The Body, page 40
The upshot is that Australia, New Zealand, the Nordic countries, and the wealthier nations of the Far East all do really well, and other European nations do pretty well. For the United States, the result is, at best, decidedly mixed. For Britain, cancer survival rates are grim and ought to be a matter of national concern.
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Nothing in medicine is simple, however, and there is an additional consideration that profoundly complicates results almost everywhere: overtreatment.
It hardly needs pointing out that for most of history the focus of medicine has been to make sick people better, but now increasingly doctors devote their energies to trying to head off problems before they even arise, through programs of screening and the like, and that changes the dynamics of care entirely. There is an old joke in medicine that seems especially apt here:
Q. What is the definition of a well person?
A. Someone who hasn’t been examined yet.
The thinking behind a great deal of modern health care is that you cannot be too careful and you cannot have too many tests. Surely it is better, the logic runs, to check out and deal with or eliminate any potential problems, however remote, before they have a chance to turn into something bad. The drawback with this approach is what are known as false positives. Consider screening for breast cancer. Studies show that between 20 and 30 percent of women given the all clear after a breast cancer screening actually had tumors. But equally, and contrarily, screenings often catch tumors that needn’t cause concern, and result in interventions that aren’t actually necessary. Oncologists use a concept called sojourn time, which is the interval between when a cancer is caught by screening and when it would become evident anyway. Many cancers have long sojourn times and progress so slowly that the victims almost always die of something else before the cancer gets them. A study in Britain found that as many as one in three women with breast cancer receive treatments that may leave them mutilated and even possibly shorten their lives quite unnecessarily.
Mammograms are in fact fuzzy things. Reading them accurately is a challenging task—much more challenging than even many medical professionals realize. As Timothy J. Jorgensen has noted, when 160 gynecologists were asked to assess the likelihood of a fifty-year-old woman having breast cancer if her mammogram was positive, 60 percent of them thought the chances were 8 or 9 out of 10. “The truth is that the odds the woman actually has cancer are only 1 in 10,” writes Jorgensen. Remarkably, radiologists do little better.
The unfortunate bottom line is that breast cancer screening doesn’t save a lot of lives. For every thousand women screened, four will die of breast cancer anyway (either because the cancer was missed or because it was too aggressive to be treated successfully). For every thousand women who are not screened, five will die of breast cancer. So screening saves one life in every thousand.
Men face similarly unhappy prospects with prostate screening. The prostate is a small gland, about the size of a walnut and weighing just one ounce, which is chiefly involved in producing and distributing seminal fluid. It is tucked neatly—not to say inaccessibly—up against the bladder and wrapped around the urethra like a neckerchief ring. Prostate cancer is the second leading cause of cancer death among men (after lung cancer) and grows more common as men get to their fifties and beyond. The problem is that the test for prostate cancer, called a PSA test, is not trustworthy. It measures levels in the blood of a chemical called prostate-specific antigen (PSA). A high PSA reading indicates a possibility of cancer, but only a possibility. The only way of confirming if cancer exists is with a biopsy, which involves sticking a long needle into the prostate via the rectum and withdrawing multiple tissue samples—not a procedure any man is likely to undertake eagerly. Because the needle can only be randomly inserted into the prostate, it is a matter of luck whether it strikes a tumor or not. If it does find a tumor, there is no telling with current technology if the cancer is aggressive or benign. On the basis of this uncertain information, a decision must be made on whether to surgically remove the prostate—a tricky operation with frequently dispiriting consequences—or treat it with radiation. Between 20 and 70 percent of men suffer impotence or incontinence after treatments. One in five experience complications from the biopsy alone.
The PSA test is “hardly more effective than a coin toss,” Professor Richard J. Ablin of the University of Arizona has written, and he should know. He was the man who discovered the prostate-specific antigen in 1970. Noting that American men spend at least $3 billion a year on prostate tests, he added, “I never dreamed that my discovery four decades ago would lead to such a profit-driven disaster.”
A meta-analysis of six randomized control trials involving 382,000 men found that for every 1,000 men screened for prostate cancer, about one life was saved—great news for that individual, but not so good for the large numbers of others who may spend the rest of their lives incontinent or impotent, the majority of them having undergone serious but possibly ineffectual treatments.
All this isn’t to say that men should absolutely avoid PSA tests or women breast cancer screening. For all their flaws, they are the best tools available, and they do indubitably save lives. But those undergoing screenings should perhaps be made more aware of the shortcomings. As with any serious medical issue, if you have concerns you should consult a trusted physician.
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Accidental discoveries made during routine investigations happen so often that doctors have a word for them: “incidentalomas.” The National Academy of Medicine in the United States has estimated that $765 billion a year—a quarter of all health-care spending—is wasted on pointless precautionary maneuvers. A similar study in Washington State put the amount of waste even higher, at nearly 50 percent, and concluded that as much as 85 percent of preoperative lab tests are completely unnecessary.
