In 1989, Prof. Charles M. Rice, virology, undertook the project of developing a treatment for hepatitis C based on the vaccine that was successful in combating yellow fever.
Despite similarities in the viruses that cause the two diseases, it would take nearly a quarter of a century until an effective mixture of drugs was put together.
On Monday, Rice — an adjunct professor of virology at Weill Cornell medicine and the executive director of the Center for the Study of Hepatitis C — was recognized along with Harvey J. Alter of the National Institutes of Health and Michael Houghton of the University of Alberta for “seminal discoveries that led to the identification of a novel virus” and received the 2020 Nobel Prize in Physiology or Medicine.
“Prior to their work, the discovery of the Hepatitis A and B viruses had been critical steps forward, but the majority of blood-borne hepatitis cases remained unexplained,” a press release from the Nobel Assembly at the Karolinska Institute stated. “The discovery of Hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and made possible blood tests and new medicines that have saved millions of lives.”
Hepatitis is the inflammation of the liver, which protects the body from infection, processes nutrients and filters the blood. This inflammation can cause the liver to become inefficient in its functions, and in the long term can cause fatigue, loss of appetite, pain in the joints and abdomen as well as nausea.
During the 1960s, hepatitis C gained national attention when a substantially large population had developed chronic hepatitis from blood transfusions from an unknown source.
In 1978, Alter discovered that there was an unknown virus that served as a common thread between many chronic hepatitis cases and Houghton used a new methodology to identify the genome of this virus, later known as the Hepatitis C virus.
“For many years, we knew that there existed some entity in blood that was neither hepatitis A nor hepatitis B. But until that entity was found, we could only refer to it as non-A, non-B hepatitis, Rice said in a 2017 interview with Seek, Rockefeller University’s research magazine. That cumbersome name really foreshadows how hard this virus would be to pin down.”
Courtesy of Rockefeller University.
Rice with a coworker in 2017.
Rice built off of the work of his co-recipients and concluded that this virus alone could cause chronic hepatitis.
He was lured into the pursuit of a cure in part because of the success vaccine for yellow fever, because the virus that causes yellow fever is in the same family as the virus that causes Hepatitis C.
“When the hepatitis C virus (HCV) was finally identified, in 1989, scientists saw that it was a member of the same family as the virus that causes yellow fever,” Rice said. “The yellow fever vaccine is one of the safest and most effective immunizations available, so it was easy to imagine that creating a vaccine for HCV would not be too arduous.”
Reality proved to be quite different than this initial expectation, as Rice and other scientists struggled to pin down the exact genome of the virus, causing challenges in creating a model of the virus they could use to develop treatments.
Rice credits his eventual breakthrough not to any technological development, but to the determination displayed by his team.
“I think the story of HCV is really one about persistence. The most crucial elements were blood, sweat, and tears,” Rice said. “We had to continue believing that success was possible, and continue trying different approaches even when we repeatedly encountered failure.”
While the work on hepatitis C is far from over — there’s still no specific treatment for patients who experience liver scarring or cancer — the world of virology has turned its attention to another virus: SARS-CoV-2.
In a press conference on Monday, Rice expressed hope that some of the molecular targets — specifically the RNA dependent RNA polymerase and the protease — used to create treatments for hepatitis C could be useful in developing COVID-19 therapeutics.
The RNA-dependent RNA polymerase synthesizes RNA, the genetic material, of the virus which allows it to replicate in a person’s body. This structure has been the target of remdesivir, a drug that is currently in clinical trials and is available to some for emergency use. Remdesivir is one of the drugs that doctors administered to President Donald Trump upon his hospitalization for COVID-19.
“Some of the targets that I think people are most excited about for SARS-CoV-2 and preventing COVID-19 are essentially, conceptually, the sort of same targets that turned out to win the war against hepatitis C, at least in terms of treatment,” Rice said at Monday’s press conference.
While receiving the Nobel Prize was an honor, it is not the utmost reward for Rice.
“Anything that we could contribute to this really just comes from an intrinsic curiosity about viruses and how they persist, and understanding sort of more about how they work,” Rice said. “The chance opportunity of having an important human pathogen land in your family of viruses that you happen to be studying. And then go from basically the beginning where it was discovered to when it can be successfully treated it’s a rare treat for a basic scientist.”