Although it might seem far-fetched, imagine the following scenario: A group of unscrupulous doctors opens a clinic in Switzerland that performs lobotomies for the treatment of autism. The doctors who run the clinic don’t call the procedure a lobotomy (that ship has sailed); they call it something else, like the “Fresh Start” procedure. The doctors put up an attractive website that explains how the outpatient procedure takes only a few minutes to perform and involves severing the nerve fibers in the brain that cause autism. They include a few parent testimonials stating that after the procedure their children’s language doubled, and then they open their doors. If a man claiming to be a billion-year-old god from another galaxy can get people to line up for a therapy that crosses the line into child abuse, then doctors in some European clinic should expect at least equal success with a quick-fix surgical procedure. It hasn’t happened yet, but there is no reason to believe that it couldn’t. Desperate to do something, anything, to cure the incurable, we continue to punish the afflicted.
5. The dose makes the poison.
When Rachel Carson wrote Silent Spring, she correctly predicted that man-made activities could destroy the environment. Thanks to Rachel Carson, we are now far more attentive to our impact on the planet. Unfortunately, Carson also gave birth to the notion of zero tolerance—the assumption that any substance found harmful at any concentration or dosage should be banned absolutely. If large quantities of DDT (like those used in agriculture) were potentially harmful, then even small quantities (like those used to prevent mosquitoes from biting) should be avoided. As a result, millions of children died needlessly from malaria.
One recent example of how the concept of zero tolerance has caused harm is thimerosal: an ethylmercury-containing preservative used in vaccines. Because vaccines are injected into babies, no preservative has generated more angst.
Preservatives were first added to multidose vials of vaccines back in the 1930s. The reason was that as the needle penetrated the rubber stopper again and again, bacteria could enter the vial. In the early 1900s, children receiving the eighth, ninth, or tenth dose of a vaccine might be inoculated with bacteria that had inadvertently been introduced into the vial, causing severe and occasionally fatal infections. By adding preservatives containing ethylmercury to vaccines, this problem disappeared. But in the late 1990s the question arose, at what price?
In 1999, some physicians worried that babies and young children might be exposed to too much mercury in vaccines. What happened to thimerosal in vaccines in the 1990s eventually mimicked what had happened to DDT in the 1970s. Exercising caution, thimerosal was precipitously removed from infant vaccines and branded with a scarlet letter. During the year or so when manufacturers were gearing up to produce thimerosal-free vaccines, some, like the hepatitis B vaccine, still contained thimerosal. About 10 percent of hospitals decided not to give thimerosal-containing hepatitis B vaccines; as a result, one three-month-old child in Michigan died of overwhelming hepatitis B virus infection and six children in Philadelphia born to mothers infected with the virus weren’t vaccinated, condemning them to the likely development of chronic liver disease (called cirrhosis) or liver cancer later in life. These hospitals had wrongly assumed that the harm from a thimerosal-containing hepatitis B vaccine (which was theoretical at best) was greater than the risk of getting hepatitis B (which wasn’t theoretical at all). Within a few years of the removal of thimerosal from vaccines given to young children, seven studies showed that it hadn’t caused harm. The only harm had come from elevating a theoretical risk above a real risk.
It’s not hard to understand how this could have happened. Mercury is never going to sound good. (There’s no such thing as the National Association for the Appreciation of Heavy Metals.) Large quantities of mercury have clearly been shown to cause harm. Indeed, environmental mercury contaminations caused by a chemical spillage in Minamata Bay, Japan, or by fumigating grain in Iraq damaged hundreds of babies and fetuses. Mercury, however, which is present in the Earth’s crust, is hard to avoid. Anything we drink that’s made from water on this planet (including breast milk and infant formula) will contain small quantities of mercury. These small quantities of mercury aren’t harmful. Only large quantities are harmful. If small quantities of mercury were harmful, we’d have to move to a different planet. Of interest, the quantities of mercury contained in vaccines were far less than those contained in breast milk and infant formulas. And mercury isn’t the only heavy metal to which we are routinely exposed. We all have trace quantities of metals like cadmium, beryllium, thallium, and even arsenic in our blood. But at quantities far less than those required to do harm.
