In 1951, the Sacklers published one of their most provocative theories, that schizophrenia might be identified by changes in blood as it clotted, and that ultrasonometry (the predecessor to ultrasound) could track physiological changes in schizophrenics.1 They proposed the controversial thesis that histamines might effectively treat schizophrenics. Marietta worked with them extensively on that paper, but she was disappointed not to be listed as one of the authors. It took several years before she shared credit with the brothers, an overview of “psychiatric research perspectives at the Creedmoor Institute.” It marked the one time four Sacklers were listed on a scientific publication.2
Marietta felt like an outsider to the family club. It was the same for Muriel Lazarus, Mortimer’s wife, who was a researcher in biochemical genetics as well as a practicing psychoanalyst.3 Another physician, however, who joined the brothers on scholarly collaborations, did become a trusted insider. Félix Martí-Ibáñez was a sociable and urbane Spanish psychiatrist. He and the Sackler brothers would go on to edit a remarkably ambitious book, The Great Physiodynamic Therapies in Psychiatry: An Historical Reappraisal. It was filled with contributions from some of the era’s leading researchers opining about treatments for mental illness, from electroshock to insulin shock to lobotomies. The Sacklers and Martí-Ibáñez predicted that the treatment of choice would soon be “narcobiotics” (their vision of some yet-to-be-invented hybrid of tranquilizers as readily dispensed as antibiotics).4 The four doctors considered themselves pioneers in the biological underpinnings of treating mental disorders. When they later discussed an ambitious book on “The Geography and the World Patterns of Schizophrenia and Other Mental Illnesses,” Martí-Ibáñez wrote a letter to the Sacklers concluding, “The research and sociologic value of this project would be portentous. This might be Nobel Prize stuff. What do you say, boys?”5
Just as Arthur Sackler was more than a mere psychiatrist, Martí-Ibáñez was a self-described anarchist, historian, novelist, and entrepreneur. His résumé impressed even the Sacklers. He grew up in Cartagena, Spain; his mother was a noted pianist, his father a scholar and prolific author of dozens of books about education.6 Martí-Ibáñez was a gifted student. He teased Arthur that he was only nineteen when he got his medical degree at the University of Madrid, five years faster than Sackler.7 In another year he earned his doctorate in philosophy with a thesis about the history of the physiology and psychology of Indian mystics. After graduation, he traveled throughout Spain, lecturing at schools and social halls. As word spread about his ever-changing topics—rotating between medicine, art, graphic design, mythology, and even urban planning—he attracted ever-larger audiences. At twenty-one he published a scandalous short essay about “homosexuality throughout the history of the West.”8 He then set off a firestorm by condemning both the “dogmatic moralists” of the Catholic Church and Spain’s growing fascist movement. Before long he championed other progressive and then unpopular campaigns, from the suffragist movement to proposing that a Marxist economy might be best for Spain. A government minister who attended one of his impassioned talks was so impressed that he named Martí-Ibáñez, then twenty-six, as the general director of public health and social service for Catalonia.9 Two years later he became Spain’s undersecretary of public health. By then, civil war wracked Spain. Neo-fascists led by General Francisco Franco battled the leftist government of the Second Republic. Martí-Ibáñez represented the Republic in the 1938 Universal Peace Congresses in Geneva, New York, and Mexico City. On returning to Spain he joined the air force’s medical corps.10 He suffered a shrapnel wound after only a few weeks and had barely recovered when the fascists captured Barcelona in January 1939. On Franco’s wanted list, Martí-Ibáñez fled with the last contingent of Loyalist troops to the French Pyrenees. Some friends there helped him escape to America.11
The sociable polymath reinvented himself in New York. Six months after arriving in the U.S., Swiss-based Hoffmann-La Roche hired him as a consultant. In his free time, he assumed editorial roles at half a dozen medical, psychological, and psychopathological journals, as well as presenting his own papers at scientific conferences.12 After three years he left La Roche to become the medical director responsible for Latin American sales for U.S.-based Winthrop-Stearns. The Journal of the American Medical Association offered him the editor-in-chief’s role for a proposed Spanish-language edition. He accepted instead an offer from Squibb for a post that put him in the middle of both drug development and marketing.13 It was in that role that Martí-Ibáñez met Arthur Sackler and Ludwig (Bill) Frohlich in the embryonic world of medical advertisement.14
It is little wonder that the man who later wrote in his autobiography, “There is only one way to defeat death—to live fast,” attracted the attention of Sackler and Frohlich.15 Martí-Ibáñez admired Sackler’s endless energy and willingness to take risks. In Sackler he had found a kindred soul for turning the medical status quo upside down. With Bill Frohlich, Martí-Ibáñez shared a genteel sophistication and love for arts and culture. At Frohlich’s East Side townhouse parties, Martí-Ibáñez regaled the guests with tales of his offbeat travels to Africa and Asia or his musings about everything from medical philosophy in the Renaissance or the Spain of Don Quixote to the lost science of alchemy. He even presented his unorthodox theory that stress might cause disease. He used Frohlich’s parties as an informal test market for his ideas. Those that provoked the best responses he turned into articles.16
