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I f you want to make an omelet, you have tobreak some eggs. And if you want to sup-ply the U.S. with flu vaccine, you have to

break about 100 million.That may change someday, as leading vac-

cine manufacturers explore the possibility oftrading their chicken eggs forstainless-steel culture vats andgrowing their flu virus in celllines derived from humans,monkeys or dogs. The tech-nology could allow compa-nies to produce their vaccinesin a more timely and less la-borious manner and to re-spond more quickly in anemergency.

Today’s flu vaccines areprepared in fertilized chickeneggs, a method developedmore than 50 years ago. Theeggshell is cracked, and theinfluenza virus is injected intothe fluid surrounding the em-bryo. The egg is resealed, theembryo becomes infected,and the resulting virus isthen harvested, purified andused to produce the vaccine.Even with robotic assistance,“working with eggs is te-dious,” says Samuel L. Katz

of the Duke University School of Medicine,a member of the vaccine advisory committeefor the U.S. Food and Drug Administration.“Opening a culture flask is a heck of a lotsimpler.”

Better yet, using cells could shave weeksoff the production process, notes Dinko Va-lerio, president and CEO of Crucell, a Dutchbiotechnology company developing one of thehuman cell lines. Now when a new strain offlu is discovered, researchers often need totinker with the virus to get it to reproduce inchicken eggs. Makers using cultured cellscould save time by skipping that step, per-haps even starting directly from the circulat-ing virus isolated from humans. As an addedbonus, the virus harvested from cells ratherthan eggs might even look more like the virusencountered by humans, making it betterfodder for a vaccine, adds Michel DeWilde,executive vice president of R&D at Aventis,the world’s largest producer of flu vaccinesand a partner with Crucell in developing flushots made from human cells.

Whether vaccines churned out by barrelsof cells will be any better than those producedin eggs “remains to be seen,” says the FDA’sRoland A. Levandowski. And for a persongetting jabbed in the arm during a regular fluseason, observes Richard Webby, a virologistat St. Jude Children’s Research Hospital inMemphis, Tenn., “it’s not going to matter

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Egg BeatersFLU VACCINE MAKERS LOOK BEYOND THE CHICKEN EGG BY K AREN HOPKIN

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OVER EASY? Researchers hope to replace the decades-oldway of making flu vaccines, which involves injectingviruses into fertilized eggs pierced with a drill.

COPYRIGHT 2004 SCIENTIFIC AMERICAN, INC.

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H igh-energy physicists have a newmachine in mind: an unprecedented ac-celerator 30 kilometers long that would

offer a precise tool to explore some of themost important unanswered questions inphysics. But the specter of the defunct Super-conducting Supercollider—and the moneythe project ended up wasting—looms large.Advocates of the machine, however, think

they can overcome national doubts by goingglobal.

Since they first began discussing a linearcollider in earnest at a 2001 conference atSnowmass, Colo., the world’s physicists haveconsistently and vigorously planned an inter-national effort. Their hopes recently rose whenU.S. Secretary of Energy Spencer Abrahamnamed it the highest “midterm” priority in a

where the vaccine came from.”Where the cell-based vac-

cine will become invaluable,Webby states, is in the case of aglobal pandemic. Should a newstrain of flu crop up outside thenormal season—one that is dif-ferent enough from previousstrains that people will have noimmunity—cell-based systemswill allow health officials to re-spond more rapidly. “Cell cul-tures are a lot easier to scale upfaster,” he explains. Techni-cians would simply remove cellsfrom a freezer and grow them inlarge volumes—something thatis not possible with chickeneggs. Although flocks of chick-ens kept in clean environmentsare available almost year-round, companiesgenerally place their egg orders six months be-fore they start vaccine production. And pre-venting a pandemic could require 10 times asmuch vaccine as a normal flu season. “Ifhalfway into manufacturing, you need a bil-lion more eggs, you’re not going to get them,”remarks Wayne Morges, a vice president atBaxter in Deerfield, Ill.

Preparing vaccines in cell cultures is notnew. Aventis, for example, currently pro-duces polio vaccines in the same monkeykidney cells that Baxter is gearing up to useto produce flu injections. And Baxter usedthe monkey cell line to replenish the U.S.supply of smallpox vaccine. So converting tocell-based systems, Katz says, would be“moving flu vaccine production into the

20th century at the beginning of the 21st.”Why has it has taken manufacturers so

long to come around to considering cell-based systems? Perhaps because current egg-based systems work so well, Webby surmis-es. Up-front costs for preparing productionplants to function with cells rather than eggsmight also be an impediment.

Clinical trials of cell-based flu vaccineswon’t begin in the U.S. until this fall, and ifapproved, the new vaccines will at first prob-ably just supplement those produced inchicken eggs. Having several different for-mulations of flu vaccine can’t hurt. Exceptmaybe for that muscle soreness that lingersfor a day or two after you roll up your sleeve.

Karen Hopkin is based in Somerville, Mass.

Dream MachineHOPES FOR A GIANT COLLIDER LIE IN A WORLDWIDE APPEAL BY DAVID APPELL

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For the Northern Hemisphere, theflu season typically runs from

November through March. Based oncollected virus samples and

infection activity, the World HealthOrganization decides which

influenza strains to include in avaccine in mid-February. By

mid-March, high-growth strains ofvaccine virus are provided to

manufacturers, and the materialsneeded to test the identity and

potency of the resulting vaccineare supplied in mid-May.

Vaccines become available inclinics in October.

Number of U.S. flu cases perseason: 29 million to 58 million

Number of Americans hospitalizedper season: 114,000

Number of deaths: 36,000

Number of vaccine doses producedthis season: 87.1 million

VIRAL TIMETABLES ALTERNATIVE MEDICINE: Researchers, including Richard Webby, a

virologist at St. Jude Children’s Research Hospital in Memphis, Tenn.,hope to speed influenza vaccine manufacturing by coming up with newoptions to the chicken egg as a virus growth medium.

COPYRIGHT 2004 SCIENTIFIC AMERICAN, INC.