Weller, Thomas (1915- )

American physician

Thomas Weller was corecipient, with John F. Enders and Frederick Robbins, of the Nobel Prize in physiology or medicine in 1954. This award was given for the trio's successful growth of the poliomyelitis (polio) virus in a non-neural tissue culture . This development was significant in the fight against the crippling disease polio, and eventually led to the development, by Jonas Salk in 1953, of a successful vaccination against the virus. It also revolutionized viral work in the laboratory and aided the recognition of many new types of viruses . Weller also distinguished himself with his studies of human parasites and the viruses that cause rubella and chickenpox.

Thomas Huckle Weller was born June 15, 1915, in Ann Arbor, Michigan. His parents were Elsie A. (Huckle) and Dr. Carl V. Weller. He received his B.S. in 1936 and M.S. in 1937, both from the University of Michigan, where his father was chair of the pathology department. He continued his studies at Harvard Medical School, where he met and roomed with his future Nobel corecipient Robbins. In 1938, Weller received a fellowship from the international health division of the Rockefeller Foundation, which allowed him to study public health in Tennessee and malaria in Florida, topics which first interested him during his undergraduate years.

Weller graduated from Harvard with magna cum laude honors in parasitology, receiving his M.D. in 1940. He also received a fellowship in tropical medicine and a teaching fellowship in bacteriology. He completed an internship in pathology and bacteriology (1941) at Children's Hospital in Boston. He then began a residency at Children's, with the intention of specializing in pediatrics, before enlisting in the U.S. Army during World War II.

Weller served in the Army Medical Corps from 1942 to 1945. He was initially given teaching assignments in tropical medicine, but he was soon made officer in charge of bacteriology and virology work in San Juan, Puerto Rico. His major research there related to pneumonia and the parasitic disease schistosomiasis, an infection that is centered in the intestine and damages tissue and the circulatory system. Before his military service ended, he moved to the Army Medical School in Washington D.C. Upon his discharge in 1945, Weller was married to Kathleen Fahey, with whom he had two sons and two daughters. Returning to Boston's Children's Hospital, he finished his residency and began a post-doctoral year working with Enders.

During 1948, Weller was working with the mumps virus, which Enders had been researching since the war. After one experiment, Weller had a few tubes of human embryonic tissue left over, so he and Enders decided to see what the virus poliomyelitis might do in them. A small amount of success prompted the duo, who had been joined in their research by Robbins, to try growing the virus in other biological mediums, including human foreskin and the intestinal cells of a mouse. The mouse intestine did not produce anything, but the trio finally had significant viral growth with human intestinal cells. This was the first time poliomyelitis had been grown in human or simian tissue other than nerve or brain. Using antibiotics to ward off unwanted bacterial invasion, the scientists were able to isolate the virus for study.

Once poliomyelitis was grown and isolated in tissue cultures it was possible to closely study the nature of the virus, which in turn made it possible for Salk to create a vaccine in 1953. Besides leading to an inhibitor against a debilitating disease, a major result of the trio's development was a decrease in the need for laboratory animals. As Weller was quoted saying in the Journal of Infectious Diseases, "In the instance of poliomyelitis, one culture tube of human or monkey cells became the equivalent of one monkey." In times prior, viruses had to be injected into living animals to monitor their potency. Now, with tissue culture growth, cell changes were apparent under the microscope , showing the action of the virus and eliminating the need for the animals. The techniques for growing cells in tissue cultures developed by Weller and his associates were not only applicable to the poliomyelitis virus, however. They were soon copied by many other labs and scientists and quickly led to the identification, control, and study of several previously unrecognized virus types. For their work, and the improvements in scientific research it made possible, Weller, Enders, and Robbins shared the 1954 Nobel Prize in physiology or medicine.

Concurrent with his work with Enders and Robbins, Weller was named assistant director of the research division of infectious diseases at Children's Hospital in 1949. He held this position until 1954. At the same time, he began teaching at Harvard in tropical medicine and tropical public health, moving from instructor to associate professor. In 1953, Weller and Robbins shared the Mead Johnson Prize for their contributions to pediatric research. Then, in 1954, Weller was named Richard Pearson Strong Professor of Tropical Public Health and chair of the public health department at Harvard. As a consequence, he moved his research facilities to the Harvard Medical School. Later, he was appointed director of the Center for Prevention of Infectious Diseases at the Harvard School of Public Health.

