It would be hard to find many examples in the past four centuries of scientists acting together to threaten humanity. Only a few are necessary, though, and there have been enough dark moments along the remarkable march of progress to generate anxiety and feed denial. Most of those moments were caused by error, not evil. Yes, in 1970 the Ford Motor Company, probably the definitive industrial symbol of twentieth-century America, introduced a car, the Pinto, that its engineers knew was likely to kill passengers. (Before the Pinto was introduced, in what may well stand out as the most remarkable memo in the history of engineering, Ford statisticians argued that the $11 cost of fixing each car added up to more than twice the amount of money—at $200,000 per burn death and $67,000 for each serious injury—that they would have had to pay in lawsuits or settlements.)
More often, there are simpler reasons to question the primacy of science and technology. In the name of improving our lives, some of the smartest people on earth have managed to ruin quite a few of them. DES, or diethylstilbestrol, was the first synthetic estrogen. It was cheap, easy to produce, and unusually potent. First prescribed in 1938, DES was given to women who had experienced miscarriages or premature deliveries. Despite mixed results in the laboratory, the drug was considered safe and effective both for a pregnant woman and her developing fetus. It wasn’t. In the United States, as many as ten million people were exposed to DES by 1971, when it was pulled from the market. “DES Daughters,” as they came to be known, are at increased risk for several types of cancer, as well as structural abnormalities of the reproductive tract, complications with pregnancy, and infertility.
Fear builds far more easily than it dissipates. Ronald Reagan once famously claimed that the “nine most terrifying words in the English language are: ‘I’m from the government and I’m here to help.’ ” If anyone needed a reminder of how far our faith in science had fallen by the end of the twentieth century, Vioxx demonstrated that five other words could prove just as frightening: “Trust me, I’m a scientist.” It was quite a crash. Pharmaceutical companies were among the most highly valued institutions in America after World War II, and it’s not hard to see why. They introduced the core values of consumer culture to American medicine. Drugs became like everything else Made in America: products meant to ease life and solve problems.
The flood of new antibiotics and the rapid development of vaccinations for everything from diphtheria to polio helped define the spirit of the country with a single word: optimism. America was a can-do nation and it possessed technology that would solve the world’s problems. From infectious disease to cancer, and from pollution to hunger, we would overcome it all. Nylon, Lycra, Teflon, Kevlar, and Mylar, for example—all made by DuPont—were all triumphs of ease and modernity. We could fix whatever was broken, cure whatever ailed us, and make life easier for everyone along the way. Today the words “DuPont,” “Merck,” and “Monsanto” are often used as epithets, and they compete with tobacco companies for the role of the most loathed American corporations. Conventional medicine and technology itself, despite their clear rates of success, seem to many people as likely to cause danger as to enhance our lives.
In a Harris poll of attitudes toward corporate America published in 2008, just 27 percent of respondents said they “somewhat or strongly” trusted the pharmaceutical industry. More than half described their views as firmly negative, which places Big Pharma slightly below Big Oil, and a bit above tobacco companies, in the esteem of the average American. The figures for the FDA were only marginally higher. What was written with sincerity only a few decades ago is now played strictly for laughs: in 2006, the satirical newspaper the Onion ran a story in its “Science and Technology” section under this headline: “Wonder Drug Inspires Deep, Unwavering Love of Pharmaceutical Companies.” The year before, a film version of John le Carré’s novel The Constant Gardener was released. Like the book, it portrayed an international pharmaceutical conglomerate as avaricious and cartoonishly evil. The plot was ludicrous and appealed to the worst possible stereotypes of mindless capitalism. But people ate it up.
Vioxx and other preventable catastrophes ensured that they would. Corporations, wrapping themselves in the mantle of progress but all too often propelled by greed, have done more than religion or even Luddism to inflame denialists and raise doubts about the objectivity of science. In 2008, reports surfaced that for more than a year, Merck and Schering-Plough concealed the fact that their jointly marketed cholesterol drug, Vytorin, was no more effective than generic statins costing less than half as much. Nonetheless, the companies still spent more than $100 million during that time to advertise the drug’s special qualities.
