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Tuesday, October 20, 2020

Explained: The discovery of Hepatitis C virus that helped three scientists win the Medicine Nobel

Three scientists share this year’s Medicine Nobel for the discovery and identification of the Hepatitis C virus. Tracing the steps they took in the 1970s and 1980s, and how it led to safer blood transfusions today

Written by Amitabh Sinha | Pune | Updated: October 8, 2020 7:27:17 am
Nobel Prize 2020, Nobel Prize for Medicine, Harvey Alter, Charles Rice, Michael Houghton, Indian ExpressThomas Perlmann, far right, Secretary of the Nobel Assembly announces the 2020 Nobel laureates in Physiology or Medicine during a news conference at the Karolinska Institute in Stockholm, Sweden, Monday Oct. 5, 2020. (AP/PTI Photo)

This year’s Nobel Prize in Physiology or Medicine rewards an effort that eventually made blood transfusion safer for everyone. American scientists Harvey Alter and Charles Rice, and Michael Houghton of the UK, have been recognised for their contributions to the discovery of a new virus that was the cause of a vast majority of chronic hepatitis cases, or cases of serious liver inflammation, in patients who required blood transfusion. This virus was eventually called Hepatitis C virus.

Since the discovery and identification of the virus in the 1970s and 1980s, a cure has been found for the disease, and effective anti-viral drugs are now available. Tests have been developed to identify blood that has this virus, so that infected blood is not given to any patient.

Still, according to the World Health Organization, about 71 million people (6 -11 million of them in India) have chronic infection with the Hepatitis C virus, which also happens to be major cause of liver cancer. In 2016, this viral infection led to the death of nearly 400,000 people across the world. A vaccine for the disease has still not been developed.

What was known about hepatitis before the discovery of the Hepatitis C virus?

Before the discovery of the Hepatitis C virus, two other viruses were known to cause hepatitis in patients. The Hepatitis A virus was known to spread mainly through contaminated food and water, and caused a relatively milder form of liver inflammation. Hepatitis B, discovered in the 1960s, was known to transmit mainly through infected blood, and caused a more serious form of the disease. Incidentally, the discovery of the Hepatitis B virus too was rewarded with a Nobel Prize in Medicine, given to Baruch Blumberg in 1976. There are vaccines available for this disease now.

The discovery and identification of Hepatitis B virus facilitated the development of a diagnostic test to detect its presence in blood. Thereafter, only blood sanitised from this virus would be given to patients, but it was observed that even this sanitised blood was able to prevent only 20% of the blood-borne hepatitis cases. It was then that the search for the new virus began.

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How was it found, and what was the contribution of each Nobel winner?

In the 1960s, Alter had a collaborated with Blumberg, the 1976 Nobel winner. Alter later moved to the US National Institutes of Health (NIH), where he continues to work. At NIH, Alter worked at the blood bank and had access to a large collection of blood samples which facilitated his investigations into cases of hepatitis caused after blood transfusion. It was Alter, along with some of this colleagues, who was able to define the characteristics of the then unknown virus.

But despite over 10 years of effort, Alter and his collaborators were not able to establish the identity of the virus. That work was accomplished by Houghton, who was working independently at Chiron Corporation, a US biotechnology firm. After painstaking work screening over a million DNA sequences, Houghton was able to identify the new virus in 1982, after which it was named Hepatitis C.

In 1997, Rice, then working at Washington University, was able to conclusively show that it was indeed this virus that was causing chronic hepatitis in human beings.

Nobel Prize 2020, Nobel Prize for Medicine, Harvey Alter, Charles Rice, Michael Houghton, Indian Express (From left) Harvey J. Alter, Charles M. Rice, and Michael Houghton (Rhoda Baer/National Institutes of Health, Richard Siemens/University of Alberta, AP/PTI)

Why is it significant?

The Nobel Prize website said the discovery of the Hepatitis C virus (HCV) was one of the important milestones in improvement in public health that had raised hopes for eliminating the disease.

“The discoveries of HBV and HCV, and the establishment of effective screening routines, have virtually eliminated the risk of transmission via blood products in many parts of the world. Thanks to the development of highly effective drugs against HCV, it is now possible, for the first time in human history, to foresee a future where the threat of this virus infection is substantially reduced and hopefully soon eliminated,” it said.

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Shahid Jameel, a virologist who has worked extensively on Hepatitis E virus (discovered later), said the simplest way to understand the importance of the work of these scientists was to know that the blood that is given to all kinds of patients has now become a lot safer. “Three main causes of blood-borne infections — Hepatitis B, Hepatitis C and HIV — all have been identified, and they no longer infect the blood that is required by patients. This has been a direct results of scientists like them. From a public health point of view, their discovery of the Hepatitis C virus was therefore a very big breakthrough,” said Jameel, now director of Trivedi School of Biosciences at Ashoka University.

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How is Hepatitis C treated?

“A vaccine for this has not been developed mainly because it’s a very fast-changing virus. But it is possibly the only chronic virus for which a definitive cure is now available,” Jameel said. “Anti-viral drugs could be developed based on the understanding of the biology of the virus to which Harvey’s lab contributed very significantly. In fact, there were a few others whose contributions were equally significant, people like Robert Purcell and Ralf Bartenschlager, but they seemed to have missed out on the Prize only because the Nobel cannot be shared by more than three people. But all in all, a very well deserved recognition for Harvey Alter, Charles Rice, and Michael Houghton,” Jameel said.
Indian effort: One of the important steps towards finding a vaccine was taken by an Indian company in the late 1990s. Hyderabad-based Shantha Biotech, which produced the first recombinant DNA-based vaccine for Hepatitis B infection, had begun work on Hepatitis C as well. It had funded the work of a US-based Indian-origin scientist who had succeeded in sequencing the entire genome of the Hepatitis C virus present in the Indian population. But no progress was made after that.

“It was an important work at that time, in 2001. We couldn’t carry it further for some reason. But no other effort has also succeeded till now,” Dr Varaprasad Reddy, founder of Shantha Biotech, told The Indian Express.

This article first appeared in the print edition on October 6, 2020 under the title ‘Virus find that won the Nobel’.

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