Pharma, page 18
Drug companies had good reason to fear Kefauver. His plans for reworking the patent system would end many of the pricing excesses that had become commonplace. That was bad enough, they thought, to make him an implacable foe. They might have been far more alarmed had they known that privately Kefauver shared with his investigative staff that he believed there was a good argument to make that drugs were an “essential commodity.” That ruling would invest in the federal government the authority to regulate prescription prices as local and state governments set the allowable rates for public utilities.IV 68
I. Kefauver won an Emmy in 1952 for “outstanding public service on television.” He was a celebrity guest on the highest-rated game show of the era, What’s My Line?, and had a bit part in a Humphrey Bogart film, The Enforcer. He was one of the few Washington politicians recognizable wherever he went and his subsequent book about the hearings, Crime in America, was a New York Times best-seller.
II. Blair’s team did not realize what the author discovered, that the addresses to which they tracked some of the companies—15 East 62nd Street and 139 East 59th Street, New York—were locations used for earlier ventures, including the phantom New York City branch of the Ophuijsen Center from Creedmoor. The Senate investigators did reveal, however, how the Sacklers transferred some entities to trusts created for their minor children, which they then managed on their behalf. And there was evidence the family owned an unnamed “photo-engraving firm which makes plates used in expensive advertisements for medical journals,” a real estate company that owned properties leased to many of the Sackler firms, and “the company that makes Lysol.” That was Lehn & Fink. Lysol was popular for decades with women for feminine hygiene. Some used it as a mostly ineffective postcoital douche for birth control, but the FDA approval of the contraceptive pill in 1960 ended that often dangerous practice.
III. When Sackler bought McAdams in 1947, he made it a member of the American Association of Advertising Agencies (AAAA), which since 1917 had represented about 90 percent of the nation’s ad firms. Arthur ran Medical Tribune from the same office as his McAdams agency. Sometimes, employees did work for both. That violated an AAAA ethics rule that prohibited ad agencies and industry-related publications from sharing the same office or workers for fear that conflicts of interest would be unavoidable. About eighteen months after Medical Tribune was created, he withdrew from the AAAA. The only public explanation for the unusual decision to leave the advertising industry’s premier trade group was not given for more than a quarter century; the AAAA’s executive vice president would say only that McAdams had been a member in good standing before it left due to “differences with other members.”
IV. There was even some discussion of federal price controls. They had been implemented on basic food items during World War I to prevent price gouging. In World War II they were again imposed on food and expanded to gasoline. The idea of mandatory price caps has been revived in Florida senator Rick Scott’s Transparent Drug Pricing Act of 2019. It would set the list price of U.S. drugs at the lowest retail list price in the U.K., France, Germany, Canada, and Japan. The Trump administration has proposed linking American drug prices to an index of fourteen nations. The pharmaceutical industry contends price caps would disincentivize innovation and result in Americans getting less access to cutting-edge drugs. In July 2019, Maryland became the first state to attempt to treat drug firms as public utilities, a move that pharma is contesting in the courts.
15 “BE HAPPY” PILLS
The scare campaign against Kefauver failed and he won in a landslide. It was bad news for pharma since he turned to preparing a final subcommittee report and also drafting legislation. While Kefauver had been fighting for his political survival, and the focus on pharma was on the fallout from the Welch/FDA scandal, a watershed moment had passed for the industry. The FDA approved Chicago’s G. D. Searle’s Enovid—put on sale three years earlier for “menstrual disorders”—to be dispensed as the first ever oral contraceptive.1 Women could now control when and if they got pregnant. Objections from social conservatives and religious groups had delayed the FDA’s decision for nearly two years. Some commissioners were uncomfortable with a medication for long-term daily use to otherwise healthy people. When the FDA finally said yes in 1960, they avoided any long-term safety questions by approving it for a maximum of twenty-four months. No one followed that directive once Enovid went on sale.2 It was wrapped in such controversy, that the lay public and much of the press referred to Enovid and later me-too competitors as the Pill. Doctors and patients thought it was simple, safe, and reliable (it was three years before a Senate investigation revealed that the FDA made its momentous decision based on clinical studies of only 132 women who had taken the Pill for a year, sometimes a little longer).3 I 4
It was impossible at the time to fully appreciate how great an impact the Pill would have. It debuted only a few years before the 1960s sexual revolution and women’s liberation movement (NOW, the National Organization for Women, was founded in 1966). Some saw in it a social tool to break the housewife-at-home-raising-a-family stereotype. As the first pharmaceutical reversible contraceptive, it introduced a newly minted term, “reproductive rights.”
