The Body Hunters (13 page)

But with the 1960s-era articulation of the rights of blacks, women, the poor, and other oppressed people, the racist paternalism of the Tuskegee study could not remain submerged much longer. One staffer in the Public Health Service, Peter J. Buxton, felt that “what was being done was very close to murder and was, if you will, an institutionalized form of murder,” and he brought his concerns to his superiors. After they delivered “a rather stern lecture” about the benefits of the study, as Buxton recalled, he brought the information to a reporter friend. In 1972, Jean Heller reported on the Tuskegee Study of Untreated Syphilis in the
New York Times
and unleashed a storm of outrage.
⁴³

Aided in part by revelations about Tuskegee, by the early 1970s unalloyed faith in medicine stalled. The heralded new drugs and medical techniques of the postwar era had ended up costing more and producing less by way of better health than most had anticipated. Between 1962 and 1972 Americans' health care bill had tripled; the cost of prescription drugs had doubled.
⁴⁴
And yet, Americans suffered higher infant mortality rates and lower life expectancies than most Europeans. In January 1970
Fortune
magazine asserted that American medicine “is inferior in quality, wastefully dispensed, and inequitably financed. . . . Whether poor or not, Americans are badly served by the obsolete, over-strained medical system that has grown up around them helterskelter.” The situation was so bad that even the business press had come to sound like rabble-rousing activists. “The time has come for radical change,”
Fortune
opined.
⁴⁵

The Tuskegee study quickly achieved notoriety as a prime example of racist medical arrogance. Prominent physicians took up their pens to decry what they called a “crime against humanity”
of “awesome dimensions.” Senate hearings and a $1.8 billion lawsuit followed.
⁴⁶
By the time the Tuskegee study was finally terminated on November 16, 1972, the untreated Tuskegee subjects had unwittingly infected twenty-two women, seventeen children, and two grandchildren. The U.S. government agreed to pay $37,500 to each syphilitic patient who was still alive and $15,000 to those who served as controls.
⁴⁷

The Tuskegee revelations proved to the public the folly of allowing the moral integrity of scientists to suffice as protection for experimental subjects. Government needed to regulate the medical research industry just as they regulated mines and factories.

The National Research Act was passed in 1974, and an entirely new actor barged into the test clinic: independent oversight committees. Under the act the integrity of informed consent, the minimization of risks, and the breadth of data supporting the goals of the research would be assessed not by investigators themselves, but by independent committees empowered to ban or alter trials that didn't pass muster. These ethics committees, called institutional review boards (IRB) in the United States, would be the final arbiters on the ethics of human experiments.

The 1974 national commission convened to elaborate on ethical principles guiding human experimentation in the United States went further. According to its Belmont Report, scientists had to practice “respect for persons,” “beneficence,” and something even more ambitious: justice. Experiments should not be conducted on the impoverished, incarcerated, and other vulnerable populations solely for the benefit of the rich and free, or to sate the curiosity of researchers.
⁴⁸

These ethical obligations echoed those articulated in another voluntary code then making the rounds. In 1975, the United States along with thirty-four other countries signed onto the “Declaration of Helsinki,” a bold document crafted by the World Medical Association, a group representing dozens of national physicians' organizations from around the globe. The declaration urged voluntary informed consent, the use of independent ethics committees, and
that investigators prioritize their subjects' well-being above all other concerns, including “the interests of science and society.” In the interests of justice, the declaration suggested, research subjects should be assured of access to the best health interventions identified in the study, and that their societies enjoy a “reasonable likelihood” of benefiting from the results of the experiment.
⁴⁹

Over the following years the new ethical principles developed in Belmont and Helsinki slowly trickled into the federal regulations governing clinical research in the United States. These regulations bound all research on American subjects and applied as well to any researchers accepting U.S. government funding no matter where they conducted their experiments.

Any drug company hankering for FDA approval to market new drugs would have to abide by the new regulations too—unless they conducted their trials outside the United States without alerting the FDA first. In that case, according to FDA rules, the Declaration of Helsinki (or local laws, whichever afforded more protection) would suffice.
⁵⁰

Between World War II and the mid-1970s regulators had arduously built a wall, brick by brick, to protect the human rights and dignity of human research subjects from the inquisitive investigators itching for access to them. The first major assault on these barriers came not long afterward. Propelled by the spread of HIV in the darkest days of the AIDS pandemic, the medical research establishment rushed the wall, and found it a challenging but not insurmountable hurdle.

From the Nazi camps to Tuskegee, when investigators needed their test subjects to suffer in order to acquire results, they often assumed the posture of the innocent bystander: in the concentration camps, inmates were going to be killed anyway; at Willowbrook, the children would have infected themselves with hepatitis if the scientists hadn't intervened; at Tuskegee, the sharecroppers wouldn't have been able to afford treatment, so what did it matter that investigators didn't provide any?

According to the new ethics regime established in the 1970s, such rationalizations would no longer be sufficient. According to Helsinki, “considerations related to the well-being of the human subject should take precedence over the interests of science.” That meant that in controlled trials new methods should be tested against the “best current” methods, not some slipshod facsimile of them, even if the best current methods would be no more than a dream to test subjects had they not enrolled in the trial.
¹

But the codes were vague, and at times contradictory, and this particular standard wasn't one that researchers were too keen on. Since doctors didn't universally dole out the best current methods to their patients, circumscribed as they might be by access to resources and information, why should clinical investigators be held to a higher standard? What if subjects didn't mind not getting the best current treatments, and were happy with second-rate—or even third-rate—regimens? What if by offering substandard care in their trials scientists could produce astounding results that might change the face of the world?

