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  Thomas Weller remembered what it was like to work in a laboratory dense with human kidneys and placentas: “I would walk across the street to the Boston Lying-In Hospital, and obstetricians would hand me these heavy placentas from babies that they’d just delivered. Some days there were no placentas. But on others there were as many as six. Back in Dr. Enders’s laboratory I set up two ring stands and balanced a thick, sterile steel rod between them. Then I draped the placentas over the rods like clothes on a clothesline.”

  NOW IT WAS TIME FOR THE BOSTON TEAM TO TEST THE VACCINE. SO Sam Katz drove to the Fernald School, where a few years earlier researchers had fed radioactive cereal to members of its science club. “We chose the Fernald School because every year there were outbreaks of measles [in the school],” recalled Katz, “and every year several children died.” On October 15, 1958, Katz injected eleven mentally retarded or disabled children with the vaccine developed in Enders’s laboratory. All the children developed protective antibodies. But eight of them had fever, and nine had a mild rash. Although the vaccine protected children from measles without causing the full-blown disease, the vaccine still wasn’t weak enough.

  Without weakening the virus further, the Boston team next tested the vaccine in mentally retarded children at the Willowbrook State School, where Saul Krugman had performed his controversial experiments with hepatitis virus. On February 8, 1960, Katz injected twenty-three children with the vaccine, and twenty-three other children were given nothing. Six weeks later an outbreak of measles swept through Willowbrook, infecting hundreds of children and killing four. None of the vaccinated children got measles, but many unvaccinated children did. Enders’s vaccine worked but, again, had caused a high rate of side effects. “[Representatives from] many pharmaceutical companies came and got material to produce vaccines,” recalled Katz. “One was Maurice Hilleman.”

  HILLEMAN WAS EXCITED ABOUT WORKING WITH THE VACCINE DEVELOPED by the Boston group. But he faced two difficult problems. Neither was easily solved.

  The first involved side effects. Although the Enders team had passed David Edmonston’s measles virus through several different human and animal cells, the virus still wasn’t weak enough. Hilleman found, in experiments involving hundreds of healthy children, that half of those given Enders’s vaccine had a rash, and most had fevers, some higher than 103 degrees. “It was toxic as hell,” recalled Hilleman. “Some children had fevers so high that they had seizures. The Enders strain was the closest thing there was to a vaccine, but to me it was just an isolate. He hadn’t made a vaccine.” Even while he was worried about the safety of Enders’s vaccine, Hilleman felt pressured by public health agencies anxious to prevent a disease that was killing thousands of American children every year. He had to find a way to make Enders’s vaccine safer, and he had to do it quickly. The toxic-as-hell problem was solved by Joseph Stokes Jr., the pediatrician who had helped Hilleman test his mumps vaccine.

  Hilleman chose Stokes because he was an expert on gamma globulin, the fraction of blood that contains antibodies. To make gamma globulin, Stokes took blood, let it clot, and stored it in the refrigerator. Eventually, red blood cells formed a clot at the bottom of the tube, and gamma globulin, contained in serum, floated to the top. Stokes knew that people infected with measles, mumps, polio, or hepatitis viruses rarely got the disease again. And he knew that antibodies were the reason why. In the mid-1930s, Stokes showed that gamma globulin taken from polio survivors protected children during polio epidemics. Ten years later, as a special consultant to the surgeon general during the Second World War, Stokes showed that gamma globulin from hepatitis survivors protected American soldiers from hepatitis. For his work on hepatitis, Stokes won the Presidential Medal of Freedom, the nation’s highest civilian award.

  Stokes proposed giving a tiny dose of gamma globulin along with Enders’s measles vaccine, hoping to modify side effects. To see if the idea worked, Stokes and Hilleman went to a women’s prison in central New Jersey.

  BUILT IN 1913 ON A SPRAWLING FARM IN RURAL HUNTINGTON COUNTY, Clinton Farms for Women was an ideal prison. An outgrowth of the turn-of-the-century prison reform movement, Clinton provided education, technical training, medical care, and a safe environment for inmates. In the early 1960s, Hilleman and Stokes made several visits to Clinton Farms. (During one early visit, they were eating lunch in the cafeteria when a waitress came to the table and asked them what they wanted to eat. Hilleman needed the prisoners to feel comfortable with his experiment, and he knew that the waitress was also a prisoner. “So what are you in for?” he asked, awkwardly, trying to make conversation. “I killed my parents,” she replied. Seeing the stricken look on his face, she added, “But don’t worry. You’re safe here.” Hilleman never asked that question again and, despite her assurances, never felt completely safe on subsequent visits.)

