They noted that two thirds of the babies had excreted the vaccine virus in their feces—a sign of the active intestinal infection that was necessary for the baby to generate protective antibodies. As for untoward effects, they wrote, “No reactions were observed in any of the 132 infants.” They reported that the vaccines appeared to be genetically stable, meaning that lab tests showed that the virus excreted in the feces of the vaccinated babies hadn’t reverted to a more virulent form of poliovirus.30
As for Poupard’s painfully gathered blood samples, the data they yielded on the babies’ antibody levels—a rise in antibodies is the gold standard of a vaccine’s effectiveness—never did see the light of day. The Wistar scientists didn’t report on antibody levels from the vaccinated infants either to the World Health Organization or in any paper in the medical literature. It’s not clear why. Nonetheless, at that meeting in Geneva in the summer of 1962, Hayflick’s human diploid cells met a warm reception.
He attended that Geneva meeting shortly after his thirty-fourth birthday. For a man not yet old enough to run for president, he had accomplished an extraordinary amount in the course of the previous three years. He had created the first self-replicating human cells shown by exhaustive microscopic examination to be normal diploid cells. He had seen what biologists for the past fifty years had failed to notice: that such normal lab-dish cells were mortal and inevitably aged and died in culture. He had posited that these normal, mortal cells had an analog: the normal, aging cells of living humans. He had shown that these normal cells launched from human fetuses appeared to be free of hidden viruses and that they could be infected with dozens of disease-causing viruses. He had put them forth as a promising new tool that could serve biologists in the lab and that could allow vaccine makers to get away from using monkey cells. And he had done so at precisely the time that a silent simian virus, SV40, was discovered to be contaminating the polio vaccine that had been injected into tens of millions of Americans.
Hayflick had even made an apparently safe and promising polio vaccine using the human cells. And as the WHO committee met in Geneva, he was in the midst of launching what he hoped would be a lasting human fetal cell strain: WI-38. With luck and persistence it might just become the standard cell strain for vaccine making.
As he returned from Geneva that summer, Hayflick had every reason to be pleased with his accomplishments and optimistic that his new vaccine technology would help the industry to turn a corner. What he hadn’t banked on was one inveterate obstacle. He worked at the NIH and his name was Roderick Murray.
• • •
As the director of the National Institutes of Health’s Division of Biologics Standards, Murray was the top U.S. vaccine regulator at a tumultuous time. An introverted, Harvard-educated physician with a square jaw and thin lips, he had been born in New Zealand and raised in Scotland and South Africa and spoke with a noticeable if hard-to-place accent. Murray was as colorless and buttoned down as the edifice he inhabited: building 29, a five-story, redbrick minimalist structure that sat on a slight rise on the NIH campus in Bethesda, Maryland. The government had erected the new building in a hurry in 1960 to house the growing DBS. After the Cutter debacle in 1955, when live polio virus paralyzed scores of children who received the Salk vaccine and then spread in their families and communities, it became clear that government vaccine regulators were outgunned. So the DBS expanded dramatically. Between 1955 and 1963 its staff grew from 54 to 249. Murray presided over the division from a corner office on the first floor of the new building; he had been promoted to head the DBS within months of the Cutter incident.
As the assistant director of vaccine regulation during the Cutter episode, Murray was a reluctant recruit to the top job. But he was obligated to take the position when it was offered, because he served as a member of the Commissioned Corps of the U.S. Public Health Service, a quasi-military operation; to turn it down would have been tantamount to disobeying orders. James Shannon, the new NIH director, may have quickly realized that Murray was ill suited to the position, for Shannon soon placed the tough Joseph Smadel in the DBS to keep an eye on Murray. Essentially, Smadel told Murray what to do, and Murray did it—until Smadel’s untimely death in 1963 from kidney cancer.31
Long before the Cutter affair, Murray had been a close witness to another vaccine disaster involving hepatitis B, then an especially frightening disease. The chronic, often-deadly liver infection was known to be caused by a virus passed by bodily fluids, but the virus had not been isolated in the lab, and there were no blood tests for hepatitis B. This meant there was no way of screening the blood supply to rid it of the virus, since people could carry it for long periods without showing symptoms of the disease. (When it did show up, it could turn the skin and the whites of the eyes yellow, a condition known as jaundice. The yellowing occurs because the diseased liver can’t package for excretion a yellow pigment called bilirubin.)