Unfortunately, we seem incapable of learning the most important lesson in toxicology: The dose makes the poison. For example, if people drink several gallons of water quickly (as has occurred during fraternity hazings), they might exceed their body’s ability to hold onto the mineral sodium. As the level of sodium in the bloodstream drops, it’s possible that they could have a seizure. This doesn’t mean that water is toxic to the brain. It only means that you shouldn’t drink several gallons of it at once. Similarly, a cup of organic coffee contains acetaldehyde, benzaldehyde, benzene, benzopyrene, benzofuran, caffeic acid, catechol, 1,2,5,6 dibenzanthracene, ethylbenzene, formaldehyde, furan, furfural, hydroquinone, d-limonene, 4-methylcatechol, styrene, and toluene. Many of these substances are known cancer-causing agents or DNA-altering chemicals. Yet no study has ever found that organic coffee causes cancer. That’s because the quantities of the chemicals contained in coffee are well within the levels considered safe. Rachel Carson’s lesson of zero tolerance doesn’t apply to the real world.
6. Be cautious about being cautious.
Rachel Carson taught us caution. Wouldn’t it make sense to ban DDT given that at the very least, it might cause harm to people. As we learned, removing it from use caused far more harm than good.
However, one could make a reasonable argument that, regarding BPA, what possible harm could come from removing a plasticizer from a toy. At the time that the FDA banned it from baby bottles and Nalgene removed it from all of its products, it wasn’t clear whether BPA was safe. Wouldn’t it make sense, then, to remove BPA in the interest of caution—under the precautionary principle? The answer is yes; it was reasonable. But we have to be careful. We have to make sure that in the name of the precautionary principle we aren’t doing more harm than good. Although removing a plasticizer from a child’s toy was without consequence (and could have been predicted to have been without consequence), the decisions to precipitously remove thimerosal from vaccines (and scaring parents and doctors) or to ban DDT from public health programs (when the only replacements were more expensive and less available) have caused children to suffer needlessly and predictably. The precautionary principle, at the very least, assumes that no harm will come from exercising caution.
Which brings us to arguably the single greatest use of the precautionary principle in modern medicine: cancer-screening programs.
During the past 50 years, doctors and scientists have proven that some cancers can be prevented. Sunblock can prevent skin cancer. The hepatitis B virus vaccine can prevent the most common cause of liver cancer. The human papillomavirus vaccine can prevent the only known cause of cervical cancer. And cessation of cigarette smoking can prevent a common cause of lung cancer. The results of these four strategies are clear.
The definition of cancer, however, is changing—and not for the better. Medical textbooks 20 years ago defined cancer as a “disease the natural course of which is fatal.” No longer. Now we detect cancers that aren’t fatal—the kind of cancers that you are more likely to die with than from. In the process of detecting these nonfatal cancers, we are probably doing more harm than good.
Gilbert Welch, a professor at Dartmouth Medical School, offers the best analogy to our current dilemma. It’s a barnyard analogy. Imagine, writes Welch, three animals in a barn that are trying to escape: a bird, a turtle, and a rabbit. When y
ou open the door, they will escape at different rates. The bird, which will invariably fly out before you have time to close the door, is analogous to the kind of cancer that will kill you no matter what you do. Even if you detect the cancer early, it doesn’t matter—you’ll die from it anyway. It’s just too aggressive. The turtle, which is so plodding that it will never effectively escape, is analogous to a cancer that is so slow growing, so nonvirulent, that it will never kill you. You will invariably die from something else first. This is the kind of cancer that you will die with and not from. The rabbit, which can be caught if the door is closed quickly enough, is analogous to the kind of cancer worth detecting. If this cancer isn’t detected early, then it will kill you. And if it is detected early, then the screening test will have saved your life.
