Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives

by Michael Specter

  And we are doing just that. Researchers throughout the country and the world are fabricating synthetic molecules that mimic those found in nature. Ten years ago there wasn’t even enough basic knowledge to attempt this kind of research. These companies are not interested in making fake corn or pursuing effective ways to manufacture fertilizer for farmers who really don’t need it. Instead, they seek to fuel cars and power factories without releasing greenhouse gases. That would not only keep us from blanketing the earth in carbon dioxide, but would go a long way toward counteracting the foolish and expedient decision to make fuel from the corn, sugar, and soybeans that the rapidly growing population of the world so desperately needs to eat.

  To accomplish any of this we will have to recognize denialism when we see it. As a society and as individuals, that means asking tough, skeptical questions, then demanding answers supported by compelling evidence. When the government, a company, or any other group makes a claim, we need to scrutinize that claim with care but without passion. Most importantly, we must learn to accept data that has been properly judged and verified—no matter what it says, or how much we might have wished that it pointed in another direction.

  I wonder, as the ice sheet in Greenland disappears, the seas rise, and our sense of planetary foreboding grows, will denialists consider the genetically engineered organisms that propel our cars and sustain our factories as a continuation of what Lord Melchett described as a war against nature? Or will they see them for what they are, the latest—and grandest—stage in our march toward human enrichment?

  1

  Vioxx and the Fear of Science

  The daily work of science can be repetitive and dreary. Even the most talented researchers spend the bulk of their lives bathed in the fluorescent light of the laboratory, hovering over a bench, staring at slides, and hunting for meaningful patterns in strings of numbers. Still, like many of his colleagues, the cardiologist Eric Topol had always dreamed that one day he might have his “eureka” moment—a flash of insight that would permit him to see clearly what others couldn’t see at all. In 2001, Topol got his wish—but not in a way he had ever imagined; there were no shouts of joy, no elation or champagne, nothing of the kind. “I was just sad,” he said, remembering the moment when he realized that one of the nation’s most popular new medications was killing people. “Then I was angry, and eventually I became outraged.”

  At the time, Topol was chairman of the Cleveland Clinic’s cardiology department, which he more than any other physician had transformed into one of the finest in American medicine. His research into how to prevent and treat heart attacks was highly valued and constantly cited. As perhaps the clinic’s most visible face, Topol was already prominent. But it was his role in helping to expose the grave risks posed by the anti-inflammatory drug Vioxx that turned him into one of the country’s best-known doctors. It also made him one of the most controversial, in part because he repeatedly stressed how little regard the Food and Drug Administration seemed to have for the hundreds of millions of people it had been created to protect.

  The cloak of invincibility had long before been stripped from any government agency, replaced by the constants of doubt and denial; politicians, scientists, doctors, and lawyers are held in lower esteem today than at any time in decades. Yet no previous incident—not the explosion of the space shuttle Challenger, Ford’s willingness to dump a death trap called the Pinto on the American public, not even the nuclear accident at Three Mile Island—demonstrates more vividly why that mistrust has become so pervasive.

  Vioxx was introduced by Merck with great enthusiasm in 1999, one of a new class of drugs called cox-2 inhibitors, which were designed to interfere with an enzyme called cyclooxygenase-2, which, among more beneficial duties, produces chemicals that cause inflammation (and pain). Before Vioxx appeared, hundreds of thousands of people who suffered the debilitating effects of arthritis and other chronic ailments faced an unpleasant choice every day: they could take drugs like aspirin or Advil, or they could endure agony in order to avoid the bleeding ulcers and other serious stomach complications those drugs can cause. Vioxx was referred to as “super aspirin,” which didn’t seem like much of an exaggeration: in early studies it offered better pain relief than any traditional remedy, and was far less likely to disturb the stomach. The drug quickly came to be seen by those who needed it most as a kind of magic potion, one that only the tools of modern medicine could have produced. Driven in part by one of the most aggressive advertising campaigns in medical history, more than twenty million Americans took Vioxx at one time or another. In 2003 alone, Merck sold more than $2.5 billion worth of the drug.

