The Vaccine Race
Page 19
It would take study upon study in the 1950s to win full acceptance of Gregg’s findings by the medical profession. The follow-up studies documented a broad range of damage that the virus did to fetuses in early pregnancy—any rubella virus, not just the Australian virus of 1940. They confirmed that rubella’s ruinous results included deafness, cataracts, heart defects, microcephaly, and associated intellectual disability. Later, autism would be recognized as another sign of the brain damage in congenital rubella survivors.17 Any combination of rubella-induced problems would come to be dubbed congenital rubella syndrome—CRS for short. Rubella, an exclusively human virus no more than three millionths of an inch in diameter, was, it was at last quite plain for all to see, a menace to life in the womb.
And there was no defense against it. The rubella virus had not been isolated in the lab. Until it was captured, there could be no vaccine.
• • •
In late September of 1962 a brief article appeared in the British Medical Journal under the title “Rubella, 1962.” The report, by three doctors in general practice in Beckenham, a London suburb, described “a widespread epidemic of rubella” between March and July that year.
The three general practitioners had seen 355 patients with rubella in that short space of time—nearly 6 percent of the patients in their practice of about 6,500. But, they wrote, this was likely an underestimate. They suspected that another 200 people had been infected but had not been seen in the office—people who had telephoned them but not come in; others who had mentioned having the disease after the fact; and still others who they suspected had been infected but had not noticed or reported the disease.
Children aged five to ten years old were by far the most often affected, the trio reported. Fully 25 percent of the practice’s patients of this age had been diagnosed with rubella. But, the doctors added, “in this group it is very probable that over 50 percent were infected. Local schools have confirmed that more than half of classes were absent during this period, presumably because of rubella.”18
What the Beckenham doctors saw was repeated in untold numbers of doctors’ offices in the United Kingdom during the spring of 1962 and again in the spring of 1963. (In the United Kingdom, as in the United States, rubella infected people throughout the year, but infections peaked in the early spring.)*19
Rubella seemed to be everywhere: The mayor of Rugby and his three children were down with German measles and confined to their home, the Times of London reported in mid-March 1962.20 “Between 20 and 35 Eton College boys have German measles and about 20 are in the school sanatorium. The others are recovering at their homes,” the newspaper added in a report about the famous prep school later that month.21
The star batter R. E. Marshall of the Hampshire cricket team “had contracted German measles and had taken them home with him—so his colleagues hope,” the London newspaper the Guardian reported in June 1962.22
And women who, early in their pregnancies, knew or suspected they had the disease wrestled with a terrible choice. They could carry the fetus to term, accepting the high risk that it would be damaged by the virus. Or they could seek an abortion.
One woman, identified only as “A Mother,” wrote to the British newspaper the Guardian in August 1963. After she contracted rubella very early in her pregnancy, her doctor told her there was only a one-in-three chance that the baby would be born undamaged.
“When he gave me the chance to enter the hospital immediately and have the pregnancy terminated, I felt I had no choice,” she wrote, adding that she nonetheless felt “a deep elemental repugnance for what I was doing.” She added: “Now when people say, or I hear myself saying, how lucky I was, I feel simultaneously a twist of revulsion. It is not lucky to have disposed of a life. What was lucky, however, was the chance that I was sent to a humane doctor.”23
Many pregnant women weren’t as certain as the letter writer that they had had rubella. For them, decisions about whether to continue a pregnancy were perhaps still more agonizing. What would have served them—and what wasn’t available—was a definitive lab test to identify rubella infection.
The first vital step toward developing such a test came in October 1962, when two groups of American researchers published papers in the journal Proceedings of the Society for Experimental Biology and Medicine. More than twenty years after Norman Gregg recognized the link between rubella and fetal damage, the virus had finally been isolated in the lab.
