Pharmageddon (18 page)

We can bring some of our current difficulties and disquiet into focus by revisiting the relation of medicine and industry in the 1930s and 1940s. In the 1930s, SmithKline and French (SK&F) bought d,l amphetamine (Benzedrine) from its maker Gordon Alles as a treatment for asthma and other respiratory problems. In an early example of what would now be called disease mongering, SK&F in the 1940s promoted the views of an “opinion leader,” Tufts psychiatrist Abraham Myerson, that anhedonia (a forerunner of today's depression) would respond to amphetamines. The company also marketed an amphetamine variant, d amphetamine (dexamphetamine, or Dexedrine), as a treatment for what they characterized and marketed as pre-obesity.

In addition to disease-mongering, the company was involved in ghostwriting and other manipulations of the literature. There is good evidence, for example, that SK&F helped draft the outlines of an article for Louis Sulman, a University of Pennsylvania otolaryngologist, who suggested that Benzedrine might prevent colds.
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They prepared illustrations and almost certainly wrote entire manuscripts for Joseph Scarano, a Philadelphia doctor who praised Dexedrine.
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They also appear to have been able to discourage University of Minnesota's Howard Diehl from publishing evidence demonstrating that Benzedrine was of no use for colds.
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And they had a research contract with Dr. Ella Roberts in which the company granted itself the right to block publication of the findings of any research if it so chose.
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Today it is de rigueur for academics to declare possible conflicts of interest, such as their links to industry. It is no longer acceptable to do as Soma Weiss, a professor of medicine at Harvard and chair of the American Medical Association's Council on Pharmacy Approval system, did in a 1939 pharmacology review endorsing Benzedrine as one of the most promising drugs ever developed without acknowledging SK&F's five-year grant to his Boston clinic.
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Though it is rare to find any declarations of conflicting interests in academic articles before 1990, this is not because they didn't exist.

When it comes to drug hazards, such as the possible addictiveness of Benzedrine, SK&F retained libel lawyers and threatened to sue the next periodical that suggested that Benzedrine was addictive. The company also actively supported publications from experts in the field that might suggest that concerns about Benzedrine's addictive potential were overblown.
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Ghostwriting, concealed conflicts of interests, obstruction of legitimate concerns about a drug's dangers, and the marketing of diseases to market a medicine are all features of the medico-pharmaceutical complex that today draw the fire of critics concerned about the corruption of medicine. The Benzedrine example indicates that such practices can be found in decades past as well. But there's a difference. Examples like these for SK&F confirmed for academics that the sales and marketing divisions of companies were populated by “scurvy knaves.”
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Up to about 1980 there had been something of a firewall between academia and industry. It was the kiss of death for any physician or scientist aspiring to an academic career to join industry. Academics were under no illusions that pharmaceutical companies were anything but a business, with a dedication to the bottom line.

But starting in the 1980s, the situation changed, giving rise at the same time to both our current concerns (and new manifestations of old ones) and the exhortations to partner with industry. The change was not that industry became more rapacious or that academics stooped to new levels of venality. The change has lain in the industrialization of a set of processes in the research, development, delivery, defense, and marketing of pharmaceuticals. Companies have not become more commercial, any more than Henry Ford was more commercial than other car manufacturers of his day when he turned to assembly line manufacture. Pharmaceutical companies may have even become more ethical and more adherent to the law's letter, but following the advice of the management consultants they hired in the late 1960s they have, like Henry Ford, turned to assembly lines.

As clinical trials became of central importance after 1962, pharmaceutical companies have dissected and reengineered their business to produce and deliver quality clinical-trial products in a timely fashion and to develop much of their marketing around them. And as clinical trials became ever more important, companies appeared to be ever more involved in doing science rather than business. Against this background efforts to encourage academics to partner with industry seemed to many less problematic.

To the major pharmaceutical companies, however, it has become increasingly clear that a prime purpose of clinical trials, beyond that of gaining regulatory approval, is to secure or maintain a marketing niche for their product and sometimes the disorder it's meant to treat along with it. Companies have no interest in doing studies to answer scientific or therapeutic questions. The only trials that count are the ones that turn up a positive result that can be published in a reputable journal with the names of leading academics as the authors. This is the process that companies have industrialized, out of which they expect quality and timely publications that optimize their ability to sell the company's product, or help them counter any claims regarding problems the drug may cause. And central to their ability to achieve these ends is the fact that they are able to sequester study data.

The many people grappling with what is going wrong on the interface between medicine and the pharmaceutical industry look at the academics who end up on authorship lines of studies like these Zoloft PTSD studies or Study 329 and to the reviewers who fail to spot problems, and instead critique the conflict of interests—the payments academics get for lectures, for participation in research, for consulting arrangements, or for the shares they may hold in pharmaceutical companies. They call for conflict-of-interest declarations or sets of rules about authorship.

The academics caught in the crossfire are often bewildered. They don't have the experience of having been paid and then changing their views—in part for the simple reason that this isn't what happens. Companies can select from among available academics those who have views that suit the task at hand. To be selected in this fashion is not a crime—some of our most celebrated scientific breakthroughs have come to light in this way. John Snow's suggestion in the midst of the 1850s cholera epidemic in London of removing the handle from the Broad Street pump was only heard because it suited the commercial interests of abattoir owners and others who were being blamed for the epidemic to sponsor a public meeting at which the finger of blame might be pointed in another direction.
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If there is a problem it lies in current patent arrangements that fail to pit competing drugs or companies against each other. As a result all experts for all companies sing from the same song sheet now in a way that didn't happen with John Snow. We do not have conditions in which facts are likely to be contested, but to blame this on the experts who are hired by companies seems to miss the mark.

