Identification of the virus
dramatically reduced infections through blood transfusions
Three virologists have won the
Nobel Prize in physiology or medicine for the discovery of the hepatitis C
virus.
Harvey Alter, of the U.S.
National Institutes of Health in Bethesda, Md., Michael Houghton, who is now at
the University of Alberta in Edmonton, Canada, and Charles Rice, now of The
Rockefeller University in New York City, will split the prize of 10 million
Swedish kronor, or more than $1.1 million, the Nobel Assembly of the Karolinska
Institute announced October
5.
About 71 million
people worldwide have chronic hepatitis C infections. An estimated
400,000 people die each year of complications from the disease, which include
cirrhosis and liver cancer. Today, the major way people get infected is through
contaminated needles used for injecting intravenous drugs, but
when the researchers made their discoveries in the 1970s, ’80s and ’90s, blood
transfusions were an important source of hepatitis C infection.
“This is a bit overdue,” says
Dennis Brown, chief science officer of the American Physiological Society. It
often takes decades before scientific achievements are recognized by the Nobel
committee. One reason for the recognition this year may be COVID-19, Brown
says. “This keeps virology and viruses in the public eye,” he says. “It might
be a push to put science at the forefront, to say when we put money into this
and when we have well-funded people working on these viruses, we can actually
do something about them.”
The trio of winners of this
year’s Nobel Prize in physiology or medicine — Harvey Alter, Michael Houghton
and Charles Rice (from left) — all played a role in discovering the hepatitis C
virus, which can cause a silent but ultimately deadly disease. “It’s hard to find
something that is of such benefit to mankind,” Thomas Perlmann, Secretary
General for the Nobel Committee, said. The discovery “has led to improvements
for millions of people around the world.”
Alter worked at a large blood
bank at NIH in the 1960s when hepatitis B was discovered. (That discovery won
the 1976 Nobel Prize in physiology or medicine (SN: 10/23/76).)
Blood could be screened so that people wouldn’t get that virus from a
transfusion, but patients were still developing hepatitis. Alter and colleagues
showed in the mid- and late 1970s that a new
virus, dubbed “non-A, non-B” was causing the infection, and that the
virus could be used to transmit the disease to chimpanzees (SN: 4/1/78).
Just over a decade later,
Houghton, working at the pharmaceutical company Chiron Corp. (now part of
Novartis), developed a way to pull fragments of the virus’s genetic material
from the blood of infected chimpanzees and developed
a test to screen out hepatitis C-infected blood (SN: 5/14/88) .
It took so long to isolate the virus’s genetic material because Houghton “had
to wait until the technology was available,” Brown says.
Over seven years, “we must have
tried 30 or 40 methods” to extract, or clone, the virus Houghton said during a
news conference. Eventually, he and colleagues turned to a method using
bacteriophage — viruses that infect bacteria — developed by researchers at
Stanford University.
“It took another two years for us
to get that to work,” Houghton said. “And when it did work, we got one clone.”
Over six to nine months the researchers confirmed again and again that the
small piece of genetic material that they had cloned was from the virus. “It
wasn’t one eureka moment,” he said. And it took even more work to convince
other scientists that they’d snagged the virus.
The blood test Houghton and
colleagues developed was used to screen blood all around the world and
dramatically decreased hepatitis C infections, said Gunilla Karlsson Hedestam,
an immunologist at the Karolinska Institute in Stockholm who described the
laureates’ contributions. Before then, “it was a bit like Russian roulette to
get a blood transfusion” said Nils-Göran Larsson, a member of the selection
committee.
But a question still remained
about whether the hepatitis C virus alone was responsible for the infection.
Rice and colleagues working at Washington University in St. Louis stitched
together genetic fragments of the virus pulled from the blood of infected
chimpanzees into a working virus and demonstrated that it could cause hepatitis
in animals. “This provided conclusive evidence that the cloned hepatitis C
alone could cause the disease,” Karlsson Hedestam said.
It also set the stage for work
that would lead to the development of drugs, which can now cure most people who
are infected with hepatitis C, Richard Lifton, president of The Rockefeller
University said during a news conference. For many years after Houghton
identified the virus’s genetic makeup, it still wasn’t possible to grow
hepatitis C in cells in lab dishes — a necessary step in drug
development.
“I remember at the time, I
thought this would be a very short-lived area of investigation for us,” Rice
said in the news conference. He thought that with the information Houghton’s
group had uncovered pharmaceutical and biotechnology companies would rapidly
take over. But hepatitis C proved more challenging. Rice and colleagues
eventually discovered a missing piece from the end of the virus that allows it
to replicate in cells. Rice’s previous work on the yellow fever virus led him
to suspect that the missing piece was there.
Rice is continuing work to
understand how hepatitis C produces varied outcomes, from mild disease that
people are able to clear on their own to serious liver scarring and cancer that
may require a liver transplant. “It’s a happy situation that it’s become more
difficult to get damaged liver tissue from hepatitis C infected people,” Rice
said in an interview with Science News. So, to study how the virus
damages the liver, the researchers have turned to a similar virus that infects
rats and mice. Like many other virology labs, though, that work is on hold
while the researchers turn their attention to studying SARS-CoV-2, the virus
that causes COVID-19.
Houghton is now working on a
vaccine against hepatitis C. “Therapeutics alone do not control epidemics,” he
said. “You need a vaccine to prevent [infection], not just drugs to treat.”
Thomas Perlmann, secretary
general of the Nobel Assembly, had to try several times before he reached Alter
and Rice to give them news of their win. The third time his phone rang before 5
a.m. EDT, Alter said he got up angrily “thinking
this was another political solicitation or somebody wanted to extend the
warranty on my car.” His anger soon turned to shock. “It’s otherworldly. It’s
something you don’t think will ever happen, and sometimes don’t think you
deserve to happen. And then it happens,” he said in an interview posted at
nobelprize.org. “In this crazy COVID year, where everything is upside down,
this is a nice upside down for me.”
Houghton discovered he’d won when
his University of Alberta colleague Lorne Tyrrell phoned him shortly after 3
a.m. PDT at his home in San Francisco. Tyrell had gotten up early to hear who
won and called to congratulate his colleague.
Houghton previously turned down
the Canada Gairdner Award because the prize committee refused to honor his
collaborators at Chiron. “I tried to persuade them to be more inclusive and
more modern,” he said. But “it would be really presumptuous of me to turn down
a Nobel.”
The terms of Alfred Nobel’s will
establishing the prizes dictate that no more than three people can share the
prize. That often leads to researchers who have made important discoveries
being left out. For instance, some researchers predicted that German virologist
Ralf Bartenschlager of Heidelberg University would share the prize with Rice,
because Bartenschlager developed methods of growing hepatitis C in cells that
enabled drug development.
“This rule of three that the
Nobel committee adheres to is, in this case, unfortunate,” Rice says. But
because this prize deals with the discovery of the virus, the door may still be
open for Bartenschlager and others to win later for the development of drugs
against the virus.
The laureates all emphasized that
science builds on the work of others and takes time, consistent funding and
tenacity.
“It’s a long story, a 50-year
saga, and I think it’s a tribute to non-directed research, when you don’t know
where you’re going but you just keep moving,” Alter said in a news conference.
“If you find something and you don’t know what it is, or why it is, keep
looking, keep persisting. With a persistent virus, persisting research paid
off.”
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