The Nobel Prize in Physiology or Medicine 2020 has been awarded jointly to
- Harvey J. Alter, National Institutes of Health, Bethesda, MD, USA,
- Michael Houghton, University of Alberta, Edmonton, Canada,
- Charles M. Rice, Rockefeller University, New York, NY, USA
“for the discovery of Hepatitis C virus”.
Hepatitis, or liver inflammation, is a major global health problem that causes cirrhosis and liver cancer. Hepatitis A is transmitted by polluted water or food. Hepatitis B and C are spread by exposure to infectious blood or body fluids.
Research
The Laureates have made seminal discoveries that led to the identification of the Hepatitis C virus. Prior to their work, the discoveries of the Hepatitis A and B viruses had been critical steps forward, but the majority of blood-borne hepatitis cases remained unexplained. The discovery of Hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and enabled the development of blood tests and new medicines that have saved millions of lives.
Harvey J. Alter was studying the occurrence of hepatitis in patients who had received blood transfusions. Despite tests for Hepatitis A and B, a large number of cases remained. Alter and his colleagues showed that blood from these hepatitis patients could transmit the disease to chimpanzees and that the unknown infectious agent had the characteristics of a virus. Alter’s investigations had defined a new, distinct form of chronic viral hepatitis.
The identification of this virus was a high priority, but the virus was not isolated for over a decade. In 1989, Michael Houghton isolated the genetic sequence of the virus. Houghton and his colleagues created a collection of DNA fragments from the blood of an infected chimpanzee. The team predicted that some fragments would be derived from the unknown virus. They used antibodies from hepatitis patients to identify cloned viral DNA fragments encoding viral proteins. One positive clone was found. It was shown to be derived from a novel RNA virus belonging to the Flavivirus family and named Hepatitis C virus.
One question remained: Can the virus alone cause hepatitis? To answer this, the scientists investigated if the cloned virus was able to replicate and cause disease. Charles M. Rice, along with other groups working with RNA viruses, noted a previously uncharacterized region in the end of the Hepatitis C virus genome that could be important for virus replication, as well as genetic variations that might hinder virus replication. Rice generated an RNA variant of the Hepatitis C virus that included the newly defined region of the viral genome and none of the inactivating genetic variations. When this RNA was injected into the liver of chimpanzees, virus was detected in the blood and pathological changes resembling those seen in humans with the chronic disease were observed. This was the final proof that Hepatitis C virus alone could cause the unexplained cases of transfusion-mediated hepatitis.
Laureates
Harvey James Alter, born in New York, USA, on September 12, 1935, earned a Bachelor of Arts degree from the University of Rochester, NY, USA, in 1956, and an M.D. in medicine in 1960. After working as a resident at Strong Memorial Hospital in Rochester, he joined the National Institutes of Health (NIH) in Bethesda, MD, USA, as a research assistant in 1961. From 1964 to 1966, he completed his training as a transfusion physician (Pathology-Subspecialty Blood Banking) at Georgetown University Hospital in Washington, D.C., USA. In both institutions, he went through numerous career stages and worked most recently as research director of the blood bank at the NIH Clinical Center in Bethesda and as a professor of internal medicine at Georgetown University.
Among other awards, Harvey J. Alter received the Karl Landsteiner Memorial Award in 1992, the Albert Lasker Award for Clinical Medical Research in 2000, the Prix International de l’INSERM in 2004, and the Canada Gairdner International Award in 2013. He is a member of the National Academy of Sciences and is a fellow of the American College of Physicians/American Society Internal Medicine.
Michael Houghton, born in the UK in the 1950s, studied biological sciences at the University of East Anglia, UK, and gained his Ph.D. in biochemistry from King’s College London, UK, in 1977. He worked first at G. D. Searle & Company, then at Chiron Corporation, Emeryville, CA, USA. Here, together with colleagues Qui-Lim Choo, George Kuo, and Daniel W. Bradley from the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA, he first discovered Hepatitis C. Since 2010, he is a Professor at the University of Alberta. Currently, he is a Canada Excellence Research Chair in Virology and the Li Ka Shing Professor of Virology and Director of the Li Ka Shing Applied Virology Institute both at the University of Alberta.