Indeed it is almost certainly a mistake to think that scientists in general are disinterested or do things for lofty motives. The history of science makes it clear that individual scientists have often been deluded or obsessive or have pursued their hunches for a variety of motives, be it a desire for fame or money or because of a grudge against someone holding competing views. Science can harness all these motivations provided others can scrutinize the data and decide whether the claims being made actually do follow these data. The objectivity of science lies in the group rather than the individual, and in this sense paying a professor for a talk should make little difference in the larger scheme of things. The problem does not lie in the involvement of private companies in science but rather in our collective failure in ensuring that all parties, including the government, play by the rules of science.

Science is not value free. It values data. Science is not about publishing the appearances of a scientific experiment, it is about replicable data. But for some reason the normal rules of science appear to be suspended in proximity to a pharmaceutical company.

In these circumstances of inaccessible evidence and failure to sponsor open, independent tests, company trials have become the petard on which medicine is being hoisted. Where briefly in the 1950s drug companies might have seen themselves as adding to medical culture by undertaking clinical trials, this is no longer how they view things. In fact, what they do now replaces any culture there once was in medicine. Diseases of many sorts now come and go at the whim of marketing departments.

Any process that generates new insights and reveals new phenomena will inevitably throw up opportunities for commercial exploitation, and science is no exception. From the developments in chemistry in the nineteenth century that laid the basis for the creation of rubber and plastic products or in physics that underpin the computer industries or space exploration today, an ever-increasing proportion of our industries are science based. Science is also the ultimate free market, where an invisible hand does lead to progress in knowledge, whether by playing on our desire to solve puzzles or on our self-interest. As such, science might appear ideologically to be on the same side as capitalism. But insofar as commerce depends on secrecy and acquisitive self-interest rather than free communication of data and other findings, business will inevitably be as inimical to science as the Catholic Church once was to Galileo or Soviet Communism later was to evolutionary biology.

Rather than focus on this secrecy, many concerned at the growing mismatch between therapeutic success and publication rhetoric see the problem as stemming from someone somewhere being corrupted. At present the focus is restricted to the relatively small amounts of money given to some doctors to deliver lectures or participate in clinical trials. If conflict of interest is as important as claimed, then there are other areas to consider also, one of which is the availability of drugs by prescription only; prescribing drugs is a large part of their job for many doctors and prescription-only privileges keep many of them in a job worth hundreds of thousands of dollars. Another area of conflict stems from current patent law, which drives blockbuster development as well as prices of company shares. In the years covering the success of their antidepressant Prozac and the emergence of Zyprexa, 1987 to 2000, Lilly employees netted $3.1 billion from stock options they exercised, quite aside from any salaries or bonuses.
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These payments also dwarf any consulting fees that the average academic is likely to receive.

The paradox that few grapple with is that in one sense we want conflicts of interest—a complete absence of conflicts would mean that no one has anything that works or anything about which they are passionate. The weaker the treatment, the more likely companies are to employ banks of speakers to compensate—but this only works in conditions where the data underpinning claims are inaccessible or the experts are bamboozled by the statistical decorations on the data into thinking that the latest fashion is something that is likely to protect us against the gales of a serious disease.

THROUGH THE LOOKING GLASS

Where the creation of bacteriology was one of the glories of nineteenth- century medical science, the role of epidemiology in identifying the toxic effects of lead in paint or fuel, as well as the effects of tobacco, asbestos, vinyl chloride, benzene, or other organic chemicals on respiratory function or tumor growth were among the glories of mid-twentieth-century medicine. This put medicine on a collision course with business.

In the nineteenth century Robert Koch's and Louis Pasteur's ideas about germs faced the typical resistance to new scientific ideas. In the twentieth century, corporations producing chemical pollutants, from vinyl chloride and benzene to tobacco, brought financial might to resisting the new scientific ideas that linked their products to cancers or other medical disorders. This financial might enabled companies to invade and attempt to colonize science with apparently independent but in fact corporate-sponsored research, through appeals to studies that have the appearance of research but which are in fact opinion pieces aimed at discrediting linkages between company products and ill health. The most famous of these defenses has been that of the tobacco industry which, under the banner “doubt is our product,” turned scientific doubt inside out, transforming it from a means to detect truth into a means to conceal the truth.
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And it was tobacco-company lobbying that led in 1999 to the US Data Access Act that ensures access to scientific data—company access, that is, to the data of independent or federally funded studies that have demonstrated harm from chemicals, yet with no reciprocal rights granted to the public or independent scientists for access to data from company studies.
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Still, medical professionals, scientists, and others who have tackled the links between polluting companies and disease have had some advantages. The people injured by chemicals have, for the most part, been healthy before exposure. This puts an elephant in the room that can't easily be ignored. In addition, while manufacture of the items of which these chemicals are typically byproducts might be good for the economy, no one thinks these chemicals are likely to be good for individuals. While not always the case, many of the classic industrial injuries induced by chemicals clustered in the neighborhood of a plant. And most importantly doctors don't make a living from prescribing vinyl chloride, benzene, tobacco, or lead.

In contrast, efforts to tackle medically induced problems have some additional hurdles to overcome. People who may be injured by
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chemicals typically have something wrong with them to begin with, so that any defense of the product can appeal to a patient's original sin as the real problem. And the injuries that a medicine causes are likely to be distributed right across the United States and Europe, making them harder to spot than the clusters of a new illness that pop up around a power plant or other new industrial facility. Also of great importance, doctors, who might otherwise spot the problem, not only make a living out of these same medical chemicals but prescribe them believing they are doing good for people.