During World War II Murray, then a major in the U.S. Army, served for several years with a medical lab in the South Pacific. He was charged with establishing standards for production of plasma—the fluid, noncellular component of blood, which was in great demand for injured soldiers. As such, he would have been keenly aware of the tragic episode in 1942 when some 50,000 army personnel contracted hepatitis B. The soldiers had received a vaccine against yellow fever that was tainted with blood plasma from carriers of hepatitis B; the plasma was used to stabilize the vaccine. Between 100 and 150 of the men died.32 (The tainted vaccine was produced at the Rockefeller Institute in New York City with blood serum donated by New Yorkers and by students, staff, and faculty at Johns Hopkins University.)33
After the war Murray joined the NIH office that was the predecessor of the Division of Biologics Standards and made himself into an expert on hepatitis B. In 1951 he and colleagues from that office, called the Laboratory of Biologics Control, demonstrated that blood plasma transfusions from seemingly healthy carriers of the virus—people with no symptoms of hepatitis such as yellowing of the skin or eyes—did indeed cause the then-untreatable disease. They showed this by injecting blood from donors suspected of having hepatitis B into sixty young, healthy “volunteer” prisoners in U.S. penitentiaries at McNeil Island, Washington, and Lewisburg, Pennsylvania. Twenty-one of the prisoners got hepatitis B. The liver tests of another six participants suggested that they, too, had contracted the disease, although they did not become jaundiced. The paper reporting this was published in 1954, the year before Murray was promoted to head the DBS.34
It is shocking today to read of physicians deliberately infecting people with a damaging and sometimes fatal virus. In the case of the Koprowski and Hayflick polio-vaccine experiments, the researchers could at least argue that the polio virus had been weakened and that the vaccinations could conceivably benefit the infants. There was nothing in Murray’s prisoner experiment that could have benefited the healthy men, aged twenty-one to thirty-five years, who participated, and who were put at serious risk of harm. The experiment flew in the face of the Hippocratic oath that Murray and the four physicians who coauthored the paper with him had sworn to uphold. (It is a common misconception that the oath pledges the new physician to “first, do no harm.” But it did commit them to “utterly reject harm and mischief.”)
Yet it is also true that the prisoner trial emanated from the Laboratory of Biologics Control at the National Institutes of Health; that it was funded by the Department of the Army and facilitated by the Department of Justice, specifically, by the Bureau of Prisons; and that it was published in the Journal of the American Medical Association, a leading medical journal. The medical research establishment, in other words, openly approved and sponsored the experiment.
The Murray experiment was just one of scores that make shocking reading today and that were carried out by U.S. medical researchers during World War II and the decades that followed it. Most of the time their experiments were conducted on marginalized groups: poor p
eople on hospital charity wards, people of color, prisoners, people dying of cancer, and orphans and the intellectually disabled in institutions. Most of the time the subjects of these experiments had no idea they were being experimented upon or being put at risk of harm and no capacity or opportunity to give free and informed consent to participate.