Searle took advantage of the Pill’s sweeping promise in its advertising campaign. It featured Andromeda, a goddess of Greek mythology, breaking free of the chains around her wrists, symbolizing women breaking free of their worries of unwanted pregnancies.5
Many greeted the Pill enthusiastically. That was matched by the fervor of those opposing it on religious grounds. Sackler had intently followed the controversy. Bill Frohlich represented Ortho Pharmaceutical, one of the companies with its own oral contraceptive. Ortho was the first to offer the pills in a circular plastic container with a movable dial that made it much easier for women to remember when to take them (start on the fifth day of menstruation, then take one a day for twenty days, and then take a five-day break before restarting the cycle).6 Arthur’s idea about how to refine the promotion strategy seemed radical: do not directly mention the Pill or birth control. Frohlich thought at first it was counterintuitive to sell a product without talking about it, but Sackler won him over. Arthur thought that protestations about the Pill might taper off if the ads pitched the idea that it empowered families to choose how much time they wanted between children. Frohlich’s full-page color ads ran in Family Circle and True Story. They featured a young woman talking to an older woman over a picket fence. “Don’t plan your family over the back fence,” was the headline at the top. At the bottom, it suggested that women talk to their doctors about ways to space pregnancies. “He can recommend a method that is dependable, simple, inexpensive, and best suited to the needs of you and your husband.” The last line, in small print, read: “This message is sponsored by Ortho Pharmaceutical Corp., to whom medical methods of family planning are a particular concern.”7 The Sackler-inspired, Frohlich-designed campaign to soft-pedal the Pill as good family planning ran into fierce opposition from the Catholic Church, which called it “immorality in advertising.”8 Priests used their pulpits across the country to urge parishioners to inundate the magazines with protests. In under a month, Family Circle, with a circulation of seven million, issued a statement from its advertising director: “The objections from readers was ferocious. We no longer are carrying the ads.”9 The magazine returned the $120,000 Ortho had paid for what was scheduled as a series of six ads. Other women’s magazines followed.
Pharma companies and Medicine Avenue had underestimated the pent-up demand among women for something that at last gave them control over if and when to have children. They also misjudged the extent to which many social commentators and the mainstream press viewed the Pill as the progenitor of grand societal change. “If the Pill can defuse the population explosion,” wrote Time in an article titled “Freedom from Fear,” “it will go far for eliminating hunger, want and ignorance.”10 “It was the twentieth century’s greatest technological advance,” The Economist later concluded.11 The Pill was groundbreaking for the reason that it had first stumped the FDA: it established the precedent that a drug need not address an infection or chronic condition. It was enough to help fulfill a personal lifestyle choice. That concept had been the pharmaceutical industry’s Holy Grail, a medication separate from sickness.12
Even without ads in most major women’s publications, the Pill was instantly a top seller. Searle’s stock doubled in the year after it went on sale.13 Ortho, with its clever packaging, sold more pills by 1962 than any other company. Its profits surged.
Sackler thought that if the Pill succeeded despite the fierce resistance, another lifestyle medication free of any moral controversy could be an even bigger blockbuster. His psychiatric training led him to conclude the next great challenge was developing a lifestyle medication for so-called mind drugs. It was possible, he speculated, that a hybrid, some type of “be happy” pill, might one day replace antibiotics as the industry sales leader. He focused on two broad classes of mind drugs: stimulants (uppers) that enhanced a patient’s mood, and sedatives (downers) that targeted anxiety and mental illness.
