Nobel Prize in medicine awarded for discovery of hepatitis C

Years later, British-born virologist Michael Houghton — then working for the pharmaceutical company Chiron —…

Nobel Prize in medicine awarded for discovery of hepatitis C

Years later, British-born virologist Michael Houghton — then working for the pharmaceutical company Chiron — found a way to clone the virus and identified antibodies created against it by the host’s immune system; this led to the development of screening mechanisms to eliminate the virus in the blood supply. Through genetic analysis, then-Washington University in St. Louis researcher Charles M. Rice characterized the virus and set scientists on a path to finding a cure.

Hepatitis C, which is often transmitted through blood transfusions, causes severe inflammation of the liver and is blamed for 400,000 deaths annually.

The Nobel Committee called the three researchers’ work “a landmark achievement in our battle against viral infections.”

“It’s hard to find something that is of such benefit to mankind as what we are awarding this year,” said Thomas Perlmann, secretary of the Nobel Committee. “This discovery … has led to improvements for millions of people around the world.”

Hepatitis viruses come in two main forms: hepatitis A, which is transmitted through contaminated water or food and is rarely deadly; and hepatitis B and C, which are carried in blood and bodily fluids and can be far more dangerous. The latter viruses are “insidious,” the Nobel Committee said, because they can linger for years in the blood of an apparently healthy person before erupting into a dangerous disease.

Before these Nobel-winning discoveries, the world had struggled to control these blood-borne pathogens. Geneticist Baruch Blumberg discovered hepatitis B in the 1960s (and was awarded a Nobel the following decade). But patients who received blood transfusions were still coming down with severe liver disease, even after the donor blood had been screened for the hepatitis B virus.

“The situation was becoming alarming,” said Nobel Committee member Gunilla Karlsson-Hedestam. “Because the disease was silent but progressive, it was impossible to know who of all the apparently healthy blood donors were carriers of the disease.”

Alter, who had worked with Blumberg, spearheaded a new NIH project to create a storehouse of blood samples, which could be used to uncover the causes of the transfusion-associated disease. He also tracked people who developed hepatitis after receiving a blood transfusion. His work showed that most illnesses weren’t caused by the A or B virus but “another infectious agent,” Karlsson-Hedestam said.

In 1978, Alter showed that plasma from patients carrying this unknown form of hepatitis could transmit the disease to chimpanzees. A dangerous new virus was clearly hiding in human blood.

But much about the pathogen remained unknown — a fact that frustrated Alter so much he was moved to write poetry. “No antigen or DNA / No little test to mark its way,” he wrote in 1988.

“… Oh GREAT LIVER in the sky

Show us where and tell us why

Send us thoughts that will inspire us.

Let us see this elusive virus.”

The answer to Alter’s lament would come not from a “great liver in the sky” but from Houghton, the British scientist.

From the blood of an infected chimpanzee, he and his team collected as many fragments of genetic material as they could find. Most came from the animal, but they hoped a few fragments would belong to the virus. Injected into a bacterial cell, these fragments would produce the same proteins that form the shell of the virus.

Next, Houghton added serum from an infected human into the petri dish. That person’s antibodies would react to encountering viral proteins, allowing the scientist to determine which bacterium was carrying the virus’s RNA. His team then analyzed the genetic fragment and realized it closely resembled a family of germs called flaviviruses, which includes the viruses that cause yellow fever and West Nile.

The experiments took the better part of a decade, Houghton wrote in a 2009 review for the Journal of Hepatology. The “eureka moment,” he said, “was in fact a very gradual and extended one.”

But the research led to the development of a test for screening hepatitis C in the blood supply. Since screening began in 1992, the risk of infection from a transfusion has fallen dramatically.

The final step to characterize the virus came when Rice sequenced its genome and created a clone of the virus. Animals injected with the clone fell ill, providing conclusive evidence that the hepatitis C virus was, in fact, the cause of the disease.

Genetic research also allowed Rice to tweak the virus so it was easier to study in a petri dish. This set the stage for the development of effective anti-viral drugs, which are now able to cure more than 95 percent of treated patients, Karlsson-Hedestam said.

“I think the story of HCV is really one about persistence,” Rice said in a 2017 interview published by Seek, the research magazine of Rockefeller University, where he now works. “The most crucial elements were blood, sweat, and tears.”

Patrik Ernfors, another member of the Nobel Committee, contrasted the decades-long effort to identify hepatitis C with the discovery of the novel coronavirus, which took only weeks after the emergence of the disease late last year. Armed with rapid sequencing technology, today’s scientists can easily discern the entire genome of a new germ, allowing them to avoid the painstaking work of their predecessors.

But the importance of identifying the viral cause of a new disease remains the same, Ernfors said. Only once scientists understand the culprit can they launch the search for a cure.

Correction: An earlier version of this article misspelled Michael Houghton’s name.