Nobel Prize Winners in Medicine Revealed
The Nobel Prize assembly in Sweden announced today the winners of the 2020 Nobel Prize in Physiology or Medicine. It was awarded jointly to Harvey J. Alter, Michael Houghton and Charles M. Rice for their contribution in discovering Hepatitis C Virus. The three scientists made huge discoveries that led to the identification of a novel virus, Hepatitis C virus. The discovery of Hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and opened the pathway to possible blood tests and new medicines that have saved millions of lives. Harvey J. Alter at the US National Institutes of Health studied the occurrence of hepatitis in patients who had received blood transfusions at the time Hepatitis B virus was discovered. Although blood tests for the newly-discovered Hepatitis B virus limited the number of cases of transfusion-related hepatitis, Alter and his team worryingly demonstrated that a large number of cases remained. Tests for Hepatitis A virus infection were then developed, and it was evident that Hepatitis A was not the reason behind these unexplained cases.
It was a major source of concern that a significant number of those receiving blood transfusions developed chronic hepatitis due to an unknown infectious agent. Alter and his colleagues showed that blood from these patients could transmit hepatitis to chimpanzees, the only susceptible host besides humans. Subsequent studies showed also that the unknown infectious agent had the characteristics of a virus. In this way, Alter’s methodical investigations had defined a new, distinct form of chronic viral hepatitis. The mysterious illness became known as “non-A, non-B” hepatitis. Then came the part of Michael Houghton, who was working for the pharmaceutical firm Chiron. He undertook the arduous work needed to isolate the genetic sequence of the virus. Houghton and his colleagues collected DNA fragments from nucleic acids found in the blood of an infected chimpanzee. The majority of these fragments came from the genome of the chimpanzee itself, while the researchers predicted that some would be derived from the unknown virus. The investigators used patient sera to identify cloned viral DNA fragments encoding viral proteins, assuming that antibodies against the virus would be present in blood taken from hepatitis patients. Following a comprehensive search, one positive clone was found and then further work showed that this clone was derived from a novel RNA virus belonging to the Flavivirus family and it was named Hepatitis C virus. The presence of antibodies in chronic hepatitis patients strongly implicated this virus as the missing agent.
Charles M. Rice, a researcher at Washington University in St. Louis, along with other groups working with RNA viruses, noted a previously uncharacterized region in the end of the Hepatitis C virus genome. Rice also observed genetic variations in isolated virus samples and hypothesized that some of them might hinder virus replication. Through genetic engineering, Rice generated an RNA variant of Hepatitis C virus that included the newly defined region of the viral genome and was devoid of the inactivating genetic variations. When this RNA was injected into the liver of chimpanzees, the virus was detected in the blood and pathological changes like those seen in human hepatitis patients were observed. This was the final evidence that Hepatitis C virus alone could be the cause of the unexplained cases of transfusion-mediated hepatitis.
Source: 1. Nobel Prize Organization. The Nobel Prize In Physiology Or Medicine 2020. https://www.nobelprize.org/prizes/medicine/2020/press-release/. Accessed 05 October 2020.