By the mid-1950s, Arthur Sackler and his Medicine Avenue partners were looking beyond promoting competing brands of tetracycline. As part of their hunt they focused on so-called fixed-dose combination antibiotics. The theory had both strong proponents and skeptical critics. Its advocates believed that when antibiotics were combined with other drugs, the resulting medications might have fewer side effects and more potency than either drug on its own. Some experts, like infectious disease researcher Hobart Reimann, thought fixed combinations could be more revolutionary than penicillin (his proposed name was multimycetin).1 The naysayers believed the underlying science was flawed. The skeptics thought it was unlikely that any fixed combination would ever have better efficacy than the antibiotic on its own. Some voiced concerns that it was possible over time the combined drugs could become antagonistic to each other, resulting in serious long-term side effects.
It was not a new theory. In the late 1940s, a sulfa and penicillin mix had tested better in the lab at fighting some common infections. It never went on sale, however, since the sulfa component spiked adverse effects. Pharma researchers at half a dozen companies had tried hundreds of combinations since then and failed to get one from the lab to the marketplace.
Still, Medicine Avenue was enthusiastic. Martí-Ibáñez wrote to Sackler early in 1956, contending that fixed-dose combo antibiotics “are a defense against the current [downward] price trend in penicillin and streptomycin.”2 The reason for their confidence was that Pfizer was close to FDA approval of the industry’s first fixed-dose combination antibiotic, Sigmamycin. It was a mixture of two parts tetracycline and one part oleandomycin, a weak relative of erythromycin.
Martí-Ibáñez held his annual Symposium on Antibiotics in New York in June 1956. Henry Welch, chief of the FDA’s antibiotic division, gave the introductory remarks to the gathering of leading researchers, academicians, and clinicians.3 He surprised many by enthusiastically endorsing fixed-dose combinations.4 “It is quite possible that we are now in a third era of antibiotic therapy,” he said.5
After he returned to Washington, Welch assigned a team inside his division to gather data that buttressed his bold conclusion.
No one outside a handful of friends knew that Welch’s endorsement had been carefully orchestrated by Sackler on behalf of his client Pfizer. Arthur had convinced Martí-Ibáñez they would all benefit if Pfizer’s advertising staff, and a few of his best McAdams copywriters, edited Welch’s talk. Pfizer, Sackler said, would buy many reprints of a good speech since Sygmamycin was only months away from going on sale. Sackler himself coined the “third era of antibiotic therapy” to herald the drug’s arrival, and it became the tagline in Pfizer’s upcoming campaign (when it became a public scandal a few years later, a twenty-six-year-old medical student who paid his tuition by working as a copywriter in Pfizer’s tiny marketing department took the blame for “jazzing up” Welch’s address).6
Sackler delivered on his promise. Pfizer bought 238,000 reprints of Welch’s opening remarks.7 Medical Encyclopedia, launched by Martí-Ibáñez and Welch, was the publisher. The duo announced their paid-subscription Antibiotic Medicine would become a free-circulation journal. Its financing? “Who better than the pharmaceutical industry,” asked Martí-Ibáñez in disclosing it would be supported by drug ads.8 More than 160,000 copies of the first issue went to physicians and a select list of influential lay people.
Martí-Ibáñez and Welch also launched a new monthly, The Medical Newsmagazine MD. It was a glossy journal that promised the latest medical and pharmaceutical news.9 Mortimer Sackler was appointed an editorial board director. The McAdams agency sold the ads.10 Welch wrote to Sackler imploring him to give an “extra push” to all his pharma clients to make it a financial success.11
Welch’s public endorsement of the science behind fixed-dose combination antibiotics excited Pfizer. It was perfectly timed for its November rollout of Sigmamycin. In lab tests the drug was particularly effective against the deadly Streptococcus pneumoniae bacterium. Arthur Sackler utilized the same aggressive tactics that had been so successful with Terramycin and tetracycline. In a massive nationwide direct-to-doctors mailing campaign, Pfizer eschewed randomized clinical trials to boast about its drug, instead relying on personal experiences by physicians. “Every day… everywhere… more and more physicians find Sigmamycin the antibiotic therapy of choice,” was the headline on a flashy brochure that accompanied free samples.12
Pfizer ran a bold four-page ad in the November issue of Antibiotic Medicine. In an accompanying editorial, Welch praised the “stand out… synergism” of Sygmamycin’s component drugs.13 It was hard not to see his words as a product endorsement by the chief of the FDA’s Division of Antibiotics.