  Topol, who suffered from an arthritic knee, loved Vioxx. Even now he readily attests to its effectiveness. “Nothing worked as well for me before or since,” he said. “Vioxx truly dulled the pain.” One February morning in 2001, though, he noticed a report that struck him as odd. Topol had been invited to deliver a lecture about the future of cardiac care to a gathering at the Medical College of Georgia in Augusta. Over breakfast at his hotel, he started to page through the copy of USA Today that he found on his doorstep. One particular story leapt out at him. “It was about Vioxx,” he said, “and this study,” called VIGOR—Vioxx Gastrointestinal Outcomes Research—“which was intended to determine whether Vioxx really was easier on the stomach than other, less powerful nonsteroidal anti-inflammatory medication.”

  Between January and July 1999, researchers had followed eight thousand patients with rheumatoid arthritis. Half took Vioxx to control their pain; the other half took naproxen, which is sold over the counter as Aleve. (It was a large and fairly conventional randomly assigned, double-blind study—which meant that the patients had no idea which of the two drugs they were taking, and neither did their doctors.) The first time the safety committee assigned to monitor the study looked at the data, it found exactly what one might have expected: people in the Vioxx group were less likely to experience significant stomach distress than those who took Aleve.

  The trial also showed something that had not been anticipated, and the news there was disturbing: participants who already suffered from heart disease were far more likely to have heart attacks if taking Vioxx than if they had been given Aleve. Nobody was sure why, and because Merck had never expressed concern about the drug’s effect on the heart, there were no cardiologists on the safety committee (which was not unusual since that wasn’t the purpose of the trial). Scientists wondered if the difference might have been due to the fact that people in the trial were required to stop taking aspirin, since it can lower the risk of heart attack or stroke. It was also possible that something previously unrecognized about the chemical composition of Aleve itself helped protect the cardiovascular system. (That would have provided a benign explanation for the differing rate of heart attacks, and Merck endorsed the hypothesis with great enthusiasm.)

  “I was not a drug safety expert and I never even had any interest in the issue,” Topol said. “My principal research was in heart disease and heart attacks, and that dates back more than twenty years.” Topol had made a name for himself as a postdoctoral researcher at the University of California at San Francisco. He then took a job at Johns Hopkins University, where he became the first physician to treat heart attacks with the powerful clot-busting agent known as tPA; he also directed a pivotal study that compared the efficacy of that drug with an older treatment, streptokinase, in saving lives. In 1991, Topol moved to the Cleveland Clinic, where for the next fifteen years he served as chairman of the department of cardiovascular medicine.

  What Topol saw in USA Today that morning in Augusta made no sense to him. “Why would a new anti-inflammatory agent prove less protective against heart attacks than the one you can buy at a pharmacy with no prescription?” he wondered. Yet, the newspaper report suggested that patients taking Vioxx were more than twice as likely to have heart attacks as those taking Aleve. For people with a history of heart disease, the risk was far higher. (Risk numbers don�
��t mean much unless they are accompanied by some assessment of the statistical probability that those risks could occur by chance. In this study, which at the time was the largest ever conducted using Vioxx, that number was .002—two in one thousand. In other words, if the study were repeated a thousand times, results like those would appear by chance twice.) “I thought, that is interesting, they are saying a highly touted experimental drug was not as good as the one you buy in the drugstore,” Topol said. “They weren’t saying anything about Vioxx causing heart attacks, just that Aleve seemed better at preventing them.”

  The distinction was crucial because after the data was made public, Merck asserted, as it would for the following three years, that Vioxx posed no increased risk of heart attack or stroke. “It did seem strange,” Topol said, “but I didn’t give it a lot of thought. After all, that’s why you do clinical studies—and so it looked like maybe Aleve had some protective effect we didn’t know about. Surprising as that would have been, it certainly wasn’t beyond the realm of possibility. Still, it wasn’t my thing and I didn’t dwell on it.”

