessed 358 US adults found that 22 per cent of those diagnosed with IED also tested positive for T. gondii. In non-infected individuals only 9 per cent had the condition.
Emil Coccaro of the University of Chicago, the lead researcher, said: “Our work suggests that latent infection with the parasite may change brain chemistry in a fashion that increases the risk of aggressive behaviour. We do not know if this relationship is causal, and not everyone that tests positive for toxoplasmosis will have aggression issues.”
Many people are believed to carry the parasite, found in cat faeces and contaminated food, without realising it.
Each year about 350 cases of toxoplasmosis are reported in England and Wales, but experts believe the number of infections could be a thousand times greater. Some estimates suggest that up to a third of people in the UK will be infected at some point in their lives.
Often, the parasite causes no symptoms, but it can lead to miscarriages, birth defects, and cause serious illness in people with weak immune systems.
It has been linked to psychiatric conditions including schizophrenia, bipolar disorder and suicidal behaviour. Roughly a third of those in the study had IED, another third had some other psychiatric condition such as depression or personality disorder, and the remainder were healthy individuals with no history of mental problems. Toxoplasmosis-positive individuals scored significantly higher on measures of anger and aggression.
Co-author Royce Lee said: “Correlation is not causation, and this is not a sign that people should get rid of their cats. We don’t yet understand the mechanisms involved. It could be an increased inflammatory response, direct brain modulation by the parasite, or even reverse causation where aggressive individuals tend to have more cats or eat more undercooked meat. Our study signals the need for more research and more evidence in humans.”
IED is thought to affect up to 16 million Americans, said the scientists whose findings are reported in the Journal of Clinical Psychiatry.
Placebo Power
Medicine is finally taming the strange power of the placebo. LINDA BUONANNO had been sick with irritable bowel syndrome for 15 years when she saw a TV advertisement recruiting participants for a new study. Desperate for help, she signed on, even after learning that the potential treatments she would be offered consisted of either nothing – or pills filled with nothing.
When the experiment ended, she begged the researchers to let her keep the pills. “I felt fantastic,” Buonanno says. “I felt almost like I was before I got sick with IBS. It was the best three weeks of my life.”
She has been trying to get her hands on more ever since. A replication study will start later this spring, and Buonanno is desperately hoping she gets in.
This is the placebo effect in action, and it may come as a surprise to learn that it works even when people know they are being given a sham treatment. That finding has brought with it the possibility of using placebos as therapy. The vision is of a future in which clinicians cajole the mind into healing itself and the body – without the drugs that can be nearly as much of a problem as those they purport to solve.
But before your doctor can prescribe you one of Buonanno’s pills, a lot of slippery questions must be tackled: what conditions respond to the placebo effect? Where are the boundaries of this nascent science? More importantly, can we harness it with predictable effects?
The placebo effect has been on a considerable journey: once just a thorn in medicine’s side, it is now the latest promising way to manipulate the mind into healing the body. Placebo controls are the gold standard of clinical trials, used to figure out whether a drug works better than nothing – but instead of obeying the rules and feeling no different when given a placebo, people often report beneficial effects.
“In drug trials, the placebo effect is the background noise they have to separate out,” says Ted Kaptchuk, the lead researcher behind Buonanno’s trial at Beth Israel Deaconess Medical Center in Boston. “But we’re saying, this noise is really important. We want to get that noise in the equation too.”
We now know that when a person is given a pill they’re told is a real medication, or any of a wide range of medical interventions, including surgery, their body creates a real physiological effect. In pain studies, placebos have been shown to dampen activity in the brain’s pain-processing areas and increase the production of the body’s own analgesic chemicals).
It may not be so surprising that pain should succumb to the power of suggestion, but the placebo effect also works on conditions that would not be considered to have a psychological component. People being treated for Parkinson’s disease with apomorphine, were only told they might receive a dose of the drug. They showed more dopamine activity in parts of their brain normally affected by the real drug. Not even the immune system is immune: in one experiment, healthy participants spent three days taking pills containing immunosuppressant cyclosporin A – a drug used to help stop the body rejecting an organ transplant – with a fruit-flavoured drink. Five days later, they took placebo pills with the same drink. Blood tests showed that immune compounds suppressed by the actual drug also dropped with just the placebo and drink. Even faked surgical interventions have been shown to create real improvement.
Great expectations
One key to unlocking the body’s self-healing mechanisms seems to be the setting up of an expectation of improvement. And it works the other way too: if you think your drug has been replaced with a placebo, even a strong painkiller’s effects will be dulled. So how can we harness this effect, given that we know very little about how it works? In pursuit of that goal, Kaptchuk founded the Program in Placebo Studies, while groups in Germany, the UK, Italy and Australia are also studying how to integrate placebo insights into patient care.
