In June 1980, a few months before Genentech set Wall Street on fire, the Sackler-owned Napp Pharmaceuticals released in the United Kingdom the first extended relief oral, narcotic painkiller, MST Continus. It was the breakthrough palliative drug for which Cicely Saunders had searched since the mid-1960s. It had taken Napp several years of trial-and-error laboratory work, and dozens of tweaks to the underlying patent technology for the pill’s delayed delivery system, to get it right. The result was an invisible dual-action polymer chemical coating that released pure morphine steadily over twelve hours. The speed at which the morphine was dispensed inside the body depended on how long it took stomach acid to penetrate the tablet, a feature Napp could fine-tune.
MST Continus meant that cancer patients who were not terminal could be discharged from the hospital and sent home to manage their pain with only two pills daily. Medical journals judged the drug as a significant advance in treating end-of-life pain. Oncologists and hospices did not seem concerned about a small-print warning Napp put on the package insert: “MST Continus tablets must be swallowed whole and not chewed.” What that did not spell out was that if the pills were chewed, the entire dose of morphine—up to 100 mg per pill—would immediately be released. It was a precaution that the Medicines and Healthcare Products Regulatory Agency—Britain’s equivalent of the FDA—thought wise but probably unnecessary. Few expected many seriously ill cancer patients would tamper with Napp’s delayed release coating.
The same month, June 1980, that Napp put MST Continus on sale, five thousand miles away, San Francisco State University hosted a conference of gay physicians. It was timed to coincide with the city’s Gay Freedom Day Parade.1 That was an annual event to commemorate three days of spontaneous demonstrations that had erupted after a June 1969 police raid on the Stonewall Inn, a Greenwich Village gay bar. Most social historians mark the Stonewall raid and public backlash as the catalyst for the 1970s Gay Liberation movement.
San Francisco may have only had 700,000 residents but its Gay Freedom Day Parade was the nation’s largest, with a quarter million attending between spectators and marchers. By 1980, an estimated two of every five adult men in the city were openly gay, by far the highest number per capita in America.2 Randy Shilts, then a reporter for the local public television station, KQED, noted in a report about the Stonewall commemoration that “after 10 years of gay freedom, the city that has come to represent that freedom is San Francisco.”3
Many expressed their newfound freedom sexually, an indulgent celebration of liberties that had been illegal until 1975 when California excluded “private consensual activity” from statutes against sodomy and oral sex.4 There was a crackdown in the early 1970s by the city’s Italian American mayor. He had eyes on the governor’s mansion and played to his morally conservative Catholic base. Police arrested some three thousand gay men for public sex felonies. Many convictions required registration as a sex offender.5
For many men who were for the first time publicly proud to be gay, promiscuous sex seemed an excusable element of social and political liberation. By 1980, it was also a $100-million-a-year business in thriving clubs and bathhouses that served as venues for anonymous sex.6
Many of the doctors at the June conference had come to San Francisco to join the two-mile Gay Freedom Day Parade celebration through the city’s downtown. Their priority, however, was sharing information about a veritable explosion in sexually transmitted diseases that had become by-products of the sexual revolution that had remade gay life in some American cities. Bathhouses were breeding grounds for infections. Adding to the health risks for promiscuous gay men was the widespread use of recreational drugs, in particular, amyl and butyl nitrate. They were liquids legally dispensed to alleviate heart pain, but their street popularity was because of the short euphoric rush that increased the intensity of sex. Nicknamed poppers, they were inexpensive and available at head shops in many cities. No one then knew that their regular use suppressed the immune system and that they dilated the body’s blood vessels, allowing viruses to enter more easily.7
Gay men accounted for more than half of all reported cases in 1980 in the U.S. of gonorrhea and syphilis.8 Two thirds of the gay men at San Francisco’s popular general clinic tested positive for hepatitis B, a liver infection spread sexually or through blood. Twenty percent of the sexually active gay men moving to San Francisco contracted hepatitis in their first twelve months. Within four years, the infection rate was virtually 100 percent.9 No one yet realized it was a problem beyond those who got infected with hepatitis; blood bank officials estimated that in 1980 San Francisco gay men donated 5 percent to 7 percent of the city’s blood. There was no test to screen for hepatitis.10
