Nobel Prize winner Charles Rice headed to University of California, Davis, after graduating from Rio Americano High School in 1970, thinking maybe he would get a degree in veterinary medicine. The college still has a world-class program in that field.
He ended up in an introductory biology class with a professor who engaged him to explore how cells reproduce, how they carry out all sorts of metabolism and how all their basic biological mechanisms work. Then that instructor, Professor Dennis Barrett now at the University of Denver, invited Rice to do some developmental research on sea urchins.
That research kindled Rice’s passion for scientific exploration. Rather than thinking about what degree he’d get in four years, he instead found himself seeking out other classes that fanned those flames.
“I guess you just never really know what your early education is going to get you poised for, and obviously, many aspects of our education we don’t use every day, but they still shape who we are,” Rice said. “In my case, the fact that I graduated with a degree in zoology was actually, kind of, by default. I had been bouncing around, taking all of these courses and that was the one where I happened to have the right courses to graduate.”
Later, from 1989 to 1996, the drive and curiosity that Rice had as an undergraduate would be what sustained him as he worked to unlock the mystery of how the hepatitis C virus replicates.
The stakes were high. Worldwide in 1990, 333,000 people died from the hepatitis C virus, according to the World Health Organization. If scientists could make the virus grow, they could start looking for drugs to treat or cure it, said Dr. Souvik Sarkar, an internal medicine doctor who leads the hepatitis C treatment program at UC Davis.
RICE FINDS MISSING PIECE
Rice built upon the discoveries of researchers Harvey Alter of the National Institutes of Health and Michael Houghton of the University of Alberta, and shares this year’s Nobel for physiology or medicine with them.
Alter recognized there was a viral agent spreading hepatitis in patients after they had a blood transfusion, and it wasn’t either the hepatitis A or hepatitis B virus commonly known at that time. Many groups went on the hunt to try and identify the genome tor of this mystery virus.
“It was shown by Harvey and others that it (hepatitis C) could be transmitted to chimpanzees and that remained pretty much the only animal model that could be used for hepatitis C in those early days,” Rice said. “And, that provided the material that Michael Houghton used to clone and identify a little piece of this virus, which was then extended to include most of the viral genome.”
Those discoveries were critical to eliminating Hep C from the storehouses of blood kept for transfusions in medical facilities around the world, Rice said. Transfusions and intravenous needle use by drug users were the primary forms of transmission.
But what still needed to be done was finding a cure. Rice’s “hugely important” technical breakthrough made that possible, said Mark Winey, dean of the College of Biological Sciences at UC Davis.
“His (research) group was able to produce a virus in a form where the virus itself could be tested as the causing agent of the liver failure and liver cancer,” Winey explained, and that virus that they were able to produce also became the basis of being able to develop therapeutics toward it.”
Rice said his team at The Rockefeller University took the viral genome sequence and created basically a clone of that sequence to show that the virus could initiate a hepatitis C infection in chimpanzees.
“That actually formally proved that, yes, this virus called hepatitis C was responsible for the disease that people have been studying and so we knew that we had all the elements of the virus in hand and could use that to establish new systems for studying it,” he said.
FINALLY A WAY TO TEST TREATMENTS
Other celebrated researchers, including Ralf F. W. Bartenschlager of Heidelberg University and Michael Sofia of the biotech company Arbutus Biopharma, would go on to develop a culturing system to study the replication of hepatitis C and use the system to develop drugs to eliminate it. Rice, Bartenschlager and Sofia won the Lasker-DeBakey Clinical Medical Research Award, often called America’s Nobel Prize, in 2016.
All these scientists became folk heroes to liver specialists like Sarkar, researchers like Winey and legions of hepatitis C patients whose main treatment was a chemotherapy that wrecked their bodies, leaving many with not only bone marrow failure but also hearing and hair loss, Sarkar said.
He worked at the NIH on the research side for hepatitis C and as a treating physician. In the chemotherapy treatment, they were using man-made versions of proteins called interferons that prime the body’s immune system to keep viruses from multiplying.
“I had a patient who was a construction worker, a really strong guy, when I was working at the NIH. This guy got completely knocked out by Interferon. He could not work,” Sarkar said “The patients would endure that so they would not progress to cirrhosis and liver failure.”
Patients needed frequent monitoring, he said, and Interferon had only a 40%-50% success rate. After discoveries by Rice, Sofia and Bartenschlager, a new class of drugs entered the picture. Perhaps the best known is sofosbuvir, which is sold under the brand name Sovaldi.
“When these drugs came, when you combine them with the other agents, you had 96% response rates,” Sarkar said. “That’s clearly advantageous. We’re talking about almost everyone getting cured. That changed the field. That made us think, ‘Yes, we can actually kill a virus. We can actually get rid of a virus, not just suppress it or have to deal with it, but we could actually cure it.’”
Most patients won’t go on to cirrhosis or liver cancer, Sarkar said, and they won’t experience side effects as awful as the ones caused by Interferon.
“Some of the great things that have happened is, once we had the treatment, we needed many fewer liver transplants,” Sarkar said. “Patients get better on their own without needing a transplant. It has decreased liver cancer significantly. And, it has cut the cost of care for this disease.”