That editorial sparked criticism of Welch’s dual roles. Many scientists believed that no government watchdog agency should sponsor a private, for-profit symposium. Although the FDA would end its role in Martí-Ibáñez and Welch’s annual Antibiotics Symposium the following year, it did not rein in Welch. It accepted his assurances that he still received only a small honorarium.
Sackler let Frohlich and Martí-Ibáñez assume responsibility for Welch successfully fending off any inquiries from his FDA supervisors. Arthur was not as involved since he was under tremendous personal stress, something he did not share with his business partners. Just a couple of months earlier a Hollywood producer had stunned the House Un-American Activities Committee with testimony that Alfred Stern and his wife, Martha Dodd, were Soviet spies. The couple had fled to Prague by that time (they never returned to the U.S.).14 Sackler worried the FBI might pick up the trail of his friendship with Stern. He had reason to worry. The Ridgefield, Connecticut, summer house where Arthur sometimes visited them was where they also met with Soviet agents.15 The FBI would come calling, but not for another four years.
In the meantime, as he fretted about the consequences of his friendship with the fugitive couple, Arthur relied on what one colleague called his “unwavering discipline” to refocus on business. In 1955, Mortimer and Raymond bought rights to L-Glutavite, four trademarked “therapeutical preparations,” and eight product-related patents, from Boston’s Gray Pharmaceutical Company.16 L-Glutavite was a proprietary mixture that Gray touted as “optimal amounts of mono-sodium L-glutamate plus a therapeutic amount of the vasodilator niacin and co-enzymes and other essential elements.”
“Broken down into ordinary layman’s English,” wrote John Lear, the no-nonsense science editor for The Saturday Review, “this means simply the familiar meat flavoring (MSG) plus vitamin B.” With Arthur providing strategic advice, Mortimer and Raymond formed the Glutavite Corporation and approached the FDA about getting it approved as a drug.17 The FDA said no approval was necessary since glutamate, its main chemical, was harmless, and vitamin B was sold over the counter. The agency warned the Sacklers not to make any therapeutic claims on advertisments to the public.18
Arthur figured out how to circumvent that. Although L-Glutavite required no prescription, the McAdams agency ran a promotional campaign directed only to doctors. Some industry observers thought it a waste of time and money to advertise an over-the-counter product to physicians who could not write a prescription for it. “That is a big misconception,” says Richard Sperber, who later directed Schering-Plough’s ethical OTC products, which included nasal spray Afrin and cold remedy Coricidin. “You need to build demand based on word of mouth. We promoted our OTC line widely, even to clinics, pharmacists, and nursing associations. There is a placebo effect that takes place for many consumers when a medical professional tells them about a pill.”19
The first Sackler advertisements for L-Glutavite were illustrated with charcoal sketches of senile men and women. Arthur believed many physicians might be willing to dispense it for their patients who complained about conditions—a glum mood, faulty memory, or a general mental fogginess—that might not be serious enough for more powerful tranquilizers. The ads promised that a “rounded teaspoonful of powder in tomato or other vegetable juice” daily would “improve cerebral metabolism.” Saturday Review’s John Lear noted, “The spectacle of three psychiatrists, members of a profession looked to with almost awesome respect for guidance in mental illness, concertedly pushing a flavoring extract mixed with vitamins as a means of arresting the pitiable deterioration of aging minds, is a painful experience.”20
The American Medical Association’s journal refused to carry the L-Glutavite ads. That was not a problem for the Sacklers. They formed a separate company that appeared to be an independent marketing firm (Medical Promotion Production Inc.).21 It placed ads in Arthur’s Medical Tribune, distributed free to the nation’s doctors. L-Glutavite also featured in Arthur’s recently launched Medical News, a weekly newsletter to another 35,000 physicians who were teachers at medical schools, held staff positions at hospitals, or served in the military.22 Ads ultimately ran in fifteen medical journals to which the Sacklers had some business connection.23
L-Glutavite was a success from the moment the Sacklers began selling it. Inexpensive to manufacture and sold at a several hundred percent markup, it returned huge profits.
