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Authors: Paul A. Offit

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BOOK: Vaccinated
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I
N THE SPRING OF
1966, H
ILLEMAN AND
T
ISHLER TOOK A TRAIN FROM
Philadelphia to New York City and a taxi to Lasker's newly built apartment overlooking Central Park West. The apartment house was a fashionable address for the powerful elite, including novelist Truman Capote, Attorney General William Rogers, and Senator Robert F. Kennedy. Lasker ushered Hilleman and Tishler into rooms decorated with paintings by Miro, Renoir, Cezanne, and Dali. The scientists sat at the dining room table, quietly and nervously, waiting to hear what Lasker had to say.

Lasker explained that she had been haunted by the recent rubella outbreak. She said she was proud that Merck had chosen to work on a vaccine, but she also knew that Harry Meyer had a vaccine, and she feared that competition would only delay development. Hilleman slowly realized what Lasker was getting at: she was going to ask him to abandon his vaccine. “I explained that we needed to make vaccine to avoid the next epidemic,” recalled Hilleman. “She said, ‘I don't think we're going to be able to do it in time because you've got two vaccines competing. And one of these vaccines is made by the federal regulator. Just whose vaccine do you think is going to get approved first?'” Hilleman remembered thinking, “Meyer's vaccine is [not] going to be approved first because he didn't make it into a vaccine yet. It was just a goddamned experiment.” Lasker asked Hilleman and Tishler to go back to Merck and think about her request.

Maurice Hilleman, assisted by coworker Eugene Buynak, inoculates a duck with rubella virus, circa late 1960s.

Standing on the street in front of Lasker's apartment after the meeting, Tishler turned to Hilleman. “I'll do whatever you want,” said Tishler. “You tell me.” Hilleman, for one of the few times in his life, succumbed to the pressure. “I'll tell you what I will do,” said Hilleman. “I'll get the [vaccine] virus from Meyer and see what I can do.” Hilleman took Meyer's virus and injected it into children living in and around Philadelphia. But he found that the virus had side effects that were intolerable. “I got [Meyer's vaccine] and put it into about twenty kids, and, Jesus Christ, it was awful: toxic, toxic, toxic. So I passed it five more times in duck [embryos] and attenuated it.”

One year after the meeting with Mary Lasker, Hilleman compared his own vaccine to his modification of Meyer's. He found that both vaccines induced antibodies and that both were safe. But he also found that his vaccine induced much higher levels of protective antibodies. Hilleman had a choice. He could either proceed with his own vaccine, which he knew was better, or he could grant Mary Lasker her wish. In 1967, Hilleman abandoned his vaccine. Later he said, “If I have only one regret in my life, it's that I let Mary Lasker talk me out of making my own rubella vaccine.”

By 1969, Hilleman had obtained a license for his modification of Meyer's and Parkman's vaccine. During the next ten years, Merck distributed a hundred million doses in the United States, and the rubella epidemic—expected to occur between 1970 and 1973—never happened. But the first rubella vaccine wouldn't be the last, because, for the only time in his life, Maurice Hilleman's vaccine would be replaced by a better one.

 

W
HILE
M
AURICE
H
ILLEMAN AND
H
ARRY
M
EYER WERE TRYING TO
make their rubella vaccines, Stanley Plotkin was making his. Meyer had used cells from monkeys, and Hilleman had used cells from ducks. Plotkin used cells from an aborted human fetus. His choice opened a door to a controversy that has never closed.

Stanley Plotkin is an energetic scientist with an avuncular style and disarming wit. Born in the Bronx, New York, he attended the Bronx High School of Science, a highly competitive school for gifted teenagers. “I've never had as much intellectual competition as I did in that school,” recalled Plotkin. “Not in college, medical school, or research.” Plotkin was inspired to a life of science by Sinclair Lewis's novel
Arrowsmith
, the story of Martin Arrowsmith, a boy from Minnesota who becomes a family doctor in the Midwest. Intellectually dissatisfied with his work, Arrowsmith is drawn to the fictional McGurk Institute in New York City and the wise, even-handed tutelage of a German Jewish scientist named Max Gottlieb. With Gottlieb's help, Arrowsmith discovers a virus that kills bacteria—a finding that he reasons will revolutionize the treatment of bacterial infections. (Sinclair Lewis wrote
Arrowsmith
ten years before the discovery of antibiotics.) Stanley Plotkin's life would soon parallel Martin Arrowsmith's.

After graduating from high school with honors, Plotkin attended New York University and then Downstate Medical Center in Brooklyn, both on full scholarships. Later he joined the Epidemic Intelligence Service (EIS) at the Communicable Diseases Center in Atlanta, now the Centers for Disease Control and Prevention. Alexander Langmuir, the head of the EIS, wanted Plotkin to study anthrax, a fatal respiratory disease, so he sent him to the city with the greatest incidence of anthrax in the United States: Philadelphia. “Anthrax was a problem in Philadelphia [because] the clothing industry [for which Philadelphia was an important center] would import goat hair from India,” recalled Plotkin. “And this goat hair was often contaminated with anthrax. Factory workers would get infected when they would inhale anthrax spores from the hair. But Alex [Langmuir] was astonished that someone was willing to go to Philadelphia. He was reminded of the apocryphal tombstone of W. C. Fields, ‘Rather here than in Philadelphia.' Unfortunately, I didn't know a damn thing about anthrax. I wanted to go to Philadelphia to work on polio.” Going to Philadelphia gave Plotkin a chance to work at the world-famous Wistar Institute. For Plotkin, Wistar would be his McGurk Institute and Hilary Koprowski, the director, his Max Gottlieb.

