On Speed

From Benzedrine to Adderall

Nicolas Rasmussen

• Publisher: NYU Press
• Year: 2008
• ISBN:
  9780814776278
• Topic: Medicina
• Subtopic: Teoria, pratica e riferimenti medici

Life in the Fast Lane: The author on the CHE

Uppers. Crank. Bennies. Dexies. Greenies. Black Beauties. Purple Hearts. Crystal. Ice. And, of course, Speed. Whatever their street names at the moment, amphetamines have been an insistent force in American life since they were marketed as the original antidepressants in the 1930s. On Speed tells the remarkable story of their rise, their fall, and their surprising resurgence. Along the way, it discusses the influence of pharmaceutical marketing on medicine, the evolving scientific understanding of how the human brain works, the role of drugs in maintaining the social order, and the centrality of pills in American life. Above all, however, this is a highly readable biography of a very popular drug. And it is a riveting story.

Incorporating extensive new research, On Speed describes the ups and downs (fittingly, there are mostly ups) in the history of amphetamines, and their remarkable pervasiveness. For example, at the same time that amphetamines were becoming part of the diet of many GIs in World War II, an amphetamine-abusing counterculture began to flourish among civilians. In the 1950s, psychiatrists and family doctors alike prescribed amphetamines for a wide variety of ailments, from mental disorders to obesity to emotional distress. By the late 1960s, speed had become a fixture in everyday life: up to ten percent of Americans were thought to be using amphetamines at least occasionally.

Although their use was regulated in the 1970s, it didn't take long for amphetamines to make a major comeback, with the discovery of Attention Deficit Disorder and the role that one drug in the amphetamine family—Ritalin—could play in treating it. Today’s most popular diet-assistance drugs differ little from the diet pills of years gone by, still speed at their core. And some of our most popular recreational drugs—including the "mellow" drug, Ecstasy—are also amphetamines. Whether we want to admit it or not, writes Rasmussen, we’re still a nation on speed.

1

The New Sensation

ON JUNE 3, 1929, a twenty-seven-year-old chemist in Los Angeles took an injection of a mystery chemical he had recently created. Beyond an estimate of how much it would take to kill him, and the expectation that his blood pressure would rise—both derived from guinea pig tests—he had little idea what the injection would do. He was hoping to discover a new allergy medicine that day. It took a little while for anything to happen, because his doctor friend had injected the drug subcutaneously, rather than directly into a vein. But within ten minutes his blood pressure started to go up sharply, worrying both men until it stabilized a couple of hours later at about one and a half times his normal level. Around the time that he starting feeling some small effect, the chemist sniffed and, optimistically, recorded that his nose was clear. Soon after, some eighteen minutes after the injection, he noticed something more interesting and unexpected. “Feeling of well being,” reads the notebook entry dryly. The chemist was enjoying this experiment. His doctor friend, Hyman Miller, sat with him for a few hours, chatting with the unusually talkative chemist and checking his blood pressure regularly, eventually inviting him home to dinner with his wife. The chemist recalled being an especially witty guest that evening. After Miller packed him off to bed, the chemist, still in good spirits, experienced a “rather sleepless night” where his “mind seemed to race from one subject to another,” according to his notebook (Figure 1). Still, he felt fairly well in the morning.¹

As a chemist, Gordon Alles called the substance he took that day beta-phenyl-isopropylamine, better known today as amphetamine. That day Alles had taken 50 milligrams (mg), five times what would become the standard dose once the substance was medically approved eight years later. Although he had no idea what it would be used for, the chemist knew right away that he had made a significant discovery. What no one could have guessed is how irresistible this powerful drug would prove to be, holding Americans in its thrall for three generations, all the way to the present day. So began the age of speed.