There’s just one problem: using placebo in this way requires deceit, which falls foul of several major pillars of medical ethics, including patient autonomy and informed consent. That was why Kaptchuk decided to try being honest with patients, and how Buonanno found herself taking pills packed with inert filler from a bottle marked “placebo”.
IBS is one of those conditions, like depression and chronic pain, that is heavy with symptoms but has neither clear biological cause nor easy cure. Buonanno had spent years in pain; and no doctor or drug seemed to help.
The staff at the medical centre had explained to her that though the brightly coloured pills contained no medication, evidence from previous studies suggested that placebos could exert real effects in IBS by provoking a response from patients’ own bodies. If she wanted to maximise the placebo’s chance of working, they told her, it was important she take the pills exactly as instructed, twice a day. On the fourth day, she realised that her symptoms were gone.
“Placebos also work on conditions not thought to have a psychological component”
Why does the honest placebo work? One theory concerns the expectations set by the intervention itself. “It’s not just the drug, it’s everything that surrounds the drug,” says Kaptchuk. Placebos are not inert substances: they are made of verbal suggestion, classical conditioning, and a lifetime’s associations learned about the cues of the medical ritual: the white coat, the office, the doctor’s manner. (Nature Reviews Neuroscience, vol 16, p 403). Any and all of these may cue the body’s healing powers.
The key word is “may”: the placebo can be difficult to use. It doesn’t work for everyone, and when it does, its effects can be unpredictable. In one pain study, for instance, some people reported feeling more pain, not less, and activity in their brain’s painkilling opioid and dopamine systems decreased, instead of increasing like everyone else’s. Another study flummoxed researchers by creating almost the opposite effect of what they intended: verbal suggestions intended to reduce nausea in one group and promote it in the other muddled the effects, not only subjectively but also physiologically.
Even when the results go your way, it’s hard to understand why. In the small trial Buonanno participated in, 59 per cent of the honest-placebo group felt better. It wasn’t much better than… placebo?
Much research is now under way to pin down what exactly makes any individual susceptible to the placebo response. Some studies implicate personality traits like optimism and a belief that you control your own destiny. Or is it suggestibility? “He’s such a good doctor,” Buonanno says of the study gastroenterologist. “So I said OK, I’ll do anything to make anything work.” Would her symptoms have still improved if she’d been more sceptical?
Other work is investigating whether any genetic links underlie the placebo response. One of Kaptchuk’s collaborators, Kathryn Hall, has found a link between placebo responses in IBS and variations of a gene that breaks down neurotransmitters including dopamine and adrenaline.
And some are even looking into doctors’ brains. Vitaly Napadow, a neuroscientist at Massachusetts General Hospital, plans to looks at the brains of physicians and patients simultaneously while he approximates a doctor-patient encounter – albeit with both parties in separate fMRI machines. If it works, this could begin to tease out what brain areas are involved when the doctor gets the placebo right.
In the meantime, there are already a few things doctors can do to exploit the placebo effect in clinical settings. In Germany, the Placebo Competence Team publishes suggestions for physicians. For example, giving a patient sufficient medical information helps, along with instructing them not to Google their symptoms. It’s also important to tell a patient which medications they’re taking and why. “It sounds trivial,” says Ulrike Bingel, one of the placebo team, at the University of Duisburg-Essen, Germany. But in post-operative wards, people are often hooked up to multiple IVs. “Is this a painkiller, is it a steroid, an antibiotic? If the patient doesn’t know, you might lose 50 per cent of the effect.”
One form of placebo conditioning has recently had promising results, and could form part of a programme to wean people off opiate painkiller addiction (see “Sleeping it off”, page 32). Buonanno’s experience hints at the power of these associations: after the study ended, she tried to continue the effect with substitute placebos from health food stores. But they didn’t look the same, and they hadn’t been prescribed to her. “Nothing” failed.
So why had it worked in the initial trial? Was it the form of the pills? The empathetic staff? The medical environment?
This spring, the new study aims to find out. Kaptchuk’s group will repeat the IBS trial, but this time it will include genetic testing, along with in-depth psychological interviews to unravel exactly which expectations and beliefs make the difference. Every word uttered by the staff will be carefully scripted to minimise the wrong impression.
While expectations come in many forms, one might be the biggest of all. “If we’re ever going to use placebos in clinical practice, they can’t be the booby prize,” Kaptchuk says. “We have to change the culture and meaning of the word placebo.”
Linda Buonnano is a good start.
Pseudoscience From Greenies Over Glyphosphate
Science, humanity’s greatest intellectual achievement, has always been vulnerable to infection by pseudoscience, which pretends to use the methods of science, but actually subverts them in pursuit of an obsession. Instead of evidencebased policymaking, pseudoscience specialises in policy-based evidence making. Today, this infection is spreading.