The historian David J. Rothman, in his excellent book Strangers at the Bedside, explains how the urgent wartime atmosphere, and all that was at risk during World War II, quickly and easily led medical researchers, funded by the government, to treat individual human beings as expendable in the pursuit of supposedly higher, humanity-benefiting ends—namely, keeping soldiers on the front lines healthy and ready for action at all costs. The public too took the World War II–era experiments in stride; everyone, even prisoners and the institutionalized mentally ill, could and should do their part for the war effort.35 Press accounts lauded the heroics of prisoners who “volunteered” for this higher purpose.36
So during World War II medical researchers on the home front tested experimental influenza vaccine by intentionally infecting young offenders; tried to give prisoners gonorrhea to study the effectiveness of preventive treatments; and injected teenagers at the Ohio Soldiers and Sailors Orphanage with heavy doses of Shigella bacteria, which causes dysentery, a violent diarrhea, in an attempt to immunize them. (The teens did develop antibodies but also became so extremely ill that the vaccine idea was jettisoned.)37 The researchers running these experiments were not outliers, dispatched to carry out a necessary evil that their mainstream colleagues shunned. They were accomplished scientists, like Werner Henle, an eminent virologist at the Children’s Hospital of Philadelphia. Or they were on their way to fame, like Jonas Salk.38
After the war the great advances of the 1940s—the new availability of penicillin the poster child among them—fueled a full-on charge by the U.S. government, enthusiastically backed by Congress, to beat down disease, just as Hitler had been beaten down. And the new, heroic soldiers in that war were the medical researchers. Their primary funding agency was the government’s National Institutes of Health, which in 1953 erected an enormous five-hundred-bed Clinical Center on its campus—a hospital reserved for research on people who were at once patients and experimental subjects.
The NIH made no distinction between the role of the researcher motivated by the quest for discovery and that of the physician whose purpose is to heal the patient and defend his or her welfare. The agency held that one person could play both roles at once, without any conflict of interest. So the NIH promulgated no rules about informed consent, and individual researchers at the Clinical Center—like those non-NIH scientists around the country whose projects were funded by the NIH—were under no obligation to inform their patient-subjects about the risks of the procedures being carried out on them, or even that they were subjects of experiments.39
Given this backdrop, it is not surprising that few if any eyebrows were raised when Roderick Murray was elevated to head the government’s vaccine-regulating branch, the DBS, one year after he and colleagues published, in the prominent Journal of the American Medical Association, the paper announcing that he had infected healthy young men with a life-threatening virus, establishing that hepatitis B was indeed a blood-borne disease.
“The men volunteered for this purpose,” Murray and his coauthors wrote in the pages of JAMA, adding in a footnote: “The service rendered by the volunteers is gratefully acknowledged.”40*
Ruth Kirschstein, a young physician and scientist who later became as close to Murray as anyone at the DBS, recalled late in her own life that “Dr. Murray . . . had had an unfortunate experience. A number of people had died of hepatitis following his studies.” She added immediately: “He was a very fine researcher.”41
Nor is it surprising that Murray, if he hadn’t already been so, had become an extremely cautious man by 1959 and 1960, when Hayflick’s first twenty-five human diploid cell strains were launched, followed by WI-26 in 1961 and WI-38 in 1962. By then Murray had witnessed at close quarters the 1942 yellow fever vaccine crisis. In the early 1950s he himself had caused hepatitis B in at least a score of previously healthy young men. He had weathered the 1955 Cutter polio vaccine incident. He had seen his predecessor at the DBS, William Workman, forced out because of that debacle. Now he was in the throes of handling the fallout from the discovery of the silent monkey virus, SV40, in the Salk vaccine. He had every reason to be risk averse.
And he was just that, according to Paul Parkman, a virologist who worked in the DBS beginning in 1963. Murray was famous within the DBS for the stack of papers, interspersed with purple sheets of carbon paper, that sat to his left on his desk. It was the pile of action items awaiting decisions—decisions that in the view of many at the DBS Murray was agonizingly slow to make and yet not at all inclined to delegate.
When obstacles arose, Murray’s approach was “Don’t feed the problem and it’ll go away,” according to John Finlayson, a blood products expert who worked in the DBS for decades, beginning in 1959.42
Murray was also tough to approach. “He was an elitist, and very proud,” recalled Kirschstein.43
As an expert, Murray knew something about hepatitis that may have been worrisome when Hayflick’s human fetal cells first came to his attention with the publication of the landmark paper in December 1961, describing the first twenty-five human diploid cell lines that Hayflick had derived and their inevitable aging and deaths in culture. What Murray knew was this: babies were sometimes born with hepatitis B. It’s now known that newborns contract the disease from their mothers during birth and not while in the womb. But that wasn’t known at the time. In Murray’s mind it must have been at least conceivable that any given strain of Hayflick’s human diploid cells might have come from a fetus infected with hepatitis B. There was no laboratory test for hepatitis B, so it was a fear that Hayflick did not have the tools to disprove.