The Sacklers arranged for a clinical study of L-Glutavite at the Bedford, Massachusetts, Veterans Affairs Medical Center. Built in 1928 as a psychiatric asylum, Bedford had a large population of elderly patients diagnosed as schizophrenics. Mortimer and Raymond were friends with Dr. Louis Fincle, Bedford’s chief psychiatrist.24 The study involved several dozen patients averaging sixty-three years of age and twenty years of institutionalization. All were given a daily glass of tomato juice; L-Glutavite was mixed into half the drinks. No one, including Fincle, supposedly knew which patients got the spiked juice.
The results were dramatic. Fincle, joined by a Boston professor of psychology, Leo Reyna, reported “marked improvements” in 73 percent of the L-Glutavite patients. They had “improved behavior and outlook,” some stopped quarreling, and others for the first time in years started dressing and feeding themselves. The progress was so marked for some patients that they were discharged to regular nursing homes. The researchers concluded that for “poor risk elderly patients” L-Glutavite was “safe and free of detrimental side effects.”25
The Journal of Clinical and Experimental Psychopathology published the results in its March 1958 issue. A press release put it on the radar of newspapers and magazines across the nation: “Chemical in Juice Aids Mentally Ill” (New York Times), “Important New Drug for the Mentally Ill” (UPI), “A Boon to the Nation’s Overcrowded Mental Hospitals” (AP).26
No one was aware of the many underlying conflicts of interest. The Sacklers owned The Journal of Clinical and Experimental Psychopathology. Arthur was its editor-in-chief and Felix Martí-Ibáñez its international editor. Mortimer and Raymond were listed on its letterhead as two directors.
On March 21, 1958, the same month that the Sacklers’ psychiatric journal reported the results of the clinical trial, a stock listing was filed at the New York Stock Exchange. Application No. A-17508 listed seventy thousand additional shares of common stock of Chemway Corp., a home products manufacturer, for the purchase of Glutavite Corporation.27 When the shares were issued that day at Chemway’s market price of 75/8, the Sacklers pocketed half a million dollars for their one-product company.28 That was in addition to $1.5 million in sales over the three previous years.29 Chemway placed L-Glutavite under its drug division, Crookes-Barnes. A Senate investigating committee later determined that Crookes-Barnes had been a “company partially owned by Sacklers.” Chemway had bought it from Mortimer and Raymond Sackler in July 1955. Arthur Sackler was one of its directors.30
The clinical trial that showed such promise for L-Glutavite in treating or even reversing schizophrenia in elderly patients was the first of its kind and sealed the Chemway deal. That result, however, was never again duplicated. In recent years, researchers have concluded the opposite, that excess glutamate might be a trigger for schizophrenia.31 Why was the L-Glutavite study conducted for the Sacklers, and published in a journal they controlled, such an outlier? No one can be certain so many years later. The author learned, however, that John “Jack” Brennan, one of the country’s leading pharmacological experts, and the president of Gray Pharmaceutical at the time the Sacklers bought its products, had an opinion. He later told a colleague at Boston’s Kendall Company that “someone had cooked the numbers.”32
The inability to reproduce the success of the L-Glutavite trial did not concern the Sacklers. What mattered to the brothers was that L-Glutavite had returned over $2 million in under three years ($18.3 million in 2019).
