Nick Bexfield of the University of Cambridge had flown from England with a new hepatitis virus that has just broken out in British dogs.
Some researchers were examining New York flu, others African colds. The blood of patients with mysterious, nameless fevers was waiting to be analyzed. There was dried African bush meat seized by customs inspectors at Kennedy Airport. Horse viruses, clam viruses: all told, members of Dr. Lipkin’s team were working on 139 different virus projects. It was, in other words, a fairly typical day.
“We get 10,000 samples a year easily,” Dr. Lipkin said. “We’ve discovered at least 400 new viruses since I came to Columbia in 2002, and the process is accelerating.”
Over the past 20 years, Dr. Lipkin has built a reputation as a master virus hunter. He has developed ways to quickly identify familiar viruses and ways to search for new ones.
“If scientists are lucky, they’ll identify one novel virus in their whole life,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. “Lipkin really stands out from the crowd.”
The emergence of H.I.V. in the 1980s first drove Dr. Lipkin to search for viruses. At the time, he was a neurology resident at the University of California, San Francisco, and was watching many patients fall ill with AIDS. It took years for scientists to discover the virus responsible for the disease. Dr. Lipkin worried that in years to come, new viruses would claim more lives because of this lag. “I saw all this, and I said, ‘We have to find new and better ways to do this,’ ” Dr. Lipkin said.
One reason that viruses can be so hard to find is that they’re so small — typically a few millionths of an inch across. Even the most powerful microscopes may not be able to reveal viruses if they’re lurking in a hiding place in the body. Sometimes scientists can detect viruses by rearing vast numbers of them in laboratories. It’s also possible to detect them by looking for antibodies in infected people. But these methods can be slow and unreliable. Dr. Lipkin thought it might be better to find viruses in a different way. He would go fishing for their genes.
“It had never been done before, and it was an obvious thing to do,” he said.
Dr. Lipkin’s first quarry was the cause of a bizarre disorder caused borna disease. Borna disease had first been discovered in horses in the late 1800s; it attacks their brains and causes them to flail uncontrollably. When scientists injected filtered brain extracts into healthy animals, they could develop the disease as well. Doctors worried that it might cross over into humans and have equally devastating effects. But no one had ever found a pathogen in an animal sick with the disease.
If a virus was responsible for borna disease, Dr. Lipkin reasoned, he might be able to find its genes in an infected brain. He and his colleagues infected rats with the disease and then extracted genetic material from them. They first identified the pieces of DNA that came from the rats themselves. After they painstakingly subtracted the host genes, they were left with a small amount of genetic material present only in the sick rats.
To see if these genes came from the cause of borna disease, Dr. Lipkin transplanted them into bacteria. The bacteria used them to make proteins. If these were proteins from the source of borna disease, then infected animals might have made antibodies precisely tailored to grab onto them. In 1990, Dr. Lipkin and his colleagues reported that when they mixed borna antibodies with the proteins, they embraced each other tightly. This discovery allowed Dr. Lipkin and his colleagues to isolate the virus, which came to be known as the borna virus.
As Dr. Lipkin earned his reputation as a virus hunter, other researchers began to bring difficult cases to him. In 1999, for example, doctors noticed a cluster of cases of encephalitis around New York City. They shipped blood from their patients to Dr. Lipkin, who was then at the University of California, Irvine. Analyzing the genetic material, he and his colleagues concluded that the encephalitis had been caused by West Nile virus. It was the first time the virus had been identified in the Western Hemisphere. Since Dr. Lipkin made the discovery, West Nile virus has spread across the continental United States.
Dr. Lipkin’s success with West Nile virus led to an invitation to come to Columbia in 2002 and set up the Center for Infection and Immunity. He and his colleagues began developing faster, more sensitive methods to find viruses. At the time, the most sophisticated technologies for identifying viruses could only compare their genetic material to one known virus at a time. Dr. Lipkin and his colleagues developed a more powerful system, known as MassTag PCR.
The researchers prepare a cocktail of genetic material from 20 or more kinds of viruses. When they mix the DNA from a sample into this cocktail, the viral segments will bind to any matching DNA. Dr. Lipkin and his colleagues can then fish out these matching segments and shoot them through a mass spectrometer to determine their mass. From these clues, the scientists can often determine what kind of virus they’re dealing with.
MassTag PCR is relatively cheap and fast, but it can miss viruses that are scarce or especially exotic. It failed, for example, to reveal the cause of three puzzling deaths in Australia. In 2006, three women received liver and kidney transplants from the same donor. For a month after the transplant, they were in good health, but then they all suddenly developed intense fevers and died. Dr. Lipkin and his colleagues analyzed samples from their bodies, but they couldn’t find any culprits with MassTag PCR.
At the time, Dr. Lipkin and his colleagues were adapting new genome sequencing machines to virus hunting. They decided to turn the machines on this mystery.
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