Among other awards, Michael Houghton received the Robert Koch Prize in 1993, the William Beaumont Prize in 1994, the Hans Popper Award in 1999, and the Hepdart Lifetime Achievement Award in 2009. In 2013, he became the first person to decline the $100,000 Gairdner Foundation International Award stating: “I felt that it would be unfair of me to accept this award without the inclusion of two colleagues, Dr. Qui-Lim Choo and Dr. George Kuo” [1].
Charles M. Rice, born in Sacramento, CA, USA, on August 25, 1952, studied zoology at the University of California, Davis, CA, USA, and received his Ph.D. in biochemistry from the California Institute of Technology (Caltech), Pasadena, CA, USA, in 1981. After postdoctoral work at Caltech, he moved to the Washington University School of Medicine, St Louis, USA, as an assistant professor in 1986. He became Maurice R. and Corinne P. Greenberg Professor at Rockefeller University in 2001. He is also an adjunct professor at the Washington University School of Medicine and Cornell University.
Among other awards, Charles M. Rice received the M.W. Beijerinck Virology Prize in 2007, the Robert Koch Prize in 2015, the Artois-Baillet Latour Health Prize in 2016, and the Lasker Award in 2016. Among other commitments, he was the editor of the Journal of Experimental Medicine from 2003 to 2007, Journal of Virology from 2003 to 2008, and PLoS Pathogens from 2005 on.
Due to the coronavirus pandemic, the award ceremony this year will be held via telephone conference on December 10, 2020. The banquet, which usually takes place in Stockholm, Sweden, in December, has been moved to 2021.
References
- [1] World-renowned virologist named recipient of Gairdner Award, Michael Houghton named recipient of major international award in recognition of groundbreaking research on hepatitis C, University of Alberta News Staff – 20 March 2013. (accessed October 5, 2020)
Selected Publications by Harvey J. Alter
- Posttransfusion Hepatitis After Exclusion of Commercial and Hepatitis-B Antigen-Positive Donors,
H. J. Alter,
Ann. Intern. Med. 1972, 77, 691–699.
https://doi.org/10.7326/0003-4819-77-5-691 - Transfusion-Associated Hepatitis Not Due to Viral Hepatitis Type A or B,
S. M. Feinstone, A. Z. Kapikian, R. H. Purcell, H. J. Alter, P. V. Holland,
N. Engl. J. Med. 1975, 292, 767–770.
https://doi.org/10.1056/NEJM197504102921502 - Clinical and serological analysis of transfusion-associated hepatitis,
H. J. Alter, P. V. Holland, A. G. Morrow, R. H. Purcell, S. M. Feinstone, Y. Moritsugu,
Lancet 1975, 2, 838–841.
https://doi.org/10.1016/s0140-6736(75)90234-2 - Transmissible agent in non-A, non-B hepatitis,
H. J. Alter, R. H. Purcell, P. V. Holland, H. Popper,
Lancet 1978, 1, 459–463.
https://doi.org/10.1016/s0140-6736(78)90131-9
Selected Publications by Harvey J. Alter and Michael Houghton
- An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis,
G. Kuo, Q.-L. Choo, H. J. Alter, G. L. Gitnick, A. G. Redeker, R. H. Purcell, T. Miyamura, J. L. Dienstag, M. J. Alter, C. E. Stevens, G. E. Tegtmeier, F. Bonino, M. Colombo, W.-S. Lee, C. Kuo, K. Berger, J. R. Schuster, L. R. Overby, D. W. Bradley, M. Houghton
Science 1989, 244, 362–364.
https://doi.org/10.1126/science.2496467
Selected Publications by Michael Houghton
- Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome,
Q. Choo, G Kuo, A. Weiner, L. Overby, D. Bradley, M Houghton,
Science 1989, 244, 359–362.
https://doi.org/10.1126/science.2523562
Selected Publications by Charles M. Rice
- Transmission of Hepatitis C by Intrahepatic Inoculation with Transcribed RNA,
A. A. Kolykhalov,
Science 1997, 277, 570–574.
https://doi.org/10.1126/science.277.5325.570
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