At 68, Rice has a love for cell biology that remains unabated. His research team had been studying the hepatitis B virus as well as a virus related to Hep C until COVID-19 became a major public health threat.
Scientists are collaborating across disciplines globally and are sharing information as fast as they can to produce effective treatments or cures for the coronavirus, he said. It took 20 years before a cure was found for hepatitis C, but after eight months of working at a swift pace, pharmaceutical companies already have vaccine candidates for COVID-19 in late-stage clinical trials.
STUDENTS, FOLLOW YOUR PASSION
What Rice wants high school and college students to know is that they don’t have to know exactly what they want to do. What he hopes they will do is pursue the study of things that engage and excite them.
Rice also took classes in wine making and grape growing at UCD, and he and his wife, Dr. Peggy MacDonald, an infectious disease researcher at Rockefeller, own a small vineyard in Amador County that supplies grapes for the Easton and Terre Rouge labels.
“Students now certainly have amazing resources to be able to access information much more easily than we had in the past when we went to the library or read from a journal,” Rice said. “I guess you still have to figure out what’s the truth and what isn’t, but my advice would be to try and work toward a career where you have a passion for what you’re doing and you really want to get up in the morning and do it.”
Rice, who was named for his father and grandfather, grew up in the Arden Park neighborhood in the 1950s and ’60s before the American River Parkway was recognized nationally as a recreational gem. In addition to Rio Americano, he got his primary instruction at Mariemont Elementary and Arden Middle School.
A New York City resident, Rice said he doesn’t get back much to the Sacramento region since his mother Roberta died 13 years ago, but does occasionally visit his friends at the boutique Terre Rouge & Easton Wines.
He especially loved his math classes and recalled his English class with Mrs. Alice Kubo as a highlight of his high school years. Caught Tuesday at home in the Greenhaven neighborhood, Kubo said she worked especially hard to help students excel in writing composition.
“Most of the students I remember really appreciated the work that I did with them in helping them write better,” said the 85-year-old Kubo, adding that she was so glad that Rice remembered her.
Kubo, an educator for 38 years, said she learned of Rice’s award when she sat down to read the print edition of The Sacramento Bee on Tuesday morning: “I read the article, and I looked at his name, but it did not say anything about where he graduated from high school. I told my daughter, ‘That name is so familiar.’”
After a Bee reporter tracked her down and jogged her memory, Kubo recalled that she had taught Rice in an English class.
TRADING URCHINS FOR VIRUSES
After graduating from UCD, Rice wasn’t sure whether he would become a vintner or pursue graduate school in the sciences. He took a year off to travel in Central and South America, and by the time he returned, he knew. He opted for graduate school at California Institute of Technology in Pasadena. They had a laboratory that was doing great work in the study of sea urchins.
“Dennis Barrett, my UC Davis instructor, had also gone to Caltech and was a graduate student and highly recommended it,” Rice said. “When I arrived there, I ended up being placed in the virology lab, not in the sea urchin development biology lab. And, that was it. I really enjoyed working on viruses with Jim and Ellen Strauss.”
Unexpected turns and chance encounters ultimately steered Rice into his life’s work, he said.
“We’re very fortunate as scientists to end up in a situation where we can be curious about things and follow that curiosity and see where it takes us — and even get paid to do it,” he said.
Another UC Davis alum, cancer researcher and Del Campo High School graduate Michael Shepard, shared much the same philosophy on pursuing passion and curiosity in an interview last year with The Bee. Like Rice, he also got a degree in zoology from Davis and won the Lasker prize.
While working at Genentech, Shepard wound up as a leader on a scientific team that figured out a strategy to directly target malignant tumors and developed a groundbreaking drug therapy known as Herceptin to quash the runaway growth.
Today at UC Davis, the zoology major has morphed into molecular and cell biology, said Winey, who’s a faculty member in that department. Students get intimately acquainted with how cancers and viruses and other microorganisms work, he said.
If you’re a parent of a child who is curious about how biology and the natural world work, Winey said, encourage them to ask questions and to use scientific methods to search for answers. And, steer them toward a research university such as UCD where, even as an undergraduate, they’ll get opportunities for experiential learning.
“We hope to make an impact on a lot of students, help them see that they can do science and think critically like a scientist, and pursue a career in science,” Winey said. “Both Dr. Shepard and Dr. Rice went on to excellent graduate programs that further developed their skills as scientists and went on to be working and very successful scientists in their own right. That’s a career path we would be excited for any of our students to follow.”
Rice is the first UC Davis alumni to have received a Nobel Prize, Winey said, and he sees it as particularly poignant that work in the field of virology has taken this year’s top science honor.
“We’re in the middle of a viral pandemic and this is a prize about virology and success in treating a viral infection,” Winey said. “It speaks to the value of basic science research, recognizing what type of virus the Hep C virus was, and then to work with that to the point of there being a therapy. That takes a lot of work, and in the COVID pandemic right now, we have a lot of work in front of us to really get to the point where we thoroughly understand the virus before we have a suite of tools for therapy and prevention. So, it’s a really poignant, timely award in that way.”