The 30-year-old discovery impacted millions worldwide

The Nobel Assembly at Karolinska Institutet has awarded the 2020 Nobel Prize in Physiology or Medicine to Harvey J. Alter, MD, Michael Houghton, PhD, DSc Hon, and Charles M. Rice, MS, PhD, for the discovery of hepatitis C virus.

In a press release accompanying the announcement, the Assembly called the discovery by Alter, Houghton, and Rice “a decisive contribution to the fight against blood-borne hepatitis, a major global health problem that causes cirrhosis and liver cancer in people around the world,” and credited the three award winners with making it possible to create new blood tests and medications that have saved millions of lives since the virus was first discovered in 1989.

“The Nobel Laureates’ discovery of hepatitis C virus is a landmark achievement in the ongoing battle against viral diseases,” the Nobel Assembly wrote. “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. For the first time in history, the disease can now be cured, raising hopes of eradicating hepatitis C virus from the world population. To achieve this goal, international efforts facilitating blood testing and making antiviral drugs available across the globe will be required.”

Alter, who currently works in the U.S. National Institutes of Health in Bethesda, Maryland, called the 4:45 a.m. phone call from Stockholm “the best alarm clock I’ve ever had,” according to a report from the Associated Press. Rice, who admitted that he initially thought the early morning call from the Nobel Assembly was a prank, said in a media briefing on Monday that seeing people successfully treated with drugs to eliminate hepatitis C within roughly three decades of the disease’s discovery was the best reward.

“It’s a rare treat for a basic scientist,” he said.

Solving the Hep C Mystery

“To summarize it, one could say that it was three steps that were required for making this discovery,” said Thomas Perlmann, PhD, Secretary-General of the Nobel Committee for Physiology and Medicine, in an interview immediately following the announcement. “And it started with Harvey Alter, who was a clinical scientist at a big blood bank at National Institutes of Health… he and others noted that many [blood transfusion patients] got chronic hepatitis…through his work — and others, but he was really central in this — it was realized that when you could start excluding blood that was positive for hepatitis B virus, patients still emerged.” Alter and colleagues discovered that not only was there another virus causing hepatitis in these patients, but that it was also transferable through patient serum, Perlmann explained, which “started the hunt for this virus.”

The second step in the process hinged on Houghton and his team at the pharmaceutical firm Chiron, where he worked at the time, Perlmann continued. Houghton and colleagues worked to isolate the genetic sequence of the virus, and in 1989 they identified a cloned viral DNA fragment derived from a novel RNA virus belonging to the Flavivirus family — hepatitis C. “The presence of antibodies in chronic hepatitis patients strongly implicated this virus as the missing agent,” the Nobel Assembly wrote.

But could this virus alone cause hepatitis among these patients? To answer the question, Rice, who was a researcher at Washington University in St. Louis, and colleagues set out to assess whether the cloned virus could replicate and cause disease.

Rice and his team “noted a previously uncharacterized region in the end of the hepatitis C virus genome that they suspected could be important for virus replication,” the Nobel Assembly explained. “Rice also observed genetic variations in isolated virus samples and hypothesized that some of them might hinder virus replication. 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 this RNA was injected into the liver of chimpanzees, 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.”

When asked why the Nobel Assembly waited until 2020 to award Alter, Houghton, and Rice for a discovery that occurred over 30 years ago, Perlmann noted that it takes time before the significance of a given discovery is completely clear, and that while the discovery of the hepatitis C virus led to immediate developments in the field of serology, the eventual discovery of antiviral drugs and blood tests for hepatitis C compounded the discovery’s significance over time.

“It’s hard to find something that is of such benefit to mankind as what we’re awarding this year,” Perlmann said. “It’s the discovery of a virus that has led to improvements for millions of people around the world.”

John McKenna, Associate Editor, BreakingMED™

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