The problem of overtreatment is exacerbated in many places by fear of litigation and, it must be said, by a desire of some doctors to inflate their earnings. According to the author and physician Jerome Groopman, most doctors are “less concerned about healing and more worried about being sued or maximizing their income.” Or as another commentator put it more drolly, “One person’s overtreatment is another’s income stream.”
The pharmaceutical industry has a lot to answer for in this respect. Drug companies commonly offer generous rewards to doctors to promote their drugs. Marcia Angell of the Harvard Medical School, writing in The New York Review of Books, has said that “most doctors take money or gifts from drug companies in one way or another.” Some companies pay for doctors to attend conferences at luxury resorts where they do little more than play golf and enjoy themselves. Others pay doctors to put their names to papers that they haven’t in fact written or reward them for “research” that they didn’t really do. Altogether, Angell has estimated, drug companies in America spend “tens of billions” of dollars on direct and indirect payments to doctors every year.
We have reached the decidedly bizarre point in health care in which pharmaceutical companies are producing drugs that do exactly what they are designed to do but without necessarily doing any good. A case in point is the drug atenolol, a beta-blocker designed to lower blood pressure, which has been widely prescribed since 1976. A study in 2004, involving a total of twenty-four thousand patients, found that atenolol did indeed reduce blood pressure but did not reduce heart attacks or fatalities compared with giving no treatment at all. People on atenolol expired at the same rate as everyone else, but, as one observer put it, “they just had better blood-pressure numbers when they died.”
Drug companies have not always behaved in the most ethical of ways. Purdue Pharma paid $600 million in fines and penalties in 2007 for marketing the opioid OxyContin with fraudulent claims. Merck paid $950 million in fines for failing to disclose problems with its anti-inflammatory drug Vioxx, which was withdrawn from sale, but not before it had caused perhaps as many as 140,000 avoidable heart attacks. GlaxoSmithKline currently owns the record for a penalty—$3 billion for a raft of transgressions. But to quote Marcia Angell again, “These kinds of fines are just the cost of doing business.” For the most part, they come nowhere near offsetting the huge profits made by the errant companies before they are hauled into court.
Even in the best and most diligent circumstances, drug development is an inherently hit-or-miss undertaking. Laws almost everywhere require researchers to test drugs on animals before they try them out on humans, but animals don’t necessarily make good surrogates. They have different metabolisms, respond differently to stimuli, contract different diseases. As a tuberculosis researcher observed years ago, “Mice don’t cough.” The point was frustratingly well illustrated on tests of drugs to fight Alzheimer’s. Because mice don’t get Alzheimer’s naturally, they must be genetically engineered to accumulate in their brains a specific protein, beta-amyloid, associated with Alzheimer’s in humans. When such doctored mice were treated with a class of drugs called BACE inhibitors, their beta-amyloid accumulations melted away, much to the excitement of researchers. But when the same drugs were tried on humans, they actually worsened the dementia in test subjects. In late 2018, three companies announced they were abandoning clinical trials of BACE inhibitors.
Another problem of clinical trials is that test subjects are nearly always excluded if they have any other medical conditions or are on other medications because those considerations could complicate results. The idea is to get rid of what are known as confounding variables. The problem is that real life is full of confounding variables even if drug tests are not. That means that lots of possible consequences are not tested for. We rarely know, for instance, what happens when various medications are taken in combination. One study found that 6.5 percent of hospital admissions in the U.K. were because of side effects from drugs, often taken in combination with other drugs.
All drugs come with a mixture of benefits and risks, and these are often not well studied. Everyone has heard that taking a low-dose aspirin daily may help prevent a heart attack. That is true, but only up to a point. According to one study of people who had taken low-dose aspirin daily for five years, 1 in 1,667 had been spared a cardiovascular problem, 1 in 2,002 had been spared a nonfatal heart attack, and 1 in 3,000 spared a nonfatal stroke, while 1 in 3,333 suffered major gastrointestinal bleeding that they would not otherwise have experienced. So for most people there is about as much chance of suffering dangerous internal bleeding from taking a daily aspirin as there is of avoiding a heart attack or stroke, but in all cases actually there is very little risk of either.
In the summer of 2018, matters became even more confused when Peter Rothwell, professor of clinical neurology at Oxford University, and colleagues found that low-dose aspirin actually is not effective at all in reducing cardiac or cancer risk in anyone weighing 154 pounds or more—but does still pose a risk of serious internal bleeding. Because about 80 percent of men and 50 percent of women exceed that threshold, it appears that a lot of people are getting no possible benefit from a daily aspirin while preserving all the risk. Rothwell suggested that people over 154 pounds should double the dose, perhaps by taking the pills twice a day rather than once, but that was really only an educated guess.
