Maurice Ralph Hilleman

Over six decades, American microbiologist Maurice Ralph Hilleman (1919–2005) unlocked the secrets of immunology and went on to develop about 40 vaccines. Among his credits are vaccines for measles, mumps, hepatitis A and B, chickenpox, meningitis, and pneumonia, all of which are routinely recommended for youngsters. Each year, Hilleman's vaccines save millions of people worldwide from death, deafness, blindness, and other permanent disabilities.

Raised on Western Frontier

Hilleman was born August 30, 1919, in Miles City, Montana, a rough-and-tumble frontier town bursting with cowboys, gamblers and barkeepers. He was the eighth child born to Robert and Edith (Matson) Hilleman. His mother, however, did not survive his birth; neither did a twin sister. Robert Hilleman, overwhelmed by the prospect of raising such a large family alone, sent the children off to live on a nearby relative's farm.

The hardships of growing up on a farm on the brittle outskirts of the rugged frontier marked Hilleman for life, yet shaped him into a gritty, stop-at-nothing scientist. The farm also served as his first laboratory, providing Hilleman with early lessons on biology and disease, life and death. He raised chickens, tended cattle, harvested hay and grew vegetables. Hilleman also helped with the family's side business—manufacturing horseradish and brooms, which were sold in town. "Life on a farm in an economically underdeveloped area of the western frontier during the Great Depression was not easy," Hilleman recalled in an article he wrote for Immunological Reviews. "But, it was of immense value in providing hands-on experience in the worlds of biology and mechanics, and in creating sobriety and an intensive work ethic that has proved highly useful."

In addition, Hilleman turned to textbooks to learn more about science. Around eighth grade, Hilleman discovered Charles Darwin's book On the Origin of Species, in which Darwin described his theory of evolution by natural selection. Hilleman read the book one Sunday at the family's ultraconservative Lutheran church and the minister, who believed in creationism, admonished him. The minister tried to confiscate the book but Hilleman told him it was public property because it belonged to the library and he would notify authorities if the minister tried to take it. Hilleman also listened to a radio station from distant Bismarck, North Dakota, which broadcast a Sunday afternoon show called Meet the Scientists, which originated at the University of Chicago.

Escaped to College

In 1937, Hilleman graduated from Custer County High School and took a retail job at the local J.C. Penney. For a poor farm boy, college seemed out of the question. A short time later, however, an elder brother returned home on break from ministerial school and told the family they needed to find a way to send the brainy Hilleman to college. Luckily, Hilleman was offered a scholarship to Montana State University. He promptly quit his job and moved to Bozeman, graduating with a bachelor's degree in 1941. Hilleman went on to study at the University of Chicago, receiving a doctorate in microbiology and virology in 1944 after writing an award-winning dissertation on the venereal disease chlamydia.

Hilleman then took a job in New Brunswick, New Jersey, with the pharmaceutical company E.R. Squibb & Sons. Though he could have stayed in academics, Hilleman chose industry, believing scientists to serve society. "Science has to produce something useful," Hilleman once told the Philadelphia Inquirer. "That's the payback to society for support of the enterprise." Within a year of joining the company, Hilleman developed a vaccine for Japanese encephalitis, which was infecting and killing U.S. soldiers stationed in the Pacific during World War II.

In 1948, Hilleman began working for the Walter Reed Army Institute of Research in Washington, D.C. There, he conducted research on respiratory viruses. Hilleman entered the field at an exciting time—the capabilities of the electron microscope had recently improved, enabling biologists to directly study small organisms, such as viruses, for the first time. Hilleman discovered that the flu virus underwent some small mutations every year. The changes, called a "drift," were so small that people who had been infected with a previous version of the strain were still naturally immune to the new virus. But Hilleman also discovered that every so often, the flu virus underwent a major genetic change, rendering it so different from previous ones that people had no immunity. This was labeled a "shift."

Prepared U.S. for Flu Pandemic

In April of 1957, Hilleman read in the New York Times about a flu outbreak in Hong Kong that had affected 250,000 people. At once he realized the flu virus had probably undergone that major shift. Hilleman believed a similar shift had occurred in 1918, launching the Spanish flu pandemic that killed 20 million people worldwide, including roughly 600,000 U.S. citizens. Looking back at the 1918 death-rate data, Hilleman predicted the new virus would cause more than a million U.S. deaths once it hit the continent.

To check his theory, Hilleman ordered the military to get throat swabs from the Hong Kong victims. After receiving the samples, Hilleman and his colleagues worked 14-hour days for more than a week to isolate what Hilleman believed was a new strain of flu. Next, the team analyzed blood samples taken from people worldwide and found that no one had antibodies to this form of the flu. This proved Hilleman's hypothesis—it was a new strain, which meant it could kill millions. Hilleman knew the flu would eventually spread to the United States so he sent vaccine manufacturers samples of the new strain. The labs made it ready for use by growing it in fertilized chicken eggs, thus weakening it and making it ready for human inoculation. One company, Merck & Company, went through 150,000 eggs per day.

