Discovery of the hepatitis C virus

Screening donated blood for the newly found hepatitis B virus cut the number of cases of hepatitis after transfusion, but Harvey Alter and his colleagues at the US National Institutes of Health showed that many cases remained. The unexplained disease became known as non-A, non-B hepatitis. Alter's group found that blood from these patients could transmit it to chimpanzees, the only susceptible host besides humans, and that the agent behaved like a virus. Yet it resisted every standard method of virus hunting for more than a decade.

Michael Houghton, working for the pharmaceutical company Chiron in California, tried molecular cloning. His team built a collection of DNA fragments from nucleic acids in the blood of an infected chimpanzee. Most of the fragments came from the chimpanzee's own genome, but some, they reasoned, would come from the virus. Assuming that patients' blood would carry antibodies against viral proteins, they used patient sera to screen the collection, and after a long search one clone reacted. It came from a positive-stranded RNA of at least 10,000 nucleotides that was not host DNA, and the virus proved to be a new member of the flavivirus family. Choo, Houghton and their colleagues reported it in Science on April 21, 1989, beside a paper describing a test for antibodies to the virus.

Sensitive blood tests followed, and they have essentially eliminated hepatitis after transfusion in many parts of the world. It was not yet proven that the virus alone caused the disease. In 1997 Charles Rice and colleagues at Washington University in St. Louis injected an engineered viral RNA into the livers of chimpanzees; virus appeared in the blood, with liver changes like those of chronic human infection.

The cloned genome also gave drug developers a target. Sofosbuvir, one of the most prescribed direct-acting antivirals, was approved in 2013, and hepatitis C became curable. Alter, Houghton and Rice shared the 2020 Nobel Prize in Physiology or Medicine.