  Topol delivered his address and returned to Cleveland, where Debabrata Mukherjee—“one of my fellows and a brilliant scientist”—had also seen the report which showed that people using Vioxx were far more likely to suffer from heart attacks than those taking over-the-counter pain medication. Mukherjee became intensely curious about the reasons for such surprising results. He dove into the data that Merck had been required to provide the FDA, and soon realized that the initial report failed to include all the essential information at Merck’s disposal. (Nor could he find any scientific support for the company’s suggestion that the results reflected Aleve’s previously unrecognized protective powers rather than the dangers of Vioxx.)

  “Deb had gone onto the FDA Web site to look at all the data presented in the advisory committee meetings—something, by the way, that I had never done,” Topol said, shaking his head with a wan smile of admiration for the diligence of his young colleague. Vioxx was not the only cox-2 inhibitor on the market; Celebrex, made by Pfizer, was introduced that same year, and Bextra had also recently been approved by the FDA. But each drug functioned in a slightly different way and the numbers for Vioxx were more disturbing than those for either of the others. Mukherjee told Topol that there was a “real problem with Vioxx in particular,” he recalled. “I had many other things on my mind so I said, ‘Nahhh, it’s not that big a deal. We have different work to do. Let’s not waste our time on this.’ Deb wouldn’t have it. He insisted that I look at the data with him, absolutely insisted. So I did.”

  Once Topol had the statistics in front of him, he saw why Mukherjee had become so agitated. “The evidence was right there,” he said. “I still cannot believe that nobody else had seen it. That’s when I began to understand what was really going on in that USA Today story. It just clicked: the company was attributing these miraculous functions to Aleve instead of investigating the potential dangers of their new drug. They were playing games: what they said at the time didn’t seem to be an outright lie, but it also wasn’t the truth that people needed to know. I said let’s write this up. After all, these data mattered. It wasn’t even a heart study, it was supposed to assess stomach complications, but you can’t just shy away from information like that. There were too many lives at stake.”

  Topol and Mukherjee quickly put a paper together, along with Steven Nissen, another prominent cardiologist at the Cleveland Clinic, who had attended the advisory meeting where Vioxx was approved. “Deb drove the research and I gave it a framework,” Topol said. The paper was the first independent analysis to include all the data the FDA had obtained from the VIGOR study, and it cast serious doubt on the supposition that naproxen offered special cardiovascular protection. The study was published in the Journal of the American Medical Association later that year. The three stopped short of calling for a moratorium on the use of Vioxx—the data at their disposal were not conclusive enough to warrant such a suggestion. However, they did warn doctors to take special care when prescribing the drug to people with heart disease. In their review, the authors stressed that Vioxx and other cox-2 inhibitors could cause serious side effects, and that a broader examination of their impact would be essential. “Given the remarkable exposure and popularity of this new class of medications,” they wrote, “we believe that it is mandatory to conduct a trial specifically assessing cardiovascular risk and benefit of these agents. Until then, we urge caution in prescribing these agents to patients at risk for cardiovascular morbidity.”

  ERIC TOPOL IS TANNED and trim, a gangly man in his fifties with an oval face, graying hair that has begun to thin, and the type of relaxed affect that only someone who moves from a climate like Cleveland’s to balmy San Diego could cultivate. Today, Topol has an entirely new kind of job: he is professor of genomics and the director of the Scripps Translational Science Institute in La Jolla. Scripps, one of the nation’s largest biomedical research organizations, is eager to apply the emerging science of genomics—the information contained within our genes—to clinical medicine. Topol believes genetics will soon provide the knowledge we need to make substantial reductions in the incidence of heart disease. And that knowledge, of genetic predispositions and their implications for individuals, is increasing rapidly. Naturally, any reduction in the rate of heart disease, which kills at least a million Americans every year, would have a profound impact on public health. The field is young, and it hasn’t been long since Scripps decided to invest heavily in it. When I visited La Jolla in the spring of 2008, the institute’s building was only partially finished. Several floors consisted of little more than concrete shells and plastic sheeting. The setting, though, was spectacular: Topol’s office looks out onto the Torrey Pines Golf Course, and beyond that, the Pacific Ocean. As I watched from his office window, dozens of people floated by on parasails before gently setting down in the shimmering green sea.