Government regulatory agencies that might have taken notice were instead focused on investigating much larger companies and broader themes of competitiveness and pricing. While the Sacklers were orchestrating their Glutavite bonanza, the FTC was putting the finishing touches on a three-year investigation into the drug industry. Its highly critical 361-page “Economic Report on Antibiotics Manufacture” was released only a couple of months after the Sacklers sold Glutavite to Chemway.33 The FTC’s damning conclusion was that the years of uniform prices for all the tetracycline brands were not by chance but rather illegal collusion.
Bill Frohlich had boasted there was “a competitive zeal in the pharmaceutical industry which would have warmed Adam Smith’s heart.” That was put to the test the following month, when the FTC filed a sweeping antitrust complaint charging Pfizer, Lederle, Bristol-Myers, Squibb, and Upjohn with conspiracy to fix tetracycline prices and using their cross-licensing agreements to exclude others from entering the market.34 The FTC also accused Pfizer of fraudulently obtaining its patent monopoly by withholding critical information from the Patent Office. When its four competitors learned about that omission, instead of reporting it to regulators, the complaint contended they blackmailed Pfizer into partitioning the tetracycline market.35
On the heels of the FTC price-fixing charges, the Securities and Exchange Commission released a report that revealed the profits of pharmaceutical companies were, on average, more than double that of other manufacturing industries.36
Pharma firms deserved larger profit margins, argued Bill Frohlich, since drug sales had been flat through World War II before “increasing almost three times as much as the increase in the Gross National Product” during the 1950s. Half the biggest-selling medications were less than five years old, which according to Arthur Sackler meant that innovation drove profits.37 While Sackler, Frohlich, and many of their colleagues shrugged at the SEC report, the part about pharma’s immense profits was a lead story in the national press. It added to a growing perception that drug prices were too high.
Even a few prominent medical voices warned about the consequences of pharma’s fixation on profits. Max Finland, an esteemed Harvard researcher who had led penicillin research on treating pneumonia, cautioned that the companies had lost sense of their original mission. At some point, Finland suggested, they should refocus on finding cures and stop judging success only by sales.38 Finland correctly predicted that the failure to focus on what was best for the patient meant it was only a matter of time until pharma would cross a line that infuriated the public and result in more government regulation.39
Drug firms were on the defensive. The idea they were obsessed with profits was wrong, they countered. Finland’s call to put public service ahead of profits was misplaced since they had spent $600 million on research and development since the end of World War II. They had also collectively introduced four hundred new medications in just three years.40
Those proclamations seemed hollow in light of an article by John Lear in Saturday Review. “Taking the Miracle Out of the Miracle Drugs” was published the same month the SEC reported about the industry’s immense profits. Lear exposed that pharma firms were anything but noble. He presented a damning indictment of how “unduly enthusiastic and sometimes misleading… massive advertising pressure” had encouraged doctors to overprescribe antibiotics.41 That widespread overuse had turned some ordinary microbes pathogenic. Lear revealed that between 1954 and the autumn of 1958, there had been five hundred hospital epidemics of resistant strains of staph infections. The deadliest outbreak killed twenty-two patients in a Texas hospital. Many doctors Lear interviewed acknowledged antibiotic resistance was a national problem. Yet he was the first to cover it in a national publication because “medical authorities discouraged writers from disseminating the fact on the grounds that people who needed hospital care would be frightened away.”42
Lear was most critical of the advertisers and marketing companies who had encouraged overprescribing of antibiotics. He noted that while some drug companies were “traditionally cautious in advancing claims for their medicines,” the industry had been “jostled and jolted… by the Madison Avenue ‘hard sell’ ” which relied on “a great deal of money” and no “restraint in promotion.”43 The problem had been made worse since penicillin had not required a prescription during its first decade on the market.44
The marketing excesses, he charged, had reached a fever pitch with the introduction of fixed-dose antibiotics. Pfizer’s Sigmamycin had been on sale for three years by the time of Lear’s exposé. Rival companies had responded with their own brands, sixty-nine fixed-dose antibiotics.45 Lear contended that studies showed that not a single compound offered therapeutic advantage over the underlying antibiotic on its own, and that the combinations were “sometimes dangerous.”46
As for Sigmamycin, he was suspicious that all the clinical studies cited in the advertisements referred to reports published in Martí-Ibáñez’s medical journals and edited by the FDA’s Henry Welch. Arthur Sackler served as an advisor on those editorial boards.47
Lear met one evening with an unidentified “eminent research physician” at his laboratory. (Physician-historian Scott Podolsky believes the anonymous tipster was Harvard’s Max Finland, whom Podolsky calls “the de facto Strep Throat.”)48
“He pulled open several drawers that were full of drug samples and advertisements,” Lear recalled. “ ‘Just take a look at that stuff!’ he told me, and then went on to say that a good part of the advertising was misleading—in fact, that some of it was downright fraudulent.”