Screening tests are valuable only if they are detecting rabbits; if they’re detecting mostly turtles and birds, then they won’t save lives. Some screening tests, like Pap smears to detect cervical cancer or colonoscopies to detect colon cancer, save lives. Both of these tests are detecting lots of rabbits. For thyroid, prostate, and breast cancers, on the other hand, the value of early screening tests isn’t so clear. Atul Gawande, a surgeon at Johns Hopkins University School of Medicine and prolific author, says it best: “We now have a vast and costly health care industry devoted to finding and responding to turtles.”
We’ll start with thyroid cancer.
In 1999, the South Korean government initiated a large nationwide screening program for the early detection of thyroid cancer. The screening test used was ultrasonography, which sends high-frequency sound waves (higher than those audible to the human ear) into the body. The sound waves then bounce back. Different structures absorb or reflect sound waves differently. As a result of the massive screening program, South Korean physicians detected more than 40,000 new cancers of the thyroid, 15 times more than had been detected before the screening program started. Thyroid cancer became the most common cancer in South Korea. One researcher called it a “tsunami of thyroid cancer.”
Virtually all of these South Korean thyroid cancers were treated by completely removing the thyroid, called a thyroidectomy. This procedure, however, comes with a price. At the very least, everyone with a thyroidectomy has to take thyroid replacement hormones for the rest of their lives. And sometimes it’s difficult to get the dose right. People suffer from symptoms of too much replacement hormone (sweating, heart palpitations, and weight loss) or too little replacement hormone (somnolence, depression, and weight gain). Worse, because the nerves of the vocal cord travel close to the thyroid gland, some people suffer vocal cord paralysis. Or they suffer from a problem with calcium metabolism because a gland called the parathyroid gland, which regulates calcium, is also nearby. Or they suffer from life-threatening bleeding after the surgery. Initially, South Korean health officials were excited that they had detected all of these cancers before patients had developed any symptoms. Then they looked at the mortality rates from thyroid cancer. No difference. The incidence of death from thyroid cancer was exactly the same before and after the massive screening program. The only tangible outcome was that now tens of thousands of South Koreans had to suffer the side effects of thyroid surgery.
Overdiagnosis and overtreatment of thyroid cancer hasn’t been limited to South Korea. In France, Italy, Croatia, Israel, China, Australia, Canada, and the Czech Republic, the rates of thyroid cancer have more than doubled. In the United States, they’ve tripled. In all of these countries, as had been the case in South Korea, the incidence of death from thyroid cancer has remained the same.
Autopsy studies confirm the problem with trying to screen for thyroid cancer. About one-third of people who have died from other causes also had thyroid cancer at autopsy. Some researchers argue that if the sections of the thyroid examined in these studies had been thinner and more numerous, the percentage of people with thyroid cancer at the time of their death would have approached 100 percent. Which isn’t to say that people don’t die from thyroid cancer. They do. The death rate from thyroid cancer in the United States is about 1 per 200,000 people. The problem with thyroid cancer is that it’s almost all turtles and a few birds. There just aren’t enough rabbits to make screening worthwhile.
Next year in the United States, about 60,000 people will be diagnosed with thyroid cancer. Women will outnumber men three to one. Virtually all will have thyroidectomies, and few, if any, will benefit from the diagnosis. If most of these small thyroid cancers don’t kill you, then maybe we shouldn’t call them cancer.
Screening for prostate cancer has also come under closer scrutiny.
In 1970, Richard Ablin, a professor of pathology at the University of Arizona, discovered the PSA test, which stands for prostate-specific antigen. PSA is an enzyme made by cells in the prostate gland. The purpose of PSA is to break up cervical mucus so that sperm can enter the uterus. Criminologists were the first to recognize the value of PSA, which offered proof for the existence of semen in rape cases, even when the rapist had had a vasectomy or couldn’t make sperm. Doctors were the next to realize the potential value of PSAs, using the test to determine whether prostate cancers had relapsed. Then physicians took a step they are now starting to regret—PSA tests were used to predict whether someone had prostate cancer. If the level of PSA in the blood was high, then urologists recommended a prostate biopsy. If the biopsy showed prostate cancer, then men either had a total removal of the prostate (prostatectomy) or they had radiation therapy to the prostate. More than 90 percent of men in the United States who have been diagnosed with prostate cancer have had one therapy or the other.