  If Topol’s life seems enviable, it hasn’t been that way for long. His persistent criticism of Merck and, by implication, of the FDA, lasted three years, during which time Vioxx killed thousands of people. Topol found himself an outcast in his own profession, shunned for his warnings and eventually driven from the department he made famous. “There were years of sleepless nights, of bitterness,” he said, speaking almost as if he were describing the ordeal of another person. “Years during which I allowed myself to wonder what on earth were we doing to people in the name of science.” He came to realize that Merck possessed data that should have led the company to question Vioxx’s safety long before it was approved.

  Research published in the British medical journal the Lancet has estimated that 88,000 Americans had heart attacks after taking Vioxx, and that 38,000 of them died. In testimony before Congress, David Graham, the FDA’s senior drug safety researcher, said the death toll may have reached as high as 55,000—almost exactly the number of American soldiers killed in the Vietnam War. (We will never know for sure; there is no precise way to account for the number of deaths caused by a drug like Vioxx, which was taken by millions of people. It’s easy to notice an increased rate of heart attacks in a large group. Proving with certainty the specific cause of any one of them is nearly impossible.)

  “This was one of the most remarkable breaches of trust in American scientific history,” Topol said. He stood up and poured coffee. “It has been years now and even today nothing fundamental has occurred to ensure that this won’t happen again. That is what amazes me. It is as if we took nothing from this tragedy but fear and a sense that those scientists were liars. One of the most important drugs of our time was released without the proper safety checks, and after the company’s own scientists wondered in writing whether it would kill people. When Americans say they are skittish about the drug system and about conventional medicine itself, can anyone really be surprised?”

  There have been a raft of studies released about Vioxx—from the Government Accountability Office, the Institute of Medicine
, and many private organizations; eventually both the Senate Finance Committee and the House Committee on Government Reform held hearings. Every report, and much of the testimony, described the FDA’s bureaucratic inefficiencies, its reluctance to take controversial positions, and Merck’s willingness to exploit those weaknesses. “The FDA set up an internal safety auditing group for drugs going onto the market,” Topol said. “They have responded by approving fewer new drugs than at any time in their history. The organization is just paralyzed.”

  By the end of the millennium, Americans had come to assume that a drug approved by the federal government was a drug they could swallow without wondering whether it would kill them. Vioxx changed all that. Thousands of lawsuits later, in 2007, the company placed nearly $5 billion into a settlement fund. That deposit permitted Merck to avoid nearly fifty thousand lawsuits. It also brought an end to hundreds of class-action cases filed on behalf of dead or injured Vioxx users, which, had they succeeded, could well have put Merck out of business. The settlement was the largest ever made by a pharmaceutical company. As part of the deal, Merck was never forced to admit fault in a single one of those deaths.

  The Vioxx episode wove strands of fear and uncertainty together with an inchoate sense, shared by large swaths of American society, that we are ceding control of our lives to technology, particularly to highly sophisticated technology we can barely understand, and that we are doing so at a speed that seems to accelerate every year. Denialism is at least partly a defense against that sense of helplessness. What person, after watching Vioxx kill her husband, wouldn’t say no to the next wonder drug? The story line—a predatory drug company lusting for profits—is not entirely new. The notion of technology as a force that does more harm than good, and of scientists toying with human life, dates back at least to Shelley and Goethe. Rousseau, the first Romantic, longed for the innocence and supposed simplicity of nature. He was convinced that science would have a pernicious effect on society, promising more than it could possibly deliver. G. K. Chesterton, in his book Eugenics and Other Evils, was even more direct, referring to organized science as “government tyranny.”