The Nobel Assembly at Karolinska Institute awarded the 2020 Nobel Prize in Physiology or Medicine to Harvey J. Alter, Michael Houghton, and Charles M. Rice. This year’s Nobel Prize goes to three scientists who made decisive contributions to the fight against blood-borne hepatitis. Hepatitis is a major global health problem that causes cirrhosis and liver cancer in people around the world. They made discoveries that led to the identification of a novel virus, the Hepatitis C virus. Before their work, the discovery of Hepatitis A and B viruses were critical steps forward. However, the majority of blood-borne hepatitis cases remained unexplained.
Liver inflammation, or hepatitis, a combination of the Greek words for liver and inflammation, mainly is a result of viral infections. However, alcohol abuse, environmental toxins, and autoimmune disease are also important causes. There are two types of this infectious hepatitis virus. The first one is Hepatitis A. It is transmitted by polluted water or food and generally has little long-term impact on the patient. The second type transmits through blood and bodily fluids and represents a much more serious threat. This is because it leads to chronic conditions, such as cirrhosis in the liver and liver cancer.
This type of hepatitis is insidious. It silently infects otherwise healthy individuals for years before complications arise. Hepatitis B and C link to significant morbidity and mortality. They cause more than a million deaths per year world-wide. This makes it a global health concern on a scale comparable to HIV-infection and tuberculosis.
In the 1960’s, Baruch Blumberg determined that a particular virus caused one form of blood-borne hepatitis. That became known as hepatitis B. The discovery led to the development of diagnostic tests and an effective vaccine. He ended up winning the Nobel Peace Prize in 1976 for Physiology or Medicine.
Harvey J. Alter was studying the occurrence of hepatitis in patients who had received blood transfusions. This study reduced the cases of transmission through blood transfusions, but there were still a worryingly number of cases that remained. The blood from these patients could transmit this virus to chimpanzees, the only susceptible host besides humans. Subsequent studies showed that the unknown infectious agent had the characteristics of a virus. We know this form of hepatitis as ‘non-A, non-B’ hepatitis.
Michael Houghton, working for Chiron at the time, tackled the difficult work necessary to isolate the genetic sequence of the virus. Houghton and his co-workers collected a group of samples taken from the nucleic acids found in the blood of the infected chimpanzees. Most of the fragments came from the genetic sequence of the chimpanzees themselves, but they predicted that some came directly from the unknown virus.
The researchers used blood from patients that they clotted and divided into all the different components to clone viral DNA fragments encoding viral proteins. They only found one clone. However, they used that to recognize a RNA virus that went on to be named Hepatitis C. The presence of antibodies in chronic hepatitis patients connected this to the virus being the missing link.
Charles M. Rice was doing research at Washington University in St. Louis when he and colleagues discovered that one end of the Hepatitis virus genome was important in the replication of the virus. Rice also observed that genetic variations in some virus samples hypothesizing that some carried the ability to hinder virus replication. Rice then generated a RNA variant of Hepatitis C virus that included defined regions of the viral genome and is devoid of inactivating genetic variations. When researchers injected this into the liver of those infected chimpanzees, they detected the virus in the blood. Pathological changes resembling those seen in humans with the chronic disease were observed. This was the final proof needed to show that Hepatitis C virus could cause the unexplained cases of transfusion-mediated hepatitis.
Significance of This Nobel Prize
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. This discovery also allowed the rapid development of antiviral drugs directed at hepatitis C. For the first time in history, this disease can now be cured, raising hopes of eradicating Hepatitis C virus form the world population.