Maurice R. Hilleman, the vaccine developer who may have saved more lives than any other scientist of the 20th century, died from cancer Sunday at Chestnut Hill Hospital in Philadelphia. He was 85.
His team at Merck & Co. developed eight of the 14 vaccines that are routinely given to young children in this country. Those vaccines effectively banished many of the most disabling and deadly childhood diseases in the United States and the rest of the world.
Hilleman was also the first to identify how the influenza virus mutates, and he virtually single-handedly spearheaded creation of the vaccine that prevented the Asian flu outbreak of 1957 from becoming a repeat of the 1918 Spanish flu pandemic, which killed 20 million people worldwide.
He played key roles in the discovery of the cold-producing adeno- viruses, the hepatitis viruses and the cancer-causing virus SV-40, among others. He was also the first to produce a vaccine against a virally induced cancer.
"Hilleman is one of the true giants of science, medicine and public health in the 20th century," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
"One can say without hyperbole that Maurice has changed the world," he added.
Hilleman's name "will be joined forever" with those of people like Louis Pasteur and Robert Koch "in the story of man's striving against pathogens," said Dr. Robert C. Gallo, director of the Institute of Human Virology at the University of Maryland.
In later life, Hilleman was an advisor to the World Health Organization, the U.S. National Vaccine Program and other groups, traveling throughout the world to promote vaccination.
He never won a Nobel Prize, because those awards are designed to honor basic research, not practical applications. But Hilleman received many other awards, including the 1988 National Medal of Science, the nation's highest honor, which was presented by President Reagan.
"If I had to name a person who has done more for the benefit of human health, with less recognition than anyone else, it would be Maurice Hilleman," Gallo said six years ago. "Maurice should be recognized as the most successful vaccinologist in history."
That was a long distance to travel for a boy born on a high-plains farm near Miles City in eastern Montana. His mother and twin sister died in the birth process Aug. 30, 1919.
Maurice and his seven older siblings were raised by relatives on a farm not far from the Little Bighorn battlefield 100 miles southwest of his birthplace. They tended cattle and chickens, raised vegetables and made brooms that they sold in town.
The future scientist took a special interest in the chickens, caring for them, learning about them, even figuring out how to hypnotize roosters. That experience proved invaluable in later years, because many of his creations were produced in chicken eggs.
"Coming from a farm," he once said, "I always had a good friend called the chicken."
When he graduated from Custer County High School in 1937, there was no money for college, and Hilleman took a job at the local J.C. Penney store, intending to make a career with the company. But when his oldest brother came home from seminary that summer, he demanded that Maurice go to college.
The future vaccine developer got a scholarship to what is now Montana State University in Bozeman and then a fellowship to the University of Chicago for graduate study. His prize-winning thesis reported the first way to identify different strains of chlamydia, one of the microorganisms that cause venereal disease.
He achieved this feat, which many at the time believed impossible, by using antibodies produced when he injected chlamydia from parrots into chickens.
His first job was at E.R. Squibb & Sons, where he developed his first vaccine, which protected American troops from the Japanese B encephalitis virus while fighting in the Pacific during World War II.
In 1948, Hilleman went to Walter Reed Army Medical Center in Washington, D.C., where he began research on the influenza virus. He showed that the virus underwent two major forms of mutation, called drift and shift.
Drift is the slow, subtle change in surface characteristics that necessitates the production of a new vaccine each year. Shift is a major change in those characteristics that produces, in effect, an entirely new virus to which the population has no resistance. A shift triggered the 1918 pandemic.
Hilleman was reading the New York Times in his basement office at Walter Reed on April 17, 1957, when he saw an article about a flu outbreak in Hong Kong that had already afflicted 250,000 people. He was struck by a reference to "glassy-eyed children," which suggested high fevers.
In his usual earthy manner, he recalled later, "I said, 'Son of a bitch. This is pandemic flu.' "
He ordered U.S. Army researchers to collect throat swabs from some of the Hong Kong victims, and his team worked nine 14-hour days to isolate the virus, which he showed to be a new strain of influenza. Blood samples from the U.S. public showed no resistance to the virus, indicating that it had the potential to cause deaths on a large scale.
Hilleman notified public health authorities about the danger and provided samples of the virus to vaccine manufacturers.
He also insisted that chicken breeders spare the lives of roosters that otherwise would have been slaughtered, allowing them to fertilize the 40 million eggs that were used to prepare the new vaccine.
As a result of his efforts, the U.S. death toll was held to 69,000, only about double the normal toll during flu season.
Later that year, Hilleman joined Merck after the company kept increasing its salary offer until it was high enough to enable him to send his daughter Jeryl Lynn to private school.
His first project for Merck was one of his few failures. His team developed one of the first polio vaccines, but Hilleman discovered that the monkey cells used to grow the weakened polio virus for the vaccine also contained another virus, SV-40, that produced cancer in animals.
Although Hilleman showed that SV-40 did not harm people, Merck withdrew the vaccine.
The company's faith in him was soon rewarded, however, when he developed the first practical measles vaccine, which used an attenuated virus grown in chicken embryos. But Hilleman soon found that the embryos also contained a chicken virus that caused leukemia.
To make his vaccine, he turned to Kimber Farms, a Northern California poultry operation that was breeding leukemia-free chickens. The company didn't want to part with its prized specimens, but Hilleman discovered that Kimber's research director was a fellow Montanan. He got his birds.
"Montana blood runs very thick," he said later, "and chicken blood runs even thicker with me."
Epidemiologists estimate that the measles vaccine has saved 1 million lives annually over the 40 years since its development, and measles has been eradicated from the globe.
Hilleman's work on the mumps virus was triggered when he came home one evening and found that Jeryl Lynn, then 5, was in the early stages of the illness. He rushed to his lab to collect swabs and culture media, swabbed her mouth, and placed the swab in beef broth in the freezer to await his return from a business trip the next morning.
When he got home, he isolated the Jeryl Lynn strain of the mumps virus and produced the first vaccine against it.
Hilleman overcame immunological problems to combine several vaccines into single shots, such as the well-known MMR vaccine for measles, mumps and rubella. He also developed a vaccine for hepatitis B, which is one of the primary causes of liver cancer -- the first vaccine to protect against cancer.
"He really had the Midas touch, being able to take an idea, change a virus or microbe or attenuate it, and develop the methodology to make that idea into a product," said Dr. Adel F. Mahmoud, president of Merck Vaccines. "Nobody else has really managed the complete cycle of discovery, development and deployment of vaccines that affect the lives of millions of people."
In 1971, Hilleman produced a commercial vaccine for Marek's disease, a viral infection that routinely devastated the chicken industry by producing lymphoma in the birds, causing millions of dollars in losses each year. His vaccine, which was made using a related virus found in turkeys, saved poultry farmers huge amounts.
"I figured I owed it to the chickens," he said.
Hilleman recently reflected on his work when an endowed chair in his name was established at Children's Hospital of Philadelphia:
"Looking back on one's lifetime, you say, 'Gee, what have I done? Have I done enough for the world to justify having been here?' That's a big worry -- to people from Montana, at least.
"And I would say I'm kind of pleased about all this," he added. "I'm not smug about it, but I'm pleased.... I devoted seven days a week. And I would do it all over again, because there's great joy in being useful, and that's the satisfaction you get out of it. Other than that, it's the quest of science and winning a battle over these
Hilleman is survived by his wife, Lorraine; daughters Kirsten of New York City and Jeryl Lynn of Palo Alto; and five grandchildren.