Two egregious examples show just how easy it is to subvert the scientific process. The campaign by Andrew Wakefield against the MMR vaccine, recently boosted by Robert De Niro’s support, is pseudoscience.
So is the campaign against glyphosate (“Roundup”) weedkiller, which has now resulted in the European parliament recommending a ban on its use by gardeners.
A large dossier claiming to find evidence that glyphosate is “probably carcinogenic” was published last year by the International Agency for Research on Cancer (IARC), part of the World Health Organisation. What could be more scientifically respectable?
Yet the document depends heavily on the work of an activist employed by a pressure group called the Environmental Defense Fund: Christopher Portier, whose conflict of interest the IARC twice omitted to disclose. Portier chaired the committee that proposed a study on glyphosate and then served as technical adviser to the IARC’s glyphosate report team, even though he is not a toxicologist. He has since been campaigning against glyphosate.
The IARC study is surely pseudoscience. It relies on a tiny number of cherry-picked studies, and even these don’t support its conclusion. The evidence that it causes cancer in humans is especially tenuous, based on three epidemiological studies with confounding factors and small sample sizes “linking” it to Non-Hodgkin lymphoma (NHL). The study ignored the US Agricultural Health Study, which has been tracking some 89,000 farmers and their spouses for 23 years.
The study found “no association between glyphosate exposure and all cancer incidence or most of the specific cancer subtypes we evaluated, including NHL . . .”
Many other studies found very little cancer risk from glyphosate use, but the IARC argued that they included some data generated by industry. Well, of course they did, because we rightly demand that industry, not the taxpayer, pays for and does the safety testing of its products and makes the results public. The IARC appeared to ignore work by the German Federal Institute for Risk Assessment, managing the glyphosate dossier for the European Commission, which judged glyphosate safe. As did the European Food Safety Authority, whose head accused the IARC and Portier of bringing in the “Facebook age of science”.
When Portier’s role and the IARC’s findings were revealed by David Zaruk, who blogs under the name the Risk-Monger, pressure started coming from many groups to censor his science-policy blog.
The publisher EurActiv was forced to shut down Zaruk’s entire blog in the week of the European parliament vote. This is how Big Green behaves in Brussels, routinely.
Dose for dose, glyphosate is half as toxic as vinegar, and one tenth as carcinogenic as caffeine. Not that coffee’s dangerous — but the chemicals in it, like those in virtually any vegetable, are dangerous in lab tests at absurdly high concentrations. So is dihydrogen monoxide, for that matter, if you inhale it, drink it to excess or let its gaseous form burn your skin (that’s H2O, by the way).
Besides, risk is hazard plus exposure, a point ignored by the IARC. If you routinely put coffee down your throat, you are exposing yourself to the infinitesimal hazard caffeine represents. If you spray a little Roundup on your garden path, you are not even exposing yourself to the more infinitesimal hazard of glyphosate.
Roundup is probably the safest herbicide ever, with no persistence in the environment. But the Green Blob hates it for three reasons. It’s off-patent and therefore cheap. It was invented by Monsanto, a company that had the temerity to make a contribution to reducing famine and lowering food prices through innovation in agriculture. And some genetically modified crops have been made resistant to it, so that they can be weeded after planting by spraying, rather than tilling the ground: this no-till farming is demonstrably better for the environment, by the way.
Under the influence, at least in part of the IARC report, the European parliament voted last week to advise the commission to ban glyphosate immediately for “non-professionals” — ie gardeners — but allow it for seven years for farmers. However, a lie is halfway round the world before the truth has got its boots on: already retailers worldwide are dropping glyphosate, Waitrose included.
Much the same happened with the ban on neonicotinoid pesticides, which was pushed through Brussels by a tsunami of angry emails from greens, in the teeth of clear scientific advice that honey bee numbers were increasing and that alternative insecticides were worse.
James Gurney, a microbiologist who blogs on a site called the League of Nerds, describes the level of scholarship in the IARC report as “on a par with Andrew Wakefield of MMR/autism fame”.
In the case of Mr Wakefield’s claim that the measles, mumps and rubella (MMR) vaccine causes autism, the push-back against pseudoscience largely succeeded in this country, though not before real harm had been done. Journalists found that Mr Wakefield had failed to declare financing from lawyers preparing to sue vaccine makers and had taken blood samples at his own children’s party; further research failed to replicate his results. His paper was retracted and he was struck off the medical register, the General Medical Council calling him dishonest and irresponsible. His message is now falling on fertile ground in the United States, however, where measles epidemics have resumed as a result.
In both these cases, superficial plausibility is lent to the scares by history. Earlier pesticides were more dangerous: copper sulphate (still used as a fungicide by “organic” farmers) is toxic; DDT insecticide did wipe out predatory birds; paraquat herbicide was used in suicides. But Roundup is far, far less dangerous than these.
