Tagamet, Black presented details of his experiments at scientific meetings, stimulating interest among chemists at Glaxo, who also determined to develop an H-2 blocker. Glaxo’s efforts led to Zantac, a drug almost identical to Tagamet. Since Tagamet had been the breakthrough compound and had come on the market in 1979, six years before Zantac, and with the prestige of Black’s endorsement, few doubted that Tagament’s sales would vastly outstrip those of Zantac.
Glaxo, far from undercutting the price of Tagamet, as might have been expected in a normal market, decided to make Zantac pricier. And it put huge resources into marketing, which focused on minor differences in the side-effect profiles of the two drugs. Much to the surprise of observers, Zantac’s revenues soon outstripped Tagamet’s, and it became the first blockbuster—a drug that makes at least a billion dollars per year.9
Glaxo and SmithKline merged at the turn of the millennium to become the biggest pharmaceutical company in the world. But before they did, Glaxo’s response to an exciting development in the science of ulcers is indicative of important shifts that were taking place in the world of medicine and corporate interest. In Australia, Barry Marshall, then a medical resident in Perth, spotted an unusual bacterium, helicobacter pylori, in tissues removed from ulcers. This led him to a series of experiments where he cultured helicobacter, drank it, produced an ulcer, and later cured his own ulcer with antibiotics.10
Marshall made overtures to Glaxo but found they had no interest in a cure for ulcers. The beauty of H-2 blockers was that once they began taking them, many patients remained on them indefinitely. Actually eliminating ulcers, the treatment of which had just become the cash cow of the pharmaceutical industry, was not what Glaxo had in mind. The decade between the contrasting scientific experiments of James Black and Barry Marshall had propelled medicine into a new world, one in which it could not be assumed that science and business were on the same side, as they had appeared to have been over the previous three decades.
Zantac was a brand like no other. It came with attention to color coding, with free pens and trinkets for doctors, and a lot of support for doctors to attend educational meetings nationally and internationally. It set a template for aggressive drug promotion. Its very success led, in reaction, to movements like No Free Lunch, a group set up by Bob Goodman to persuade doctors to remain independent of pharmaceutical companies by refusing the free pens, lunches, and the like that companies handed out so liberally. Glaxo’s aggressive marketing at the end of the 1980s also made many doctors more receptive to the idea that evidence-based medicine, which emerged in the 1990s, could be used as a way to contain the power of marketing.
But No Free Lunch and similar efforts to eliminate conflicts of interest fail to ask just what it is that would make a brand appealing to doctors. A brand is something whose value lies in the perception of the beholder—and in this case doctors repeatedly tell us that the evidence about a drug’s benefits and risks trumps the color coding of the capsule or the lunches, no matter how good they might be. And insofar as creating a brand involves building a set of exclusively positive associations and eliminating any negative associations, this is not going to be done by getting the color right.
The problem is that a brand is meant to be an uncomplicated good. It is a partial truth that seduces by directing our attention away from any messier realities. It doesn’t fart; it doesn’t have body odor. Against a background of clinical complexity it offers a point of reassurance. But it is, by this definition, incompatible with a medicine, which is—or was—understood to be a poison whose delivery involves a judicious balancing of risks and benefits.
The combination of brands like this and prescription-only privileges leads to a tragedy in the classic sense of that word—as with Hamlet, “whose virtues else be they as pure as grace as infinite as man may undergo, shall in the general censure take corruption from the particular fault.” Here’s how. Brands married to product patents have created the conditions that have made blockbusters possible, and the fortunes of pharmaceutical companies increasingly now depend on the success of these blockbusters and their branding. They have to be hyped to the max and their hazards concealed. These dynamics of brand creation are, through prescription-only status, welded to an profound bias in medicine—doctors tend to attribute any benefits in a patient’s state to what they have done and couple this with a tendency to overlook any harm they might have done. Doctors have to be enthusiastic about treatment—their very enthusiasm can make the difference between success and failure. Being readily able also to spot the harms they do would likely in many cases lead to clinical paralysis.
The fortunes of pharmaceutical companies hinge on this weld holding fast. The tragedy is that there is little risk of it coming undone: both companies and clinicians are biased to attribute any harms to the disease being treated—it is depression that gives rise to suicidality in patients on antidepressants, not the drugs; it is the poor state of a person’s arteries that leads to coronary artery bypass surgery and is responsible for any confusion after the surgery rather than anything that happened on the operating table; it is schizophrenia that gives rise to a disfiguring neurological condition, tardive dyskinesia, rather than treatment with anti- psychotics. For thirty years the outcomes for lung cancer have remained almost unchanged. Millions of people have died during this period, after having radical surgery, intense radiotherapy, or intense chemotherapy. If these treatments extended the life of some yet overall life expectancy remained the same, there must also be an equal number whose lives were shortened by treatment, but you will hunt high and low to find any whose deaths are attributed to the treatment rather than the disease.
When it comes to the harms following ingestion of over-the-counter or illegal drugs, from the end of the nineteenth century the medical profession had no difficulty seeing their problems and expressing opinions through bodies such as the AMA. But once the drugs are made available by prescription only through the clinician, there is no independent voice of any standing to urge caution. Against this clinical background, the dynamics of branding produce something close to a pure toxin for medical care.
The contrasting fates of reserpine and Prozac bring this out. In the early 1950s, reserpine, one of the first antihypertensives and first tranquilizers, was linked to suicide induction. Owing to the differing patent regimes at the time, twenty-six different companies produced reserpine and so no one manufacturer could have made it into a proprietary blockbuster. Therefore no company had an incentive to defend it to the death, and as a result while many doctors refused to concede a treatment they gave might have caused a problem, the views of others could be heard. A link between reserpine and agitation was established and reserpine fell into disfavor.
But in 1990, when similar concerns erupted that Prozac could trigger suicides, the situation was quite different. There was and could be only one Prozac, and Lilly had all their eggs in the Prozac basket. They could not readily admit their brand might have a flaw. As Leigh Thompson, Lilly’s chief scientific officer put it in an internal e-mail that later came to light in a court case:
I am concerned about reports I get re UK attitude toward Prozac safety. Leber (FDA) suggested a few minutes ago we use CSM database to compare Prozac aggression and suicidal ideation with other antidepressants in UK. Although he is a fan of Prozac and believes a lot of this is garbage, he is clearly a political creature and will have to respond to pressures. I hope Patrick realizes that Lilly can go down the tubes if we lose Prozac and just one event in the UK can cost us that.11
Several years later company documents for Lilly’s post-Prozac blockbuster Zyprexa made it clear that
The company is betting the farm on Zyprexa. The ability of Eli Lilly to remain independent and emerge as the fastest growing pharma company of the decade depends solely on our ability to achieve world class commercialization of Zyprexa.12
Prozac, Zyprexa, and other such blockbusters are products that come with a life plan that covers their use in all global markets.13 Even before the launch of potential blockbusters, ways of promoting their use in children and the
