This month, Sydney Spiesel explains and ventures an opinion about mercury in vaccines, mercury in dental fillings, new hope for diabetics, the perils of avian flu, the merits of episiotomy, and a bit of age-old wisdom. (Click here for the May round-up.)
Mercury in Vaccines: Why you can stop worrying about thimerosal.
State of the Science: The claim that a spate of autism has been caused by the past presence of mercury in vaccines, through the preservative thimerosal, is affecting public-health policy. Even though there is strong evidence to refute the thimerosal-autism connection and even though—let me hasten to reassure you—the mercury is now gone, families in my pediatric practice continue to be afraid to immunize their children. Thimerosal came to be incorporated into vaccines nearly 80 years ago for a good reason. Is there cause today to think that the mercury-containing preservative is or was unsafe?
Prognosis: No. Different forms of mercury are associated with different levels of toxicity. Methyl mercury, an organic compound whose molecules directly and easily penetrate the nervous system, causes extremely serious environmental damage and poses a major health risk, especially to pregnant women and children. But neither thimerosal nor ethyl mercury, the compound into which the body breaks it down, cross the blood-brain barrier and enter the nervous system. Both are eliminated from the body quite rapidly and do not accumulate between vaccine doses. In the tiny amounts formerly associated with vaccines, there is no sign that either is toxic.
Fall-out: Mercury was eliminated from vaccines in 1999 out of concern that the thimerosal panic would lead to widespread refusal of vaccines. That decision was prudent, if only to preserve faith in immunization, but it was also costly. Since a Royal Commission in Australia investigated a vaccine disaster there in 1928 (go read about the history, really!), it has been clearly established that vaccines packaged in multidose containers must contain a preservative. The alternative is to bottle vaccines in tiny single-dose containers, taking meticulous care to ensure that the vaccine is not contaminated in the manufacturing or bottling process. This method has greatly increased costs and led to vaccine shortages in the past few years. As public funding for children's health and access to medical insurance drops, many poor children may be priced out of the market for vaccines. That would reduce the average rate of immunization—and raise the rate of illness.
Mercury in Teeth: It's safe for dentists to use, too.
State of the Science: The legislators of my home state of Connecticut have shown a remarkable ability to enact well-intended but wrong-headed laws governing medical practice, and they might be about to do it again. At issue is another use of mercury, this time in dental fillings. Dentists have been using mercury-containing amalgam (called dental amalgam) to fill cavities in teeth since the early 19th century. This material is easy to use, durable, and relatively inexpensive. But questions about the harmful effects of dental amalgam have led to proposals either to outlaw it outright or to forbid it by extending Connecticut's existing "zero-mercury" statute. Maine and New Hampshire already have laws requiring dentists to inform their patients about dental amalgam's mercury content. How much risk, to the patient or to the environment, does the amalgam pose?
Prognosis: Very little, if any. The environmental risk is virtually eliminated by a device called an amalgam separator that dentists use to prevent the material from entering the environment via the sewage stream. (The amalgam is recovered and reprocessed.) The risk to patients with amalgam fillings is similarly low: A recent study of more than 1,500 veterans detected no evidence of neurological harm related to the fillings, confirming the results of several previous studies.
So, how to explain the frenzy over amalgam fillings? Like thimerosal, dental amalgam is prey to risk confusion. The clear environmental harm caused by dumping large amounts of mercury or its compounds makes it harder to accept that tiny individual exposure to metallic mercury probably doesn't matter much. A few dentists have exploited the confusion to promote the lucrative practice of removing old amalgam fillings and replacing them with mercury-free materials. Law firms interested in setting the stage for class-action suits have also stoked fears.
Contrarian thought: Conspiracy theorist that I am, I wonder if the agitation over minor mercury sources obscures the real cause of mercury contamination of our seafood and water: coal-fired power, ore processing, and garbage incineration. U.S. power plants dump almost 50 tons of mercury a year into the air, and other industrial sources contribute another 100 tons annually. The Environmental Protection Agency recently gave the power plants a free pass until 2018, at which time they must reduce the 50 tons they currently emit to 15. Are the trivial and demonstratively non-harmful uses of mercury by dentists—or, in the past, to protect vaccines from contaminants—distracting us from the serious environment-poisoning?
Diabetes: Saving the cells that make insulin.
State of the Science: More than 14 million patients in the United States have diabetes, which requires lifelong insulin injections and attention to diet and medical care and if untreated results in these complications. Diabetes is caused by malfunctions in the production of insulin (Type 1) or its utilization (Type 2). Insulin is a hormone that controls the entry of sugar into many kinds of body cells. When things are going right, it is manufactured by "beta cells" in the pancreas. But in Type 1 diabetes—5 to 10 percent of cases, most of them children or young adults—the body fails to produce insulin because of a perversion of the immune system. With this autoimmune disease, T lymphocyte cells—which normally identify and destroy abnormal cells—are misdirected and attack the pancreatic beta cells. The cause is unclear; many doctors suspect a combination of genetic susceptibility and perhaps a virus infection as the trigger.
Prognosis: Immune-suppressant drugs can stop the destruction of beta cells, but at great cost: They need to be administered forever, and they block the body's ability to fend off viral and bacterial infections and to eliminate malignant cells that develop into cancer. A recent little-noticed study by Bart Keymeulen of Brussels Free University offers hope of a better alternative. Keymeulen and his colleagues selected diabetics early in the development of their disease—before all their beta cells had been destroyed—and injected a highly purified antibody that attaches only to T lymphocyte cells. Without treatment, these patients would have gone on to lose all their insulin-producing cells and become severely diabetic. But after less than a week of the treatment, the haywire T cells seemed to lose interest in attacking the insulin-producers, and the destruction somehow abated. The effects remained powerful 18 months later.