A Seattle study showed that an unusually large number of gay men had contracted shigellosis, a bacterial infection spread through contaminated food, water, or feces. Seventy percent of those infected had found their sex partners at bathhouses. A study in Denver found that gay men had on average three sexual encounters every time they went to a bathhouse. There was a one in three chance they left a bathhouse with gonorrhea or syphilis.11 Chicago’s Howard Brown Memorial Clinic recorded an epidemic infection rate of hepatitis B, about half of its gay patients. At the New York Gay Men’s Health Project, a third had gastrointestinal parasites. In San Francisco, local clinics reported a stunning 8,000 percent increase in intestinal parasites over seven years, mostly young men in their thirties. It was so common by 1980 that medical journals dubbed it “Gay Bowel Syndrome.”12
The doctors who gathered for the 1980 San Francisco conference knew that parasitic diseases like shigellosis, amebiasis, and giardiasis thrived in the feces of infected patients. Unprotected anal intercourse was one way the intestinal bugs spread. The other high-risk, yet popular, sex practice was rimming. The medical journals referred to that as “oral-anal intercourse.”13
As Randy Shilts later wrote in And the Band Played On, his seminal book about AIDS and the deadly failure of the federal government to respond, “the success of the Gay Liberation movement which had started in the late-1960s, had by 1980, however… become a victim of its own success.”14
By that summer, doctors started seeing an uptick in gay patients with multiple immune-related illnesses. In New York, Los Angeles, and San Francisco, clinics noticed young and seemingly fit gay men who were inexplicably ill with tuberculosis and rare atypical interstitial pneumonias (chronic swelling of the lungs’ tiny air sacs).15
Gaëtan Dugas, a twenty-eight-year-old flight attendant for Air Canada, saw a Toronto specialist about purple lesions that had broken out on his back and face. His lymph nodes had been swollen for a year. A biopsy confirmed Kaposi sarcoma. Dugas kept working as an air steward, traveling thousands of miles annually to more than a dozen cities across the U.S., Canada, and Haiti. He later estimated to medical researchers that he had about 2,500 sex partners during the 1970s.I
A month later, a San Francisco resident, Ken Horne, was also diagnosed with Kaposi. Blood tests revealed his white blood cell count was extremely low and something undetermined was suppressing his immune system.
In July, a thirty-three-year-old German chef, who had worked in Haiti for three years, was admitted to the emergency room of Manhattan’s Beth Israel Hospital. “He came to New York after he’d gotten sick in Haiti with weight loss and uncontrollable bloody diarrhea,” recalled Dr. Donna Mildvan, then a thirty-five-year-old infectious disease specialist. A stool test revealed he had amoebic parasites, the type of intestinal bug common to travelers.
“He didn’t get better. That was extraordinary,” she recalled.
The chef kept going in and out of the hospital for the next six months.
“We’d get him a little more stabilized,” Mildvan said, “he’d go home for a while, and then he’d be back.” He kept losing weight, developed sores, and lost sight in one eye.16
Mildvan and her team were detectives hunting for the mystery of what their patient was so sick with. They ran dozens of tests and researched rare illnesses. They debated a wide range of treatments, including a massive dose of antibiotics, but feared if it was an immune disease, the antibiotics would hasten the disintegration.17
By the fall, Mildvan suspected a virus was the culprit. Beth Israel had no virology lab. She and a colleague withdrew fluid from their patient’s eye and rectal lesions and sent those to the lab at Montefiore Medical Center in the Bronx. Their report concluded that sexually transmitted herpes had caused the rectal lesions and herpes-related cytomegalovirus (CMV) was present in the eye fluid. Those viruses were not unusual. What astonished Mildvan was that they almost never caused illnesses as serious as the ones in her patient. Over the coming months, he continued deteriorating. He became blind when the CMV spread to the other eye. A CT scan showed his brain had shrunk like that of an elderly man with dementia.
“He curled up in a ball,” recalled Mildvan, “staring blindly into the distance. He was incontinent. And he died.”
Two weeks later she treated another gay male patient, a nurse with no foreign travel. He had the same CMV infection in an eye, but was deathly ill with Pneumocystis carinii. Mildvan knew that it was a rare pneumonia, only affecting those with compromised immune systems. He died after ten days at the hospital.