Sackler wanted Martí-Ibáñez as a partner in his own ambitious plans to remake how the pharmaceutical world sold its products. The two spoke about it frequently but no early idea seemed quite right. When Martí-Ibáñez left Squibb, he opened a private psychiatric practice in Manhattan. He also became a regular lecturer at New York Medical College and Flower and Fifth Hospital.17 Arthur hired him as a special consultant at the McAdams agency, and later made him a director of a wholly owned subsidiary, McAdams International.18 In the spring of 1951, they formed MD Publications Inc., a shell company they agreed to keep inactive until the right opportunity arose. No one was aware that the Sacklers had put up most of the seed money and held a controlling stake. MD Publications shared office space with the McAdams agency.19 I 20
Neither Martí-Ibáñez nor Arthur Sackler hid their considerable ambition. That sparked strong reactions from people who either admired their naked drive or considered it crass and overbearing. A series of seemingly unconnected events would soon put the duo into medical publishing, a venture that made them rich and presented an opportunity to wield unseemly power with the FDA.
In the marketing pitches Arthur had made to middle management at pharma firms, many thought his ideas too risky and him overconfident. He was, they concluded, trying to turn drugs into another lucrative ad business, like the ones that flourished for cars, tobacco, and consumer goods. Sackler did not endear himself to those midlevel managers when he tried going over their heads to top executives.21
When Sackler met Thomas Winn, Pfizer’s sales director, he said that he would make Charles Pfizer a household name if the company gave him a big enough budget.22 That decision could only be made by the company’s CEO, John McKeen. It took another outsized personality like McKeen to embrace Sackler and trust him with something as critical as Pfizer’s rollout of its much anticipated broad-spectrum antibiotic, Terramycin. McKeen set aside $7.5 million—then a record—for ads and promotion. The company even agreed to install a specially built telephone switchboard to handle what Sackler promised would be a record volume of calls.
On March 15, 1951, Pfizer sent over eight hundred telegrams to every drug wholesaler in the country alerting them to imminent FDA approval. It offered a deep discount for early buyers.23 It was the start of what Business Week called “the Terramycin blitz.”24
The eight-man “details team” group McKeen had hired stood at pay phones across the country, waiting for a call from headquarters to begin visiting doctors. Over several weeks, crisscrossing the country, they pitched Terramycin to several thousand physicians. Pfizer drafted seventy third-year medical students to assist the detail men.25
Sackler knew no matter how hard they worked, the Pfizer field force was too small to reach every doctor. So he unleashed a blitzkrieg of direct mailers to clinicians and physicians, as well as pharmacists, including those at hospitals (about 85 percent of all hospitals had in-house pharmacies then).26 Physicians known as heavy prescribers received two to three direct mail pitches daily for nearly a year.27 Sackler employed a team of copywriters who worked on multiple campaigns, from letters to glossy brochures to Rolodex–ready file cards. One mailing was thousands of handwritten postcards that looked as if they were sent from exotic locations, such as India’s Taj Mahal, Egypt’s pyramids, and the Great Barrier Reef. Everyone had a brief story of how Terramycin was eradicating diseases in each country. Signed “Sincerely Pfizer,” those cards quickly became collectibles.28
Pfizer soon introduced its in-house magazine, Spectrum, and had reprinted it as an eight-page glossy color insert in the prestigious Journal of the American Medical Association. Before Sackler released his advertising onslaught, JAMA’s pages were virtually free of branded drugs and featured mostly medical supplies. In the early 1950s, even tobacco companies placed cigarette ads.29 Sackler saturated JAMA with his Pfizer campaign. Its ad pages jumped more than 500 percent over a couple of years, more ads than Life, and 75 percent of its antibiotic ads were for Terramycin.30 At rates of more than $1,000 a page, and thousands of pages annually, JAMA and other premier medical journals grew dependent over time to pharma’s promotion money. By the late 1960s, JAMA’s $15 million in ad revenues was 40 percent of the AMA’s income.31
Pfizer agreed with Sackler’s recommendation to concentrate the bulk of Terramycin’s print campaign in JAMA. To advertise in a handful of other leading journals might have seemed a commonsense strategy. It was, instead, as with much connected to Arthur Sackler, more complicated and calculating. Arthur knew that Congress’s legislative effort to curb false and misleading advertisements, the 1938 Wheeler Lea Act, bypassed the FDA by empowering the Federal Trade Commission with oversight of accuracy in drug ads. But there was a loophole: since doctors were judged capable of assessing the accuracy of drug promotion, ads in medical journals were free from oversight.32 Sackler had focused on the medium in which the government was powerless to constrain his copy. Ads that boasted that Terramycin was “one of the most complex structures to ever be found in nature” were Sackler’s way of making the drug appear to be far more innovative than it was.33 II 34
It was not long before Sackler was the first to experiment with radio ads. Some of his tactics became standard for the industry, including twenty-four-hour sales marathons and rich bonuses for sales reps. He helped persuade the American Medical Association that drug advertising would benefit if the companies had information about the prescribing habits of doctors. The AMA’s Business Division started sending rudimentary monthly reports measuring the impact of ads on a cross-section of five hundred physicians nationwide.
