The Nobel Prize in physiology or medicine was awarded Monday to researchers from the United States and Britain whose discoveries helped save millions of lives from the ravages of blood-borne hepatitis, a major global health problem that causes cirrhosis and liver cancer.
Years later, British-born virologist Michael Houghton — then working for the pharmaceutical company Chiron — found a way to clone the virus and to identify antibodies created against it by the immune system. That led to the development of ways to screen and eliminate the virus from the blood supply. Through genetic analysis, then-Washington University in St. Louis researcher Charles M. Rice characterized the machinery of the virus and set scientists on a path to finding a cure.
Their research helped almost eliminate the risk of getting hepatitis C through blood transfusions and led to the development of antiviral medications that can clear the virus from the bodies of infected patients.
“One of the greatest thrills for me has been having identified the first patient [with hepatitis C] and now seeing that not only he was cured, but everyone else I’ve followed over the years was cured,” Alter told reporters Monday morning. “I could not have imagined this, not in my lifetime.”
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.”
Health policy analyst Sonia Canzater, senior associate for the Hepatitis Policy Project at Georgetown Law School, said she hoped this year’s choice of laureates would draw attention to the lingering challenge of fighting hepatitis C, which is still the most common blood-borne illness in the United States. Even though the disease is curable, each year it kills tens of thousands of Americans and hundreds of thousands of people around the world.
“Maybe we’ll really start effecting some change toward elimination now that this has been featured in the most prestigious medical award,” she said.
Hepatitis viruses come in several 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 hepatitis B.
“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.”
Alter, who had worked with Blumberg, spearheaded a new NIH project to create a storehouse of blood samples that 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, before 1970, 30 percent of people who got heart transplants at NIH later came down with liver disease. Yet most illnesses weren’t caused by the A or B virus — there had to be “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. The pathogen was small enough to slip through filters, suggesting it was a tiny virus rather than a bacterium.
But much about the germ 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 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 that includes the pathogens that cause yellow fever and the West Nile virus.
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.”
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 it. Animals injected with the clone fell ill, providing conclusive evidence 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 powerful antiviral drugs, which are able to eliminate the virus in more than 95 percent of treated patients, Karlsson-Hedestam said. Few other viral diseases have such an effective cure.
Though hepatitis C has been mostly eliminated from the blood supply, it is still transmitted through shared needles and non-sterile medical equipment. A combination of stigma and the high cost of treatment means that many of the 2.4 million Americans living with chronic hepatitis C infections cannot access the lifesaving drugs, Canzater said.
“We’ve had these medications for going on a decade, and we have on paper all the resources needed to eliminate this disease,” she said. “It’s just the will that is really needed in this country to get it down to zero.”
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. Scientists must understand a pathogen to fight it.
The award is also a testament to the significance of long-term basic research, Alter said. When he began his work, he was not sure what kind of pathogen he was looking for, let alone what might be done once he found it. Discovering hepatitis C required the support of an employer such as NIH, which would allow him to spend decades categorizing samples and tracking the progress of patients.
From the time Alter began his experiments, it took almost two decades to identify the hepatitis C virus and nearly a half century to develop a cure. “But with a persistent virus,” Alter said, “persisting research paid off.”
In what has become an annual ritual, the announcement also sparked discussion of the Nobel Prize’s shortcomings. This is the fifth year in a row the laureates for the medical prize have been all male; only 12 women have been awarded the prize in its 120-year history. And in awarding the prize to just a few people, the Nobel Committee overlooks the large teams comprising hundreds of researchers who make most discoveries possible.
“What I did and my colleagues in the lab did, I’m very proud of,” Rice said. “But really, we’re just one part of a cast of thousands that are working together and are responsible for where we are today.”
An initial news alert sent out directing readers to this report misspelled Houghton’s name.