It took the disastrous new scourge of AIDS to lay bare the contradictions. When the Centers for Disease Control first reported on a strange immune deficiency in healthy young gay men in 1981, government officials and drugmakers reacted with studied indifference. So hostile was the Reagan administration to the interests of homosexuals that the surgeon general was “flatly forbidden to make
any
public pronouncements about the new disease,” according to journalist Laurie Garrett.
²
Drug companies were reluctant to develop drugs for the deadly infection because they felt the “target market would be too small,” FDA historian Philip Hilts wrote. “It was said that to develop a drug to treat an illness affecting fewer than 200,000 people would yield too small a profit.”
³

For medical researchers, though, AIDS presented a breathtaking vortex of research questions. By 1984, amid intense competition among medical researchers, scientists had isolated the cause of the disease.
⁴
The culprit was a retrovirus, an organism that can only survive and replicate by pirating live cells. HIV is an especially ominous intruder: it infects the immune system itself, hijacking the command centers of pathogen fighters called CD4 cells and instructing them to cease all activities save sending out copies of their new viral commander. Thus crippled, the body is dangerously vulnerable to infections. The retrovirus replicates at a rapid clip, churning out ten billion copies every day, some proportion of which have slight variations—mutations—that would make treating the disease complex.
⁵

It was several years and thousands of deaths later before a drug that fought the virus appeared on the scene. Articulate, angry, and accomplished activists such as Larry Kramer, an impassioned playwright, were convinced that if they pushed the NIH, the FDA, and the drug companies hard enough, viable AIDS treatments would be found. “Laboratories have drugs that they're not giving us,” fumed Kramer in 1995. “I think that they should go before the equivalent of a Nuremberg Tribunal for War Crimes.”
⁶

Retrovir (AZT), released in 1987 by a company that would later become part of GlaxoSmithKline, wouldn't exactly be the answer
to their demands. AZT, a nucleoside analogue, incorporated itself into the RNA of the virus, rendering it ineffective. A sizable public investment had gone into the development of AZT. The compound had been synthesized by government-funded scientists in 1964, the National Cancer Institute had run the tests that revealed its anti-HIV properties, and the government had helped conduct clinical trials on the drug. Nevertheless, the drug's manufacturer decided to charge poorly insured and dying AIDS patients $8,000 for a year's worth of treatment. Aware that it was about to release the only approved drug available for a deadly disease, the company would make AZT its “largest contributor to revenue and earnings,” analyst Jonathan Gelles gushed in 1987. “The profit margin will be about three times the company's 13 percent average.”
⁷

The
New York Times
, among others, called the price tag “inhuman,” and public demonstrations forced the company to moderate its fee, but by 1994, Retrovir was indeed the $1.6 billion company's second bestselling drug, bringing in over $300 million a year.

Lucrative or not, AZT was no cure-all. The drug worked only after being metabolized into its active form, and persisted in the body for just two hours.
⁸
Half of those who tried it quit soon afterward because of its toxic side effects, such as fatigue and bone marrow problems. Nevertheless, the network of hospitals and researchers organized by the government to coordinate studies of experimental AIDS therapies, the AIDS Clinical Trials Group (ACTG), was recharged with new focus. Perhaps the drug would protect HIV-infected people from neurological damage or from coming down with AIDS altogether. It might even prevent infected pregnant women from passing the virus on to their babies. Soon ACTG researchers would launch massive new trials using the problematic drug. “People were very nervous about having this drug used in thousands of patients so fast,” said Maureen Myers, an AIDS researcher with the National Institute of Allergy and Infectious Diseases, but “we also knew we were going to have limited time to do the things we wanted to do.”
⁹
It would be eight years before the drug industry released a new kind of HIV drug.

Throughout those years the public pressure to do something was intense. Already, the ACTG had come under fire for its methodical ploddings. “The AIDS Clinical Trials Group has proved to be a massive, dysfunctional failure in its inept efforts to lengthen the lives of HIV-infected people,” the activist organization ACT UP charged in 1990. “This skewed application of increasingly limited government research funds must stop immediately,” another activist railed in a letter to the
Washington Post
. “We cannot wait.”
¹⁰

And yet, few HIV-positive Americans and their physicians were willing to take part in ACTG studies that compared AZT to a placebo, such as one that measured the effects of the drug in retarding neurological damage. Even though patients eligible for the trial were not yet sick and would only be involved in the study for a short while, neither patients nor physicians were willing to risk forgoing the newly available AZT, no matter how limited its benefit. After eleven months of recruiting, the study had enrolled only forty out of a needed three hundred subjects. The researchers were forced to drop the placebo group.
¹¹

Such problems did not plague one of ACTG's most important early trials. In its trial testing whether AZT might prevent pregnant HIV-positive women from infecting their babies—a trial coded “076”—researchers had happened upon their first real breakthrough. In placebo-controlled trials in the United States and France, AZT had slashed the transmission of HIV from mother to child from 24.9 percent on placebo to just 7.9 percent. In the study 100 mg of AZT had been administered five times a day to infected pregnant women for months before delivery; during delivery, the women got an IV infusion of the drug, and the baby got a dose of AZT syrup every six hours during its first six weeks of life. Given the extensive volumes of drug required, and the med's still costly price tag, the entire regimen cost around $800.
¹²
As soon as the effect of the drug was clear—the data was analyzed about midway through the trial—the placebo group was dropped and all the mothers were given the AZT regimen, saving one of every seven of their babies from the deadly infection.
¹³