The Nobel Prize in Physiology or Medicine 2020 has been awarded jointly to Harvey J. Alter, Michael Houghton and Charles M. Rice for the discovery of Hepatitis C virus.
Hepatitis, or liver inflammation, is mainly caused by viral infections. However, other important causes include alcohol abuse, environmental toxins and autoimmune disease. In the 1940s, two main types of infectious hepatitis were found. The first type, Hepatitis A, is transmitted via polluted water or food and typically has little long-term impact on patients. The other type is transmitted via the blood and bodily fluids. As a result, it represents a more serious threat and can lead to chronic conditions such as the development of cirrhosis and liver cancer. Most importantly, many individuals with this type can be silently infected for many years before any serious complications arise. Blood-borne hepatitis is associated with significant morbidity and mortality, making it a major global health concern.
In the 1960s, Baruch Blumberg identified that one form of blood-borne hepatitis was caused by a virus – Hepatitis B. Blumberg was subsequently awarded the Nobel Prize in Physiology or Medicine in 1976. During this time, Harvey J. Alter was studying the occurrence of hepatitis in patients who received blood transfusions. While blood tests for Hepatitis B virus reduced the number of cases of transfusion-related hepatitis, Alter demonstrated that a large number of cases remained. Studies also showed that blood from these hepatitis patients could transmit the disease to chimpanzees. The mysterious illness became known as “non-A, non-B” Hepatitis.
Identification of Hepatitis C virus
Michael Houghton, while working for Chiron, undertook work needed to isolate the genetic sequence of the virus. Houghton and team used patient sera to identify cloned viral DNA fragments encoding viral proteins. The team found one positive clone. Further investigation revealed that this clone was derived from a novel RNA virus belonging to the Flavivirus family – Hepatitis C virus.
To determine whether the virus alone could cause hepatitis, Charles M. Rice and other research groups noted a previously uncharacterised region at the end of the viral genome. Rice also observed variations across isolate viral samples and suggested that some of them might hinder viral replication. Using 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 transferred into the liver of chimpanzees, researchers detected the virus in the blood and found that the pathological changes mimicked those seen in humans with chronic disease.
Significance of this Nobel Prize-awarded discovery
This discovery is a landmark achievement in the ongoing battle against viral diseases. Their work has allowed for highly sensitive blood tests for the virus to become available, which has essentially eliminated post-transfusion hepatitis in many parts of the world. Most importantly, their discovery has enabled the development of antiviral drugs for Hepatitis C virus. For the first time, the ability to cure the disease is possible, raising hopes for future eradication of Hepatitis C virus worldwide.
Image credit: By Image Team – canva.com