Pfizer’s McKeen told the New York Security Analysts Society that the company’s great success was the result of “using vigorous promotional techniques.”35 That was an understatement. One of Sackler’s Madison Avenue competitors, William Castagnoli, said it “is hard to quantify his influence on medical advertising, his impact was so great.… As head of McAdams, he took a chemical company new to the prescription drug market, Pfizer, and made it a force in the industry.”36 The Medical Advertising Hall of Fame later noted, “No single individual did more to shape the character of medical advertising.… His seminal contribution was bringing the full power of advertising and promotion to pharmaceutical marketing.… [His] campaign for Terramycin forever changed the industry’s marketing model.”37
Terramycin sales exceeded even McKeen’s lofty expectations. Pfizer bought a surplus submarine shipyard in Groton, Connecticut, and converted it into the world’s largest fermentation plant.38 It operated at capacity to produce Terramycin around the clock. In under a year, Pfizer’s detail team had ballooned from eight to three hundred (on its way to two thousand in five years).39 Those most sought after were college graduates with chemistry, biology, or pharmacology degrees.40 Still, they went through twelve months of training. They were taught that while technical knowledge was key, it was also important to cultivate a personal connection with the doctors they visited. Sales representatives asked for and remembered the details about families, outside hobbies, and favorite sports. Half of physicians surveyed later said that the best of them were more like a friend than a salesman.41 Each sales rep would be responsible for about three hundred doctors.42
McKeen made certain Pfizer’s researchers and attorneys were relentless in getting FDA approvals for Terramycin in other formats, from pills to powders to eye drops, while expanding the conditions for which it could be prescribed to nearly forty. Americans were spending $100 million on broad-spectrum antibiotics like Terramycin, more than on penicillin, sulfanilamides, vitamins, nostrums, hormones, and botanicals combined.43 Pfizer’s profit margin was 50 percent, Lederle and Parke-Davis 40 percent and 35 percent, respectively. To handle the booming international demand for Terramycin, Pfizer opened offices in thirteen countries (some European countries had import duties that were incentives for American firms to open foreign subsidiaries).44 Terramycin’s success meant Pfizer accounted for a quarter of worldwide antibiotic sales, making it the number one firm in revenues in the pharmaceutical industry.45
Pfizer’s aggressive marketing and sales tactics not only recast the company but transformed the industry. Traditionalists bitterly complained that Sackler’s “hard sell” was unseemly and disturbing.46 However, as competitors saw sales and profits set records for Pfizer, they did their best to copy the playbook. Rivals expanded sales departments and beefed-up marketing to doctors. Merck, playing catch-up, merged with Sharp & Dohme, a small firm well known for its experienced sales team.47
While Pfizer’s Terramycin was a marketing wonder, it also benefited from the elevated regard with which the public still held the industry. Expectations for the latest drugs were high. Besides antibiotics, there were new medications to treat glaucoma, arthritis, and schizophrenia; a second generation of tranquilizers; oral contraceptives; and even a first to reverse an opioid overdose. Research was under way on an antianxiety that would kick off a revolution for meds marketed as “emotional aspirin.” There was hope a polio vaccine might wipe out the disease made infamous in a country where most people had personal memories of how it had put Franklin Roosevelt into a wheelchair.
