Cooking up millions of viruses for a new vaccine

As soon as Doris Bucher learned that a new strain of swine flu had turned up in the United States, she e-mailed the Centers for Disease Control and Prevention offering to send materials that might be useful in making a vaccine. Her colleagues at the C.D.C. had a better idea. Less than a week later, they sent a sample of the new type of virus, influenza A(H1N1), to Dr. Bucher, an associate professor of microbiology and immunology at New York Medical College. Dr. Bucher, a cheerful, fast-talking scientist who has been involved in flu research for 40 years, runs a laboratory here in Westchester County that is highly regarded for its skill at turning flu viruses into "seed stock"–a form of the virus that will grow rapidly in eggs so that drug companies can use it to make hundreds of millions of doses of vaccine. Federal health officials have not yet decided whether to call for a swine flu vaccine, but they say it is important to be ready for quick production of millions of doses. Because the virus is new, some people may need two shots to build immunity. The vaccine would probably be separate from seasonal flu vaccine, meaning a total of three shots might be recommended for certain people. Creating the seed stock is an essential first step for any vaccine. So the C.D.C. has sent samples of the new strain to about 10 other government and academic laboratories in this country, Australia, Britain, Hungary and Russia. For the past five years, Dr. Bucher's laboratory has provided seed stock for one of the virus strains included in the seasonal flu vaccine used all over the world. "Our job is to make it grow really well," she said. "We're good at this." One of the group's strengths has been in developing a "high-yield donor," meaning an influenza virus that grows well in eggs and that, when injected into eggs along with a new strain like H1N1, will swap some of its genes with the new strain. An array of new viruses results, and the researchers can sort through it to pick ones that have donor genes inside the ball-shaped viral particles, so they will grow well in eggs, but that will retain the new strain's traits on the outside–enabling the vaccine to spark immunity when injected into people. The unlikely headquarters of this major player in the world's supply of flu vaccine is a modest cluster of small to midsize laboratories with a half-dozen freezers, a walk-in incubator at 95 degrees Fahrenheit and a walk-in cold room. In the midst of it all is Dr. Bucher's cluttered office, her desk awash in documents like "virus certificates" from the C.D.C. and handwritten bills for 84 dozen eggs. A vial containing millions of swine flu viruses in a milliliter of fluid (about a fifth of a teaspoon) arrived at her lab on April 28, packed with dry ice in a plastic foam box inside a cardboard carton stamped, "infectious substance affecting humans." The viruses had been grown from a cotton swab rubbed in the nose and throat of a child in California who received one of the first diagnoses of the flu in this country. Dr. Bucher's team opened the box in a laboratory hood, a specially ventilated compartment that prevents any samples from escaping, and set to work. Wearing specially fitted masks, double gloves, surgical caps and other protective gear, their first task was to make more of the virus, by injecting it into fertilized eggs from leghorn hens. Creating seed stock is a quirky business that melds high-tech science and simple tools from 100 years ago. In one lab, members of the team amplify virus genes, cut them up with enzymes and analyze their origins. In others, their colleagues candle eggs, mark the shells with a pencil, pierce them with a drill bought at Sears and shoot them full of swine flu viruses. Basically, the process involves repeated rounds of injecting the two types of virus into eggs, and sorting and purifying what grows. Each round of virus growth takes about 42 hours. The ultimate goal is to create a uniform seed stock from a single virus, and to produce 80 vials of it, each containing millions of viruses, that will be sent to drug companies, the C.D.C. and the Food and Drug Administration. Dr. Bucher said she expected to ship out those 80 vials by May 25. Members of the research team said they were used to working with flu viruses, and this one did not alarm them. Rene Devis, a research associate, admitted that he did feel a bit concerned at first. "But you do what you have to do, especially if you can help save a life," Mr. Devis said. "You don't think of yourself." The swine flu came along just about a week after Dr. Bucher's team had finished a seed stock for the next seasonal flu vaccine and started work on other projects. Now they are back to flu viruses, and working so hard that Dr. Bucher fears they will burn out. What if they make a seed stock, and then health authorities decide there is no need to make a vaccine after all? "We'll put it in the freezer," Dr. Bucher said.