When the flu did hit the United States the following fall, 40 million doses of the vaccine were ready and distributed, saving probably hundreds of thousands of lives. The U.S. death toll still hit 69,000. Fifty years later, public-health agencies creating the annual flu vaccine still use Hilleman's discoveries concerning virus mutations. While preparing for the pandemic, Hilleman left Walter Reed and joined Merck on New Year's Eve in 1957 to run its viral research program. Merck had offices and labs in West Point, Pennsylvania, and Whitehouse Station, New Jersey.

Developed Mumps, Other Vaccines

In the 1960s, Hilleman developed the mumps vaccine, thanks in large part to his daughter's infection. In 1963, five-year-old Jeryl Lynn woke her father in the middle of the night, whining about a sore throat. Seeing her swollen glands, Hilleman realized it was the mumps, a disease caused by a virus that grows in the salivary glands. At the time mumps was common, infecting about 200,000 U.S. children a year. Of those, about half developed a mild form of meningitis, an infection of the brain. Sometimes, the meningitis caused permanent deafness or death.

Hilleman saw opportunity in his daughter's suffering. Though it was the middle of the night, he drove to his Merck lab to pick up some swabs. He then swabbed his daughter's throat and preserved the virus in some beef broth in the freezer. Hilleman had been eager to collect the virus because he was leaving on a trip to South America the following day and knew the virus would be gone by the time he returned.

Later, Hilleman isolated the mumps virus from the swabs. Next, he took chicken embryo cells and grew the virus in it to produce what is called an attenuated form of the virus. An attenuated virus is weak enough that it will not cause the disease, but strong enough to force the body into using its natural defenses to trigger immunity. Making the mumps vaccine took several years; it was not available until 1967. Hilleman's other daughter, Kirsten, participated in the trials.

Hilleman also developed vaccines for measles, rubella, chickenpox, bacterial meningitis, flu, and hepatitis B. In developed countries, his vaccines have virtually wiped out many of these once-common childhood maladies. Of the fourteen vaccinations routinely recommended for youngsters, Hilleman developed eight. "Over his career he certainly contributed more vaccines than anyone, and probably more than anyone will ever contribute," Merck colleague Roy Vagelos told the Lancet's Ivan Oransky. "I don't know how many people will have been spared a disease because of the vaccines he developed, but it's a lot."

Another breakthrough came in 1971 when Merck released Hilleman's new MMR vaccine, a one-shot injection that protects children from measles, mumps, and rubella. Another crowning achievement was Hilleman's development of a vaccine for hepatitis B, a debilitating blood-borne virus. Because one complication of hepatitis B is hepatoma, a liver cancer, his vaccine was hailed as the first to prevent a human cancer. It hit the market in 1981.

Besides developing vaccines to eradicate human diseases, Hilleman also developed vaccines for the poultry industry. In 1971, Hilleman introduced a vaccine for Marek's disease, a virus that causes lymphoma in chickens, at one time causing millions of dollars in losses each year. In addition, Hilleman is credited with co-discovering numerous viruses, including the hepatitis A virus and the rhinoviruses that cause colds.

Left Mark on Medical World

Though Hilleman retired from Merck in 1984, he continued office hours and consulted with national and international public health organizations until his death. He continued working, believing vaccines for malaria, tuberculosis and AIDS were necessary.

According to colleagues, Hilleman was an enigma of sorts. The six-foot-one-inch scientist was known to punctuate his sentences with country-boy obscenities. Hilleman also made peers nervous because, unlike many scientists, he insisted in watching over all stages of a project, managing basic research, clinical research, and even development and production. After vaccine trials, Hilleman frequently popped into the manufacturing facility to ensure quality control. "I ran into conflict with just about everybody," Hilleman told Nature Journal's Alan Dove. Asked if anyone else could have had as successful a career, he said no. "It takes somebody who's a bastard," Hilleman conceded. "I don't think there are basically any people at all left who would have the dedication."

Hilleman died of cancer at a Philadelphia hospital on April 11, 2005. His first wife, Thelma Mason, preceded him in death in 1962. He was survived by two daughters, as well as his second wife, Lorraine Witmer, whom he married in 1963. Though Hilleman remained loyal to his work, his second wife said he always made it home for family dinner each night, even if it meant driving back to the lab later on.

Because of Hilleman's achievements, human life expectancy has grown by leaps and bounds. Speaking to the Philadelphia Inquirer's Susan FitzGerald shortly after Hilleman's death, Paul A. Offit, chief of infectious diseases at Children's Hospital of Philadelphia, said: "It's safe to say his vaccines save in the order of eight million lives a year. I think it can be said without hyperbole that he was a scientist who saved more lives than any other modern scientist."

Periodicals

Economist, April 23, 2005.

Immunological Reviews, August 1999.

Independent (London), April 20, 2005.

New York Times, April 12, 2005.

Philadelphia Inquirer, April 12, 2005.

Online

"The Man Who Saved Your Life," New Jersey Association for Biomedical Research, http://www.njabr.org/njsor/science_superstars/maurice_hilleman/printer/ (December 31, 2005).

"Maurice Hilleman," Nature Medicine, http://www.nature.com/nm/journal/v11/n4s/full/nm1223.html (December 31, 2005).

"Maurice R. Hilleman," The Lancet, http://www.thelancet.com (December 31, 2005).