Across town, at New York University Medical Center, a leading dermatologist had begun seeing young men in otherwise good health who had the purple Kaposi sarcoma lesions. Dr. Alvin Friedman-Klein had been practicing for twenty-five years and the NYU skin clinic was America’s largest. Still, he had only seen fifteen cases of Kaposi in his career. Now he had two dozen young patients in less than a month, none of them fitting the cancer’s target demographic of older Jewish or Italian men.
“That’s when it clicked,” Mildvan recalls. “It’s a new disease. Something’s going on.”
That same month, Ronald Reagan was inaugurated as the fortieth president of the United States. His successful campaign for the White House was in part based on a pledge to reduce the size and role of government. He delivered on that in January, proposing deep spending cuts. The proposed budget for the Centers for Disease Control was slashed in half.
It was not a good time to cut funding for the only government agency responsible for collating data and planning how to respond to any deadly transmissible new illness. For the next four years the medical community could agree on little, not even on whether the culprit was viral or bacterial. It is not always easy to tell. Infections that cause meningitis, pneumonia, and chronic diarrhea can be caused by either. Chicken pox is a virus. Smallpox was a virus (past tense because it was the first deadly disease to be eradicated by a widespread twentieth-century vaccination program).
If the “new disease” that puzzled Mildvan and other doctors turned out to be from a bacterium, it would mean that some single cell microorganism that had coexisted with humans peacefully for thousands of years had somehow mutated into a virulent pathogen. That is what happened in the fourteenth century when bubonic plague killed 50 million people, 60 percent of Europe’s population. Antibiotics are effective against bacteria because they interfere with their cell walls and either stop them from replicating or force them to self-destruct. The drugs accomplish that without inhibiting or damaging human cells.18 Epidemiologists estimate that if antibiotics had existed during the bubonic plague, the death toll would have been cut by 90 percent.19
Antibiotics are useless, however, against viral invaders. Viruses do not have internal growth mechanisms that antibiotics destroy. They cannot survive alone but instead live inside human cells and hijack the reproductive mechanism of those cells. The 1918 Spanish influenza pandemic killed nearly 100 million people.20 Pharmaceutical companies have discovered and marketed a series of antiviral medications since 1972, but they were effective only if dispensed early during an infection, and even then, only lessened the severity of symptoms and reduced the infection’s duration.
Another weapon, vaccines, tricks the immune system into recognizing a virus and providing some “acquired immunity.” Even if the new disease was a virus, Mildvan and her colleagues were familiar with the limitations of antivirals and knew that vaccines took many years to develop. Sometimes, a vaccine might not even be possible if the proteins on the surface of the virus mutate regularly. Slight modification in the proteins of the flu virus, for instance, means that last year’s vaccine might not be effective against this year’s influenza strain.
Whatever the cause, there was no disagreement that gay men were the first victims. In early 1981 there were stories about a “gay cancer” or “gay pneumonia,” reported only in gay newspapers, the New York Native, San Francisco Sentinel, and Australia’s Sydney Star Observer. Lawrence Altman, the New York Times medical correspondent, wrote his first article about it that July. Titled “Rare Cancer Seen in 41 Homosexuals,” Altman began: “The rare and often rapidly fatal form of cancer… diagnosed among homosexual men.” He quoted a CDC spokesman, Dr. James Curran, who added to the speculation that it might be a gay-only disease. “The best evidence against contagion,” Curran told him, ‘is that no cases have been reported to date outside the homosexual community or in women.’ ”21 (The Village Voice condemned Altman’s piece as a “despicable attempt of The New York Times to wreck the July 4 holiday break for every homosexual in the Northeast.”)22
People began talking and writing more about the mystery symptoms. In Uganda, dubbed “Slim Disease,” it left its victims terribly emaciated. Doctors treating men imprisoned at New York’s Rikers Island named it after that prison, Rikers Island adenopathy (swollen lymph glands).23 Most of the media stayed focused, however, on the gay nexus. Some wrote about the Gay Plague.24
When the doctors at the National Institutes of Health treated their first AIDS patient in June 1981, they named his condition as GRID, gay-related immune deficiency. Before that patient died in four months, seven different NIH divisions tried solving the mystery as to what had savaged his immune system. After his October death, the three departments with the most expertise in immunodeficiency disorders launched a joint project. It was directed by Samuel Broder, the chief of NIH’s Clinical Oncology Division, Vincent DeVita, the head of the National Cancer Institute and the National Cancer Program, and Tony Fauci, chief of the Laboratory of Immunoregulation.25