Amphetamines, the stimulant gold standard, had long been promoted as a cure for all types of depression. The surging demand for amphetamines doubled after World War II following the AMA’s approval to advertise them for weight loss.14 Burroughs Wellcome introduced Methedrine to shed extra pounds. Abbott targeted narcolepsy with Desoxyn, its methamphetamine tablet. Ciba’s entry was not an amphetamine, but a new drug that competed for the same market: Ritalin.15 In 1950 Ciba had released Dexamyl, a combination of Dexedrine and Lilly’s Amytal barbiturate that some doctors dubbed “among psychiatry’s greatest hits.”16 Ads featuring all-American housewives touting it for treating “nervous tension, anxiety and agitation” had helped make it one of the most widely dispensed by general practitioners.17 Rivals tried copying that success with their own amphetamine-sedative combinations, helping to expand the market throughout the 1950s.18
By the 1960s, the American amphetamine market hit a record eight billion pills annually. That output was constant for the rest of the decade. Authorities later discovered that about half that production was diverted illegally to street dealers or unscrupulous diet doctors. Some popular weight loss clinics were unmasked as virtual subsidiaries of generic amphetamine manufacturers. Their profits were enormous; 100,000 10 mg amphetamine pills cost the diet center $71 and were resold on average for $12,000. Its broad popularity had resulted in a spike in recreational abuse and adverse reactions.19 That finally caught the media’s attention. A series of national stories about former users recounting “amphetamine induced psychosis,” antisocial behavior, and crippling paranoia added to the drug’s darker narrative. The FDA had been slow to recognize the problems. It had such a benign view of stimulants that as late as 1963 it weighed approving Ciba’s Dexamyl for over-the-counter sales.20
Sackler knew there had been little innovation in amphetamines in the thirty years since their discovery. And he had never found it useful during his Creedmoor research. He admired amphetamine’s commercial success but he was skeptical about its long-term prospects and doubted it could be the basis for the hybrid mind/lifestyle drug he envisioned.
What about sedatives? The postwar barbiturate market was huge, second only to antibiotics.21 There were 1,500 competing brands in the U.S. An estimated third of those manufactured were resold on the street—with names such as goofies, yellow jackets, and pink ladies—for recreational highs. They delivered big profits, rivaling the gross margins of the industry-leading antibiotics.22 Barbiturates, as with amphetamines, had become a victim of their success. The federal Narcotics Bureau in 1947 listed them the most abused drug. Overdoses set a grim record in 1950 with one thousand dead.23 The following year, The New York Times concluded that barbiturates “are more a menace to society than heroin or morphine.”24
Congress responded with the Durham-Humphrey Amendment, meant to address the barbiturates problem by fixing vague language in the 1938 Food, Drug, and Cosmetic Act.25 Before the amendment, prescriptions were required only for narcotics and sulfa drugs.26 Thirty-six states had not waited for federal intervention, instead requiring prescriptions for barbiturates. The state rules were a confusing hodgepodge of regulations. More than half had no restrictions on the number of refills. The Durham-Humphrey Amendment invested the FDA with the power to deem any drug as dangerous “because of toxicity or other potentially harmful effect.” Once the FDA made that threshold decision, the drug would be by prescription only.27
One of the law’s omissions, however, was that it did not require drug companies to include side effect warnings to patients. Pharma firms only had to provide the drug data to pharmacists, who were then supposed to warn patients about potential abuse.