  Edna Mahan, the prison’s director, revolutionized life at Clinton Farms by taking the locks off doors and prohibiting guards from carrying guns. Prisoners could walk off the grounds any time they wanted. “The prisoners would leave the prison, travel down the road, get into a passing truck, and get themselves pregnant,” recalled Hilleman. “The nursery was full of babies.”

  Stokes and Hilleman injected six infants with Enders’s vaccine in one arm and gamma globulin in the other. None of the infants had a high fever, and only one had a mild rash. Encouraged, they tested hundreds of children. In the end, Stokes’s gamma globulin strategy worked. Subsequent studies during the next few years showed that the percentage of children with rash decreased from 50 percent to 1, and with fever from 85 percent to 5.

  Edna Mahan died in 1968, only a few years after Hilleman performed studies in her prison’s nursery. In a small cemetery on the prison grounds, her elaborate tombstone is surrounded by forty tiny crosses, each representing babies who died in the prison from infections that are now easily prevented by vaccines.

  THE SECOND PROBLEM THAT WORRIED HILLEMAN WAS THAT ENDERS’S vaccine might cause cancer. Although measles virus didn’t cause cancer, Hilleman had reason to be concerned. His fears stemmed from an event that had occurred fifty years earlier.

  In 1909 a farmer walked into the Rockefeller Institute in New York City carrying a dead chicken under his arm. Hands thickened by hard work, wearing thick bib overalls and heavy boots, the farmer watched as scientists, technicians, and graduate students milled through the lobby of one of the country’s premier research institutes. Finally he got up the courage to ask where he could find Peyton Rous’s laboratory. The farmer was certain that Rous, an expert in animal diseases, would know what had happened to his chicken.

  A Baltimore-bred, Johns Hopkins–trained pathologist, Peyton Rous was thirty years old when he took the chicken from the farmer, laid it onto his laboratory bench, and dissected it. Just under the right breast was a large cancerous tumor. Rous found that the cancer had also spread to the liver, lungs, and heart. He asked the farmer whether any other chickens in his flock had a similar problem. “No,” the farmer said, “only this one.” Apparently, the cancer wasn’t contagious.

  Rous wanted to find what had caused the chicken’s cancer. So he removed the tumor and carefully ground it up with sterile sand, completely destroying all the malignant tumor cells. Then he suspended the disrupted tumor cells in salt water and passed them through unglazed porcelain, which acted as a filter to trap bacteria. Rous found that when he injected the fluid that had passed through the filter into other chickens, tumors developed in those chickens as well. Within a few weeks, cancer had killed them all. “The [chickens] became emaciated, cold, and drowsy, and shortly died,” he said. Because the tumors were caused by something passing through the filters, Rous knew that it couldn’t be bacteria. And he knew that it couldn’t be the cancer cells, because they had been destroyed by the sand and were too big to pass through the filters. It was something else. Rous reasoned that the agent that had passed through the filters was a virus.

  On January 11, 1911, Peyton Rous, in a paper ti
tled “Transmission of a Malignant Growth by Means of a Cell-Free Filtrate,” was the first person to prove that viruses could cause cancer. Immediately other investigators tried to duplicate Rous’s findings in mice and rats, but without success. Reasoning that cancer-causing viruses were at most a phenomenon unique to chickens, Rous gave up his investigations in 1915, and for the next four decades researchers relegated tumor viruses to the cabinet of freaks.

  Although many cancer researchers working in the 1910s through the 1940s ignored Rous’s findings, evidence continued to mount in favor of cancer-causing viruses. In the early 1930s Richard Shope, a veterinarian from Iowa, found that viruses caused giant warts on wild rabbits in the southwestern United States. (Although many consider them to be mythical creatures, jackalopes—jackrabbits with antelope horns—might be rabbits infected with Shope’s wart-causing virus.) A few years later, researchers found a virus that caused tumors in the mammary glands of mice. But it wasn’t until the 1950s, when Ludwik Gross, a Polish refugee, found a virus that caused leukemia in mice, that cancer-causing viruses came out of the cabinet and into the mainstream of virus research. Ten years later William Jarrett, working at the University of Glasgow in Scotland, found another virus that spread easily from one cat to another, causing leukemia. Not only did viruses cause cancer, but some cancer-causing viruses were also contagious.