In July 1982 the disease had a new name, one that would become the accepted medical standard: human immunodeficiency virus (HIV). The most critical, and often lethal stage of HIV infection was named acquired immunodeficiency syndrome (AIDS). The CDC used the word AIDS for the first time in a weekly report that September.26
The virus that led to AIDS was sexually transmitted, an equal opportunity infector of men and women. In Africa, where it had its genesis, and where scientists later discovered an almost exact primate strain they named simian immunodeficiency disease, it was overwhelmingly a heterosexual disease.II27 That was the same in the early cases in Europe as well as later for intravenous drug users and hemophiliacs. Gay men were not the reason AIDS started in the U.S. They were simply its first victims. HIV was an opportunistic disease that took advantage of immune systems already under assault from multiple sex partners, recreational drug use, and repeated infections of sexually transmitted diseases.28
Fear in heterosexual America was about whether they might “catch it” from a gay colleague or neighbor. The gay community, particularly men, were cast as scapegoats for the undiagnosed disease. In the coming years, confusion, misinformation, and rumor spread. People’s fears fueled their worst prejudices.
The CDC did not help. In explaining how the disease was transmitted between people, the CDC said it was a result of the “exchange of bodily fluids.” Did that mean vaginal or anal intercourse? Oral sex? Kissing? Perspiration from an infected person? Not even the best journalists were clear what that encompassed. The New York Times’s Lawrence Altman told The Atlantic in 2014: “The journalism community was behind for quite a while in not being more specific about what ‘bodily fluids’ meant. But also, public-health officials weren’t explicit in what they meant by bodily fluids. It was a time when the words ‘penis,’ ‘vagina,’ ‘sperm,’ ‘intercourse,’ ‘rectal intercourse’—those terms weren’t part of the everyday public vocabulary. They may have been in private, but it wasn’t as it is today.”29
At the NIH, Broder, DeVita, and Fauci had assembled a public health emergency team.30 Although that effort drew little public attention, according to Broder “much of the critical work for perhaps the first three to four years of the AIDS epidemic originated with the NIH.” In a later oral history, he expressed frustration that “some scientists and organizations that might have made a contribution, did not respond to the AIDS emergency.”31
A few did not believe the virus would become widely transmitted. That view was reinforced when the CDC confirmed it was possible to get the disease through intravenous drug use.32 Those new patients were overwhelmingly heterosexual. Since they were drug addicts, however, it only added to the perception that AIDS was a disease that affected the fringes of society. “People always ask when AIDS is going to spread to the general population, as they call it,” asked Dr. Sheldon Landesman, an infectious disease expert. “That’s absurd. It implies that those who have AIDS aren’t part of the general population. It implies that they are giving it to us” (emphasis in original).33 III 34
Broder recalled that from 1982 to 1984 while the NIH researchers chased many theories, “there was an enormous sense of pressure and urgency, because there was so little known and so little we could do. As additional cases became known, there was a substantial level of stress and a certain public distrust and confusion, all of which made everyone’s life more difficult.”35 Adding to the anxiety at the NIH, says Broder, was that there were “all sorts of crazy people, who in the Andy Warhol sense of the term, could obtain not only 15 minutes’ worth of fame but possibly build a career [by] promoting ideas without a scientific foundation. This greatly confused the public and to some extent damaged science.”36
The NIH researchers had developed tests to spot drugs that might suppress the AIDS virus in tissue cultures. They found none despite testing hundreds.
By 1984, Broder’s team had focused on antiretroviral drugs, hoping they might hinder the virus from replicating in humans. Burroughs Wellcome, Pfizer, and Merck and Roche worked with those products in their labs. He did not have a receptive audience when he met with top management at the drug firms. “I went to one prestigious company, hat in hand,” he later recounted. “I got about one minute and thirty seconds of a high-ranking officer’s time. It was very disappointing for me. It was emblematic of the issue. There was no real interest in it.”37
Dani Bolognesi, a Duke surgeon, arranged a meeting between Broder and scientists at Burroughs. Broder was interested in a twenty-two-year-old chemotherapy, Zidovudine, also known as azidothymidine (AZT). An academic with NIH funding had developed AZT in the mid-1960s but Burroughs later bought the rights to it. It had never been put on sale because it proved both toxic and ineffective.
