Why did it take more than 20 years to discover the hepatitis C virus, but only a week to discover the new coronavirus?

The first Nobel Prize in 2020 was awarded to three scientists who discovered the hepatitis C virus over 20 years. Thanks to technological advances and the accumulation of predecessors, it was not so difficult to "discover" the new coronavirus this year.

Editor/Ding Lin New Media Editor/Chen Xuanzhi

As the world is fighting a fierce battle against the novel coronavirus, this year's Nobel Prize in Physiology or Medicine was awarded to the three discoverers of the hepatitis C virus.

▲The announcement of the 2020 Nobel Prize in Physiology or Medicine (from the Internet)

Prior to their work, the hepatitis A and B viruses had been discovered, but more than 80% of blood-borne hepatitis cases remained “unexplained.” The discovery of the hepatitis C virus revealed the cause of the remaining chronic hepatitis cases and made possible blood tests and new drugs that have saved millions of lives.

To “discover” a pathogenic virus, several conditions must be met

Patrik Ernfors, an expert from the Nobel Prize Committee, emphasized the importance of the discovery of the virus in an interview with the media.

"The first step (to defeat viral infectious diseases) is to locate the virus that causes the disease," he said. "Once we have completed this step, we are at the starting point for developing related drugs and vaccines."

As described by the Nobel Prize Committee, the discovery of hepatitis C virus took scientists decades. This is because confirming the pathogen that causes an epidemic disease usually requires the following points:

(1) The suspected pathogen must be found in all patients, and the pathogen nucleic acid can be detected in the patient's clinical samples;

(2) The pathogen can be successfully isolated from the patient's clinical samples;

(3) The isolated pathogens can cause the same disease symptoms after infecting host animals.

▲Among the discoverers of the virus, Harvey J. Alter's systematic study of transfusion-related hepatitis showed that an unknown virus was a common cause of chronic hepatitis; Michael Houghton isolated the gene of a new virus called hepatitis C virus; Charles M. Rice provided the final evidence that hepatitis C virus alone can cause hepatitis.

The three scientists and many people who quietly contributed to their work achieved these three difficult steps. Today, the discovery of viruses is no longer such a long process. "Virus hunters" can identify hundreds of viruses every year.

The speed of novel coronavirus discovery "breaks the record"

At the end of 2019, a number of cases of "unknown cause of pneumonia" occurred in Wuhan, and the pathogen was quickly identified as the "new coronavirus."

According to Xinhua News Agency, on January 2 this year, after receiving the case specimens sent by Hubei Province for testing, the China CDC immediately launched a "relay race": extracting nucleic acids, gene sequencing, comparative analysis... After more than 30 hours of continuous work, the genetic code of the virus was finally deciphered in the first place. Based on this full genome sequence, nucleic acid detection reagents were quickly developed.

The second step is virus isolation. The isolation and cultivation of coronavirus is not easy, and the specimens have undergone freezing and thawing and long-distance transportation, which makes the isolation more difficult. However, after five days, the researchers isolated and identified the new coronavirus in the first time and obtained the world's first electron microscope photo of the new coronavirus, which "put the final nail in the coffin" for the rapid identification of the pathogen.

On January 12, the Chinese Center for Disease Control and Prevention, the Chinese Academy of Medical Sciences, and the Wuhan Institute of Virology of the Chinese Academy of Sciences, as designated agencies of the National Health Commission, submitted the novel coronavirus genome sequence information to the World Health Organization, and published it in the Global Influenza Sharing Database for sharing. This provides an important foundation for global vaccine development, drug research, and epidemic control.

"China identified the pathogen in record time and shared the full genome sequence information of the virus with the World Health Organization and other countries," said Tedros Adhanom Ghebreyesus, Director-General of the World Health Organization.

Compared to the rapid "discovery" of the new coronavirus, the discovery of the hepatitis C virus was slow. This is obviously due to the development of science and technology. For example, nucleic acid testing was the key to the discovery of the new coronavirus, and the most primitive gene sequencing technology was not developed until the late 1970s.

In 1972, after Harvey Alter proved that a "non-A, non-B" virus was the cause of chronic hepatitis, the isolation of the virus was delayed. It was not until 1989 that Michael Houghton and others used the latest molecular technology to isolate the nucleic acid of the hepatitis C virus; in 1997, Charles Rice's team used genetic engineering methods to "transform" active hepatitis C virus and proved that the virus itself can cause hepatitis C.

