Thomas Hoving and the Metropolitan’s curator of Egyptian Art had underestimated the final costs for the Dendur design developed by architects Kevin Roche and John Dinkeloo. A reflecting pool offset by a spectacular wall of stippled glass along the north side was meant to evoke the temple’s original location on a hillside near the Nile. It alone broke the budget. There were also big cost overruns for an underground employee parking garage, a reinforced loading dock, a protective environmental room for fragile antiquities, and a hydraulic lift designed to buttress the reassembled temple.
Hoving, however, not wanting to alienate Sackler further, did not ask him or the brothers to speed up their payout. Since the family would not allow any dilution of their extensive naming rights to the new wing, Hoving had to raise several million more from donors who were willing to do so without having their name “on a plaque on the wall.” Almost two years after the Sacklers had agreed to donate $3.5 million, the construction on the new wing was not even at the one-third mark. The Sacklers were in no rush, however. They were busy on many other fronts.I1
While the Sacklers’ increasingly high-profile lifestyle played out in the New York papers and art publications, their pharmaceutical ventures stayed out of public view. Arthur was still immersed in his publishing empire and at McAdams, with its roster of top drug companies. Mortimer’s focus was the trio’s foreign operations while Raymond ran Purdue Frederick as its president.2
Arthur’s cash cow was Roche and the Valium account. He had refined the promotion campaigns over time and had made Valium impervious to all competitors. It was the top-selling medication in the country by a wide margin, a spot it had held since 1968. Valium defied all odds by enlarging its lead over competitors by adding on average more than seven million new customers annually.3 Librium, its chemical cousin, was not far behind, and in a dead heat with Ayerst’s Premarin. Roche’s blockbuster benzodiazepines were prescribed 103 million times in 1975, representing more than two billion pills.4
Sackler’s enhanced marketing strategies that kept the benzos flying off the shelf did not come cheaply. Roche had set a record when it committed $10 million in 1963 for Valium’s rollout. In 1975, it spent a staggering $400 million on Sackler-designed campaigns for its blockbuster benzos, about 40 percent of the industry’s billion dollars allocated to marketing and promotion.
Roche and other companies paid for the enormous expenditures by keeping the prices high on their branded drugs sold in the United States. It was a windfall for Arthur. Michael Sonnenreich told the author that Sackler “made a lot of money in the beginning because he got bonuses based on sales volume. Later it changed to very large flat fees. Very large fees.” The Swiss drugmaker, grateful to Sackler for the drugs’ success, also provided him with millions in interest-free loans as advances against future advertising work, money he invested in the stock market.5
Roche did not mind paying Sackler huge fees because it understood how important he was in making the drug ubiquitous. “It would be very hard to find any group of middle-class women in which some aren’t regularly on Valium,” Vogue quoted a New York psychiatrist in 1975.6 As patients reported to their doctors that the drug helped treat muscle spasms and cramps, inflamed and aching joints, convulsions, sleep, and anxiety, the list of ailments it treated had turned it into “Valium the Versatile.”7 And Sackler’s promotion and Roche’s detail team complemented its many therapeutic uses with the message about its benign side effect profile.
Millions of patients taking Valium were certain it was safe. Their doctors had assured them of that. And that so many friends were using it reinforced that comfort. The 1970s housewives who were Valium’s core customers had heard horror stories about barbiturates from their mothers. Feminist psychologist Phyllis Chesler wrote in her seminal 1972 Women and Madness that Valium was a pharmaceutical straitjacket, a chemical way of making women happy while keeping them locked into a subservient, second-class societal status.8 Although the book was a commercial success and critically acclaimed, it did not hurt Valium’s sales.
As the drug maintained its dominance, medical researchers debated whether patients developed a tolerance to benzos and therefore needed ever-higher doses to achieve the same therapeutic effect. In the early 1970s it seemed as if there was a new study every six months, each contradicting the findings of the preceding one. The scientific back-and-forth played out far away from the attention of the public. As with oral contraceptives, in which it had taken the voices of female activists and reporters to raise credible alarms, eventually women’s publications and female journalists slowed Roche’s juggernaut and began changing the widely held view that Valium and Librium were harmless be-happy pills.