Likewise, early vaccines did carry risks. In the 1950s polio vaccines, grown in monkey tissue, were contaminated with SV40, a virus associated with cancer in monkeys. Many children were infected with the virus as a result. Fortunately, SV40 proved neither infectious nor carcinogenic in human beings, but it was a bullet dodged. Today such contamination is impossible.
Pseudoscience is bad enough when it infects astrologers, 9/11 truthers and crop-circle makers. But when its symptoms show up in mainstream bodies, such as the World Health Organisation, it’s time to be worried.
Ultrasound to Zap Prostate Tumours
A device that allows a concentrated beam of soundwaves to kill tumours while leaving the surrounding cells unharmed is being tested on British prostate cancer patients.
After years of setbacks, researchers believe that they have found a way to turn the “zapping therapy” into a viable alternative to surgically cutting out the prostate gland, which can leave men with incontinence or erectile dysfunction.
Each year more than 47,000 men in Britain are diagnosed with the disease and 30 die from it every day. It is the second most common cancer in the country after breast cancer. About one in 12 patients — nearly 4,000 a year — go under the knife, with many having the gland removed altogether in spite of the risks.
Scientists have found that they can kill the cancer using ultrasound. Soundwaves at frequencies higher than humans’ hearing range can pass harmlessly through the body, but they are able to cook cells at up to 90C (194F) when they are concentrated on a particular point.
Although this technology, known as high-intensity focused ultrasound (Hifu), has been used experimentally for more than a decade many doctors have found it difficult to implement because the steel in the ultrasound device often disrupts the magnets in the MRI scanner that is used to guide it. This means that some parts of the cancer can survive the treatment. Health regulators will not endorse the technique until there is better evidence that it works.
However, these problems may have been fixed with a new model of the Hifu device that does not contain any steel.
Doctors at St Mary’s hospital in London have begun testing the device on patients and believe that as many as 6,000 British men could benefit from it each year. After a patient is given general anaesthetic, the doctor then inserts an ultrasound scanner and the new Hifu projector. The scanner picks out the tumour, where the vibrations from the Hifu converge and heat up the cancerous cells until they die.
Mathias Winkler, a consultant urologist who is working on the study, said that the new approach was much more precise and could save the NHS thousands if it became a robust alternative to prostate surgery. “At the moment it’s a bit like being an archer who is told he can look and take aim at a target, but only fire after being blindfolded,” Mr Winkler told The Mail on Sunday.
“Using both machines simultaneously is like taking off that blindfold. By being more precise, we hope to achieve higher cure rates with Hifu, with a lower cost to the patient in terms of reduced quality of life.”
Treat Sugar Like Tobacco
Holiday time and there’s a sound that I’d forgotten till I was thinking about this piece yesterday. It was to be heard in the first moments after the seatbelt signs went off as your resort-bound plane became airborne. It was the rasp and click of several dozen cigarette lighters.
We smoked on the beaches, in the fields, in the streets, in the hills. We smoked in the trains, the planes, the taxis, the stations, the offices, the factories, the cinemas, the theatres, the stadiums and the open-air swimming pools. And now we smoke in none of these places. Had you told a Briton in 1966 that her sons and daughters would grow up in a land that prohibited smoking in practically every public place, she’d have thought you mad. Yet that’s what we’ve done, interfering with the ability of the individual to live and destroy his life freely. The result has been a huge, almost incalculable benefit to public health.
Getting Britain to stop smoking involved four main drivers. The first was to increase taxes on the product to get people to buy fewer fags, pipes and cigars. The second was to make life difficult for the manufacturers by gradually stopping them from advertising. The third was to proselytise against smoking as a habit in schools, on cigarette packets themselves, and in public information campaigns of growing stridency. Smoking was bad for you and if you did it you were an idiot and you’d upset your kids.
The fourth and indispensable driver was to harass smokers almost wherever they went. In the 1970s bans started, almost invariably justified by the risk that smoking posed to others but in fact aimed at making it as hard as possible for people to indulge a legal but self-destructive habit. Smokers were driven out of offices into smoking rooms, then out of smoking rooms on to pavements. I finally gave up a quarter of a century of smoking when my office became smoke-free and I faced the prospect of standing in a doorway wearing an invisible sign reading “Incontinent Loser”.
Every ban was opposed at every stage and was delayed for a variety of conservative, libertarian and even quasi-socialist reasons (“the worker’s last wee pleasure” etc). But the four drivers together eventually prevailed. We gave up smoking and we began to reap the health benefits.
Now we’re obese instead. Some of us (and here I look in the mirror) more than others. Cheap, available calories served up in ways that are delicious and pleasantly packaged, together with more sedentary lifestyles, have created a health crisis of a different kind. To take just one consequence of this combination of temptations, a reasonably robust recent academic study estimates that — on present trends — the cost of treating diabetes in the UK will increase from £9.8 billion to £16.9 billion by 2035. Those who saw the documentary Fixing Dad on BBC Two this week, in which two grown sons took it upon themselves to help their father with his diet-induced type 2 diabetes (he was looking at a foot amputation), will understand the cost to families of this condition and the effort required to reverse it.
