Nobel Laureate Medicine 2020: Charles M. Rice

A loss for the world’s sea urchins turned into a win for virology research.

When Dr. Charles M. Rice, PhD, entered a doctoral program at the California Institute of Technology, he expected to continue his studies on sea urchins. Instead, he was placed in a virology lab, creating a whole new set of interests. And viruses soon replaced sea urchins as the focus of Rice’s research.

His decades of work related to the hepatitis C virus led to discoveries that earned him one-third of the 2020 Nobel Prize in Physiology or Medicine. Rice, the Maurice R. and Corinne P. Greenberg professor in virology at Rockefeller University, shared the prize with Dr. Michael Houghton, PhD, of the University of Alberta, Edmonton, Canada, who identified the hepatitis C virus in 1989 along with colleagues Qui-Lim Choo and George Kuo; and Dr. Harvey Alter, MD, of the U.S. National Institutes of Health (NIH).

“Historically, we haven’t done too well at curing chronic viral infections; this is a success story that may help to ignite efforts in other infectious disease areas and to come up with better solutions.”

“I was happy that the award was made in the hepatitis C research field – it has been a spectacular story – a real success story,” says Rice. “The early attempts to treat it did work, but the success rate in the early days was about five percent. When you fast forward to today, we can now cure almost everyone in 8 to 12 weeks. The saga stretched on for more than 40 years – it was a much longer road than we thought. It turned out to be very difficult virus. Historically, we haven’t done too well at curing chronic viral infections; this is a success story that may help to ignite efforts in other infectious disease areas and to come up with better solutions.”

The Nobel Prize medal and diploma were presented to Charles Rice at the Residence of the Swedish Consul General in New York. Photo: Florence Montmare

The potential for making a contribution to a critical human health problem drew Charles Rice to the hepatitis C studies, he says. Before that, he had become interested in biology while attending college and participated in research with a professor on the development of sea urchins, including taking a course at the Woods Hole Marine Biology Laboratory in Massachusetts. The inexplicable placement in a lab with viruses rather than sea urchins when Rice arrived at graduate school set him on his path.

Read more: Harvey J. Alter: A scientist’s scientist

The first cell-based system for hepatitis C

Charles Rice’s research on this group of viruses started with the virus that causes yellow fever and led to ways to make and modify yellow fever virus RNA in the lab so that it could be studied. He started applying this knowledge to the hepatitis C and found an undiscovered segment on the end of hepatitis C virus RNA, and wondered if the missing piece might be needed for the virus to replicate. Rice was able to construct a virus with this “tail,” but that also failed to replicate.

However, after employing an approach to correct mistakes in the lab-made hepatitis C virus genome RNA, he was able to show in 1997 that this sequence was correct and infectious in animals – but unfortunately not in cells in the lab. With more tweaking, in 1999, investigators in Germany and later Rice in the US developed the replicon system – “host cells that contained many copies of a gutted, but replicating virus RNA” – and this was the first cell-based system for hepatitis C.

“It took 15 years to get a lab system where the entire virus lifecycle could be studied.”

“It was a huge boost for the field but theses RNA contained adaptive mutations and were still unable to make virus particles. Five years later, in 2005, three independent labs showed that a unique virus isolate, from a patient with severe early liver disease, could replicate efficiently without adaptive mutations and make infectious virus particles. It took 15 years to get a lab system where the entire virus lifecycle could be studied,” adds Rice.

What surprised him about the research was “how recalcitrant the virus was at getting it to behave itself in cell culture.”

“I didn’t think it was going to be so hard to study,” he says.

Charles Rice. Photo: John Abbott

”This didn’t have to happen”

Like most scientists recently, Rice has been doing research related to the SARS-CoV-2 virus and COVID-19 disease.

“We have a significant program underway including helping others to develop neutralizing antibodies, similar to those approved for treatment under emergency authorization,” notes Rice. “We’re [also] trying to understand what the coronavirus needs to propagate.”

“This didn’t have to happen. It’s distressing to see how it unfolded in the U.S. and we could have done much better to get it in check.”

In January, Rice called the status of the pandemic in the U.S. “pretty grim; the U.S. botched what should have been done. “This didn’t have to happen. It’s distressing to see how it unfolded in the U.S. and we could have done much better to get it in check,” he says.

The change in leadership at the federal level hopefully will bring improvement, he notes. Fortunately, the mobilization of scientists and industry around the world has been “spectacular” in terms of getting vaccines developed in record time, he adds.

“Hopefully with vaccines and public measures, we will get back to some sort of normal state. One of the questions still unanswered is how long immunity from the vaccines will last. Even if the immunity starts to wane and those vaccinated get infected, it will probably help prevent people from being transmitters or getting severely ill.”

So much still to be discovered

The pandemic certainly has raised awareness about the importance of research. “The study of the fundamental aspects of yellow fever virus, and hepatitis C, have certainly helped guide our coronavirus studies,” says Rice.

“The study of the fundamental aspects of yellow fever virus, and hepatitis C, have certainly helped guide our coronavirus studies.”

He also is studying the hepatitis B virus, in the hopes of producing a durable cure. “Of the 250 million people infected, only a small percentage is being treated,” he says. “Treatment is usually for life as it doesn’t eliminate the virus but there is now more enthusiasm to come up with a treatments that at least lead to a ‘functional cure’ – one that teaches the body how to control the virus even after treatment stopped.”

With so much going on in the lab, Rice jokes that he currently is devoid of free time, but when he does get a break, he enjoys playing with his two Australian shepherds and hiking and fishing in remote areas for a change of pace from New York City.

“You never know what’s going to pop up. Scientists are continually humbled by complexity and beauty of what they find.”

The prospect of new discoveries drives Rice’s enthusiasm for his research.

“Just the fact that there is so much we don’t know, so much still to be discovered,” he says in explaining the satisfaction he gets. “You never know what’s going to pop up. Scientists are continually humbled by complexity and beauty of what they find.”

Charles Rice. Photo: Florence Montmare

Facts

Charles M. Rice, PhD.

Age: 68

Born: Sacramento, California, U.S.A.

Nationality: American

Education: B.S. zoology, University of California, Davis, Ph.D. Biochemistry, California Institute of Technology

Personal: Spouse, no children.