News like that has become routine. In early 2009, the British company AstraZeneca was found to have somehow mislaid unfavorable studies about its antipsychotic drug Seroquel. At about the same time, more than one hundred students at the Harvard Medical School publicly questioned the ethics of their professors, some of whom are frequently paid as consultants by the pharmaceutical companies whose products they are supposed to judge. The situation got so bad that the Institute of Medicine, the branch of the National Academy of Sciences charged with providing advice on critical issues of medical research, denounced physicians who accepted money from drug companies. “It is time for medical schools to end a number of long-accepted relationships and practices that create conflicts of interest, threaten the integrity of their missions and their reputations, and put public trust in jeopardy,” the IOM concluded in a report. Just two weeks later, the Scientist revealed that Merck had published a journal filled with favorable articles about more than one of the company’s drugs, without ever bothering to disclose that the publication, the Australasian Journal of Bone and Joint Medicine, was sponsored by the company itself. “To the jaundiced eye, [the journal] might be detected for what it is: marketing,” Public Citizen’s Peter Lurie said. “Many doctors would fail to identify that and might be influenced by what they read.”
If all that wasn’t sufficiently damning, the Baystate Medical Center in Springfield, Massachusetts, revealed that Scott S. Reuben, its highly influential former physician in charge of acute pain treatment, fabricated data from twenty-one medical studies that claimed to show the benefits of painkillers like Vioxx and Celebrex. “The pharmas are in big trouble in terms of credibility,” said Rob Frankel, a brand consultant who focuses on medical industries. “They’re just above Congress and used-car salesmen.”
THIRTY YEARS AGO NOBODY discussed the principal motive behind scientific research: nobody needed to. It was a quest for knowledge. Today, the default assumption is that money matters most of all, and people tend to see science through the prism of commerce. At least until Viagra was introduced, and endorsed on television by Bob Dole, a former candidate for the presidency, no drug had been marketed more successfully than Vioxx. In 2000, the year after it first appeared, Merck spent $160 million advertising their painkiller. They were able to do that thanks to the advent, just three years before, of direct-to-consumer advertising. Only two countries allowed pharmaceutical companies to advertise prescription drugs directly to consumers: New Zealand and the United States.
In America, such ads virtually always consist of glossy promotional materials used to announce major medical advances. (The federal government requires that they include tiny print “information” presented in medical jargon, the meaning of which, for most consumers, is nearly impossible to understand.) These advertisements are not really intended to educate patients, nor to help them become more sophisticated about their own health. They are purely an attempt to get doctors to fill more prescriptions, and they work with stunning regularity. “Blockbuster” drugs like Vioxx, Viagra, and the cholesterol medicine Lipitor can become a multinational corporation’s central source of income.
Our regulatory system encourages companies to invest in marketing, not in research: in the United States, a new drug typically takes a decade to develop and costs hundreds of millions of dollars. With stakes that high
, and lawsuits waiting for any company that commits even the smallest error, pharmaceutical firms are far more likely to profit from aggressive sales of products that are already available than from introducing anything new. One reason the ads succeed is that it is nearly impossible to spend a day without seeing one or more major drugs advertised on television. (Another reason is the amount of money companies spend. The marketing budget for AstraZeneca’s heartburn pill Nexium, a sure moneymaker, is bigger than the comparable budget for Budweiser beer.)