There was some resistance in Burroughs to helping the NIH. AIDS was a terrible disease, Burroughs executives acknowledged to Broder, but it was too small a market.
“They made it clear that on the basis of 3,000 patients, there was no way they could practically get involved,” Broder recalls. “As I left, I said, ‘You know, we’re going to have more than 3,000 cases. It is going to be commercially viable for you.’ ”38
They called him back to the conference room where he laid out some of the cataclysmic predictions the CDC had run. Broder said that nothing would get done unless the NIH had a private partner.
Burroughs finally agreed to help. Although the company owned the license to AZT, it had done so little with it that at first it could not even produce samples as it was missing a critical DNA constituent. The NIH sent the missing DNA strand to the company, who finally made enough of the drug for testing at the NIH. The results were good. It was the first drug, according to Broder, that “inhibited HIV viral replication” in the test tube.39
AIDS activists wanted human trials started as quickly as possible. For every day delayed, they contended, someone else died. They protested the failure of Ronald Reagan’s administration to declare AIDS a health emergency capable of infecting anyone.40 In the early years of HIV and AIDS, there were aftershocks from the 1976 swine flu fiasco. Dr. David Sencer, who had been the much maligned CDC commissioner during the swine flu debacle, had said after resigning his government post that if he was ever faced with scientific uncertainty over a possible infectious epidemic, he would err on the side of caution. Sencer had returned to public service as New York City’s health commissioner. Activists accused him of “dragging his feet” when it came to the city’s response to AIDS. At a time when action and speed were essential, Sencer fell short once again.
While once slow or negligent to cover HIV and AIDS, or to cast it as a fringe epidemic, mainstream media outlets by the mid-1980s raced to report that AIDS infections were about to explode. The front covers of national magazines fed a new fear. “Now No One Is Safe from AIDS” (Life); “AIDS: Fatal, Incurable, and Spreading” (People); “The Most Lethal Disease” (Time).41 An American doctor writing in The Lancet compared its potential “vast scope of death” to the fourteenth-century bubonic plague.42 Oprah Winfrey, in her first show about AIDS, passed along a dire prediction: “Research studies now project that one in five—listen to me, hard to believe—one in five heterosexuals could be dead from AIDS at the end of the next three years.… One in five!”43
Fifty million Americans did not die, of course, in the next three years. In the first fifteen thousand cases of AIDS in New York City, the Health Department listed only eight as having contracted the virus from heterosexual sex.44 Still, the real numbers did not seem to matter. Fear often overruled reason. Mortuaries refused to handle bodies, hospitals turned away patients or put them in isolation. There was talk of whether sanitariums, or modern-day leper colonies, should house the sick. One debated “solution” was tattooing those infected so prospective sex partners had advance warning.45
Nationally syndicated columnist Pat Buchanan wrote in 1984 for The American Spectator that AIDS was “a killer disease… especially in cities like New York and San Francisco, the Sodom and Gomorrah of the Sexual Revolution.” The sexual liberation that was an essential element in the Gay Liberation movement, according to Buchanan, “is ending, and it is revealed for what it always was: an egregious assault upon the ecology of the human body. Call it nature’s retribution, God’s will, the wages of sin, paying the piper, ecological kickback, whatever phraseology you prefer. The facts demonstrate that promiscuous homosexual conduct is utterly destructive of human health.” Buchanan predicted that “short of some dramatic behavioral change, the gay community may self-destruct.” And he warned that he was not spreading “scare talk,” but that the HIV virus might mutate into the “real final epidemic” that would threaten “continuation of human life on this planet.”46
Five months later Reagan appointed Buchanan as the White House director of communications and an assistant to the president.47
The heated rhetoric produced real results. Gay men, even some suspected of being gay, lost their jobs. There were campaigns to ban them as teachers or sports coaches. Some communities petitioned their local hospitals to exclude them from health care jobs.48
In the midst of the hysteria over AIDS, Samuel Broder and his NIH team had begun the human clinical trials on AZT in July 1985. Testing for an antiviral could take eight to ten years. The FDA approved AZT in a speed record of twenty months. For many Americans who had friends or relatives who were sick with HIV/AIDS, and unaccustomed to the snail’s pace of modern drug approval, the twenty months seemed an eternity.49
To avoid any further delay over legal and commercial marketing rights, the government allowed Burroughs Wellcome to claim the patent. The company renamed the drug Retrovir. From its first day of sale, Burroughs marketed AZT as a “breakthrough” and as “finally light at the end of the tunnel.”50 National media covered AZT as effective for anyone who tested positive on the HIV antibody test.51 Burroughs ignored advice from the FDA that because of the drug’s toxicity it should be limited to the sickest patients, only those with full-blown AIDS.
