In the mid-1990s, Leonard Seeff, a hepatologist at the Veterans Administration Hospital in Washington, D.C., overheard Kaplan discussing the Warren Sera Collection, as it came to be known. Seeff immediately wondered whether any of the blood samples contained antibodies to the hepatitis C virus. If they did, Seeff could answer a question that had been impossible to investigate: How prevalent was hepatitis C in the 1940s and ’50s before it was even known to exist? No one knew. But if the virus was present in these frozen samples, Seeff could study the 40-year course of the disease in an instant.
“He said if you find any positives for hepatitis C, I’ll give you a bottle of champagne,” Kaplan recalls.
The samples were defrosted for the first time in 40 years, and more than 8,500 army recruits were retroactively tested for the virus. Seventeen were positive. Hepatitis C had been at the Warren Air Force Base in the 1950s. And eight of those recruits were still alive.
Zelma Buskell, Seeff’s study coordinator, traveled across the country to meet most of the veterans and take new samples. Not any of them knew how they got the virus, though one veteran remembered injecting drugs during that time, to Buskell’s surprise.
“You think of drug use as starting with Vietnam,” she says. Finding the recruits in generally good health contradicted the grim outlook most physicians held for hepatitis C patients. “People who’d been infected 40 years earlier were still alive,” says Seeff, who reported his results in 2000. “It was not inevitably a fatal disease.”
A First Date
The story could have ended there, except for one inquisitive scientist at the National Institutes of Health. In 2001, Yasuhito Tanaka, now at Nagoya University, spent a year in the NIH laboratory of Harvey Alter, the virologist largely credited with the discovery of hepatitis C. Tanaka wanted to know when hepatitis C entered the U.S., so he asked Seeff for viral samples to sequence.
After making his way through just 4 percent of the viral genome, Tanaka found he couldn’t complete the sequences and set the project aside. It was all but forgotten until Pybus heard about it in 2011 from another Japanese colleague and asked Tanaka to send what he had.
Pybus suspected his methods, unavailable just a few years earlier, could wring some vital history out of Tanaka’s work. Tanaka had sequenced the middle region of the code for NS5B, the enzyme that makes new genome copies during replication. Pybus compared the sequences with genomes of modern-day hepatitis C virus. The number of differences between them, explains Pybus, “is indicative of how long it’s been since they shared a common ancestor.”