Bad diet and poor exercise are more insidious problems than smoking because they are less discrete. One cigarette is a bad idea anywhere; one bag of crisps and an afternoon on the sofa isn’t. But theoretically the same rules of influencing people ought to apply. Folk are doing X which is incredibly bad for them, bad for their families and hugely expensive. How are we going to change it to Y?
Forgive me here, David Hockney and others, if I ignore those of you who argue that we shouldn’t try. There are millions of people alive today who otherwise wouldn’t be because they wore crash helmets, buckled seat belts and gave up cigarettes. They’re evidence enough. So the only question is what drivers we use in the anti-obesity campaign and how effective they are.
Here, what is interesting is that we have only deployed a few of the tools that we used in the smoking campaign. We’ve rather weedily targeted the food companies with labelling requirements, we’re bringing in a sugar tax in 2018 and we issue public health publications on weight loss and exercise. In these areas we could be much more aggressive.
We could ban the advertising of foods that contain too great a proportion of sugars and calories, enforce warning labelling (“This food is UNHEALTHY”) and allow manufacturers producing good food to market them more aggressively. We could specify the display of nutritional information in all canteens and workplace restaurants.
Then there’s nudging — the strategy in which you alter behaviour without people realising you’re doing it: segregated cycling and running lanes along our commuter routes and to schools; jolly signs on lifts urging people to use the stairs, and decorated stairwells and calorie measurements on the steps; an “escalator challenge”. And so on.
But we’ve left out the central idea of compulsion and perhaps it’s time to bring it in. Often things don’t change unless the community says, in effect, what it collectively thinks of a particular act — usually in the form of law.
Of course, we could try to attach the same opprobrium to being fat as to being a smoker. Some pundits (step forward Katie Hopkins) enjoy this idea and it has its attractions. I’m pretty convinced, though, that “shaming” people because of their weight would produce more harm in the shape of disorders, breakdowns and bullying than it would gain in altering behaviour.
Here instead is a grab-bag of ideas that would convey the same message, some or all of which will one day be enacted. Ban fast-food outlets from stations and airports. Ban the sale of confectionery and sugary drinks to the under-16s. Ban the sale of oversugared products in supermarkets (as measured by a ratio of sugar to other nutrients). Ban the bringing into schools of unhealthy foods. Ban the presence in offices (like our own here at The Times) of vending machines that seem to sell mainly crisps and chocolate. Specify a weight-to-height ratio limit on air passengers wishing to avoid a surcharge.
This all seems outlandish and dictatorial at the moment. So too, back in the late 1980s, did the idea that you wouldn’t be allowed to smoke on planes. Now try doing it, even in the loos. The cops would be waiting for you at the next stopover with some sparkly handcuffs and a charge. In 2016 we wouldn’t have it any other way.
IN 1347, an epidemic of unimaginable ferocity struck Europe. People first experienced flu-like symptoms, but within days painful swellings developed, which turned black, split open and oozed pus and blood. The Great Pestilence, later dubbed the Black Death, swept across the continent within four years, killing up to half the population. The disease persisted in Europe until the 1700s, always circulating somewhere, killing people off.
We speak of it nowadays as history. In fact, it is more like natural history: infectious disease is part of the ecology of our species. Until 1900, and despite considerable competition from violence and starvation, it was our biggest killer, causing half of all human deaths. Now, it accounts for fewer than a quarter of all deaths worldwide, most of them in poor, tropical regions. In rich countries it is only a few per cent. And the toll is falling.
But we shouldn’t be complacent: plagues will return. The 1960s notion that infectious disease was on the way out ended when HIV appeared in the 1980s. Since then, many infections like bird flu, SARS and Zika have caused alarm. But it took a near-disaster –the worst ever outbreak of Ebola – to scare the inertia out of governments. As a result, we are at last preparing for the inevitable. A clutch of programmes being launched this year will improve our grip on microbial killers. And the world now has an emergency medical response team – which, astonishingly, it never had before. But we aren’t there yet. If a novel virus struck now, we would still be in trouble.
For all our high-tech modernity, and in many ways, because of it, the risk that new infectious diseases will evolve is actually getting worse. Pathogens began circulating regularly among humans only after we started farming and settled in towns. One reason was that we caught infections from our livestock: flu from ducks, tuberculosis from cows. But crucially, there were enough of us in close proximity that a germ could always find a new host and keep spreading, persisting among people and adapting to us.
Now we are crowding into cities and travelling more, especially within the tropics where pathogen diversity is highest. That plus globalised trade, migration and climate change reshuffle wildlife, people and pathogens. Farms and towns invade the habitats of animals with viruses that can jump to us, or to our densely packed livestock, also booming as demand for animal protein soars.