Burroughs stunned AIDS families and activists, the medical community, and the NIH team that had developed the drug when it set the price at $10,000 per patient per year (not including transfusions and blood work). It was the most expensive drug in pharmaceutical history. Under tremendous public blowback, Burroughs cut the price to $8,000, still the highest-priced drug on the planet. Thirty-five percent of AIDS patients had no health insurance or had polices that did not cover the drug.52 When Burroughs stuck with its exorbitant price tag, the federal government stepped in and subsidized the costs for many patients who would have otherwise been refused treatment.
“What makes the cost of AZT hard to swallow,” wrote the New York Times editorial board in 1989, “is that all the invention and much of the risk was undertaken by the Federal Government.”53
When a generic drug company announced it would make an inexpensive, generic copy of AZT, Burroughs sued and prevailed in federal court. During that litigation, which eventually wound its way to the Supreme Court, Burroughs contended that the NIH had no right to the patent. It described Broder’s lab only as “a pair of hands” that had helped the company, nothing more.
Although North Carolina–based Burroughs was savaged in the press for its AZT pricing, and criticized in academic and government circles for its cynical framing of the drug’s discovery, its shareholders were happy. AZT was the only large successful launch for the parent company, British-based Wellcome. It had gone public the year before AZT went on sale. In February 1987, the month Burroughs put AZT on the market, the company’s share price shot up 500 percent. Its list price for AZT was so expensive that investors expected record profits. They were right. The share price doubled again in 1989. By then, AZT brought in a third of the company’s $425 million profit. AZT itself passed $2 billion in sales by 1994.54
In San Francisco, AIDS had ravaged the Castro neighborhood, a vibrant hub of gay life. On January 25, 1988, the thousands who marched through city streets were not celebrating gay pride. They were protesting the exorbitant price of AZT. The handmade signs reflected the mood of the protesters. “Burroughs Wellcome AZT Scandal.” “Greed Kills People.”55
Wellcome met often with AIDS activists and victims’ families. Its press spokesman said all the right things about compassion and mercy. It never discussed pricing or gave in to demands that it disclose its business records that would have shown what it cost the company to manufacture the drug.
Bristol-Myers started clinical trials in 1989 with a second AIDS drug, DDI (dideoxyinosine), which also showed promise in slowing the rate at which the virus replicated. It was evident the NIH and National Cancer Institute had learned their lesson from Burroughs’s price-gouging. Under the terms of a contract with Bristol, the government could force it to license DDI, to generic manufacturers if it did not set a “reasonable price.”
“Hallelujah,” was the reaction from playwright Larry Kramer, the founder that year of the activist organization AIDS Coalition to Unleash Power (ACT UP). “I pray that this magnificent example by Bristol will be duplicated by the manufacturers of numerous other life-saving drugs.”56 Kramer and other activists might not have been happy with any of the drug companies that suddenly seemed eager to develop AIDS drugs if they had known that the pharma firms were earning millions more on every medication because of a little-known 1983 statute, the Orphan Drug Act. It was designed to encourage drug companies to develop medications to treat rare diseases, everything from multiple sclerosis to Huntington’s to muscular dystrophy to ALS.57 Many of the estimated two thousand diseases were genetic conditions but some were infections and autoimmune disorders, as well as rare cancers. They were dubbed orphaned since pharmaceutical companies avoided them because the tiny markets made it difficult to turn a profit. The FDA’s Office of Orphan Products Development proposed that for a drug to qualify under the law, the disease it treated should not affect more than 0.05 percent of the U.S. population, at the time a maximum of 100,000 patients. However, when the FDA realized that excluded multiple sclerosis, Tourette syndrome, and narcolepsy, the agency eliminated measuring by a percentage of the population and instead set the maximum at 200,000. In practice, however, the number affected by an orphan disease frequently proved much smaller, usually under 10,000 and sometimes only a few hundred worldwide.58
The congressional sponsors of the Orphan Drug Act realized the government needed to offer substantial incentives in order to stimulate interest in the pharma industry. The law built financial inducements into every stage of orphan drug discovery and subsequent amendments made the tax credits and research subsidies even more generous. The act included four years of taxpayer grants of up to $500,000 annually to underwrite early research. Companies got a 50 percent tax credit on whatever they spent on R&D. The remaining 50 percent of costs were a deductible business expense. That meant that the federal government paid for about 70 percent of the R&D costs for orphan drug projects.59 The law also simplified applying for academic and NIH co-sponsorship, waived processing fees, and expedited FDA approval. The gauntlet of three ever more rigorous trials was dramatically abbreviated.60 The FDA also provided grants on a competitive basis for clinical trials it deemed important.
