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Transmission electron micrograph of hepatitis C virus particles. Source: Cavallini James/BSIP/SPL

On October 5 this year, Michael Houghton, the person in charge of Zhu Guilin on the project, was awarded the Nobel Prize in Physiology or Medicine for the discovery of hepatitis C virus. Zhu Guilin and Guo Jinhong were not among the three winners. The other two winners were Charles Rice of Rockefeller University in New York City and Harvey Alter, who worked at the National Institutes of Health. The Nobel Prize is regarded as the highest honor in science. But for Houghton, winning the Nobel Prize and other top honors gave him mixed feelings. “I’m happy to receive awards,” he said, “but it is sweet, because these awards do not directly reward our entire team.”

Houghton has been running for his two colleagues, hoping that their contribution to the hepatitis C virus can be recognized. “Without their efforts, I doubt whether I can succeed.” He said at a press conference after the announcement of the Nobel Prize.

“Karon University”

Houghton began searching for the hepatitis C virus in 1982, when he worked for a California biotechnology company called Chiron(Chiron). The company is nicknamed “Kailong University” because of its profound academic background. It strives to develop cutting-edge technology and enjoys a reputation in the industry.

At that time, the delivery of blood contaminated with the hepatitis C virus infects 160 people in the United States every day. If left untreated, the hepatitis C virus can damage the liver and cause liver cancer. Today, despite the availability of blood screening technology and treatment methods, the World Health Organization estimates that there are still 71 million people infected with hepatitis C virus in the world.

By the mid-1970s, researchers had determined that the mysterious virus was not two types of viruses known to damage the liver.Viruses-hepatitis A and hepatitis B. However, since it is impossible to clarify the substance that infects the subject of blood transfusion, scientists can only use the method of exclusion to name this blood-borne disease-“Non-A, Non-B hepatitis”.

At that time, the polymerase chain reaction (PCR) has not yet begun to be used on a large scale, unlike now that PCR can be used to easily amplify DNA. Sequencing a new virus a few weeks after it emerged—just like the new coronavirus at the beginning of this year—was unimaginable at the time. Houghton first used samples of infected and uninfected chimpanzees provided by Daniel Bradley of the Centers for Disease Control and Prevention to screen for viral nucleic acid.

Zhu Guilin joined Houghton’s laboratory in 1984, and the two later became friends. The job of searching for contaminants is so difficult, and the entire team has made no progress for several years. As the head of the laboratory, Houghton reports the results to the management of Chiron every 6 weeks. Some people in the management directly stated that they felt that the entire project was a waste of money. “I have been under the pressure of being fired at any time,” Houghton said. “But what I was thinking was: Is there better things waiting for me?”

screening sequence

In the laboratory next door to Houghton, Guo Jinhong, who joined Chiron in 1981, is working on a medically important protein-tumor necrosis factor.

After several years of research, Zhu Guilin and Houghton have screened tens of millions of genetic sequences, but they have not found any signs of this cunning virus. One day, seeing Zhu Guilin unhappy, Guo Jinhong made some suggestions: the whole team needs to change direction. For the technology they use, the virus level is too low to be detected by direct detection. Guo Jinhong suggested that they extract RNA fragments from infected samples and express them in bacteria to increase their abundance. Then use antibody-bearing serum from people with non-A and non-B hepatitis to screen these “banks.” This method assumes that the infected person may carry antibodies that can recognize the sequence of the virus, allowing the team to find the sequence from the library they have built.

Bradley also recommends this method, but it seems a bit risky-antibodies to non-A and non-B hepatitis viruses have never been isolated before-which made Houghton hesitate. But in 1986, Guo Jinhong persuaded him to give it a go. He also helped design the experimental method and joined the exploration team.

Hidden fame

Since then, several prestigious awards have honored the scientists behind the discovery of hepatitis C. Many awards have been awarded to Houghton, but he successfully persuaded some organizers to also award honors to Zhu Guilin and Guo Jinhong. In 2013, Houghton unexpectedly rejected Gerdner, a prestigious (approximately US$75,000) award of 100,000 Canadian dollars. Award (Gairdner Award). He had hoped to persuade the Galdner Foundation to include Zhu Guilin and Guo Jinhong on the list of winners, which were also awarded to Bradley and Alter. After being rejected by the foundation, Houghton gave up the award and bonus.

Houghton said that he accepted the Nobel Prize because he has no hope of changing the rule that Nobel Prize winners are always limited to three people. “When various awards come in, this discovery is a bit changed,” Houghton said. He quickly named the names of nearly ten other scientists, all of whom contributed to the discovery of the hepatitis C virus or later research. “All these outstanding scientists deserve recognition.”< /p>

“This is indeed the result of the joint efforts of many people in the field.” said Ralf Bartenschlager, a virologist at Heidelberg University in Germany. Bartenschlager was once considered a candidate for the Nobel Prize for hepatitis C virus. Guo Jinhong, Zhu Guilin, and Bradley made important contributions, as did other researchers, he said. But Bartenschlager believes that the Nobel Prize Committee’s allocation of awards is understandable: Alter’s work shows that mysterious non-A, non-B hepatitis can be passed from infected humans to chimpanzees through blood transfusion; the Houghton teamThe virus was identified; Rice and colleagues demonstrated that the hepatitis C virus itself can cause hepatitis.

“This has always been difficult.” Bartenschlager said. The Nobel Prize Committee did not comment publicly on why they chose these winners.

Guo Jinhong said that when the news of the Nobel Prize spread, he was indeed a little disappointed. “Limiting the number of winners may be a bit outdated in today’s world of collaboration and team research,” he said. But he also said that winning prizes was never the goal. “What inspires me is the dream that can bring change to people all over the world-in many cases it can save lives,” he said. “I also want my children to know that trying to do something that makes you passionate How important.”

When asked how he felt when the Nobel Prize was announced, Zhu Guilin choked up. “I’m very happy,” he said, “very happy.” Even though his name did not appear in all the awards, it did not detract from his work, which helped save countless lives and shaped a generation of molecular virologists and clinicians. fact. “It’s like my child; I’m so proud,” Zhu Guilin said, “How can I not be proud?”


1. Choo, Q.-L. et al. Science 244, 359–362 (1989).

2. Kuo, G. et al. Science 244, 362–364 (1989).

The original titled The unsung heroes of the Nobel-winning hepatitis C discovery was published in the News section of Nature on October 19, 2020

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