Public health experts have been warning for years of “emerging” diseases, which can go from unknown to epidemic if the pathogen mutates or the ecology of its hosts changes to make its spread easier. And it is viruses that epidemiologists are most worried about. Bacteria can be deadly, and antibiotic resistance could mean diseases from gonorrhoea to ordinary bladder infections become incurable, but work has at least begun on new drugs. In contrast, viruses can evolve and spread faster, there are thousands we know nothing about, and we have few drugs against them. The worst emerging infections since 2000 have all been viruses.
None is more alarming than the 2014 outbreak of Ebola in West Africa. The virus infected 50 times more people than any previous outbreak, and reached big cities for the first time. As a bat virus still unaccustomed to humans, it spread fairly slowly, but an even slower international response allowed it to kill more than 11,000 people before old-fashioned methods, like isolating cases and quarantining their contacts, snuffed the outbreak out.
There was no other option. We were unable to produce a vaccine in time even though we already had experimental Ebola drugs and vaccines, and their deployment was accelerated, with regulation and manufacture taking months instead of the usual years. Researchers have since discovered that as it spread the Ebola virus was adapting to people, and getting better at transmitting. It almost spiralled out of control in Nigeria. “The world was close to an abyss,” says Tom Frieden, outgoing head of the US Centers for Disease Control and Prevention.
To combat the next plague, we will need vaccines, drugs and diagnostic tools – and just as importantly, some way to deploy them effectively. “We do not have that,” says Jeremy Farrar, head of UK medical research agency the Wellcome Trust. But we might if, in the wake of Ebola, we can build on momentum in three key areas: working out what the enemy is, arming ourselves against it and being ready to act forcefully and fast.
MRI Scan For Prostate Cancer
Hospitals in London have developed a faster, more accurate way to diagnose men suspected of having cancer of the prostate that could transform how the disease is managed. One-stop day clinics offering the new Rapid Access to Prostate Imaging and Diagnosis (Rapid) pathway were piloted in 2018 and, after promising results, are being rolled out across the city and, it is hoped, to the rest of the UK too.
The Rapid pathway not only speeds up diagnosis, the world-leading imaging and biopsy technology it employs makes the process safer and better at separating the men who require aggressive treatment (radiotherapy or surgery) from those who don’t. About a third of men referred to clinics using the system because they have a raised PSA (the blood test used by GPs to check for prostate issues) can be reassured within hours that they don’t have cancer, while those who need further investigation can start it earlier, typically the same day.
The pathway centres around the use of MRI and targeted biopsy of the prostate through the skin between the legs, rather than the conventional ultrasound sampling technique that involves passing needles into the prostate via the rectum. The MRI scan gives doctors a detailed view of the gland and can be used to rule out cancer in 25 to 40 per cent of men. If the MRI does highlight a suspicious area, the image can be overlaid on the ultrasound scanner used to direct the biopsy needles through the skin between the anus and scrotum and ensure that exactly the right area is sampled.
The conventional “blind” rectal approach used in most clinics is more random and can miss worrying areas or pick up other “insignificant” abnormalities that lead to unnecessary treatment. Yet, because of a lack of MRI scanners or experienced radiologists to interpret the images, one in four men seen in NHS urology clinics because of a raised PSA is still not having a scan before being offered a biopsy. And it’s not just the risks of being over or underdiagnosed that could harm their health. Rectal biopsy (pushing multiple needles through the faeces-covered anterior wall of the rectum) carries a 1 in 50 chance of serious infection, compared with 1 in 500 for the skin approach (transperineal). Indeed, in some studies as many as 1 in 12 men undergoing rectal biopsy went on to develop sepsis, itself a potentially life-threatening condition.
The latest guidance from the National Institute for Health and Care Excellence (2019) advocates the use of MRI as a second step in men being investigated for a raised PSA. However, this only applies to England, and the rest of the UK has been slower to meet this standard. Even within England there remains something of a postcode lottery. The situation with the safer transperineal biopsy is even more varied, with Professor Hashim Ahmed, the lead researcher on the Rapid team, estimating that only about a quarter of men are being offered it.
There are huge resource issues in rolling Rapid out across the whole NHS (not least in these strange Covid times), yet the lessons are clear. Results from the initial pilot build on convincing data from the earlier landmark Promis study that confirmed the benefits of MRI as a second step when investigating men and, if I were to have a PSA result that came back high, I would not agree to a biopsy unless I had an MRI. And if the scan confirmed that I had a suspicious lesion, I would want that biopsy done through the skin rather than through my backside, as would every urologist I know.
Faster, safer and more accurate diagnosis is essential if we are to have a national screening programme for prostate cancer, and better diagnostic pathways such as Rapid can only make the introduction of one more likely.