The public seemed unfazed when the first studies appeared indicating that lifestyle choices, not simply bacterial pathogens, might affect health and longevity. Smoking was tied to lung cancer for the first time in 1950 and later, when Pfizer released Terramycin, a report concluded diet might contribute to heart disease.48 Arthur Sackler was in a tiny minority; he was so against smoking that he did not allow it inside the McAdams offices.49 But most people, even many physicians, refused to believe that smoking and food could lead to chronic or fatal diseases. Even if true, however, the overriding faith in science and pharma was strong. Many shrugged it off; there would be a pill one day to take care of it, much as there was an antibiotic to treat infectious diseases.50
Pfizer and its rivals did not simply want to rely on a combination of public goodwill and a marketing blitz to keep antibiotic sales at record levels. They began a unified lobbying effort to get a major modification to the U.S Patent Law. The language they wanted would set a lower innovation threshold for granting a drug patent. It would give legal protection to antibiotics discovered through mass, routine screening of microbial soil samples.51 When Congress modified the statute the following year (1952), it opened the door to a larger number of drugs on an ever-quicker pipeline from the lab to the marketplace.
That was the same year a Pfizer biologist got permission for “Project Piglet,” in which he tested sub-therapeutic doses of antibiotics on pigs. The result? It accelerated their growth. Pfizer used those findings to market antibiotics to farmers who began using them in feed for cattle, pigs, and chickens.52 CEO John McKeen liked that sales for farm animals were consistent and did not depend as they did with humans on epidemics or outbreaks of disease. Pfizer created the first separate sales and marketing team for agricultural products and other pharmaceutical firms followed. In a few years, bulk sales of antibiotics for agricultural uses accounted for a quarter of all production.53 III 54 No one worried that daily exposures to antibiotics might kill only the weakest bacteria in animals and that the surviving organisms would become stronger and far more robust pathogens.55
The Terramycin launch was barely over when Arthur was again restless. It would be good, he thought, to have something on which he and his two brothers could work together. Arthur decided to buy the small New York drugmaker Purdue Frederick Company, the company he had pitched unsuccessfully in 1948 to his friend Alfred Stern. Not much had changed in four years. Purdue’s annual revenues were still anemic and its best-selling product remained its “cerebral tonic,” Gray’s Glycerine Tonic Compound.56 Operating out of a small office at 135 Christopher Street, the company was struggling to adapt to the rapid changes of the postwar pharmaceutical industry.57
Although Arthur had put up most of the money to buy Purdue Frederick in June 1952, the Sackler brothers agreed they owned it equally. None of their names, however, appeared on the New York State incorporation papers.
Mortimer asked what they would do with Purdue.
“We will sell what they have better than they did,” Arthur said. “And then we will find our own products as we go along.”
I. In a New York Times profile thirty years later, Arthur Sackler denied any ownership in MD Publications, claiming instead he had been a consultant and had started a “well-known medical news magazine” for the company. Martí-Ibáñez was dead by the time of that interview. However, a Senate investigative staff later uncovered evidence that Arthur Sackler had funded the MD Publications start-up through his McAdams ad agency. Also, documents from Arthur’s estate after his 1987 death confirmed that the Sackler brothers had indeed owned a majority interest in MD Publications.
The author discovered that the year before Arthur Sackler founded MD Publications, he had created the Angiology Research Foundation for the clinical testing of drugs for vascular diseases. The year after creating MD Publications, he incorporated the Inter America Medical Press and International Medical Press, both designed to help foreign drug companies promote their products in the U.S. The Sackler ownership interests remained secret.
II. When Pfizer released chlorpropamide in a few years, it targeted pre-diabetic patients who needed to stabilize their insulin levels. Sackler’s promotion claimed an “almost complete absence of unfavorable side effects.” In fact, Pfizer had commissioned a pre-release study that revealed “serious side effects” in 27 percent of test patients.
III. Research was even conducted for three years in New York on mentally deficient spastic children to determine whether low-dose antibiotics might boost childhood growth rates. It did, but pharma companies never sold their products to add quick bulk to children. In 1954, when penicillin discoverer Alexander Fleming visited the U.S., he was skeptical when he learned about that research. “I can’t predict that feeding penicillin to babies will do society much good. Making people larger might do more harm than good.” Although pharma did not market antibiotics to children for accelerated growth, children in the U.S. and Western Europe inadvertently ingested the drugs. Estimates are that through the 1950s, about 10 percent of every container of milk had penicillin residue from treated cows. At that time, farmers used the same penicillin developed for humans on cows.