One pair of physicians, Thomas Weller and Franklin Neva at the Harvard School of Public Health, had cultured the virus by inoculating plates of human amnion cells with the urine of Weller’s ten-year-old son, who was ill with rubella. But their method of identifying the virus in a lab dish took so long—from two and a half to four months—that it rendered it useless for worried pregnant women.24
The more practical achievement came from Paul Parkman, the mild-mannered son of a post office clerk and a homemaker from the tiny town of Weedsport, New York. Parkman was a young physician and virologist at the Walter Reed Army Institute of Research in Washington, DC. With his colleague Malcolm Artenstein and his boss, Edward Buescher—and with throat washings from a score of young military recruits who were hospitalized with rubella at Fort Dix, New Jersey, in February and March of 1961—Parkman had devised a way to get around a vexing property of the rubella virus.
Unlike viruses such as polio, which tears through cells in culture, exploding them and leaving chaos and debris in its wake, rubella was seemingly indolent in a culture dish, leaving no clear signs that it had infected cells. Parkman’s group came up with an indirect test to prove that the virus was present in culture. They first inoculated throat washings from the Fort Dix recruits onto African green monkey kidney cells, keeping uninoculated monkey cell cultures as controls. Seven to fourteen days later they added another virus, a gut virus called ECHO-11, to all of the cultures. ECHO-11 destroyed the uninfected control cells in two or three days. But rubella virus blocked ECHO-11’s effects, leaving the kidney cells intact.25 It was a cumbersome way to identify a virus, but it was certainly quicker than Weller and Neva’s method. And in the face of an epidemic, it was a welcome development.
• • •
In London that autumn of 1962, a pediatric resident at the Hospital for Sick Children on Great Ormond Street—nicknamed “GOSH,” for “Great Ormond Street Hospital”—read the new papers on the isolation of the rubella virus with keen interest.
Stanley Plotkin, who had helped test Koprowski’s polio vaccine while at the Wistar Institute in Philadelphia, had paused his research career to complete the training in patient care that would qualify him as a pediatrician. That summer, just after his thirtieth birthday, he had finished a first year as a pediatric resident at the Children’s Hospital of Philadelphia. This second year of residency, which he was spending at GOSH, would see him through to full qualification as a pediatrician. After that, he had reassured Koprowski, he intended to return to the Wistar.
Plotkin was born in 1932 in the Bronx, the son of a telegrapher and a bookkeeper—first-generation U.S. immigrants whose own parents had fled the hostile climate for Jews in eastern Poland. A slight, bookish, precociously intelligent child, he was nearly felled by pneumococcal pneumonia in 1936, before antibiotics were available. He was plagued by asthma and at age nine was sent alone to the National Home for Asthmatic Children in Denver, where he contracted influenza, was hospitalized, became comatose, and again nearly died. He emerged months later weighing forty-three pounds, the left side of his face stilled by a facial nerve paralysis called Bell’s palsy.26 (The paralysis was transient in Plotkin’s case; it isn’t always.)
Plotkin was a quiet, studious boy who frequently skipped grades in school. He graduated from the Bronx High School of Science at sixteen, after working furiously to keep up with peers who were two years older. He says that to this day he has never inhabited a more competitive academic environment.27
Both books dripped with a romantic view of science. Microbe Hunters declares on its first page that it is the story of “bold and persistent and curious explorers and fighters of death” and reminds readers that scientists’ achievements “are on the front pages of the newspapers.” Arrowsmith is flush with the thrill of discovery, the agony of being bested by a competitor, and the eventual rewards of long, painstaking hours in the lab. (The central character, Martin Arrowsmith, is also confronted with the corrupting temptations of wealth, fame, and the flesh.)
Inspired, Plotkin attended New York University on a fully funded state scholarship, then sat a three-day exam trying to win one of thirty-five sought-after scholarships that would pay his way through any in-state medical school. Without the scholarship, financing an MD would be impossible for his family.