Because of the PSA test, prostate cancer is now the most commonly diagnosed non-skin cancer in the United States. So, what’s happened to the incidence of death from the disease? Nothing. The risk of dying from prostate cancer hasn’t changed in the last ten years. Indeed, about 50 percent of men more than 60 years old have been found at autopsy to have prostate cancer after they had died from something else; in men more than 85 years old, that number climbs to 75 percent. In other words, as had been the case for thyroid cancer, men are more likely to die with prostate cancer than from it. Prostate cancer, like thyroid cancer, is mostly turtles and birds.
In 2012, the United States Preventive Services Task Force recommended against PSA-based screening tests for prostate cancer. But not before a lot of harm had been done. High PSA tests invariably lead to prostate biopsies, which can cause pain, bleeding, difficulties with urination, and bloodstream infections requiring hospitalization. And, aside from the psychological trauma of being diagnosed with prostate cancer, therapies for the disease are brutal. Prostate surgeries and radiation commonly cause incontinence and erectile dysfunction. Worse, five of every thousand men will die from prostate surgery. And all for nothing. By 2015, three years after the task force had issued its recommendations, the number of people screened for and diagnosed with prostate cancer had declined; many physicians had gotten the message.
Two years before the task force changed its recommendation, Richard Ablin, the discoverer of PSA, penned an op-ed piece for the New York Times. Noting that the annual bill for PSAs was $3 billion, he wrote, “As I’ve been trying to make clear for many years now, PSA testing can’t detect prostate cancer and, more important, it can’t distinguish between the two types of prostate cancer—the one that will kill you and the one that won’t. I never dreamed that my discovery four decades ago would lead to such a profit-driven public health disaster.”
Mammography screening for breast cancer is also being reevaluated. Although it is clear that mammography, which was first introduced into the United States in the mid-1970s, saves lives; the question is how many and at what cost.
In 2012, Archie Bleyer and Gilbert Welch published a study in the New England Journal of Medicine titled “Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence.” They found that, with the advent of screening mammographies, the incidence of breast cancer in the United States h
ad doubled. For every 100,000 women screened, the number of women diagnosed with breast cancer had increased from 112 to 234. In other words, every year 122 more women (per 100,000) were being diagnosed with breast cancer. At the same time, the number of women presenting with late-stage breast cancer (the kind that often results in death), decreased from 102 to 94 (per 100,000). This meant that only 8 women among 122 appeared to benefit from the screening. Eight. The others were treated with mastectomy, radiation therapy, and chemotherapy without benefit. The authors concluded that, although the incidence of death from breast cancer had clearly decreased during the era of screening mammography, most of that decrease was due to better treatment, not better screening. They also estimated that during the three decades of mammography, about 1.3 million women had been diagnosed with a cancer that would never have killed them. The authors concluded that, “screening is having, at best, only a small effect on the rate of death from breast cancer.”
Another study involving hundreds of countries also cast doubt on the time-honored notion that mammographies save lives. Investigators found that different countries had different rates of screening. In some countries, as few as 40 percent of women were screened; in others, as many as 80 percent were screened. If mammographies were making a difference, then countries that screened more women should have had lower rates of deaths from breast cancer. But deaths rates from breast cancer were the same in both groups of countries. The only difference was that in countries with higher rates of screening, more women had mastectomies, radiation, and chemotherapy. With no obvious benefit. As a consequence of these and other studies, the recommendations for mammography have changed. Doctors used to recommend that all women between 40 and 74 years of age get a mammogram every two years. Now the United States Preventive Services Task Force recommends screening starting at 50, not 40 years of age. There were just too many noncancers that were called cancers—and women were suffering needlessly as a result.
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