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I don’t wish to minimize the enormous, and undoubted, benefits of modern medicine, but it is an inescapable fact that it is far from perfect and in ways that aren’t always widely appreciated. In 2013, an international team of researchers investigated common medical practices and found 146 in which “a current standard practice either had no benefit at all or was inferior to the practice it replaced.” A similar study in Australia found 156 common medical practices “that are probably unsafe or ineffective.”
The simple fact is that medical science alone cannot do it all—but then it doesn’t need to. Other factors can significantly affect outcomes, sometimes in surprising ways. Just being kind, for instance. A study in New Zealand of diabetic patients in 2016 found that the proportion suffering severe complications was 40 percent lower among patients treated by doctors rated high for compassion. As one observer put it, that is “comparable to the benefits seen with the most intensive medical therapy for diabetes.”
In short, everyday attributes like empathy and common sense can be just as important as the most technologically sophisticated equipment. In that sense at least, perhaps Thomas McKeown was on to something.
* The “Gram” in Gram-negative and Gram-positive bacteria has nothing to do with weights and measures. It is named for a Danish bacteriologist, Hans Christian Gram (1853–1938), who in 1884 developed a technique for distinguishing the two major types of bacteria by what color they turned when stained on a microscopic slide. The difference between the two types has to do with the thickness of their cell walls and how easily or not they are penetrated by antibodies.
23 THE END
Exercise regularly. Eat sensibly. Die anyway.
—ANONYMOUS
I
IN 2011, AN interesting milestone in human history was passed. For the first time, more people globally died from non-communicable diseases like heart failure, stroke, and diabetes than from all infectious diseases combined. We live in an age in which we are killed, more often than not, by lifestyle. We are in effect choosing how we shall die, albeit without much reflection or insight.
About one-fifth of all deaths are sudden, as with a heart attack or car crash, and another fifth come quickly, following a short illness. But the great majority, about 60 percent, are the result of a protracted decline. We live long lives; we also die long deaths. “Nearly a third of Americans who die after 65 will have spent time in an intensive care unit in their final three months of life,” The Economist noted grimly in 2017.
There’s no question that people are living longer than ever. If you are a seventy-year-old man in America today, you have only a 2 percent chance of dying in the next year. In 1940, that probability was reached at age fifty-six. In the developed world at large, 90 percent of people reach their sixty-fifth birthday, the great majority of them in a healthy condition.
But now it seems we have reached a point of diminishing returns. By one calculation, if we found a cure for all cancers tomorrow, it would add just 3.2 years to overall life expectancy. Eliminating every last form of heart disease would add only 5.5 years. That’s because people who die of these things tend to be old already, and if cancer or heart disease doesn’t get them, something else will. Of nothing is that more true than Alzheimer’s disease. Eradicating it altogether, according to the biologist Leonard Hayflick, would add just nineteen days to life expectancy.
Our extraordinary improvements in life span have come at a price. As Daniel Lieberman has noted, “For every year of added life that has been achieved since 1990, only 10 months is healthy.” Already nearly half of people aged fifty or more suffer from some chronic pain or disability. We have become much better at extending life, but not necessarily better at extending quality of life. Older people cost the economy a lot. In the United States, the elderly constitute just over a tenth of the population but fill half the hospital beds and consume a third of all the medicines. Falls among the elderly alone cost the U.S. economy $31 billion a year, according to the Centers for Disease Control.
The time we spend in retirement has grown substantially, but the amount of work we do to fund it has not. The average person born before 1945 could expect to enjoy only about eight years of retirement before being permanently eliminated from the living, but someone born in 1971 can expect more like twenty years of retirement, and someone born in 1998 can, on current trends, expect perhaps thirty-five years—but all funded in each case by roughly forty years of labor. Most nations haven’t begun to face up to the long-term costs of all these unwell, unproductive people who just go on and on. We have, in short, a lot of problems ahead of us all, both personally and societally.
Slowing down, losing vigor and resiliency, experiencing a steady, ineluctable diminution in the ability to self-repair—in a word, aging—is universal across all species, and it is intrinsic: that is, it is initiated from within the organism. At some point, your body will decide to grow senescent and then to die. You can slow the process a little by following a carefully virtuous lifestyle, but you can’t escape it indefinitely. Put another way, we are all dying. Some of us are just doing it more quickly than others.
We don’t have any idea why we age, or actually we have lots of ideas; we just don’t know if any of them are correct. Almost thirty years ago, Zhores Medvedev, a Russian biogerontologist, counted some three hundred serious scientific theories to explain why we age, and the number has not shrunk in the decades since. As Professor José Viña and colleagues from the University of Valencia put it in a summary of current thinking, the theories fall into three broad categories: the genetic mutation theories (your genes malfunction and kill you), the wear-and-tear theories (the body just wears out), and the cellular waste accumulation theories (your cells clog up with toxic by-products). It may be that all three factors work together, or it may be that any two of the above are side effects of the third. Or it may be something else altogether. No one knows.