For more details of the Rapid pathway and the hospitals offering it, visit the NHS at tinyurl.com/yb42mdzq.
PSA is a protein produced by the prostate gland, and raised levels in the blood suggest a problem that can range from infection and age-related enlargement to cancer
PSA is not an accurate screening tool. Three quarters of men with a raised PSA do not have cancer, and as many as one in six men who do will have a normal PSA.
Despite advances in the diagnosis and treatment of prostate cancer, the proportion of British men who died from the condition has remained fairly constant for the past 50 years.
Last year there were just under 50,000 new cases diagnosed in the UK and nearly 12,000 men died from the disease
Exercise
Are you sitting comfortably? Well, get up! Stay healthy and supple by adding these basic movements to your daily routine
Things have changed a lot since the days when humans chased animals for food and had to walk long distances for water. But our bodies haven’t: we are still built to move in all the ways our ancestors needed to. Add in today’s personal transport, mechanical conveniences and screens that glue us to our chairs, and what do you get? Achy hips and backs, stiff necks, sore knees, and a significant downgrading of many markers of good health.
Generally, it is better to think about pain and discomfort in the body not as tissue damage or trauma but as a request for change. We have spent two decades coaching everyone from athletes to ordinary people who just want to feel better. We’ve found that motion can counteract the effects of modern living, enhance your capacity for easy movement and improve all the body’s systems (digestive, circulatory, immune, lymphatic). The following moves are basic body maintenance, and suitable for everyone. They are the key to being able to do all the things you love well into old age.
Motion can counteract the effects of modern living, enhance your capacity for easy movement and improve the body’s systems
Some of these moves you will already be doing; you may just need to do them a bit differently. And many of the others can easily be worked into your day. Stand on one leg while you brush your teeth. Sit on the floor to watch TV. Walk during phone conversations. And squeeze your bum while standing in a queue (no one will know). What you once thought of as idle moments are, in fact, little opportunities to move – opportunities that will add up to a big change in the way you feel. Do them daily or as often as you can.
Sit on the floor (three ways)
Spending 15 to 30 minutes a day sitting on the floor helps take your hip joints into ranges they don’t normally reach and loads your spine in advantageous ways. Both payoffs help undo some of the pain-inducing positions the body adopts when you sit in a chair for a freakish amount of time to work on a computer or binge-watch a box set.
We suggest switching between three positions:
1 Crisscross: sit with legs crossed in front of you, like you did at primary school.
2 90/90: sit with one leg bent at 90 degrees in front of you (your thigh straight out from your hip). Slightly resting on the front leg’s side of your bum, bend the other leg at a 90-degree angle so that its foot is behind you. Change sides after five minutes.
3 Long sitting: sit with your legs straight in front of you, back straight or with your torso leaning slightly forward.
Get up off the floor unaided
What goes down must come up, but can you get straight up off of the floor from a cross-legged position without holding on to anything or placing a hand or knee on the floor? Don’t worry if you can’t – it takes practice, but it’s worth working on: the ability to rise without assistance is not only a predictor of a longer life (research supports that acing this test correlates to decreases in all causes of mortality and morbidity), it’s an indicator that your body is stable, supple and efficient.
Squat
In some cultures, squatting is as common as sitting in a chair. It’s not seen as a strength training exercise, but is an innately human position that is beneficial for the knees, hips, back and pelvic floor. The ideal squat is with knees bent, bottom a few inches above the floor, hip creases well below the knees, toes pointing forward, and heels flat on the floor. If that’s too difficult, simply squat as low as you can go – feel free to hold on to a door or the back of a chair for stability – and hold for between five and 10 breaths.
Make like a bird
If you’ve ever practised yoga, you may be familiar with pigeon pose, another great move for your hips (like sitting crisscross). This setup is similar but easier, and just as effective. Place your right foot on a bench (or tabletop), letting your knee drop to the side and your calf lie across the bench perpendicular to your body. Place your left hand on your right foot, “stapling” it to the bench, and rotate your torso to the left. Next, rotate to the right. Continue alternating between the two positions for two minutes or for as long as possible. Switch sides.
Stand on one leg
It’s well known that balance diminishes with age and that falling is a real danger for older people. But falls are the third most common cause of unintentional injury worldwide for ages 18 to 35, too. Try standing on one leg for 20 seconds, then switch sides. If you can master that, try it standing inches from a blank white wall. A wall with no visual cues makes it harder. Then try it with your eyes closed.
On the bounce
Skipping is another excellent way to enhance your balance capabilities. But if you haven’t picked up a rope since you were 10, consider bouncing, a modified version of skipping: with your hands resting lightly on a counter, rise up on your toes and quickly bounce up and down 50 times. You don’t need to lower your heels to the ground each time; just drop them part-way as you bounce.
