Three scientists behind major hepatitis discoveries awarded Nobel Prize

5 Oct 2020

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Harvey J Alter, Michael Houghton and Charles M Rice have been awarded the Nobel Prize in Medicine for their discoveries about blood-borne hepatitis.

Three scientists behind the discoveries that helped us better understand hepatitis C have been awarded the 2020 Nobel Prize in Physiology or Medicine. Harvey J Alter, Michael Houghton and Charles M Rice have made significant contributions to research on blood-borne hepatitis that causes cirrhosis and liver cancer.

The announcement was made today (5 October) by the Royal Swedish Academy of Sciences, which described the three scientists’ work as leading to the identification of the novel hepatitis C virus.

Prior to their work, the existence of hepatitis A and hepatitis B had been established. However, the majority of blood-borne hepatitis cases remained unexplained until the discovery of hepatitis C. Once established, hepatitis C explained the remaining cases of chronic hepatitis and made possible blood tests and new medicines that have saved millions of lives.

Harvey J Alter

Following the discovery of hepatitis B by Baruch Blumberg in the 1960s, Alter was working at the US National Institutes of Health studying the occurrence of hepatitis among patients who received blood transfusions.

While tests for hepatitis B and hepatitis A helped reduce the number of infections during transfusions, his work suggested there was another mystery virus at work in some cases.

Alter and his colleagues 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 that at first was called “non-A, non-B” hepatitis.

Michael Houghton

Working at pharmaceutical firm Chiron, Houghton and his co-workers created a collection of DNA fragments from nucleic acids found in the blood of a chimpanzee infected with the virus.

While this showed the majority of the fragments came from the chimpanzee’s genome, some were derived from the unknown virus. On the assumption that antibodies against the virus would be present in blood taken from hepatitis patients, the investigators used patient sera to identify cloned viral DNA fragments encoding viral proteins.

Eventually, one positive clone was found and would eventually be shown to be derived from a novel RNA virus belonging to the Flavivirus family and dubbed hepatitis C.

Charles M Rice

After the virus was discovered and named, Rice was working at Washington University and discovered a previously uncharacterised region in the end of the hepatitis C virus genome. Suspecting it to be important to virus replications, he and his team observed genetic variations in virus samples that may have played a part in it spreading.

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 injected into the liver of chimpanzees, the virus was shown to resemble its effects in humans with the chronic disease.

This helped prove hepatitis C virus alone could cause the unexplained cases of transfusion-mediated hepatitis. Thanks to their discoveries, highly sensitive blood tests for the virus are now available and these have essentially eliminated post-transfusion hepatitis in many parts of the world and allowed for the rapid development of targeted antiviral drugs.

Commenting on his contribution to the discovery, Alter said: “To see so many people get cured is astounding.”

Colm Gorey was a senior journalist with Silicon Republic

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