McCall’s raised a few concerns in autumn 1971 with “The Over-Medicated Women,” as did Ladies’ Home Journal with “Women and Drugs.”9 The turning point for the 30 million American women taking Valium did not happen until 1975 when a British clinical trial demonstrated that a significant percentage of long-term patients who abruptly stopped taking it suffered withdrawal symptoms. Millions of Valium patients could no longer ignore the controversy. Roche’s contention that the study was flawed was lost in a deluge of mainstream press coverage that suddenly focused on the drug’s risks.10
Vogue got everybody’s attention with “Danger ahead! Valium—The Pill You Love Can Turn on You,” in which a New York psychiatrist and addiction expert, Marie Nyswander, concluded that Valium could cause “a far worse addiction” than heroin.11 Nyswander, according to Vogue, was in a position to say that since she specialized in using methadone to wean addicts off heroin. Ms Magazine followed with “Do You Take Valium?,” sobering first-person accounts of middle-class suburban women who described debilitating “physical and mental anguish” when they stopped taking the drug.12
Time’s medical editor, Gilbert Cant, addressed the pros and cons in “VALIUMANIA,” a cover story for The New York Times Magazine.13 Valium, he noted, had become the symbol for a broad range of prescription medications charged with “turning America into an overtranquilized society of near zombies seeking peace of mind in a little bottle.” Cant was the first to question whether Roche had “overmarketed” its best-selling drug, especially with its heavy-handed promotion to women.
He also cited Nyswander, the doctor who had raised “worse than heroin addiction” in Vogue. She was, he wrote, “a highly respected Manhattan psychiatrist” and noted that in her opinion “Valium is the most addictive drug in common, legal use.… She stands virtually alone.” Still, Nyswander ramped up her doom-and-gloom forecast, warning there could eventually be two million Americans addicted to Valium, four times more than the number of heroin addicts. And she predicted that Valium would eventually prove lethal.14
That was a startling assertion given that Valium seemed quite tame in comparison to many other prescription and street drugs. Within a month of each other in 1970, Janis Joplin died from heroin and Jimi Hendrix from barbiturates. The following year a Paris medical examiner skipped an autopsy and ruled the cause of death of the Doors’ Jim Morrison at twenty-seven was a heart attack. Rumors Morrison had died of a heroin overdose, though, gained traction within days.15 Meanwhile, adding to the perception that Valium was not too potent, Ronald Reagan’s national security advisor, Robert McFarlane, later tried killing himself with thirty Valium pills. It put him into a deep sleep and he woke up at a local hospital.16
Most physicians thought Nyswander was grandstanding by publicizing her contrarian views on the country’s most popular drug. Some believed she was “riding to fame on the back of Valium,” and dismissed her condemnations as baseless overstatements.II17 Dr. Adam Lewenberg, the medical director for New York’s Addiction Treatment Center, later said, only half in jest, “the definition of a Valium addict is a patient who takes more Valium than his doctor.”18
The small but growing number of patients who had difficulty weaning off Valium pleaded with federal agencies to intervene on the benzos.19 The FDA was on the sidelines but not for lack of will. It was locked in a multiyear legal battle with Roche over its proposal to put prescription limits on Valium and Librium.20 The FDA had sought help from the Justice Department since the Controlled Substances Act had given Justice the power to restrict drugs subject to abuse.21 The FDA passed along the data it had compiled about Valium’s potential for dependence and abuse.22
In late 1975, the Justice Department did what the FDA could not do on its own. Valium and Librium were upgraded to Schedule IV, limiting the number of refills doctors could write. It also applied criminal penalties to diversion and illegal sales.23 Even possessing the drug without a prescription could mean jail time. A visitor to an Illinois prison received a two-to-six-year sentence after guards at a security check found seven Valium pills. An Alabama man got four years after a policeman discovered he had nine Valium pills he had taken from his roommate’s prescription supply.24
The FDA ordered Roche to add the “stress of everyday life does not require treatment with an [antianxiety] drug” on the Valium inserts sent to doctors and pharmacists. The government hoped that might reduce the widespread overprescribing.25 Roche, as it always did, took the FDA to court. It would take five years to settle the standoff, with the agency agreeing to weaker language: “may not require” instead of “does not require.”26 While Roche had kept the FDA tied up in court over a few words on Valium’s insert, it was unable to do much to delay changing public attitudes about its star drug. The drumbeat of news about possible dependence and unreported dangers fanned fears. Physicians became more cautious in dispensing the benzos after the DEA opened investigations into hundreds of so-called permissive prescribers.27 States started removing benzos from formulary lists of drugs covered by Medicaid.28 Restrictions on the number of refills forced devoted users to shop for doctors. As prescriptions got tougher to obtain, some patients found replacement meds, often riskier drugs such as barbiturates.29
The cumulative result was that Roche’s juggernaut had slowed. Valium was still America’s top selling drug, but its market was no longer expanding.