The Orphan Drug Act’s final inducement—an exclusive seven-year selling monopoly—was an attempt to ensure the drug company had enough time to earn money without worrying about competitors.61 Although shorter than the seventeen years for mass-market drugs, the orphan patent barred all competition. It not only banned generics but also me-too drugs, unless those meds offered a “major” improvement in safety or efficacy. Some pharmaceutical analysts called it a “platinum mini-me patent.” It was one of the most unique and powerful pricing tools available to drug companies.62 The mistaken assumption by the statute’s drafters was that orphaned drugs would never be very profitable.63 AIDS changed that.
In 1985, Burroughs applied for AZT to be designated an orphan drug for “the treatment of AIDS.” The FDA approved that designation in July. It meant that in addition to all the assistance Burroughs had gotten from the NIH, it was now eligible for substantial additional subsidies and tax credits. Other drug companies realized that to get the same benefits, they had to artificially fragment the AIDS patient population into subgroups smaller than 200,000. In that way they created rare diseases small enough to qualify for orphan status. Within a decade, there were seventeen orphaned variations of antiviral HIV treatments, a dozen for AIDS-related Pneumocystis carinii pneumonia, nine for diarrheal and weight loss illnesses, and five each for Kaposi sarcoma, encephalitis, anemia, and tuberculosis, among others.64
Ellen Cooper, chief of the FDA’s antiviral division, complained that the pharma companies were dividing the “AIDS related complex” population into arbitrary subclasses. There was nothing the FDA could do to stop it. The Orphan Act was clear that only Congress could make changes, and no elected official wanted to sponsor anything that might be interpreted as slowing the search for an AIDS cure.
The drug companies had learned to game the system. A study later determined that they “stack seven-year monopolies for the same drug on top of each other for indications that differ only negligibly.” In other instances they “seek orphan designations for drugs that are barely modified versions of existing orphans and that offer little additional therapeutic improvement.”65 A large loophole the companies exploited was that once they got drugs approved for a small number of patients in the final stages of AIDS, they encouraged doctors to dispense it “off-label” for the much larger market of those infected with HIV. Off-label is when doctors dispense drugs to treat conditions other than the one for which the FDA approved it.66 LyphoMed, for instance, got a 1984 approval for pentamidine to prevent and treat Pneumocystis carinii pneumonia for end-of-life AIDS patients. However, more than 80 percent of its sales was for the off-label treatment of pneumonia in HIV patients. LyphoMed increased its price 400 percent over two years. When its seven-year orphaned monopoly expired, it got another seven years for developing an aerosol version that qualified for new orphan status.
Nearly thirty years later not much has changed. As a new generation of AIDS drugs was introduced from biotech companies, they sought orphan protection. The most notable as of 2019 is Gilead’s Truvada, a breakthrough pre-exposure prophylaxis when combined with safer sex practices (it is referred to widely as PrEP, pre-exposure prophylaxis).67 It is not a new drug. Gilead, a California biotech company, had originally gotten FDA approval for it in 2004 for slowing the progression of HIV in those already infected.
