The Nobel Committee has awarded this year’s Nobel Prize in Physiology or Medicine for the discovery of the hepatitis C virus, one of the most common causes of liver cancer. The prize was given to Harvey Alter of the U.S. National Institutes of Health (NIH); Michael Houghton of the University of Alberta, Edmonton; and Charles Rice of Rockefeller University.
The hepatitis C virus is transmitted via blood. Although many people quickly clear an infection, some develop chronic inflammation of the liver that quietly destroys the organ over years or decades, ultimately leading to cirrhosis and cancer. Patients often end up needing liver transplantation—or dying.
Half a century ago, doctors knew that recipients of blood transfusions were at higher risk of liver disease, and in 1967, Baruch Blumberg, also at NIH, discovered the hepatitis B virus, which won him one half of the 1976 Nobel Prize in Physiology or Medicine. But hepatitis B did not explain all of the cases of hepatitis seen in patients who had a blood transfusion. This year’s Nobel laureates did work over 3 decades to identify the hepatitis C virus, show it was responsible for most of the unexplained cases of hepatitis in blood transfusions, and make it possible to screen blood donations for the virus.
“There’s no doubt about the contributions these three have made,” says Jens Bukh, a virologist at the University of Copenhagen who has also done landmark studies on hepatitis C. “They are fantastic collaborators and also fantastic people. … They have had a profound impact on how this research field has developed, not only through their discoveries, but also in supporting other young scientists who have joined the field.”
In the 1970s, Alter and his colleagues studied hepatitis in transfusion recipients and showed that even though screens for the hepatitis B virus could reduce the number of cases, many remained. Hepatitis A, a virus transmitted via water or food, wasn’t the explanation either. In 1978, Alter showed that plasma from patients with unexplained hepatitis could cause disease when transferred to chimpanzees, indicating it was caused by an infectious agent. In additional experiments using chimpanzees—the only animals susceptible to hepatitis C—Alter and his colleagues showed the disease was likely caused by one or more viruses.
In the 1980s, Houghton, then working at the pharmaceutical company Chiron, and his colleagues searched for the possible culprit by sifting through collections of DNA snippets called complementary DNA (cDNA) collected from infected chimpanzees. However, most of the genes they identified in their initial screens belonged to the apes.
The pioneering work of this year’s laureates is a landmark achievement in our ongoing battle against virus infections.
They then tried a different approach. They collected RNA (the genetic molecule that helps code for proteins) from the serum of infected chimps and used the RNA to make a new cDNA collection. They put that collection into bacteria that could produce the proteins encoded by the DNA snippets. Finally, they used serum from an infected patient—which they assumed would carry antibodies to the virus—to identify any bacterial colonies that might produce a viral protein. Out of 1 million bacterial colonies they screened, one coded for a protein from a virus. The researchers described their work in 1989 in a paper in Science in which they named the disease hepatitis C.
The researchers then developed a blood test and showed it could identify samples suspected of transmitting the unexplained cases of hepatitis. This allowed blood donations around the world to be screened, which dramatically reduced the number of newly infected people. Before these discoveries, “it was like Russian roulette to receive a blood transfusion,” says Nils-G?ran Larsson, a member of the Nobel Committee. Transmission though the blood supply is now nearly eliminated, notes Ralf Bartenschlager, a virologist at the University of Heidelberg who shared the Lasker-DeBakey Clinical Medical Research Award with Rice and Michael Sofia in 2016 for work on hepatitis C. “They made blood transfusion safe,” he says. “That has prevented countless cases.”
But it was still unclear whether the virus alone was responsible for the disease or it needed an accomplice of some kind. Rice, then working at Washington University in St. Louis, tried but failed to infect chimpanzees with versions of the virus constructed in the lab. He suspected that, like many RNA viruses, the new virus mutated very quickly, leading to many clones that did not cause disease. He then worked out an “average” sequence less likely to contain disabling mutations. In a 1997 paper, also in Science, he showed that this engineered version of the virus—alone—could cause infection and liver disease in chimps.
Eventually, the trio’s discoveries also led to the development of antiviral treatments that can now cure about 95% of hepatitis C patients. Those therapies, along with blood screening, “saved millions of lives worldwide,” Nobel Committee member Gunilla Karlsson Hedestam said today. “The pioneering work of this year’s laureates is a landmark achievement in our ongoing battle against virus infections.”
At a press conference today, Alter said he is working to make sure every patient he has worked with over the years gets treatment; he says close to 90% of them already has. “Everyone has been cured. It has been so dramatic. I think one of the greatest thrills for me has been having identified the first patient [with likely hepatitis C] and now seeing not only that he was cured, but that everybody else I have followed over the years is being cured. I never could have imagined that, not in my lifetime.”
Yet about 71 million people worldwide are still suffering from a chronic infection and transmission continues, primarily in developing countries. The main transmission routes today are contaminated medical equipment, childbirth—when the mother is infected—and sharing contaminated drug injection needles. The World Health Organization estimates about 400,000 people died of hepatitis C in 2016, mostly from cirrhosis and cancer.
Egypt is one of the worst affected countries in the world, with up to 15% of people affected in some regions. The country’s epidemic started half a century ago, when needles were widely reused during a campaign to treat schistosomiasis, a snail-borne parasitic disease. Recently, Egypt has led the way in combatting the virus, treating millions of people with the new drugs and conducting a countrywide screening campaign to find undiagnosed cases.
Many scientists today expressed their hope that the Nobel Prize will help further reduce the disease’s toll. “The discovery and treatment of HCV [hepatitis C virus] is an incredible success story for fundamental science,” evolutionary biologist Oliver Pybus of University of Oxford tweeted. “Congratulations to the laureates and let’s hope this adds momentum to global HCV elimination efforts.”
Bukh hopes the prize will spur investment in a possible vaccine. Because hepatitis C causes few acute symptoms, it is very difficult to identify all those infected, he says. “Treatments are great, but they can’t control the virus in poor regions,” he says. “A vaccine is really needed to control this virus.”
With reporting by Kai Kupferschmidt and John Travis.