“Look, you’re walking around a big story. Why don’t you step into it?” the physician said to Lear.
“I might if I had enough information.”49
The physician pulled from the drawer a folder with a banner of bold type that said, “Every day, everywhere, more and more physicians find Sigmamycin the antibiotic therapy of choice.”
Lear said, “Below that were reproductions of what appeared to be the professional cards of eight doctors around the country, with addresses, telephone numbers, and office hours. The doctor said he had himself conducted some experiments with Sigmamycin, and at one point he had written to the eight doctors to ask the outcome of their use of the drug in clinical tests. As he told me this, he reached into one of the drawers and brought out eight envelopes, all stamped Return to Writer—Unclaimed. I asked him if I might report his experience, and he said that he couldn’t get involved in any kind of exposé. He pointed out, however, that there was nothing to prevent me from writing to the doctors myself.”50
When Lear wrote to them asking why they were enthusiastic about Sigmamycin, he encountered the same roadblock as his friend. The telephone numbers on the cards were false, the addresses made up. The “doctors” were fakes, none of them existed.51
Lear’s discovery put Sackler and Pfizer’s CEO, John McKeen, in an uncomfortable spotlight. McKeen visited Lear at the magazine’s office and claimed he belatedly understood how the ad might be misleading. Pfizer had taken steps to avoid doing it again, he assured Lear. As for Sackler, Arthur blamed the fake doctors on an overly enthusiastic copywriter.52 Lear interviewed Welch the following month and pressed him on whether his financial arrangements with Martí-Ibáñez was a conflict of interest given his role as the chief federal regulatory cop for antibiotics. Once again, as he did with his bosses at the FDA, Welch swore he only received a token honorarium for all his nongovernment work.53
The controversy kicked off by Lear’s article forced the FDA to act. Welch’s bosses decided that October that although he was an “outstanding scientist” who had “no conflict of interest,” it would be better if he resigned from his outside editorial roles.54 It was too little too late. Lear’s searing exposé about the fake doctors prompted the FTC to bring its first ever unfair practice complaint against a drug company (the FTC trial examiner found Pfizer guilty, but refused to issue any penalty since Pfizer promised not to do it again).55
More bad news came in December 1959. The FDA announced three over-the-counter earwax removal products were “voluntarily withdrawn from the market.” That decision had been forced by months of press accounts of patients who had developed alarming side effects. The recall included Cerumenex, the country’s top selling eardrop solution. It was one of Purdue Frederick’s most successful products. The Sacklers set about slightly reformulating the eardrops to get Cerumenex back on shelves (a “new and improved” version went on sale in a year and still topped the market).
The worst news for pharma that month was not, however, the recall of a few over-the-counter meds. It was instead that the entire industry had come into the crosshairs of the crusading and ambitious Tennessee senator Estes Kefauver. He wanted to find out if drug firms were more concerned with profits than in finding medications to cure illnesses. What followed was a watershed moment for the modern pharmaceutical industry.