  In 1966, more than fifty years after he had examined the farmer’s dead chicken, Peyton Rous won the Nobel Prize in medicine for “the discovery of tumor-inducing viruses.” Rous received the prize, which cannot be awarded posthumously, when he was eighty-six years old.

  TODAY WE KNOW THAT SOME OF THE VIRUSES THAT CAUSE CANCER belong to the family of retroviruses, the most famous of which is human immunodeficiency virus (HIV), the virus that causes AIDS. When John Enders handed a vial of measles vaccine to Maurice Hilleman, it was loaded with a retrovirus that caused leukemia in chickens. Although they didn’t know it, chicken leukemia virus had contaminated the eggs that the Enders team had used to make their vaccine.

  At the time Hilleman wanted to make his measles vaccine, chicken leukemia virus—similar to the one that had infected Peyton Rous’s chicken—infected about 20 percent of all chickens in the United States. The virus infected the liver, causing liver cancer; the kidneys, causing kidney cancer; ligaments, tendons, and skin, causing soft-tissue cancers; and cells of the immune system, causing leukemia and lymphoma. About 80 percent of chickens infected with chicken leukemia virus got leukemia. The virus was a tremendous headache for farmers, causing $200 million in lost revenue every year. Worse, in the early 1960s, researchers didn’t know whether viruses that caused cancer in chickens could cause cancer in people. But they did know that animal retroviruses like chicken leukemia virus were capable of causing human cells in a test tube to become cancerous. “I wasn’t going to license a vaccine with this virus in it,” said Hilleman. “That would be the most unethical thing.” Despite pressure from people such as Joe Smadel, director of the federal agency that licensed vaccines, to bring Enders’s vaccine to market quickly, Hilleman refused to ignore the remote possibility that chicken leukemia virus could cause cancer in people. “Here was a vaccine that had been grown in cell culture, still highly virulent, and grown in cells that were loaded with leukemia virus,” recalled Hilleman. “And I’d be damned if I was going to vaccinate all of these kids with [a virus causing] leukemia. I wouldn’t do it. The government wanted to move forward because kids were dying [of measles]. When I told Smadel that we weren’t going to bring out the [vaccine] with leukemia [virus] in it, he had a temper tantrum.”

  Although chicken leukemia virus was common, no one had found a way to detect it. And because contaminated eggs appeared perfectly normal, researchers couldn’t tell which eggs were infected and which weren’t. Hilleman was stuck. Fortunately, in 1961 a virologist at the University of California at Berkeley, Harry Rubin, found a way to detect chicken leukemia virus in the laboratory. “The Rubin test changed everything,” recalled Hilleman. With Rubin’s test now in hand, Hilleman could use eggs and chick embryos that didn’t contain chicken leukemia virus to make his vaccine. First, Hilleman tried to breed his own flock of leukemia-virus–free chickens. But Merck was a company better suited to making drugs than to breeding chickens. So Hilleman turned to his friend Wendell Stanley for help. Stanley, who had won the Nobel Prize in medicine in 1946 for his work determining the structure of virus particles, directed Hilleman to a small farm in the Niles section of Fremont, California, Kimber Farms, where researchers had successfully bred a flock of leukemia-virus–free chickens. Hilleman found this hard to believe—he knew how much trouble he was having breeding them at Merck—but he was willing to give it a shot. So he got on a plane and flew to San Francisco. Then he drove forty miles to Fremont.

  NILES WAS SMALL, CENTERED ON AN OLD FLOUR MILL, A SOUTHERN Pacific Railroad switching yard, some fruit packing plants, and a company that excavated sand and gravel.