From the end of World War II until 1982, Weller also continued his research on two types of helminths, trichinella spiralis and schistosoma mansoni. Helminths are intestinal parasites, and these two cause, respectively, trichinosis, which can also severely affect the human musculature, and schistosomiasis. Weller was concerned with the parasites' basic biology and performed various diagnostic studies on them. His contributions to current understanding of these parasites are significant, advancing an understanding of the ailments they cause.

Weller spent a portion of the same period (1957 to 1973) establishing the basic available knowledge concerning cytomegalovirus (commonly known as CMV), which causes cell enlargement in various organs. Weller's most important finding in this area regarded congenital transmission of both CMV and rubella, a virus also known as German measles . A pregnant woman infected with either of these viruses may pass the infection on to her fetus. Weller showed that infected newborns excreted viral strains in their feces, providing another source for the spread of the diseases. His findings became significant when it was also learned that children born to infected mothers often risked birth defects.

In 1962, Weller, along with Franklin Neva, was able to grow and study German Measles in tissue cultures. These two also went on to grow and isolate the chickenpox virus. Subsequently, Weller was the first to show the common origin of the varicella virus, which causes chicken pox, and the herpes zoster virus, which causes shingles. In 1971, Weller was the first to prove the airborne transmission of pneumocystis carinii, a form of pneumonia that later appeared as a frequent side effect of the human immunodeficiency virus commonly known as HIV .

Weller was elected to the National Academy of Sciences in 1964. In addition, he served on advisory committees of the World Health Organization , the Pan American Health Organization, the Agency for International Development, and the National Institute of Allergy and Infectious Disease. He continued his position at Harvard until 1985, when he became professor emeritus. While at Harvard, he helped establish the Public Health Department's international reputation. In 1988, Weller gave the first John F. Enders Memorial Lecture to the Infectious Disease Society of America. In addition to his Nobel Prize, Weller was the recipient of many awards and honorary degrees during his career.

See also Laboratory techniques in immunology; Virology; Virus replication; Viruses and responses to viral infection

Robbins, Frederick Chapman

(b. 25 August 1916 in Auburn, Alabama; d. 4 August 2003 in Cleveland, Ohio), virologist, pediatrician, and Nobel Prize winner.

Robbins was the eldest of the three children of William Jacob Robbins, a professor of plant physiology, and Christine (Chapman) Robbins, also a botanist. When Robbins was two the family moved to Columbia, Missouri, where his father became the chair of the department of botany at the University of Missouri. When Robbins was twelve the family moved to Europe for two years, where Robbins attended the Sillig Institute in Vevey, Switzerland. When he returned to Columbia, Robbins entered David H. Hickman High School as a junior at the age of fourteen. A gifted athlete and a superb student, Robbins played football in high school and polo at the University of Missouri, which he entered in 1932 as a member of the Reserve Officers’ Training Corps. Robbins in 1936 received an AB and in 1938 a BS in premedical studies from Missouri and then transferred to Harvard Medical School, from which he received his MD in 1940. When Robbins began his training in pediatrics at Children’s Hospital Boston, affiliated with Harvard, students were required to spend one year in the laboratory before seeing patients. Although he had not intended to pursue a research career, Robbins’s year-long immersion in diagnostic bacteriology sparked an interest in the study of infection.

In 1942 Robbins interrupted his medical training to enter the U.S. Army. Because of his experience in bacteriology and virology, Robbins was assigned to the Fifteenth Medical General Laboratory as the chief of the virus and rickettsial disease section, a unit responsible for monitoring, studying, and controlling outbreaks of disease among troops and civilians. Robbins was sent from Washington, D.C., to North Africa and then to Naples, Italy, where he investigated outbreaks of infectious hepatitis and typhus and identified a rickettsial infection called Q fever as the cause of an outbreak of pneumonia. Robbins was awarded a Bronze Star for meritorious service and in 1946 left the army having achieved the rank of major. Robbins returned to Children’s Hospital and to pediatrics, first as an assistant resident and then becoming the chief resident.

Robbins returned to research in 1948. He received a National Research Council fellowship in virology and reported to the laboratory run by John F. Enders in the research division of infectious diseases at Children’s Hospital to work on culturing viruses. Also in 1948 Robbins met Alice Havermeyer Northrop, a research assistant, whose father, John H. Northrop, had been a Nobel laureate in chemistry. The couple married at her parents home in Princeton, New Jersey, on 19 June 1948 and had two children.