Plotkin recalls that he applied to half a dozen medical schools while he was awaiting the exam results. In an era when Jews were not welcome as medical students, he heard back from none of them. Then he heard from the state. Plotkin had placed fifteenth among the test takers and won full funding at any New York medical school.
“We definitely have to accept you, since you’ve won this scholarship,” he recalls being told by an administrator at the State University of New York’s Downstate College of Medicine in Brooklyn, the only medical school that accepted him.
By the time he landed in medical school in 1952, Plotkin the undergraduate had fallen in love with Shakespeare, studied philosophy, and dissected a cat, a shark, and a fetal pig. None of which quite prepared him for Kings County Hospital—the huge, busy hospital in the Flatbush section of Brooklyn that was the teaching hospital for the Downstate College of Medicine. It was a world apart where, as Plotkin recalls, “after dark the medical student was king.”
He rotated through the specialties and soon knew that he didn’t want to be a surgeon. He would avoid holding retractors in the operating room by swapping duties with another classmate so he could instead care for patients on the ward. Yet the prospect of specializing in internal medicine didn’t thrill him either. It seemed like a road to treating unhealthy adults just to keep them in a holding pattern.
Pediatrics was different. There he might influence the whole of a life. And there vaccine research was desperately needed. That realization came home to him as he cared for children who were brain damaged and deafened by meningitis—an inflammation of the membranes that enclose the brain—caused by the bacterium Haemophilus influenzae. By the end of his third year in medical school, Plotkin knew that he would become a pediatrician. He was also determined to be a research scientist.
For his rotating internship—a mandatory yearlong boot camp for newly minted doctors—he chose to go to Cleveland Metropolitan General Hospital, because there the director of pediatrics was Frederick Robbins, who two years earlier had won a Nobel Prize. Plotkin found that he was too busy taking care of patients to do any research, but he enjoyed the proximity to the man who, with Enders and Weller, had discovered that poliovirus could be grown in nonnervous tissue, opening a whole new world to virologists.
As he finished his internship in Cleveland, Plotkin’s next step was clear. Because he was between eighteen and twenty-six years old, the Selective Service Act of 1948 required twenty-one months of military service from him. The only way to avoid this was to go to work for what was, in the letter of the law, a branch of the U.S. military: the Commissioned Corps of the U.S. Public Health Service. So he signed up with the Epidemic Intelligence Service, the “disease detective” branch of the CDC, itself part of the Public Health Service.*
After introductory training in Atlanta, Plotkin surprised his CDC supervisor, Alexander Langmuir, by requesting assignment to an anthrax investigations unit in Philadelphia. But Plotkin, as usual, had done his homework. He had been reading groundbreaking papers by a polio vaccinologist named Koprowski, who was just taking over the Wistar Institute. And the CDC’s anthrax project was based at the Wistar. His move there, he says, was the single most important decision of his professional life because it landed him in the lab of his own “Max Gottlieb.”
Plotkin remembers vividly the moment, shortly after he arrived at the Wistar in August 1957, when he first presented himself in Koprowski’s office, hoping, in addition to his CDC work on anthrax, to talk his way into a polio research position in Koprowski’s lab. Displayed prominently on Koprowski’s desk was a cartoon depicting a particularly brutal-looking Neanderthal man. Its caption read: “We welcome your suggestions.” It set Plotkin to laughing, which in turn made him fear that the illustrious Wistar director would think he was an idiot.
Koprowski did not think so and made room for the twenty-five-year-old Plotkin in his nascent polio lab. In August 1957 this lab consisted, until the Wistar’s renovations could be completed, of a big semicircular second-floor room without air-conditioning. There Koprowski’s first hire, the young lab technician Barbara Cohen, sat measuring the amount of poliovirus in clear tubes of chimpanzee stool that Koprowski’s team had sent back from the Belgian Congo. (Feeding experimental polio vaccine to chimpanzees was Koprowski’s prelude to vaccinating hundreds of thousands of people in central Africa.)