The Durham-Humphrey Amendment did not dent barbiturate sales. Because it did not have the resources, the FDA did not enforce its “prescription only” rule for six years, and then it went only after bromides, a cruder early-generation sedative.28 Even then, requiring a prescription for barbiturates only meant that millions of habitual users began shopping for doctors willing to write prescriptions without asking too many questions.29
Sackler saw a glimmer of promise in the hypnotic qualities of strong barbiturates such as Lilly’s Seconal. It could be useful in controlling seizures and constant agitation, two debilitating physical symptoms of mental illness. They were not optimized for serious mental disorders, however, and did not treat bipolar or schizophrenia. Smith Kline filled that market in 1954 in America when it rolled out Thorazine, a tranquilizer accidentally discovered in the late 1940s by a French surgeon who had been hunting for malaria cures. “Tranquilizer” was the new word in the pharma world, having appeared the first time the previous year in promotion for a hypertension drug from Ciba.II 30
Smith Kline marketed Thorazine as an antipsychotic.31 It was so potent that in Europe it was informally dubbed “a medicinal lobotomy” and dispensed only to patients suffering severe psychosis.32 Smith Kline’s first ad featured a close-up of a man’s head, electrodes attached to his forehead, and a large rubber stopper jammed into his mouth. It announced “Thorazine: Reduces Need for Electroshock Therapy.” Psychiatrists, particularly those who worked in public asylums, wrote nearly 80 percent of the three million Thorazine prescriptions in its first year.33 The drug arrived at a time when psychiatric institutions were increasingly vilified in scandalous public reports about cruelty and violence toward patients.34 Thorazine marked the start of a pharmaceutical revolution in the treatment of those with disabling mental illness, moving away from the custodial-institutionalized care that had been the standard since the early nineteenth century. Thorazine’s widespread use spurred a decline in the number of patients committed to New York’s mental institutions—the largest state population—by 19 percent, the first reduction since records were kept.35 Fewer patients meant lower costs, saving state governments $1.5 billion in the decade after Thorazine’s introduction. The director of Washington, D.C.’s, eight-thousand-bed St. Elizabeth’s Hospital heralded Thorazine as marking the end of “bedlamism,” the word used by asylum workers to describe the chaos and disorder that was the hallmark of many insanity wards.36
Smith Kline trumpeted its success at the nation’s mental hospitals, although no one seemed to have figured out the early taxpayer savings might be canceled out later by increased medical costs for the outpatient care of those who relapsed or whose illness worsened.37 III 38
Despite the big sales numbers, Smith Kline worried there was a limit to the size of Thorazine’s market. The better the drug worked, the greater the falloff in sales as patients were discharged from mental institutions. Smith Kline tried expanding the market by targeting doctors who cared for those patients who returned to society. Ads in JAMA featured a man fishing in a stream, personifying the mental calmness that was touted as the drug’s hallmark. “Continuing therapy is almost always well tolerated, and is central to most patients’ continued well-being,” read the copy.39 Smith Kline next tried adding “senile agitation” as a treatable condition. Ads, illustrated with an elderly man wielding his cane in a threatening manner, promised Thorazine would “control the agitated, belligerent senile” and “help the patient to live a composed and useful life.”40 It even tried marketing it for chronic nausea. But that was like using a sledgehammer to put a thumbtack on a corkboard. Few patients were so distressed by even the worst nausea to put up with side effects that could include difficulty breathing, severe fever and muscle pain, trembling, seizures, and even rarely, suicidal depression.41
Sackler was waiting for something more like a Thorazine-lite, a mood-altering medication that could offset anxiety while not being too sedating. He told his pharma clients about the great profit potential in a discovery of “emotional aspirin,” a medication that treated a person’s psychological well-being as well as antibiotics cured serious infections. Sackler knew from his tenure at Creedmoor that any drug that addressed anxiety or depression would have a greater side effect profile than aspirin. He hoped that by putting the concept of “emotional aspirin” into the research and development milieu, it might spark pharma firms to make it a laboratory priority.
Drug companies undoubtedly had the incentive for such a project. There was an enormous market for relieving the stress and anxiety that many Americans perceived as an unfortunate but integral part of twentieth-century life.42 Magazines and newspapers ran stories about stress from the Cold War and how the fast pace of technology added to daily pressure. Composer Leonard Bernstein had in 1950 named his Second Symphony “The Age of Anxiety,” after W. H. Auden’s Pulitzer Prize–winning poem of the same title. The government provided significant financial incentive for discovering a drug as Sackler envisioned. When the Mental Health Study Act was passed in 1955, it established a Psychopharmacology Research Center at the NIH. That new government division focused on biological psychiatry and had a multimillion-dollar research budget, which it shared with interested pharma firms.43 Some drugs under review were still experimental although they showed promise in the lab. Lithium had been discovered in the early nineteenth century but clinical studies for treating mania had only begun in Denmark in the mid-1950s (the FDA did not approve it until 1970). The same was true for LSD-25, a synthetic compound discovered by a Swiss scientist in 1951, but only subjected to therapeutic testing for mental illnesses in the mid-1950s at the Rockefeller Institute for Medical Research.IV 44
