The 2020 Nobel Prize in Physiology or Medicine has been awarded to three scientists (Harvey Alter, Michael Houghton and Charles Rice) who have made a decisive contribution to the fight against hepatitis C, a major global health problem that causes cirrhosis and liver cancer in people around the world.
In the nineteen-seventies, Harvey Alter was working at the US NIH on the occurrence of hepatitis in patients who had received blood transfusions. At that time only hepatitis A and hepatitis B were known. In their early work, Alter and his colleagues showed that a large number of cases of transmissible hepatitis were no due to hepatitis A or hepatitis B viruses. They showed that blood from these hepatitis patients could transmit the disease to chimpanzees, the only susceptible host besides humans. Subsequent studies also demonstrated that the unknown infectious agent had the characteristics of a virus. This led to the characterization of distinct form of chronic viral hepatitis called “non-A, non-B” hepatitis.
Unfortunately, all the traditional techniques to isolate “non-A, non-B” hepatitis agent in cell culture failed. So, Michael Houghton, working at the American pharmaceutical firm Chiron, had the idea of using molecular biology tools to identify the genome of this mysterious agent. Houghton and his co-workers created a collection of cDNA fragments derived from nucleic acids found in the blood of an infected chimpanzee, with the idea that some of these fragments would be derived from the unknown virus. To identify viral fragments, they used patient sera to screen cloned viral cDNA fragments potentially encoding viral polypeptides. Following a comprehensive search, one positive clone was found, and they showed that this clone was derived from a novel RNA virus belonging to the Flaviviridae family and it was named Hepatitis C virus.
The discovery of Hepatitis C virus in 1989 was a major breakthrough. The next question was whether this virus alone is responsible for hepatitis? That is when Charlie Rice, working at Washington University in Saint Louis, came into action. He developed the molecular tools to further investigate this infectious agent. Through genetic engineering, Rice generated the first a full-length RNA variant of hepatitis C virus. When this RNA was injected into the liver of a chimpanzee, 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.
The Nobel Laureates’ discovery of hepatitis C virus is a landmark achievement in the ongoing battle against viral diseases, the Nobel Assembly said in a statement. “Thanks to their discovery, highly sensitive blood tests for the virus are now available, and these have essentially eliminated post-transfusion hepatitis in many parts of the world, greatly improving global health. Their discovery also allowed the rapid development of antiviral drugs directed at hepatitis C.”
Having been working on hepatitis C virus since 1993, I was involved in some of the steps that led this worldwide endeavor. This is one of the best success story in research on infectious diseases. In a quarter of century, we went from the identification of a new virus to the development of treatments that cures more than 95% of infected people. I spent almost 3 years in Charlie Rice’s lab where we all shared our enthusiasm in searching for new ways of investigation to understand how this virus interacts with host cells. I am very proud that Charlie got this price. He is the most dedicated scientist that I have ever encountered. He is also always open to share his discoveries and reagents with the international community, and most importantly, he remains a very humble scientist which contrast with the current narcissism invading our societies. He is a role model who should inspire us all.