  Kimber Farms, part of the poultry-genetics mania that began in the early 1900s, was founded in the early 1930s by John Kimber, whose father was an Episcopal minister and mother a professional musician. Kimber was enormously successful, proving that the quality and size of an egg, the thickness of the shell, and the number of eggs produced could all be controlled by scientific breeding. He developed disease-free eggs, disease-resistant chickens, and hens that could lay two hundred and fifty eggs per year—accomplishments communicated to local farmers through his newsletter, Kimberchik News. But the notion of genetically breeding animals for food didn’t sit well with critics, who saw Kimber’s breeding operation as heartless and cruel. “Efficient, white-gowned workers in the antiseptic laboratories of Kimber Farms had little time for sentiment,” recalled Page Smith and Charles Daniel, authors of The Chicken Book. “To them the baby chickens, half of whom were killed at birth and incinerated or fed to the hogs, hatched by the millions in their enormous incubators, [were] seen primarily as items on an assembly line. The fact that they were alive was, it seems fair to suggest, incidental.”

  To make chickens and eggs free of leukemia virus, Kimber scientists took eggs from hens that weren’t infected with the virus, dipped them in organic iodine, and carefully put them into a sterile incubator. Male and female chickens born from these eggs made more chickens. Within a single generation, researchers at Kimber had bred chickens that were free of chicken leukemia virus. But it wasn’t easy. The chickens were housed two hundred feet upwind from the nearest poultry house and screened to prevent contact with flies and rodents. Furthermore, caretakers had to put on protective clothing and shoes and step in a foot-pan containing disinfectant before entering the building. At the time, Hilleman didn’t have the facilities or expertise at Merck to duplicate these procedures.

  When Hilleman arrived at Kimber Farms, he walked into the main office and asked to speak to the principal investigator, Walter Hughes. He asked Hughes if he could buy some of his leukemia-free chickens. “That’s our research flock,” said Hughes. “I can’t sell you those chickens.” Hilleman considered his next move. “Do you have a boss?” he asked. Hughes escorted Hilleman into the office of the director of poultry research, W. F. Lamoreux. The result was the same. Lamoreux didn’t want to sell his chickens. Hilleman tried harder: “One year from now there are going to be a lot of dead kids from measles, and you can do something to stop it.” Lamereux wasn’t moved. “We’re not selling our chickens,” he said. As Hilleman was leaving the office, he stopped, turned around, and tried one more time. Recognizing a familiar accent, he asked Lamoreux where he was from. “Helena,” said Lamoreux. “Miles City,” replied Hilleman, extending his hand. “Take them all,” said Lamoreux, smiling broadly. “One buck apiece.”

  The first measles vaccine required a virologist and a chicken breeder. If both hadn’t been born and raised in Montana, the road to a lifesaving vaccine might have been much longer.

  HILLEMAN LATER SET UP HIS OWN FLOCK OF LEUKEMIA-VIRUS–FREE chickens on the
Merck grounds, and between 1963 and 1968 he made millions of doses of Enders’s measles vaccine. The vaccine worked. Despite the burden of its having to be given with gamma globulin, it decreased the incidence of measles in the United States. But Hilleman wasn’t the only researcher, and Merck wasn’t the only company to make measles vaccine. Two other pharmaceutical companies introduced their own vaccines. One, a vaccine made in dog kidneys by a veterinary vaccine maker, was on the market for only three weeks. “That vaccine was more dangerous than measles,” recalled Hilleman. The other vaccine, made by killing natural measles virus with formaldehyde, was given to about a million American children before researchers found that immunity was dangerously short lived. Public health officials withdrew the killed measles vaccine after it had been sold for only four years.

  For his work on the measles vaccine, Maurice Hilleman was interviewed in 1963 by Charles Collingwood of CBS. The segment was titled “The Taming of a Virus.”

  Despite the success of Hilleman’s measles vaccine, the need to give it with gamma globulin made it cumbersome to use. To solve the problem, Hilleman took Enders’s measles vaccine and passed it forty more times through chick embryo cells. He called this new strain the Moraten strain, for Mor eAttenuated En ders. Merck first distributed the Moraten strain in 1968. Since then, it has been the only measles vaccine used in the United States. Between 1968 and 2006, hundreds of millions of doses have been given. As a result, the number of people infected every year with measles in the United States has decreased from four million to fewer than fifty. Worldwide, the number of people killed by measles every year has decreased from eight million to about five hundred thousand. Measles vaccines save more than seven million lives a year. And the descendants of Kimber Farms’s original flock of chickens, still maintained on the grounds of Merck, are used to make vaccines today.