In 1982, a molecular biologist at a California biotech startup called Chiron joined the hunt. Michael Houghton, in collaboration with Bradley, tried every technique of molecular biology and immunology to search for a protein or genetic sequence that would lead them to the virus. The pair used cutting-edge methods to examine infected blood and liver tissue, looking for genetic material with a high molecular weight that would indicate the presence of a virus. After several years, the researchers had screened 200 million to 300 million genetic sequences, but found nothing.

Then, in 1985, Chiron colleague George Kuo persuaded Houghton to reconsider an approach he had thought too risky. With colleague Qui-Lim Choo, they cloned all the nucleic acids (the building blocks of DNA and RNA) they could find in samples of infected human and chimp blood, the latter provided by Bradley. Then they introduced these genetic sequences into bacterial genomes, so that the bacteria were “persuaded” to manufacture the proteins determined by those sequences. To find the sequences that would yield rare viral proteins, Houghton explains, “we just used infected serum samples to screen lawns of bacteria on dinner plates of culture medium.” This produced extremely smelly dinner plates, because the bacteria was the infamous intestinal E. coli.
Two years and millions of proteins later, the team had found several candidates; it took another year to identify a single clone from infected blood that caused antibodies to bind to it and was not present in normal blood. That clone provided a “handle” to identify the virus and pull it out of infected blood.

Houghton, Choo and Kuo were certain they had found the virus, but they still had to convince the rest of the world. Hepatitis expert Harvey Alter at the National Institutes of Health had developed a famous library of infected blood samples, some containing non-A, non-B contaminated blood. Alter had sent his samples to 40 other research groups, but none had been able to identify the samples with non-A, non-B. “We were the 41st,” says Houghton. “We cracked the code straight away.”

Next, the Chiron group developed a blood test using the clone, which made it possible to screen all donated blood for the virus now known as hepatitis C. By the early 1990s, the U.S. blood supply was clear of the virus, and with an important source of new infections eliminated, the yearly rate of infection has dropped from almost 250,000 to about 25,000. Now the major risk factors for hepatitis C infection in the West are the use of shared needles and other shared drug paraphernalia. Sexual transmission is another source of infection, though a number of studies suggest that in a long-term monogamous union, the risk of passing the infection is remote. The rate of transmission is higher for those who have sex with many different partners.

The Chiron discovery, which earned Houghton (on behalf of the team) and Alter the Lasker Prize for medical research (on Alter’s part, not only for providing the crucial blood samples but also for having co-discovered non-A, non-B ), launched wide-ranging efforts to control the hepatitis C virus. Two decades later, advanced therapies can cure the disease in some people. The most effective treatments combine interferon, a naturally produced human immune chemical that fights viral infections, and an antiviral drug called ribavirin, developed years earlier to combat other viruses. Deborah Taylor, a senior investigator at the U.S. Food and Drug Administration, has shown that interferon, on its own, is blocked by the protein envelope that encapsulates the hepatitis C virus; although it is not yet known how ribavirin works or how the two chemicals cooperate, neither can work alone.

Because the body swiftly eliminates injected interferon, the chemical is now typically delivered in “pegylated” form, with the interferon peptide, a short protein chain, attached to a larger molecule that takes much longer for the body to eliminate. Combined with ribavirin, the therapy now cures about 50% of chronically infected hepatitis C patients. It’s still unclear why only some patients respond, though some genotypes, or variants, of the virus respond better than others. But that the treatment prevails at all is remarkable, according to Jules Dienstag of the Massachusetts General Hospital, who notes that this is the first therapy that has managed to cure a chronic viral infection. In many hepatitis C cases, after a year’s therapy, the virus disappears forever.