Researchers try to keep pace with biological threats

Before Sept. 11, smallpox had been conquered, plague was a chapter in Medieval history, and anthrax was a heavy-metal band.

In government, military and academic labs, a few scientists were studying these and other rare scourges that might be used in warfare or terror attacks.

But the big pharmaceutical companies were focused instead on diseases with bigger markets -- such as HIV, influenza, meningitis, chicken pox or pneumonia.

So, when the terrorism of Sept. 11 put fear of bioterrorism on the front page, America opened its medicine chest to find that its defenses against the most likely bioterror agents were wanting.

Dr. Tara O’Toole, of the Johns Hopkins Civilian Biodefense Studies Center, told Congress that the United States had effective vaccines or drug treatment for just 12 of the 50 most serious pathogens thought to be likely bioweapons agents.

Developing and producing new vaccines to defend Americans against even the most likely bioterror agents could take a decade, and hundreds of millions of dollars -- each, experts say.

But there is new momentum.

“There is, every day, more and more marshaling of resources and thoughts to try and become prepared,” said Dr. Myron Levine, director of the University of Maryland Center for Vaccine Development.

Last year’s federal budget included about $350 million in public health spending related to bioterrorism defense preparations. Sen. Edward M. Kennedy, D-Mass., and others have proposed spending more than $1.4 billion on biodefenses in the current year. The Bush administration has discussed an $800 million figure.

U.S. Health Secretary Tommy G. Thompson has ordered the National Institutes of Health, the Centers for Disease Control and Prevention, and the Food and Drug Administration to join hands and work with private industry in the United States and abroad.

“He knows the urgency of it and is getting personally involved to make sure we don’t have any insurmountable barriers,” said Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases.

The government has its best head start with smallpox -- one of mankind’s most feared and deadly and disfiguring diseases until it was eradicated in the world population in the 1970s.

Routine smallpox immunization for American children halted in 1972, and the immunity of those vaccinated before then has largely worn off.

Experts see no need to develop a new vaccine. The old one worked well. The problem is supply.

The CDC still has 12 million to 15 million doses of the old vaccine stored in warehouses. That seemed like plenty before Sept. 11. But “that certainly is not enough to contain pockets of deliberately started epidemic disease in this country,” Fauci said.

To boost its stockpiles, the federal government last year hired the British firm Acambis P.L.C. to produce 40 million doses of a purer, safer vaccine by 2004, at a cost of $343 million. That schedule has since been accelerated to 2002.

“Forty million would be a very good start on being able to curtail an epidemic,” Fauci said.

In the interim, the CDC has launched a study at the University of Maryland and three other centers to find out whether the 25-year-old vaccines still work, and whether they would work if diluted.

Dilution “would automatically increase the existing stock by five to 10 times,” said Dr. Carol O. Tacket, chief of adult clinical studies at the UM Center for Vaccine Development and a principal investigator in the study.

Universal vaccination is rejected by most experts because the vaccine itself carries small, but significant risks, including encephalitis. If all 270 million Americans were vaccinated, more than 500 could be expected to die from it.

The anthrax vaccine in America’s bio-arsenal is far more problematic. Approved only for the military, it is in such short supply that it has been given to less than one-quarter of the 2.3 million soldiers scheduled for inoculation.

It requires six painful shots over 18 months, with annual boosters. And it is slow to confer immunity.

Worse, the government’s only supplier, BioPort, of Lansing, Mich., has been shut down since 1998. It has failed two inspections by the U.S. Food and Drug Administration in its bid to start up its production line. It awaits a third.

“It’s not your optimum vaccine,” Fauci said. “Its efficacy has not been fully tested in a bioterrorism situation. It’s logistically difficult to make, and it takes a long time to develop immunity.”

Development of new anthrax vaccines is now under way at the NIH, at the Defense Department and in private labs in the United States, Britain and Israel.

Dr. Neal Halsey, director of the Institute for Vaccine Safety, in the Johns Hopkins Bloomberg School of Public Health, says the FDA has said it could approve such vaccines without efficacy trials. But researchers will have to show the vaccine protects animals, and produces just the right antibodies in people.

Experts caution that vaccines are not always the only answer to a disease threat. For example, people exposed to anthrax can be saved by 60 days of antibiotic treatment, so long as they’re treated before symptoms appear.

There is no vaccine for pneumonic plague. But 10 to 14 days of antibiotics can provide a cure, even after symptoms begin.

Where entirely new vaccines are needed, researchers face huge hurdles.

“There’s a lot that has to happen, between knowing how a disease works, and whether you can protect animals and humans, what antigens work and how to deliver them,” said Dr. Ripley Ballou, a vaccine researcher who spent years pursuing a malaria vaccine for the Walter Reed Army Institute of Research. “These questions take a lot of time.”

It takes $100 million to $300 million to bring a new vaccine to market.