Nineteen seventy-five, when the media assault on Valium peaked, also marked a turning point for another blockbuster, Ayerst’s Premarin. About half of all menopausal women in America were using it (30 million prescriptions).30 On December 4, a report in NEJM made the front page of all major papers and was the lead story on the network evening newscasts.31
Two extensive clinical studies delivered alarming results about estrogen and uterine cancer.32 Women taking estrogen for one to four years were 5.6 times more likely to develop that cancer than those not on the hormone. Women on estrogen for seven years had a fourteen-fold increased risk. In an accompanying editorial, Dr. Kenneth Ryan of the Boston Hospital for Women concluded the studies showed the estrogen risk for endometrial cancer was the same as the risk of lung cancer from smoking twenty or more cigarettes daily.33 Dr. Harry Ziel, who directed one of the studies, told The New York Times, “This is not an innocuous drug that can be used like salt and pepper. Doctors should restrict its use to women with incapacitating symptoms, since it has a life-threatening risk.”34
The FDA called an emergency meeting of its advisory panel on obstetrics and gynecology. It took a year to issue a new labeling requirement, a lengthy insert that pharmacists were supposed to distribute so that patients were aware of the increased risk of endometrial cancer and potential risks of abnormal blood clotting a breast and gallbladder cancers.35
Health activists and writers Barbara Seaman and Gary Null got a rare interview with Robert Wilson, the physician who had been at the forefront of medicalizing menopause and pushing Premarin. Seaman and Null met with Wilson after another article in JAMA had sparked a second round of national speculation about whether Premarin’s undisclosed health risks made it too dangerous for long-term use. They asked Wilson for his thoughts about the latest science, particularly the studies showing a dramatically higher endometrial cancer risk for women on estrogen. Wilson was dismissive. “That’s the worst lie in the world, the worst fallacy. I have over 40 doctors working all over the world, Switzerland, Czechoslovakia, all over the world, and we haven’t seen one case of cancer!” That was not true, no doctors were working with him.
Did he still believe that women should take Premarin and other estrogen medications starting at age fifty?
“They say we should do nothing to retard menopause. Just think of that. Isn’t that dreadful? The estrogen regimen should start at age 9. Nine to 90. It’s necessary to begin then, and to check your estrogen levels all through life, so that it never leaves you. Don’t allow it to.”36
There was no support in the medical community for Wilson’s extreme view that estrogen be dispensed from ages “9 to 90.” The drug that he helped make a blockbuster (more than 35 million prescriptions in 1975) would be at the center of a debate between proponents who thought its benefits—symptomatic relief, stronger bones, and maybe some heart protection—outweighed the risks. Additional studies soon added weight to the risk side of the equation. One raised the specter of a breast cancer link while another pointed to a higher risk for coronary disease.37
In the aftermath of the 1975 cancer studies, Premarin’s sales plummeted by half over five years.38 Women felt vulnerable since there was no screening test that might identify endometrial cancer in its earliest stages.III39 Over time, however, fear faded as the drug companies spent millions to promote successfully a more refined version of Robert Wilson’s “feminine forever” thesis. Paid celebrity endorsements—model Lauren Hutton and singer Patti LaBelle—pushed Premarin as a life-changing medication.40 Popular women’s magazines again ran stories about how hormones helped women over forty stay healthy, look better, and maintain active sex lives.41 Gynecologists, many the recipients of large inducements from Ayerst, reembraced the drug. Premarin would, by 1990, again become the best-selling drug in the U.S. for a decade, exceeding by a third its mid-1970s pre–cancer scare peak.42
It took nearly twenty years for Prempro, a “new and improved” replacement, to reach the market. By then, Wyeth and Ayerst had merged into Wyeth-Ayerst Laboratories. Prempro was the first ever estrogen plus progestin pill. Progestin, a synthetic version of the natural hormone progesterone, had demonstrated its effectiveness in providing protection against uterine cancer. Wyeth-Ayerst was convinced that it needed the combination HRT to reach the market for women who avoided the company’s hit Premarin because of cancer concerns. Prempro won FDA approval even though it had not conducted a randomized clinical trial.43 It also became a best-seller. Between Premarin and Prempro, Wyeth-Ayerst dominated the HRT market; the two drugs accounted for two thirds of the annual 90 million HRT prescriptions.44 Sales stayed strong until Prempo too was unmasked as putting millions of women at risk, the same as had happened with the Pill and with Premarin.45
Robert Wilson did not live to see the final chapters play out in the hormone saga. He died in 1981. And he thought he had taken a family secret to his grave. He would have succeeded if his wife, Thelma, had not confided it after his death to their younger son, Ronald.