Beyond the risks of hidden hepatitis infection, Murray was likely troubled too by the idea that the human cells might transmit cancer to vaccinees through a hidden, cancer-causing virus of the sort that the agency was spending huge amounts of money in that era to discover.
Whether religious or moral views also colored Murray’s thinking about the use of aborted fetal cells in vaccine making isn’t known. But it was common knowledge in the DBS that Murray was profoundly anticlerical; this emerged whenever the deeply Catholic James Shannon, the NIH’s director, insisted that prayers be offered at public ceremonies.
Whatever his views, Murray was in a position of public accountability, and he was faced with a challenge the moment that Hayflick and Moorhead’s landmark paper appeared in print. For the paper proselytized for the use of the new cells in viral vaccine making, “in particular poliovirus vaccines.” In the midst of the SV40 crisis as he was, Murray needed to respond to Hayflick. If he was not going to give the nod to companies to use the new human fetal cells, he needed a very good reason why.
As many people in power who are faced with thorny decisions continue to do today, Murray outsourced the problem. In January 1962, the month after the Hayflick-Moorhead paper was published, he convened a panel of eight NIH experts to study the cells and to weigh in on their promise, or perils, for use in making virus vaccines—as opposed to using monkey kidney cells. The group was both illustrious and powerful—it included people like Wilton Earle, a giant of cell culture, and Smadel, the Salk vaccine booster who had done all he could to stifle Bernice Eddy’s findings that something in rhesus monkey kidney cells caused cancer in hamsters.
One year later, in January 1963, the group published its answer to Murray in the form of a dense, six-page paper in Science, the high-profile journal that is the unofficial house organ of American science.44
While the report conceded the recent burst of interest in the human diploid cells and said that “further investigation” of their potential use in vaccine making was justified, it cau
tioned that they were “not precisely characterized, genetically or otherwise, and may be subject to random fluctuations in properties.” And it made clear that such “random fluctuations” might not be good ones.
“Continuously cultured cells eventually develop characteristics suggestive of malignant change, which theoretically might be attributable to some as yet undefined viral activity,” the committee declared. “Even though no virus has been shown to be involved in these particular changes, there can be no absolute guarantee that a given strain of continuously cultured cells will never yield a previously unknown virus . . . that is infective and [disease-causing] for some cells . . . under some conditions.”45
One could not, in other words, prove a negative. And Hayflick’s cells were going to be held to that standard, regardless of the real, demonstrated, and costly deficiencies of freshly harvested monkey kidney cells.
Hayflick fought back in the strongest way he knew how. He enlisted his former mentor from Galveston, the cell-culture guru Charles Pomerat, and the respected chromosome expert T. C. Hsu as coauthors with him and Moorhead on a Science paper that appeared a few months later, rebutting the committee’s findings point by point.46
But the damage was done. Murray now had official approval for resisting Hayflick’s cells, in the form of the combined wisdom of eight NIH experts, published in the top science journal in the country.
• • •
Across the Atlantic the reception of the human diploid cells couldn’t have been more different. Even while the just-hatched WI-38 cells were incubating in the room next to Hayflick’s lab in the summer of 1962, the World Health Organization expert meeting on human diploid cells convened.
Eight months earlier the WHO had launched a study of Hayflick’s cells by scientists in six countries.47 (They studied WI-26, since the first twenty-five WI strains had been lost in the freezer accident and WI-38 hadn’t yet been derived.) Then, during three perfect mid-July days on Lake Geneva, the scientists hunkered down and scrutinized their results. The meeting was chaired by Sven Gard, the chair of virology at the Karolinska Institute, and attended by Hayflick and, among others, Frank Perkins, a big, outgoing, silver-haired British scientist who carried index cards with jokes, some of them raunchy, written on them. He would pull one out and read it during a meeting or over dinner, as the occasion demanded. Perkins was impressed with the human diploid cells and was fast becoming an important Hayflick ally. His opinion mattered, for he was the United Kingdom’s top vaccine regulator.
The Vaccine Race Page 17