The less-than-perfect lab space did not deter Plotkin, who was thrilled to be taken on by a man he judged to be not only highly intelligent but also highly cultured, a man with a breadth of vision and a zest for life that Plotkin simply wanted to be around.
And as the Wistar’s face-lift progressed under its new chief, so did Plotkin, eventually moving into a third-floor lab, where he worked on anthrax when not laboring in Koprowski’s second-floor polio operation. There he learned how to grow and count polioviruses, how to isolate different strains of the virus, and how to weaken them for use as vaccines. His name began appearing on Koprowski’s polio papers.
In the spring of 1959 Koprowski offered Plotkin the opportunity to go to the Belgian Congo himself, to work with Koprowski collaborators—expatriate Belgians—who were vaccinating tens of thousands of children in Léopoldville with Koprowski polio vaccine. Plotkin jumped at the opportunity. Plotkin’s CDC bosses, loath to appear to be taking sides in the vaccine race, made Plotkin take a leave of absence from his CDC duties during the two-month trip.
“The culture shock engendered by a visit to an undeveloped country was unforgettable,” Plotkin wrote later. “More importantly, it taught me that vaccine development did not end in the laboratory and that field studies were not only essential but difficult and even dangerous.”28
When he wrote “dangerous,” he meant it. At one point during the vaccination campaign, Plotkin and his Belgian colleagues were vaccinating infants in the city of Kikwit when they were surrounded by an angry crowd who believed that the researchers were desexing their children because they were drawing blood, to determine the babies’ antibody status, from the femoral vein, located in the groin. In an effort to calm the crowd, one of the expatriate Belgians drew blood from his own child’s femoral vein, in full view of the crowd. This failed to quell the anger. The scientists were forced to call the local army base, which sent a unit of soldiers in trucks to escort the researchers out of the area.
Koprowski made the
most of his protégé’s African adventure, inviting print, radio, and TV reporters to a buffet luncheon and press conference just after Plotkin returned to Philadelphia in June 1959. It would mark the “first announcement of effectiveness of Wistar Institute oral polio vaccine during a recent epidemic in the Belgian Congo,” the press release announced. And it would feature Plotkin, “who has just returned from making a survey of the mass inoculation.”29
Plotkin, who as a fifteen-year-old had dreamed of being a microbe hunter, had, at the tender age of twenty-seven, become a certified member of that club.
• • •
Plotkin began his one-year residency at the Great Ormond Street Hospital in central London in July of 1962. He was working at a mecca for what he and other doctors called “clinical material,” meaning people with diseases, in this case children referred from all over the southern part of England. Because GOSH was one of only two children’s hospitals in a city four times as big as Philadelphia, kids with run-of-the-mill earaches and sore throats were few and far between.
Instead children with serious childhood ailments, from congenital heart disease to cystic fibrosis, turned up at the hospital, giving an ambitious young pediatrician all the disease exposure that he could dream of. To boot, it was not he but the housemen—brand-new doctors, called “interns” in the United States—who were responsible for looking after the patients staying on the wards. That left Plotkin with duty at the outpatient clinic—and time for research.
Plotkin had chosen GOSH with a view to working with one member of Koprowski’s far-flung network of colleagues, Alastair Dudgeon, a brisk, impeccably dressed virologist with an upper-class accent and an omnipresent bowler hat, who had twice been decorated for bravery during World War II, when he commanded a company of the British army’s Seventh Battalion Rifle Brigade in North Africa. Dudgeon was interested in congenital infections—infections acquired in the womb and carried in newborn babies into the world. As Plotkin began working with Dudgeon in July, across the Atlantic Hayflick was in the process of launching WI-38. In September the report from the doctors in the London suburb of Beckenham was published, documenting a glut of patients with rubella. In October the papers from the American virologists were published, announcing that they had captured rubella in lab dishes. It was as if an unseen hand had now put in place all the elements necessary for the drama that would follow.