On Speed: The Many Lives of Amphetamine

2. Benzedrine: The Making of a Modern Medicine

2 Benzedrine The Making of a Modern Medicine ALLES HAD FOUND a splendid partner to make his creation a blockbuster. Although Smith, Kline & French could not yet boast many scientifically impressive pharmaceuticals in its product line (Figure 8), the firm had the marketing skills to turn a mere chemical into a successful medicine. The period in which amphetamine underwent this transformation, 1935 through 1937, was the twilight of the age when pharmaceuticals remained largely unregulated. In the United States, federal law still required only the accurate labeling of medicines. Apart from listed narcotics, a doctor’s prescription was not legally required to purchase drugs from pharmacies. However, much had changed since the turn-of-the-century crisis generated by the free market in drugs. The contents of medicines were now truthfully labeled and were “pure”—thanks to the 1906 Federal Food and Drug Law. And, as we saw, the AMA Council on Pharmacy required manufacturers to provide scientific evidence that a drug was effective as claimed, and safe in typical doses, before approving advertising in participating medical journals. Marketing plans needed to take science into account. So, like any company with a new medicine to offer, SKF had to arrange for convincing safety studies with amphetamine. The firm also had to identify some medical conditions that the drug helped, and to gather evidence from clinical trials proving amphetamine beneficial by the scientific standards of the day. Arranging for this efficacy testing meant selecting some of the drug’s many effects: perhaps the way it kept one awake, or made the mind race, or another effect on the brain like the “feeling of well-being” Alles reported—or perhaps some of the adrenaline-like effects on involuntary muscles. Through clinical studies testing these specific amphetamine actions on patients with certain conditions, a few would be defined as the drug’s official, 25 medically useful effects, and the rest as side effects. Following AMA review and approval of the evidence, the manufacturer would then market the drug to doctors using journal advertising, as well as direct mail and the sales force of “detail men.”1 Safety studies for the AMA Council were straightforward in those days. SKF only needed to conduct animal testing to establish the drug’s toxicity, that is, to determine precisely what dose levels were probably lethal and whether any obvious harms occurred from taking high doses. The firm also had to test the drug more formally on people in the relevant dose range—that is, doses well below lethal levels but high enough for medically valuable effects to be felt—to check for dangerous or unpleasant side effects. After some delays and false starts, in mid-1936 the firm commissioned a toxicity study from University of Pennsylvania pharmacology professor Edward Krumbhaar, a friend and close neighbor of SKF vice president Boyer. Krumbhaar documented no harm from massive doses in rats over several weeks, then moved on to dogs, rabbits, and guinea pigs. Eventually he published his findings, and, meanwhile, SKF prepared a summary of his results to mail to doctors already experimenting with the drug, to help allay any safety concerns.2 To demonstrate that amphetamine was safe for people to take orally, SKF commissioned a study by a University of Pennsylvania medical school (Penn) professor of internal medicine named Wallace Dyer. Because amphetamine was thought of as an artificial adrenaline, one of the most obvious issues was the rise in blood pressure that it caused. This effect might be beneficial for those with low blood pressure , but it might be a dangerous side-effect for patients with high blood pressure. To establish whether such people would have to be be ruled out for Benzedrine Sulfate prescriptions, whatever the drug’s medical use might be, Dyer recruited subjects with normal, low, and high blood pressures from among his patients in the Penn hospital. At first he gave them all 10–20 mg of amphetamine a day, and then, after a few months, on instructions from SKF, he raised the doses to 30 mg per day. Today, Dyer’s experiment would be ethically unacceptable, since his patients with high blood pressure stood a particularly good chance of being harmed and could not reasonably be expected to bene fit. In those days, however, doctors had few doubts about their own beneficence, and there was nothing very unusual about such experimentation . Only after the Nazi medical atrocities of World War...