The Rockefeller University » Hospital Centennial

Breaking the Dogma and Gaining a Novel Treatment: Discovering Double-Stranded RNA in a Virus Leads to Interferon Therapy

Tamm, Igor

At Rockefeller, in the early 1940s, Oswald Avery, Colin MacLeod, and Maclyn McCarty discovered that the genetic material in living cells is DNA, a double-stranded molecule whose double helical structure was described in 1953 by James Watson and Francis Crick. In the following decade, scientists began to appreciate that viruses differ from cells in the nature of their genes. Some viruses, like cells, contain DNA but others contain RNA. In the early 1960s Peter Gomatos (1929- ) and Igor Tamm (1922-1995) were studying reoviruses, about which little was known other than that they were found in the respiratory tracts of humans and animals. In 1963, they made the important discovery that the genetic material of reoviruses consists of double-stranded RNA. This was the first description of double-stranded RNA in any biological system, and Gomatos and Tamm soon found double-stranded RNA in another virus, the wound tumor virus of plants. They conducted extensive studies of reovirus replication, and in collaboration with Robert Langridge determined the three-dimensional structure of the RNA by x-ray crystallography. Subsequently many other viruses causing diseases in humans, animals, insects, and plants were found by various investigators to have double-stranded RNA as their genetic material.

Double-stranded RNA was later shown to have important roles beyond its role as the genetic material of viruses. Double-stranded RNA inside virus-infected cells, or added to cells as a purified substance, induces the cell to make interferon, which inhibits virus multiplication. Interferons have been developed by other researchers to treat diseases including hepatitis B and C, and multiple sclerosis. Double-stranded RNA has also been shown to be involved in the regulation of cellular processes, and small doubled-stranded RNAs (iRNAs) have been used as inhibitors of such processes. These are being used to study gene regulation and are also being extensively investigated as possible therapeutic agents for a variety of diseases.

Peter Gomatos received the BS from the Massachusetts Institute of Technology (1950) and the MD from The Johns Hopkins University (1954). After an internship at Johns Hopkins Hospital (1954-1955), he served as a medical officer in the U.S. Navy (1955-1957) and a resident in medicine at the Massachusetts General Hospital (1957-1959). He received a PhD from the Rockefeller University in 1963 and was a guest investigator there until 1965, when he joined the Sloan-Kettering Institute as head of the Laboratory of Animal Virology. He remained at Sloan-Kettering until 1982. He served on active duty in the U.S. Army until 1992 in varying capacities including service at the Walter Reed Army Institute of Research and as Associate Director of the Division of AIDS and Head of the Treatment Research Program, at the National Institutes of Allergy and Infectious Diseases, NIH. He subsequently has served as a consultant to a variety of agencies including the West Palm Beach Health Department, the Naval Medical Research Unit-3 in Cairo, Egypt, and the Veterans Administration.

Reovirus RNA. From Science 1963, 141; 694-698

Igor Tamm attended the State English College in Tallinn, Estonia, from 1939 to 1944 and the Tartu University Medical Faculty in Tartu, Estonia, from 1942 to 1943. He escaped the German occupation of Estonia, entered medical school at the Karolinska Institutet in Stockholm, and in 1945 transferred to Yale Medical School, where he received the MD in 1947. After further training in internal medicine at Yale-New Haven Hospital, Tamm joined the Rockefeller Hospital's Laboratory of Virology in 1949. In 1959 he succeeded Horsfall as head of the lab, and he became professor and senior physician in 1964. Tamm was named Abby Rockefeller Mauzé Professor in 1986, and professor emeritus in 1992. He was the first American to receive the Alfred Benzon Prize from Denmark, and was awarded the Sarah L. Poiley Memorial Award from the New York Academy of Sciences. Tamm was elected to the U.S. National Academy of Sciences (1975). With Frank Horsfall, Tamm edited the authoritative text, Viral and Rickettsial Infections in Man.

Selected Publications

Gomatos PJ and Tamm I. The secondary structure of reovirus RNA. Proc Natl Acad Sci USA, 1963, 49:707-714
http://www.pnas.org/content/49/5/707.full.pdf+html

Langridge R and Gomatos PJ. The structure of RNA. Science, 1963, 141:694-698. Gomatos PJ and Tamm I. Animal and plant viruses with double-helical RNA. Proc Natl Acad Sci USA, 1963, 50:878-885
http://www.pnas.org/content/50/5/878.full.pdf+html

Hospital Centennial

Breaking the Dogma and Gaining a Novel Treatment: Discovering Double-Stranded RNA in a Virus Leads to Interferon Therapy

Selected Publications

Further Reading