Adrenalin: New Medicine for a New Century

Alles, appropriately enough, was born in 1901, the year that Parke-Davis & Company of Detroit launched its brand-name “Adrenalin” on the market. At the time the drug business was undergoing drastic change. Adapting to dramatic advances and new attitudes in medicine presented a great challenge to pharmaceutical firms accustomed to selling mostly traditional herbs and tinctures. In Europe, the past few decades had seen the triumph of a totally new approach to healing. Called “scientific medicine,” it was based in part on the careful, quantitative analysis of how well different treatments worked when administered under controlled conditions, like those found in the large hospitals that had recently been linked to medical schools. This new approach was also based in the laboratory work of experimental biologists, especially in the fields of bacteriology and physiology. Bacteriologists like Louis Pasteur and Robert Koch had identified the microbes that caused many dreaded illnesses, and also invented new vaccines that could prevent some of them. In the case of a few diseases such as diphtheria, they had even invented serums that could be used to save those already ill. Meanwhile, physiologists had been probing the chemical function of the different organs and discovered that some controlled bodily function by releasing powerful biochemical signals, or “hormones.” In 1894, British physiologists identified a hormone made by the adrenal gland, soon named “adrenaline,”² by showing that an extract of the organ raises blood pressure when injected in experimental animals (implying that the adrenal gland plays a role in regulating circulation under some circumstances). Several scientists in Germany claimed success in isolating the hormone, and drug companies working closely with them put purified adrenal hormones on the market around 1900. But the most successful was Parke, Davis “& Company’s ‘Adrenalin’” preparation, based on a procedure developed by the leading American pharmacologist of the day, J. J. Abel of Johns Hopkins University (although it was the Japanese biochemist Jokichi Takamine who, after working briefly with Abel in Baltimore and improving his method, patented it and sold it to Parke, Davis). This product, arguably the first important new drug to emerge from advances in physiology, was a milestone (Figure 2).³ The life sciences were proving that they could yield practical benefits in the form of new medicines that could aid both doctors and patients, and nowhere was the potential more exciting than in the new science of the glands.

Adrenalin was also a special landmark for American medicine since it was invented in the United States, and commercialized by an American company, at a time when that nation lagged woefully behind Europe in both medical science and pharmaceuticals. To bring the American medical profession up to French and German standards, medical leaders in the 1890s had launched an aggressive reform program to introduce much more science into the medical school curriculum.⁴ The crisis in American medical education around the turn of the century coincided with a crisis in the nation’s pharmaceutical industry. That Adrenalin, a scientifically credible drug, had come from an American firm in 1901 was surprising, because the American drug industry was mainly selling snake oil at that time. There had long been makers of “ethical” drugs, medicines whose mostly plant-based ingredients were accurately disclosed and which were marketed mainly to doctors for prescription. In the late nineteenth century, however, these drugs were being crowded out by junk nostrums or so-called patent remedies—in 1900, these dubious drugs represented 72 percent of pharmaceutical industry sales, more than double their share of the American drug market twenty years earlier. Hype and mystery were the leading ingredient in the “patent” medicines (a misnomer, since the formulas of these potions and pills were typically secret, and, in any case, were not patentable). Many also featured a hefty percentage of alcohol, like Doctor Hotstetter’s Celebrated Stomachic Bitters (64 proof) and Peruna, the best-selling cure-all (56 proof). These sold especially well in areas under the control of Temperance forces.⁵ Some patent medicines promised health based on the recent breakthroughs of medical science, like Radam’s Microbe Killer, and Radol, a “marvellous radiotized fluid” that supposedly cured cancer. Fortunately for gullible users, Radol contained no actual radium; both were basically water. Such fraudulent products were still seen as a menace to public health by the scientific medicine reformers, since users, believing they were being treated, avoided seeing doctors for (marginally) more effective professional care. But, in 1901, the most sinister pharmaceuticals were the patent remedies that contained the few really powerful drugs then known to medicine, particularly morphine-based sedatives and cough syrups, and invigorating cocaine-based tonics and decongestant snuffs. Product labels often did not reveal the presence of these ingredients, so it was easy to get hooked, or to overdose.⁶

All these useless and dangerous medicines were available by mail order and over the counter at pharmacies everywhere, but the American medical profession shared responsibility for their unhealthy popularity. A study in the 1890s found that 90 percent of doctors had actually prescribed a patent remedy. Patent medicine makers disguised their products as drugs with scientific credentials, fooling physicians with technical-sounding names (like “Fellows’ Syrup of Hypophosphites”), serious-looking advertisements in medical journals (Figure 3), professional “detail men” who called on doctors with samples and informational sales pitches, and commissioned research articles in reputable journals testifying to the therapeutic power of their remedies. In all of this they resembled the practices of the ethical drugmakers who, unwilling to neglect the lucrative nostrum business, were in truth not so very different.⁷ For instance, for decades after its 1901 invention, one of the leading products of the Philadelphia firm Smith, Kline & French was an elixir called Eskay’s Neurophospates. Like the venerable Fellows’ Syrup, the only active drug in Neurophosphates was strychnine. This ingredient has some inconsistent stimulating effects, but it was included in nerve tonics mainly for psychological reasons, exploiting the common belief that powerful poisons are powerful cures. Strychnine, in combination with phosphorous, was standard in tonics designed for that popular and poorly defined epidemic of the period “neurasthenia” (depression understood as nervous depletion or chronic fatigue).⁸ That a new medicine like Neurophosphates could be launched on the market by a reputable, ethical firm in the same year as Adrenalin, and then enjoy decades of success, speaks volumes about the American pharmaceutical business at the beginning of the twentieth century.