 

T
HE
W
ISTAR
I
NSTITUTE OF
A
NATOMY AND
B
IOLOGY, THE OLDEST
independent institute for medical research in the United States, sits in the center of the campus of the University of Pennsylvania in West Philadelphia. An impressive three-story brownstone building, the institute, founded in 1892, was named for Caspar Wistar, the nation's leading anatomist in the eighteenth century and the man for whom the plant wisteria was named. Wistar wrote the first textbook on anatomy in the early 1800s and developed a series of anatomical teaching aids that included wax-preserved human limbs and organs. The institute's museum of anatomy contained a cyclops; Siamese twins; two Indian mummies; seven wax-injected human hearts; the death masks of Oliver Cromwell, Sir Isaac Newton, and Voltaire; and the largest number of human and animal skeletons in the world. A massive whale skeleton hung from the ceiling. Although the Wistar Institute had been founded to advance studies of anatomy, by the early 1960s Hilary Koprowski had made it one of the world's leading institutions for the study of cancer and viruses.

The Wistar Museum, circa 1940s. An X-ray of a living person injected with a dye to visualize arteries (foreground), was donated by the Eastman Kodak Company in 1939.

Born in Poland, Koprowski had come to Wistar from Lederle Laboratories in Pearl River, New York. Like the fictional Max Gottlieb, Koprowski had a thick accent and a passion for science. In the 1950s Koprowski was locked in a race with Albert Sabin to make the first polio vaccine using live, weakened human polio viruses. Koprowski was winning the race. He was the first to weaken polio virus by passing it through rats, the first to give the vaccine to children, and the first to test it in thousands of people. But Sabin's vaccine, made by growing polio virus in cells from monkey kidneys and monkey testicles, was eventually judged to be safer than Koprowski's. By the early 1960s, Albert Sabin's polio vaccine would be dropped onto sugar cubes and given to children throughout the world, eliminating polio from many countries. Although he lost his race with Sabin, Koprowski directed a research institute that developed vaccines against rubella and rabies and advanced our understanding of how and why cells become cancerous.

 

A
FTER COMPLETING HIS STUDIES ON ANTHRAX,
P
LOTKIN LEFT
W
ISTAR
. “By 1961 I had finished my work on polio and anthrax and was looking for something else,” he recalled. “So I decided to leave Wistar and complete my pediatric training at the Great Ormond Street Hospital in London. Before leaving, I wrote several grants [seeking funds] to study rubella. During my year in London an outbreak of rubella started in the United Kingdom that was considerable.” Working with Alistair Dudgeon, a British virologist, Plotkin saw hundreds of babies permanently harmed by the virus. “It was an experience that you don't get from reading books,” he said.

After a year in England, Plotkin returned to the United States. “I was ready to start my own lab at Wistar, focused on rubella, and Hilary Koprowski was very supportive. Lo and behold, the epidemic crossed the Atlantic and swept across the United States, leaving behind thousands of damaged babies: something the popular press was talking about. During the height of the epidemic, 1 percent of all babies in Philadelphia were born to mothers who were infected with rubella.” Plotkin was forced to tell hundreds of mothers that rubella virus had probably damaged their unborn fetuses. Many chose to end their pregnancies. “It was a powerful experience,” he recalled.

By offering women the option to abort their pregnancies, Plotkin had technically violated the Hippocratic Oath, a pledge that he had taken when he graduated from medical school. In the fourth century
B.C
., Hippocrates wrote, “I will not give to a woman an abortive remedy.” Virtually every medical school in the United States reads the Hippocratic Oath to graduating students, but the oath has been modified since Plotkin took it. Hippocrates' prohibition of abortion has been removed. Also gone are his edict forbidding euthanasia: “I will neither give a deadly drug to anybody who asked for it, nor will I make a suggestion to this effect”; discouraging sexual contact with patients: “Whatever houses I may visit, I will come for the benefit of the sick, remaining free of all mischief, and in particular of sexual relations with both male and female persons, be they free or slaves”; forbidding surgery: “I will not use the knife” (not such a terrible idea in 400
B.C
.); and educating medical students for free: “to teach them this art, if they desire to learn it, without fee and covenant.”

Leonard Hayflick in his laboratory at the Wistar Institute, circa late 1960s.

Plotkin was desperate to make a rubella vaccine. But unlike Meyer and Hilleman, he didn't look for rubella virus in the backs of people's throats. “I looked for rubella in the fetus and not in the throat,” recalls Plotkin, “because I couldn't be sure that patients weren't carrying other viruses in their throats, whereas the fetus is in a sterile environment.” In 1964, a twenty-five-year-old Philadelphia woman was eight weeks pregnant when she noticed a faint red rash on her face. Fearing that she had rubella, she came to see Plotkin. After confirming her worst fear, Plotkin advised her of the risks to her baby. A few weeks later, the fetus arrived in his laboratory. Because this was the twenty-seventh aborted fetus that Plotkin had received and because he captured rubella virus from the third organ that he tested—the kidney—Plotkin called his vaccine virus
R
ubella
A
bortus 27/3 (RA27/3).

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