sulfanilamide tragedy of 1937, the 1938 Food, Drugs and Cosmetics Act encouraged a move toward making new drugs available by prescription only. The calculation was that the sulfa drugs were better categorized with insulin and the steroid and thyroid hormones, which were typically if not exclusively administered by doctors. After World War II, in 1951, the prescription-only status for new medicines in the United States was copper-fastened in place with the Humphrey-Durham amendments to the 1938 act, despite vigorous, sustained, and widespread opposition to the move. Critics complained that a system put in place for addicts was inappropriate for free citizens. But by the early 1950s, one of the side effects of having medicines that really worked was becoming clear—drugs that could really benefit, could really harm also. In 1952, Leo Meyler’s Side Effects of Drugs appeared, a first-ever medical compendium of drug-induced injuries.4 This new potential for harm took dramatic shape in 1961 with limbless babies born to mothers who had taken thalidomide during pregnancy as a supposedly safer hypnotic than the older barbiturates.5
When it came to his hearings in 1959, Senator Kefauver was exercised by the prescription-only status of the new drugs, a unique characteristic found in no other market. As he put it, “He who orders does not buy; and he who buys does not order.” As a consequence, when it came to drugs available by prescription only ordinary consumers could not protect themselves against the monopoly element inherent in trademarks or patents. Patients were critically dependent on their doctors to be uninfluenced by trademarks, patents, or marketing ploys. Doctors had a choice whether to give their patients the latest on-patent and branded drug or perhaps an older, more effective and less expensive drug, but patients had little choice other than to do as prescribed by their doctor.6
Thalidomide had been available over the counter in many European countries but exactly the same problems arose in the United States where the premarketing samples were available by prescription only. Indeed the problems may have come to light as quickly as they did because doctors in Germany were not inhibited in recognizing the potential for harm of an over-the-counter drug, as they might have been in the case of a drug essential to their livelihoods. But in the United States in 1962, in the face of the thalidomide disaster, retaining the prescription-only status of drugs seemed to make sense: doctors retained some patina of skepticism about drug claims due to medicine’s long-standing opposition to quackery, and doctors appeared to be the people who would be able to quarry information from drug companies about possible adverse side effects of their products.
Before 1962 prescription-only status was still something of a novelty—after 1962 it became the center of the distribution system for new drugs when companies were required not only to make their drugs available only through doctors but also to prove that their drugs worked for some medical condition in order to get FDA approval. This combination of controls must have looked pretty foolproof in 1962, but it has not turned out to be an effective way to constrain the pharmaceutical industry within a medical framework. Quite the reverse. When a pharmaceutical company gets a drug on the market for lowering cholesterol, for osteoporosis, or for erectile dysfunction, this now marks the point at which the company begins to sell the condition, the point at which they can gear up to reengineer the medical marketplace to suit their product, as Abbott did with bipolar disorder to make it Depakote-friendly. It seems extraordinary now that no one in 1962 seems to have realized that if pharmaceutical companies were restricted to marketing drugs for diseases, they might start to market diseases.
Had pharmaceutical companies not been required to demonstrate a drug’s efficacy in treating a particular disorder, we might all have ended up with a lot fewer diseases recorded in our medical records. The first antidepressants would have been marketed as tonics or stimulants. To get St. John’s wort, an herb with SSRI properties, we just have to feel stressed and buy it over the counter where it is sold as a tonic, but to get Prozac now, we have to be officially diagnosed as depressed. In a similar fashion, the statins might have been marketed on the promise of restoring inner youthfulness, or getting our arteries in shape, rather than for a supposed cholesterol disorder, or the biphosphonates might have been aimed at restoring youthful bones rather than for osteoporosis. As insurance companies reimburse in response to diagnoses, fewer diagnoses would likely have reduced our need for doctors in addition to reducing the number of diseases.
The third medical requirement of the 1962 amendments was that companies demonstrate their products worked in well-controlled clinical trials. This was smuggled into the final bill through the efforts of Louis Lasagna, a professor of pharmacology and a believer in controlled trials, who was attempting at the time to encourage some use of controlled trials, rather than trying to make them mandatory.7 Lasagna himself had undertaken the only controlled trial of thalidomide ever done, through which it sailed—an effective hypnotic free of significant side effects.
The copper-fastening of prescription-only arrangements that came out of the Kefauver hearings would alone have put doctors in the sights of pharmaceutical company marketing departments in a way they had never been before. But constraining companies to market their drugs for diseases and to demonstrate their efficacy through what was then a new medical invention, the controlled trial, made it necessary for companies not just to have doctors in their sights but to understand doctors better than doctors understood themselves.
In the case of some hugely profitable trademarked drugs, such as Marlboro, medicine has played an honorable part in bringing lethal problems to light. But what would have happened had tobacco been available by prescription only? It is clearly helpful for ulcerative colitis. In all probability it could be shown to be just as good an antidepressant as Prozac and the SSRIs—so the market might have been substantial. How quick then would doctors have been to do the independent studies that pinpointed the problems linked to smoking or to insist on the seriousness of the risks while the tobacco industry was systematically creating doubt about those risks?
Doctors don’t view themselves as consumers, subject not only to the extraordinary pressures that modern marketing can bring to bear on any consumer but also, by virtue of prescription-only arrangements, to these forces in the most concentrated form that exists anywhere on the globe. Typically, they blithely go their way without seeing the need to understand marketing. They bunker down behind a Maginot Line of what they believe are untainted controlled trials and evidence-based medicine, unaware that the tank divisions and air force of their opponents give daily thanks for that Maginot Line.
THE RISE OF THE BLOCKBUSTER
The possibilities for a new generation of branded medicines—and extraordinary sales—that opened up on the back of a regime that allowed drugs to be patented and that made these drugs available on a prescription-only basis were first revealed in the course of a battle in the 1980s between pharmaceutical giants Glaxo and SmithKline over the ulcer drugs Tagamet (cimetidine) and Zantac (ranitidine).
James Black was one of the most successful medicinal chemists ever; he was also one of the first to win a Nobel Prize while working in the pharmaceutical industry. Black had initially worked for Imperial Chemical Industries, where he had developed the concept of a beta-blocker. These drugs, which blocked the beta-adrenergic receptors on which stress hormones like epinephrine exert their effects throughout the body, turned out to be particularly useful for treating hypertension, the most rapidly growing medical market in the 1970s.
Black then moved to SmithKline, where he turned his attention to the antihistamines, helping to distinguish among two different histamine receptors, H-1 and H-2. This opened the way to develop H-2 blockers that would target histamine receptors in the gut, reducing gastric acid production, then thought to be responsible for ulcers. Tagamet was the result, a drug that embodied a genuinely novel approach to the treatment of duodenal ulcers, then one of biggest problems in internal medicine.8 Within a few years of its introduction, surgery for ulcers had become a rarity—had Tagamet been available earlier, it would have saved my mother much misery. This epitomized the best hopes of both science and industry—new and innovative products making it into healthcare and making a big difference to patients.
In