The research that converted it to its current blockbuster status was done through government and private funding. The CDC in 2006 was researching medications to block HIV from infecting healthy people. Gilead sent free doses of Truvada to the CDC, where two years of lab work and tests on primates led to breakthroughs for which the CDC applied for a series of patents. A San Francisco AIDS researcher conducted parallel research with $50 million in federal grants.The NIH sponsored double-blind, placebo-controlled human clinical trials. The Bill & Melinda Gates Foundation contributed $17 million toward those trials.68 Gilead again donated the medicine. The 2010 results of the clinical studies—up to a 44 percent reduction in the risk of HIV infections—drew national headlines.69
The U.S. government patented the new prophylactic use for Truvada in 2015. Gilead sued to block that, saying that it had given Truvada free of charge for the testing and its own scientists had created the old drug at the turn of the century.
Courts have so far sided with Gilead. Truvada costs $6 a month to manufacture. Gilead sells it to patients for $1,600 to $2,000 a month (a markup of 25,000 percent).70 It has ranked every year since its release as a prophylactic in the top twenty drug sales in the United States, more than $3 billion annually, some $30 billion since it went on the market. Gilead’s patent does not expire until 2021.
Two AIDS activists and a physician penned a 2018 New York Times op-ed. “The United States is failing miserably in expanding its [Truvada’s] use. Less than 10 percent of the 1.2 million Americans who might benefit from PrEP are actually getting it. The major reason is quite clear: pricing. With a list price over $20,000 a year, Truvada, the only PrEP drug available in the United States, is simply too expensive to become the public health tool it should be.… In under 40 years, we’ve lost more Americans to H.I.V. than to combat in all of our wars combined. Science has delivered answers, but Gilead’s greed and the government’s inaction are keeping it from those who need it most. There’s a pill that stops H.I.V. We can make it possible for everyone who needs that pill to get it.”71
I. Because he had so many sexual contacts and also traveled extensively while infected, Dugas was later referred to extensively as Patient 0 (zero), thought to be the person who almost single-handedly spread AIDS across North America. In fact, the letter assigned to him later by AIDS researchers was not a zero but an alphabetical O, shorthand for “Out of California.” Dugas spent considerable time in San Francisco and Los Angeles, and some early researchers believed the strain of virus he carried was unique to the American West Coast. There was no patient zero, and according to scientists and epidemiologists, while Dugas might have spread the virus faster and farther than if he was not an infected, promiscuous flight attendant, he was not the first person ill with the disease in the U.S.
II. In 1992, a journalist, Tom Curtis, kicked off a firestorm in Rolling Stone with a thesis that HIV in Africa was caused by the 1959 testing of a live polio vaccine on more than a million people in the Belgian Congo. Researchers dismissed it out of hand as a baseless conspiracy theory designed to sell magazines. In 1999, Edward Hooper, a BBC correspondent, wrote a densely sourced 1,000-page book, The River, published by Little, Brown. Hooper reached the same conclusion as Curtis had but had explosive new reporting that a precursor of HIV had been accidentally introduced into the oral polio vaccine that had been administered in the Belgian Congo. Hooper charged the vaccine was grown in African chimpanzee cells, some of which were infected with simian immunodeficiency disease (SIVcpz), an almost identical strain to HIV. The doctors involved with the original research denied using chimpanzee cells in the vaccine. Papers published in Nature and Science examined stored samples of the 1959 vaccine and a molecular analysis revealed no chimpanzee DNA. There were no genetic traces of either HIV or SIV. In 2004, a study in Nature found that even if chimpanzee cells from the Congo had been used in the vaccine, the primates in that area had a virus genetically distinct from human HIV strains. Subsequent epidemiological studies dated the origin of HIV in humans to “at least 30 years prior to OPV (oral polio vaccines) in central Africa.” The new data led Oxford’s Edward Holmes, a preeminent virologist and evolutionary biologist, to conclude: “Scientifically, it is the end of the OPV theory.” In 2019, scientists extracted a nearly complete HIV genetic code from a 1966 sliver of tissue from a deceased patient in the Republic of the Congo. By dating its genetic sequencing, they concluded that the virus that led to HIV emerged in humans a century ago.
III. Infection from blood put the nation’s ten thousand hemophiliacs at risk. Eventually, half would be infected with HIV and four thousand died of AIDS. Blood banks did not then screen donations for transmissible viruses or bacteria, but even if they had, there was no test yet to spot AIDS.