Rheumatoid arthritis afflicts more than two million Americans, and it can be devastating. Many of those people were overjoyed when advertisements for Vioxx began blanketing the airwaves in 1999. Suddenly, men who couldn’t bend over were tying their shoes again, walking dogs, and regaining lives that slowly had been consumed by pain. Dorothy Hamill skated across millions of television screens on behalf of Vioxx, overcoming arthritis and moving with the nimble certainty of a teenager at the Olympics. “People dancing in the streets, twirling their partners in joy,” Topol said. “That’s all anybody ever saw.” Go talk to your doctor about Vioxx, the ad would say. And people did, by the millions. In 1996, American pharmaceutical companies spent $11.4 billion on direct advertisements; by 2005 the figure was more than $29 billion. Doctors were overwhelmed with requests, and for the most part were only too happy to comply, writing nearly one hundred million prescriptions for Vioxx alone between 1999 and 2004.
The words “ask your doctor” have become code for “change your prescription.” Often, what people ended up with was no better than the cheaper and more readily available drugs they were taking in the first place. And just as often, the drugs for sale were so new to the market that their safety was hard to gauge. “Americans must face an inconvenient truth about drug safety,” Henry Waxman, the veteran California congressman, said when asked his position on the impact of these advertisements. Waxman is perhaps the most astute congressional observer of American medicine, and since the election of Barack Obama, in his new role as chairman of the House Energy and Commerce Committee, he may also be the most powerful. “The truth is that we inevitably allow drugs on the market whose risks are not fully known,” he said. In 2006, the Institute of Medicine suggested a moratorium on such advertising, a brief pause before permitting companies like Merck to hawk powerful chemicals as if they were Cheerios or vacuum cleaners. That would certainly have saved many of the lives lost to Vioxx.
People tend to see what they are looking for, however, and to millions, pain relief was all that mattered. When it comes to getting a message across, the Super Bowl, where ads for drugs like Vioxx and Viagra have been ubiquitous, will always matter more than the New England Journal of Medicine. In this atmosphere, Eric Topol was largely on his own, and he became the target of Merck’s fullest fury. “Merck went after me with all they had,” he told me. Topol had collaborated with Merck often—at the time of his clash with the company over Vioxx he was actually running one of its trials, for the anti-platelet drug Aggrastat. Like most people in his profession, Topol considered Merck a remarkable place. During one stretch beginning in 1987, it was named by Fortune magazine for seven straight years as the most admired corporation in America, a record that remains unmatched. Merck seemed to prove that profits and decency were not incompatible. “I was in no way predisposed to have negative feelings toward Merck,” Topol said. “In fact it was quite the contrary.” None of that mattered, though, because they came after him with a cleaver. “They said my first paper was ‘data dredging,’” by which they meant a pedantic report full of numbers that proved nothing. “They told anyone who would listen that I had been a fine researcher until the day that paper was published, but at that moment I had suddenly lost it. And at the time all I had said was, ‘Wait a minute, there needs to be some more study here.’ ”
By the end of 2001, however, Topol had moved on. He had begun to focus primarily on genomics and his research switched from treating heart attacks to preventing them. Others were studying whether Vioxx increased the risk of heart attacks, and he felt he had done all he could to address the issue. At the time, Topol had no idea how divisive Vioxx had become at Merck itself. It turned out that scientists there had worried as early as 1996 about the effect the drug would have on the cardiovascular system. The reason for that concern was clear. Vioxx altered the ratio of two crucial substances, the hormone prostacyclin and a molecule called thromboxane, which together help balance blood flow and its ability to clot properly. Suppressing prostacyclin reduces inflammation and pain, and that made Vioxx work. Suppress it too powerfully, however, and thromboxane can cause increased blood pressure and too much clotting, either of which can lead to heart attacks. By 2002, Merck decided to embark on a major study of the cardiovascular risks caused by Vioxx—just as Topol and his colleagues had suggested. The trial would have produced useful data fairly rapidly, but just before it began, the company abruptly scuttled the project. In the end, Merck never made any significant effort to assess the cardiovascular risk posed by its most successful product.