Dennis Brown, chief scientific officer of the American Physiological Society, said in an interview with the media: "They are waiting for the technology to mature."

The 'forgotten' discoverer of human coronavirus

In addition, scientists were able to quickly identify the "real culprit" new coronavirus thanks to their familiarity with this type of virus - the discovery of the new coronavirus was based on previous developments in virology, including the hepatitis C virus, which is also an RNA virus.

▲Schematic diagram of hepatitis C virus (Source: sciencenews.org)

Human coronaviruses first revealed their true appearance in the 1960s, and humans have known about them for more than half a century.

The first person to "see" the human coronavirus was a woman, British virologist and virus imaging expert June Almeida.

Almeida's real name before marriage was Joan Hart. She was born in Glasgow, Scotland in 1930. Her father was a local bus driver, and she herself did not receive much formal school education. At the age of 16, because she could not afford the tuition for university, she found a job as a technician in the histopathology laboratory of the Glasgow Royal Hospital. A few years later, after getting married, Almeida's family immigrated to Toronto, Canada.

At the Ontario Institute for Cancer Research, Almeida not only mastered the use of electron microscopes, but also innovatively invented a method to image viruses more clearly - using antibodies to aggregate the viruses into clusters.

▲British virologist and virus imaging expert Joan Almeida (from the Internet)

Almeida's talents were recognized by British scientists, and she was attracted to return to the United States in 1964 to work at the School of Medicine affiliated to St. Thomas' Hospital in London (British Prime Minister Boris Johnson was treated in this hospital after being infected with the new coronavirus). After returning to the United States, Almeida began to work with David Tyrrell, who was the head of a common cold research laboratory.

Tyrrell's team found that many common cold-related viruses can be cultured in the laboratory when studying nasal lavage samples from volunteers, but not all of them. Among the many samples is a sample numbered B814, which comes from the nasal lavage of a primary school student in southern England.

Unlike the sore throat symptoms of a typical cold, B814 can cause the infected person to become listless; in addition, B814 can be inactivated by fat solvents, which means that the pathogen has a lipid outer membrane, which is also different from typical cold pathogens.

Tyrrell was curious: Can we see the true face of the virus directly under an electron microscope? They sent some samples to Almeida's laboratory, but Tyrrell didn't hold out much hope. After all, this sample could cause symptoms in the volunteers infected by it, but it could not reproduce in the commonly used culture environment. Viruses that have not been enriched and purified are not only very rare under an electron microscope, but also interfered with cell tissues.

Almeida exceeded all expectations. Using the “negative staining” method she learned in Canada to process the samples (increasing the contrast of the image), she was able to see the virus particles under the microscope, describing them as “similar to the influenza virus, but not exactly the same.”

What she saw was actually the first human coronavirus.

▲Electron micrograph of coronavirus taken by Almeida in 1966 (Source: Wikipedia)

In fact, Almeida had seen similar virus particles when he was studying mouse hepatitis virus and chicken bronchitis virus.

But her paper, submitted to a professional journal, was rejected during peer review because reviewers said her images of viruses infecting mice and chickens were “no more than poorly imaged influenza virus particles.”

The paper based on the findings of the B814 sample was published in the British Medical Journal in 1965. The image of the virus particles seen by Almeida was published in the Journal of General Virology two years later. The name "coronavirus" was also given by Tyrrell, Almeida and other researchers based on the microscopic images.

Almeida then moved to the Royal Graduate School of Medicine in London (now Imperial College London Medical School) to continue her research, where she was awarded a PhD. She ended her career at the Wellcome Institute in the UK, during which time she obtained several patents in the field of viral imaging.

Joan Almeida died in 2007 at the age of 77.

Almeida is not a "Nobel Prize-level" scientific star that everyone is paying attention to, and perhaps few people feel sorry for her - her electron microscopic photos of rubella virus and hepatitis B virus appear in some textbooks, and she participated in the discovery of a "non-threatening" cold virus, "that's all."

References

[1] bbc.com/zhongwen/simp/science-52300930

[2] nytimes.com/2020/05/08/obituaries/june-almeida-overlooked-coronavirus.html

[3] nationalgeographic.com/history/2020/04/june-almeida-discovered-coronaviruses-decades-ago-little-recognition/

[4] news.cctv.com/2020/01/09/ARTI9Vp9Lra4Tvltz3r7es96200109.shtml

[5] xinhuanet.com/world/2020-04/10/c_1125839503.htm

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