If Keymeulen's experimental treatment can be developed for safe clinical use, expect a definitive treatment for Type 1 diabetes that halts the destruction of insulin-producing cells when begun early enough. In that event, the disease would be far milder, though treatment would still be required. Ultimately, embryonic stem-cell research may succeed in fully correcting Type 1 diabetes by replacing the killed-off beta cells with new ones. That advance could make the lives of diabetics completely normal.
Caveat: This promising new treatment, which needs much more refinement and testing before it is ready for general use, will surely be costly. The technology is expensive to develop, and there will be an added surcharge to reflect what the market will bear. But (as the makers know) at any reasonable price the treatment will be perceived as a bargain compared with the estimated $1,000 per patient per year that diabetes presently costs to manage.
Bird flu: This is what you should worry about.
State of the Science: If you ask infectious-disease experts to identify the two biggest challenges immediately facing medicine, most would name a coming influenza pandemic and the loss of effective antibiotics because of increasing resistance. In a way, we may be approaching a confluence of those two concerns.
Presently, the H5N1 strain of type A flu is decimating chicken flocks throughout Asia. This strain has so far rarely crossed over to infect humans and probably has genes that don't efficiently promote human infection. But there is great concern that one day it will co-infect a human patient carrying a human flu infection and that a resulting combination will produce a highly infectious and lethal new human flu. A recombination between human flu and flu from some mammal, most likely a pig, probably resulted in the devastating Spanish Influenza pandemic that killed between 50 million and 100 million people in 1918.
Prognosis: If H5N1 does develop a human strain, we are in big trouble. The virus is almost 100 percent lethal when it sweeps through flocks of chickens and has killed about half of the 50 or so people who have so far been infected. We will never be able to make, distribute, and administer enough vaccine fast enough to make a significant dent in a worldwide epidemic. The best hope is to widely distribute an inexpensive, safe, and effective chemoprophylaxis drug, which cuts down the risk of serious influenza by interfering with the virus particle's ability to attach to a host cell or to multiply in it. The least-expensive and most-available of these drugs is perhaps amantadine (which, by the way, probably has the most beautiful chemical structure of any medication).
Caveat: The trouble is that Chinese farmers are sprinkling amantadine into the drinking water of their chicken flocks, probably with local government complicity. This thoughtless, nonsensical, and dangerous practice has been shown to have the predicted effect: H5N1 influenza virus in China and Vietnam has become resistant to amantadine. If H5N1 emerges from Asia as an efficient and virulent human pathogen, we will have lost the best tool we had to limit the devastation. And that would be the confluence of the two big fears of infectious disease experts—a new flu pandemic and widespread resistance to treatment because of thoughtless use of a prophylactic drug.
Episiotomy: Think twice.
State of the Science: About one-third of all vaginal births in the United States include an episiotomy. Proponents believe that uncontrolled tearing of the vagina is both harder to repair than a neat surgical incision and poses a greater risk of complications like urinary incontinence or poor sexual function.
Prognosis: Now it turns out that as widely held and reasonable-seeming as the beliefs about routine episiotomy are, they are nonetheless wrong. Katherine Hartmann and her colleagues critically reviewed and aggregated the results of many studies and found that the practice has no benefit and in fact may contribute to poorer outcomes for mothers. The researchers urge that routine episiotomy is unnecessary and say further studies should define the circumstances in which it is valuable (when fetal distress requires a very fast delivery, for example).
Lesson: To a much greater extent than most people realize, medical practice is determined by adherence to tradition and by reasoning from plausibly related research or personal clinical experience. This probably sounds terrible, but it shouldn't. It's the product of a normal style of human thinking—the one that directs us to infer that if one event closely follows another they are probably related in a cause-and-effect way (which is sometimes right but often wrong). In addition, most questions in medicine about cause and treatment have never been asked in a serious, rigorous way. As a result, every doctor has at some time blindly, desperately, and irrationally ordered some last-ditch treatment, because we have a patient who needs help and we cannot think what else to do. And if our treatment "works"—that is, the patient improves—few of us have the intellectual rigor to resist associating it with the patient's improvement.
Fortunately, more and more long-held beliefs and traditional practices are being skeptically examined. I'm a pediatrician, and I don't do episiotomies, but as I read Hartmann's paper I was stimulated to think of the many things I do, all blessed by tradition and reason, that are nonetheless probably incorrect and maybe harmful. I hope it will not be too painful to shake off fusty beliefs that I am irrationally sure of and replace them as new ideas, supported by evidence, are introduced.
Age-old Wisdom: Newer treatments aren't necessarily better.
Contrarian thought: One of my greatest irritations about modern medicine is the degree to which it devalues old knowledge. My young colleagues and students, as bright and thoughtful as they are, don't bother to look at papers that are more than five years old—it's as if that's Neanderthal work.
So, I was pleased to open one of my favorite journals this week, the Lancet, to find a letter by two British surgeons, Peter Bewes and Maurice King. Their note commented on a paper published earlier this year that used the best methods of evidence-based medicine to compare two up-to-date ways of managing leg fractures in children. Bewes and King pointed out that the paper's authors neglected to include an older method that is low-tech, more conservative, and may offer substantial advantages over the newer methods. The old method has a better track record than the modern ones of keeping the bones in a good position as they heal and of preventing the infections that can occur when healing bones are pinned in place. They worry that with the publication of this new study, the older method may be rejected out of hand. Bravo to these authors for reminding us not to neglect ideas just because they've been around for a while!
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