Thelma was a registered nurse and had worked with her husband in his gynecological practice. In 1963, the couple had coauthored “The Fate of the Nontreated Postmenopausal Woman: A Plea for the Maintenance of Adequate Estrogen from Puberty to the Grave,” in the Journal of the American Geriatrics Society. The first sentence set the tone: “The unpalatable truth must be faced that all postmenopausal women are castrates.” The solution they suggested was for every woman to start taking estrogen beginning in puberty and continuing to death.46 IV 47
Given their collaboration, it is no surprise that Thelma was on Premarin most of her life. After her husband’s death, she told her son that she was battling breast cancer. He visited her at the family home in Cold Spring Harbor, New York. As he later told author Trisha Posner:
“This isn’t the first cancer I’ve had.”
He thought he had not heard her correctly. She could tell he seemed confused.
“It’s not my first cancer.”
“I heard you,” he said slowly. He had left home to attend college and later had enlisted in the Air Force, spending years in Florida, far away from his family. But he had kept in touch with his mother and couldn’t imagine that she had had cancer before and never told him.
“When?”
“Over ten years ago,” she said, her eyes cast downward. “I had breast cancer. I had a mastectomy then.”
She could see the surprise on his face.
“Your father wanted me, no, needed me, to be a shining example of his work.”
The couple feared that if news of her breast cancers became public, it would have ruined her husband’s reputation.
Which of them had decided not to tell their own children?
“We all decided it.”
“Who is all?”
“Me. Your father. Even the men at Wyeth. They urged us not to tell.”V
I. That same year, 1975, Arthur was again in the news when the New York attorney general sued him and Marietta in their role as trustees of New York’s Museum of the American Indian. They were accused of not paying enough for museum artifacts they took and for a sweetheart deal on free storage at the museum of some of Arthur’s collection. The Sacklers prevailed and the lawsuit was dropped, but the dustup reinforced the feeling in the New York art world that he was driven more by wheeling and dealing than collecting.
II. It took almost two decades for uncontroverted evidence that Nyswander was mostly right: that the benzos were addictive and it was possible to overdose in extremely high doses. Benzodiazepines suppress the respiratory system the same as barbiturates, tranquilizers, sedatives, and opiates. They are most fatal when mixed in large quantities with other drugs that slow respiration (between 1996 and 2013, there was a sharp spike in benzo-related deaths, many times mixed with opioid painkillers).
III. The only screening test then recommended by the American Cancer Society (ACS) was an annual pap smear. The following year, 1976, the ACS added mammography breast exams to its list of recommended screening procedures. In 2013, researchers discovered that pap tests in some instances found cells that were useful in early detection of ovarian and uterine cancers.
IV. Wilson was not the first to use “castrates” in referring to women. The prestigious New England Journal of Medicine published the work of three doctors in 1960 that suggested estrogen might help prevent heart disease in postmenopausal females they described as “castrated women.”
V. Thelma Wilson died in 1988 from complications of her breast cancer.