This free market pharmaceutical pandemonium outraged the more scientific-minded medical professors. The same reformers who were trying to educate doctors scientifically so they could “distinguish the rank fraud from the efficacious remedy, honestly made and sold,” turned their attention to disciplining the American drug industry. Extravagant publicity and dubious company-sponsored research had too long been “debauching our medical journals” and “tainting our textbooks,” thundered George Simmons, editor of the influential Journal of the American Medical Association (JAMA). In 1905, Simmons helped found the American Medical Association (AMA) Council on Pharmacy and Chemistry (later, Council on Drugs), consisting mainly of pharmacology professors and chemists, to police drug advertising in JAMA. Medicines that failed accurately to disclose their active ingredients could not be advertised. Ethical drugs with adequate labeling could be advertised, but only in ways that the Council considered justified. To win Council approval for an advertising claim, careful laboratory work and careful clinical trials were required. Doctors’ testimonials boasting a handful of amazing “cures,” commonly commissioned by drug makers, were no longer sufficient. A number of other major medical journals joined with JAMA by only running Council-approved ads, making this voluntary system of regulation the main guarantee of a drug’s rational use for many years. (In fact, until the Second World War, this system remained much more effective than the regulation provided by federal Food and Drug law, which, from 1906, only ensured truthful labeling.) The net effect of the reforms for drug firms wishing to compete in the ethical field was to put an ever greater premium on science, as a source of new products, to justify claims of effectiveness, and also for general marketing use.⁹ With its impeccable scientific pedigree, Adrenalin was an early example of what all good medicines were now supposed to look like.

The different actions of adrenaline on the body made pharmaceuticals containing the hormone medically useful in numerous ways. Adrenaline could restart the heart if injected straight into it, a procedure sometimes necessary in cases of shock, including allergic or “anaphylactic” shock—not uncommon in doctors’ offices at the time because it can be caused by one too many serum injections. The hormone also constricts capillaries, making it popular with surgeons, who mixed it with a local anesthetic such as cocaine to slow bleeding during operations. All manner of elective surgery on soft tissues became safer and thus more popular. On the blood vessels of the lungs, adrenaline has an opposite effect, easing lung circulation and relaxing the air passages. This made it a very popular drug for asthma, more effective at halting an asthmatic attack than cocaine, sold at the time for asthma because of its similar effects. Sprayed into the nose, it was also a handy—if short-acting—decongestant. Adrenaline has a range of other effects, too, stimulating tear and sweat glands, causing the pupils to widen, and relaxing the intestinal muscles. Though less marketable, these actions of the hormone aroused great interest among physiologists.

Especially fascinating to scientists at the time was that each of these effects of adrenaline on various parts of the body looked exactly like the effects of electrical stimulation of certain nerves. The nervous system is divided into two main sections: the central nervous system consisting of the brain and spinal cord, and the peripheral nervous system. In the early twentieth century, the peripheral nerves were themselves usually subdivided into two groups: on the one hand, the sensory and motor nerves (grouped with the central nervous system now, and sometimes then), with which we feel and carry out voluntary movements, and, on the other, the involuntary or “autonomic” nerves that govern all the many functions over which we have little control, such as digestion, blood circulation, sexual function, pupil dilation, sweating, and salivating. Many of the muscles that perform these involuntary functions are, in fact, controlled by two sets of peripheral nerves, each with distinct structures and opposite functions: the sympathetic and the parasympathetic. Stimulate the sympathetic nerve to the eye of an anesthetized cat, and its pupil widens; stimulate the parasympathetic, and the pupil narrows. Adrenaline triggers the same effect on the eye, and indeed on most organs, that sympathetic nerve stimulation would cause. Soon after adrenaline was on the market and widely available for physiologists to use in their experiments, suspicions began to grow that nerves may actually transmit their impulses chemically, and not just electrically. Sympathetic nerves might transmit their signals with adrenaline, and the parasympathetic nerves might use another chemical, identified (in a parallel line of research) as acetylcholine. Decades would pass before physiologists stopped debating, especially about the central nervous system. But the theory that nerves transmit signals chemically gained support in medical science gradually throughout the teens and twenties, thanks partly to the availability for experiments of adrenaline, nerve juice in a jar.¹⁰