Instead, the company issued a “Cardiovascular Card” to sales representatives. More than three thousand members of the sales force were instructed to refer doctors with questions to the card, which claimed—falsely—that Vioxx was eight to eleven times safer than other similar painkillers. The sales reps were told to produce the card only when all else had failed, to help “physicians in response to their questions regarding the cardiovascular effects of Vioxx.” The FDA, realizing that doctors needed to understand the gravity of the findings from the VIGOR trial, issued a strongly worded letter instructing Merck to correct the record. “Your claim in the press release that Vioxx has a ‘favorable cardiovascular safety profile,’” the letter read in part, “is simply incomprehensible, given the rate of heart attack and serious cardiovascular events compared to naproxen.” The company reacted swiftly: “Do not initiate discussions of the FDA arthritis committee . . . or the results of the . . . VIGOR study,” the sales force was told. If doctors proved too querulous, the Merck representatives were instructed to respond by saying, “I cannot discuss the study with you.”
In the summer of 2004, the Lancet asked Topol and the gastroenterologist Gary W. Falk, a colleague of Topol’s from the Cleveland Clinic, to sum up the state of knowledge about Vioxx and similar drugs known, as a class, by the name coxibs. Their editorial was published that August under the title “A Coxib a Day Won’t Keep the Doctor Away. Topol was taken aback when he realized how little had changed. “It was amazing to see that nothing had been done in three years,” he recalled. “It was not even clear that Vioxx protected the stomach. It cost four dollars a day for these darn pills.” On September 29 of that year, Topol happened to dine with Roy Vagelos, Merck’s much-admired former chief executive, who had been retired for nearly a decade. Topol was visiting a New York-based biopharmaceutical company called Regeneron whose board Vagelos chairs. There were few people in medicine for whom Topol had as much respect. “We started talking about Vioxx,” he said. “It was the first time I ever spoke to Roy about it. I remember that conversation well: it was at Ruth’s Chris Steak House in Westchester. Roy went on for a while. He was entirely opposed to the Merck approach to Vioxx. And he didn’t mince words.”
The following morning a Merck cardiologist called Topol and told him the company was removing Vioxx from the market. Another trial had shown that patients taking the drug were at increased risk of heart attack and stroke. That study, APPROVe, began in 2000 as an attempt to discover whether Vioxx helped prevent the recurrence of colon polyps. It didn’t. “I was shocked,” Topol said. “But I thought that it was responsible for them to pull it. And Steve Nissen came down to my office, also very pleased, and said, ‘Isn’t that great? They are pulling the drug.’ We both thought it was the right thing to do.”
For Topol, that could well have been how the story ended. But Merck began to mount a press offensive. The message never varied: Merck put patients first. “Everything they
had ever done in the course of Vioxx was putting patients first. All the data was out there,” Topol said, still stunned by the brazen public lies. “This just wasn’t true. It wasn’t right. I called and tried to speak to Ray Gilmartin”—Merck’s chief executive. “Neither he nor anyone else returned my calls.” (That itself was significant: after all, Topol ran one of the most important cardiology departments in the country; he was also the director of a Merck drug trial.) “This was a breach of trust that really rocked the faith people have in institutions like those,” Topol said. “We are talking about thousands of heart attacks. There were simply gross discrepancies in what they presented to the FDA and what was published in journals. I took them on. I had to.”
That week, Topol wrote an op-ed piece for the New York Times. He called it “Vioxx Vanished.” The Times had a better idea: “Good Riddance to a Bad Drug.” Noting that Vioxx increased the risk of heart attacks and strokes, Topol wrote that “our two most common deadly diseases should not be caused by a drug.” He also published a column in the New England Journal of Medicine, called “Failing the Public Health”: “The senior executives at Merck and the leadership at the FDA,” he wrote, “share responsibility for not having taken appropriate action and not recognizing that they are accountable for the public health.”
Denialism: How Irrational Thinking Hinders Scientific Progress, Harms the Planet, and Threatens Our Lives Page 4