Working together, Robbins, Enders, and the research scientist Thomas H. Weller immediately began developing a strategy for growing viruses in tissue culture. Bits of tissue were placed in small flasks with a nutrient fluid. The flasks were incubated at body temperature, and every few days the nutrient fluid was removed and replaced. Changing the nutrient fluid regularly kept the tissue viable longer and made it possible to consistently and successfully grow viruses in substantial quantities.

Robbins and Weller did not expect much when Enders suggested that because they had some poliovirus stored in a freezer, they might try inoculating some of their tissue cultures with that virus. Other researches had attempted to culture the poliovirus but had failed. To their surprise, Robbins, Enders, and Weller found that using their technique they were able to grow the poliovirus in many kinds of tissue. Their ability to culture large quantities of pure poliovirus led to the development of polio vaccines by Jonas Salk and Albert Sabin.

In studying viruses in tissue culture, Robbins also observed and identified what Enders called the cytopathic effect: cells in cultures inoculated with viruses died more quickly than cells in noninfected, control cultures. The team found that cell death, which leads to a change in the acidity of a culture fluid, can be detected by use of an indicator dye in the culture medium. The ability to observe cell death in tissue culture provided a way of identifying and typing viruses quickly and easily without having to infect animals.

Toward the end of his fourth year working in Enders’s laboratory, Robbins began to consider offers from other researchers, including Salk, but accepted a position at Western Reserve University (later renamed Case Western Reserve University) in Cleveland. Robbins and his family moved to Ohio in May 1952, and Robbins became a professor of pediatrics at the university and the director of the department of pediatrics and contagious diseases at Cleveland City Hospital (renamed MetroHealth Medical Center).

In October 1954 Robbins, Enders, and Weller were informed that they had been awarded the Nobel Prize in Physiology or Medicine “for the discovery of the ability of poliomyelitis viruses to grow in cultures of various types of tissue.” The discovery revolutionized virus research and led to the development a usable vaccine for polio. Robbins was thirty-eight years old, the youngest member the team.

Robbins was much admired as a pediatrician, teacher, and researcher at Case Western Reserve University. He was described as modest but friendly and outgoing and tireless in his work. In 1966 Robbins was named the dean of the medical school, a position he held until 1980, when he resigned to become the president of the Institute of Medicine of the National Academy of Sciences. Robbins continued his affiliation with Case Western Reserve University for more than fifty years. He developed a program designed to enrich the lives of hospitalized children. Run by a nursery school teacher appointed by Robbins, the program influenced the practice of pediatric medicine in hospitals nationwide. In the mid-1980s, having become increasingly concerned about acquired immunodeficiency syndrome (AIDS), Robbins brought together scientists from Case Western and the National Institutes of Health and government officials in Africa to establish an AIDS and tuberculosis research program in Uganda. In 1990 Robbins helped to launch the Case Western Reserve University Center for Adolescent Health. He became the center’s director in 1992.

Robbins was an avid reader of books of all kinds and a member of the Rowfant Club, a forum for the critical study of books. Robbins and his family vacationed in Maine each summer, where they spent time hiking, sailing, and playing tennis. Robbins died of congestive heart failure on 4 August 2003 in a hospital in Cleveland. He was eighty-six. His remains were cremated, and in a private ceremony his family scattered his ashes in the garden of their summer home in Maine.

The laboratory research methods developed by Robbins and his colleagues have been used by scientists around the world to isolate and identify viruses. Robbins’s contributions to the practice of medicine and his and his colleagues’ discoveries have enabled scientists and physicians to improve the lives of millions of people.

Frederick C. Robbins and Thomas M. Daniel, eds., Polio (1997), contains an autobiographical essay by Robbins, “Reminiscences of a Virologist,” in which he describes some of the highlights of his career. Edward D Berkowitz, A History of the Institute of Medicine (1999), describes Robbins’s work at the Institute of Medicine. Istvan Hargittai, The Road to Stockholm (2002), describes Robbins and colleagues’ path to the Nobel Prize. Obituaries are in the New York Times and Cleveland Plain Dealer (both 5 Aug. 2003).

Bonnie LaFave