Commercial and medical interest in adrenaline did not wait for the neurophysiologists to solve their puzzles. Academic biochemists and drug firms in the first decade of the twentieth century sought new ways to extract adrenaline out of adrenal glands from the slaughterhouse. Nothing proved better than Takamine’s and Parke, Davis’s extraction method, however. Other scientists searched in plants for chemicals of similar chemistry and physiological effect, hoping to get around the Takamine patent on the best production method from animal material. Still others looked for synthetic drugs to substitute for natural adrenaline. One of these was the Cambridge University–trained physiologist Henry Dale. Working with chemist George Barger at the British drug company Burroughs-Wellcome, the young scientists created a series of chemicals similar in structure to adrenaline. The most active molecules all shared certain key structural features with adrenaline, in particular a benzene ring with a short side-chain of carbon. Surprisingly, some of these synthetic adrenaline variants had actions that mimicked sympathetic nerve stimulation—but not in exactly the same way as adrenaline. For example, one of them raised the blood pressure much longer than adrenaline did, but did not relax the lungs nearly as much. They named it “Tyramine,” and Burroughs-Wellcome sold it as a treatment for shock. The 1910 paper in which Barger and Dale described these experiments quickly became a classic for pharmacologists, an example of how one could discover new remedies by systematically exploring a wide range of chemicals related to a hormone or other natural drug. As novel chemicals, these new remedies could then be patented and marketed as improved, scientific medicines, a lesson not lost on the pharmaceutical industry. Drug discovery was on its way to becoming a routine business function.¹¹

The Drug Lab behind the Allergist’s Office

By the 1920s Adrenalin had been joined by a number of other purified hormone medicines, as the drug business transformed itself into the science-based industry that we know today. Indeed, the advance of physiology and the thirst for new scientifically credible medicines had set off a “gold rush” in the hormone field. The 1921 appearance of insulin, the pancreas-derived hormone that turned a diabetes diagnosis from a death sentence into a manageable condition, was especially sensational. Insulin had been introduced to medicine through a collaboration between the University of Toronto physiologists who discovered how to extract the hormone, and the Eli Lilly firm of Indiana, which manufactured and marketed it. There was money in glands, without a doubt. Forward-thinking drug firms avidly sought top-notch academic scientists to help them, and every hormone researcher ambitious to be the first to purify the hormone of this or that gland wanted an industrial partner. The reason was summed up by the pharmacologist J. J. Abel, who, in 1918, lamented that a university scientist who wanted to isolate the hormone of the pituitary gland had “no chance to solve a problem of this sort without generous financial assistance.”¹²

Pituitary glands, for example, cost ten times more than any part of the cow found in stores, and a biochemist would typically have to process tons of raw material, starting from great vats of bodily fluid or finely ground raw meat, only to end up with a few tiny crystals of pure hormone. The German biochemistry professor Adolf Butenandt spent the greater part of the 1920s trying to identify and purify a male sex hormone. He finally succeeded in 1931 by distilling 25,000 liters of urine—a swimming pool’s worth—collected from Berlin policemen (who were considered manly and therefore a good source for the hormone). His industrial partner, the Schering drug firm, handled much of the large-scale urine extraction. Butenandt’s rival in St. Louis, E. A. Doisy, had similar help from Parke, Davis in isolating an estrogen from four tons of pig ovaries. Vitamins were just as hard to get. In the teens, a ton of rice bran was required to produce five grams of vitamin B1 for study, and thirty thousand eggs were used to isolate 0.1 gram of riboflavin.¹³ So collaborations between pharmaceutical firms and academic researchers made good economic sense: the university scientists would get the money, technical support, and other material resources they needed, and the sponsors would get a new drug to market, usually based on the patented procedures of their scientist partner. Gordon Alles’s formation as a biochemist took place in this heady, entrepreneurial atmosphere. Brilliant, energetic, and, at 6 feet, 200 pounds, physically powerful (Figure 4), Alles majored in chemistry at the California Institute of Technology in 1922, just as this institution was starting to transform itself from a sleepy technical college into the scien...