Step up your steps
There is nothing better for your body than walking. Walking doesn’t just stress (in a good way) the bones, joints and muscles, it also increases circulation and decongests your system. Walking also promotes better sleep and weight loss, and strolling around your area might help you get to know your neighbours, so it fosters community too.
If you go walking with someone else (which we highly recommend – conversation makes the miles fly by), this can help stave off loneliness, something we now know is detrimental to physical and mental health. Aim to build up your step count, with a goal of between 8,000 and 10,000 steps a day.
Load up
Adding weight to increase the force on your body is known as loading. That force elicits a positive adaptation response in your bones, muscles and other tissues, making them stronger and healthier. You don’t have to lift weights to load – you can do it while walking.
One way is by “rucking”, which involves walking carrying a backpack loaded with between two and 4.5 kilos of stuff (tinned foods work well). Walking uphill is another form of loading, because it increases the workload on your body. Walking briskly has a loading effect too. All three are excellent ways to improve your cardiovascular system.
It’s not enough to work out if you’re going to park yourself in a chair for the rest of the day
Sit less, stand more
Research shows that women and men who sit for more than six hours a day are, respectively, 37% and 18% more likely to die early than people who sit for less than three hours a day. The message here is that it’s not enough to work out – even if you work out hard – if you’re going to park yourself in a chair the rest of the day. But change your mindset and you will change your body, too: standing burns twice as many calories as sitting, and will make you less prone to aches and pains.
If you can, get a standing desk, or start working on a counter. If that’s not possible, take lots of standup breaks during the day and always opt for the “harder way”: taking the stairs rather than the lift, standing while you wait for the bus, leaning on the counter at a bar, giving your seat on the sofa to someone else at a party. After a while, it will become second nature.
Fidget
One reason we encourage standing is because it causes us to frequently and naturally adjust our posture for comfort. Not only do this and other types of fidgeting – such as changing position on the floor, or sitting in a variety of positions at your desk – keep the body moving, they also increase calorie burning. One study, from the Mayo Clinic/Arizona State University Obesity Solutions, found that compared with lying still, sitting increased energy expenditure by only 6%. But sitting and fidgeting increased it 54%. (Standing and fidgeting increased it by 94%).
Extend your hips
Most things humans are designed for – getting up and down, walking around carrying stuff, lifting – require hip extension. When this is restricted, it inhibits movement. To improve it, try the “couch stretch”: stand with your back to a couch, leave one foot on the floor, tuck the other knee into the area where the seat and back meet, or as far back as you can reach. Rest your shin and foot, toe pointed, on the back of the couch. Squeeze your bum and inhale for a count of five, then release and exhale for five. Do five times then swap sides.
Circle your arms
Remember arm circles in PE? Swap those baby-size revolutions for sweeping ones to keep shoulders and neck muscles supple. Stand tall with your arms above your head. In wide arcs, circle your arms out and down 10 times. Repeat in the other direction.
Rub your feet (and toes)
As well as being our foundation, feet are also the site of proprioceptors, sensors that tell us where our body is in space, helping us maintain balance. Unfortunately, most of us have desensitised our feet by walking around in shoes that block information from the ground. Help remedy this by going barefoot more often and by massaging the heels, arches, balls and tops of your feet for several minutes at a time. Use your fingers to spread your toes and to twist the front of your foot back and forth.
Research shows women and men who sit for more than six hours a day are more likely to die than people who sit for less than three hours a day
Roll with it
We’re big fans of using foam rollers or balls (although a tennis ball will do) to address pain in various areas of the body. Place it beneath the achy area (perhaps your calf), tighten the muscle as you breathe in for four seconds, hold it in place for four seconds, then relax the muscle and breathe out for eight seconds. Repeat. Continue the process as you move around both up and down and across the sore muscle.
Get in seven to eight
Hours of sleep that is. Yes, technically that’s not moving, but adequate sleep helps sustain movement, giving you the energy you need to mobilise as nature intended.
Breathe deeply
When people come to us with persistent back and neck pain, the first thing we look at is their breathing. Breath is like a canary in a coalmine: if you can’t breathe deeply in a position – whether it’s lifting weights at the gym or carrying a box out to the garage – you don’t have command of that position. We recommend regular deep breathing exercises and to focus on breathing through your nose, which activates breathing musculature more efficiently.
Squeeze your bum
Glutes – the big muscles in your rear – control the pelvis so that it doesn’t pitch forward and cause you to have a swayed banana back, and the strain and instability that come with it. You can improve your glute strength and hip extension by alternately squeezing your butt for five seconds, then relaxing for two over the course of several minutes. Do it while waiting in a coffee queue, while washing the dishes and brushing your teeth. Make every second count.
Built to Move: The 10 Essential Habits to Help You Move Freely and Live Fully by Juliet and Kelly Starrett is published by Orion Spring