11 September 2001>News Stories>On Many Fronts, Experts Plan for the Unthinkable: Biowarfare

On Many Fronts, Experts Plan for the Unthinkable: Biowarfare
NYTimes . 23 October

THE CONGRESS Congressional office buildings were closed after a letter sent to a senator tested positive for anthrax last week.

Protection against biological and chemical attack was never very high on lists of national priorities until the days after Sept. 11, when it collectively occurred to Americans how vulnerable they were.

An envelope that might (or might not) be filled with ominous powder, the possibility that someone might slip across a border with a jar of viruses, the impossibility of guarding every subway entrance and roof ventilator against a terrorist with a spray can: "In these times," said Dr. Frank Bia, an expert on infectious diseases and microbiology at Yale, "the unthinkable has become thinkable."

Here are assessments of the nation's ability to defend itself against germ warfare from a variety of perspectives, covering what has been done, what is being done, where gaps remain, what might be done to fill them and how quickly.

Knowing the Enemy

The current warning system for a bio warfare attack consists of Americans themselves people who might show up at the doctor's office with a skin lesion or flulike sniffles and fever.

By then, it may be too late in two ways. The deadly infection or toxin may have already spread through the body. And, it is too late to protect others; the exposure would have happened hours to days earlier.

The ideal would be something like a smoke detector, continually sampling air and sounding an alarm when something dangerous is found.

But biological agents are far more difficult to identify than chemical ones like nerve gas. "There are only a few kinds of chemicals," said Calvin Chue, a scientist at the Center for Civilian Biodefense Studies at Johns Hopkins. "With the biologicals, it's a different and complex story."

THE POSTAL SERVICE A New York City police officer inspects a mailbox in Manhattan.

Even seemingly clean air contains billions of germs, and deadly bacteria often have harmless relatives. A detector would test thousands, if not millions, of samples. Not only would it need to avoid false alarms but also report the cases where a pathogen was indeed floating in the air.

"Some organizations we've talked to said, `We'd rather not have your system here even if it had a 1 in 10,000 chance of a false alarm,' " said Dr. Richard Wheeler, an adviser to the Energy Department's Chemical and Biological National Security Program.

The military has spent hundreds of millions trying to develop such detectors, with some success. But they remain expensive, bulky and not 100 percent accurate.

THE SCIENTISTS Dr. R. John Collier is developing antitoxins to fight anthrax.

Similar technology for civilian settings is even further off. A Washington subway station has been outfitted with a prototype detection system designed to sound an alarm, identify a pathogen and tell response teams where the pathogens are.

But the system can detect only chemical toxins, not biological weapons like anthrax and smallpox. The eventual goal is to add those capabilities. Scientists at Lawrence Livermore National Laboratory have begun testing a system that is about the size of a lectern and collects air samples and runs them through a chemical analysis that would hook antibodies onto the pathogens and cause them to glow. That work is still at least a year from fruition.


Training and Talking

The response to confirmed anthrax cases in Florida, New Jersey, New York and Washington, is being viewed as a painful drill that has exposed gaping deficiencies in the country's ability to cope with bioterrorism. Experts on infectious diseases cited a number of areas that needed to be improved, including these:
  • Training for doctors, nurses, police, firefighters and others in how to respond to bioterrorism emergencies.
  • Expanding laboratory capacities to meet the surge in demand when thousands of specimens are sent for tests.
  • Communicating crucial information to doctors better and faster so they can quickly treat infected patients and assure people who are worried but well.
  • Finding ways for hospitals, which have cut costs by greatly reducing their number of beds, to open beds in an emergency.
"Our imaginations have not been broad enough," said Dr. Frank Bia, an expert in infectious diseases and microbiology at Yale. "When someone comes to the emergency room with something unusual, doctors must trust their instincts and sixth sense to make the pieces fit together."

Solving puzzling cases requires knowledge about exotic infections. But because anthrax and similar infections have occurred so rarely in this country, most doctors and nurses have, at best, only textbook knowledge about them.

Dr. Bia said the health system should tap the expertise of the many foreign doctors practicing in the United States who have treated anthrax in their native countries. "They are a resource right now," he said.

Health officials acknowledge that a major weakness in the response to anthrax has been the lack of effective communication.

Doctors often learn about new medical advances and refresh their memories about rare conditions in the conferences called grand rounds. But few hospitals have sponsored grand rounds on bioterrorism.

Dr. Stephen Baum, president of the Infectious Disease Society of New York, said he planned to hold such conferences at Beth Israel Hospital in New York City, where he is chief of medicine.

Last Thursday, an estimated 50,000 doctors, nurses and health workers viewed a teleconference on anthrax sponsored by the Centers for Disease Control and Prevention. Those who saw the program applauded its quality. But others did not have the required computer connections.

The capacity of laboratories needs to be expanded to deal with bioterrorism, said Dr. Baum, a member of the committee.

He said there must be "a unified way" for firefighters, police officers and emergency medical workers to respond to ill patients and potentially infectious material.

Then there is the nitty gritty. At least twice in the anthrax outbreak, generators have failed at the Centers for Disease Control and Prevention, delaying the laboratory work needed to determine who was infected.


Seeking a Better Vaccine

While drugs are useful in treating infections by some potential germ agents like anthrax, vaccines are prized by medical experts because they can prevent infections altogether or, in the case of anthrax, work with antibiotics to combat an infection.

The present anthrax vaccine is not ideal it requires six separate injections with an annual booster and is in any case reserved for military use.

Only one company, BioPort of Lansing, Mich., is licensed to make anthrax vaccine. But BioPort inherited an antiquated plant that has had trouble meeting Food and Drug Administration standards. Because of these problems, BioPort has been unable to make any vaccine since 1998.

A new anthrax vaccine is being developed by the DynPort Vaccine Company under contract to the Department of Defense.

Last week the Centers for Disease Control and Prevention applied for permission from the F.D.A. to use the stockpiled military vaccine for anyone allergic to antibiotics or who failed to respond to them in the event of anthrax exposure.

"Not only would some people be given just the vaccine but it might be something used in combination with antibiotics," said a spokesman for the C.D.C.

Military doctors who have considered the threat of deliberately spread anthrax concluded several years ago that people who may have been exposed to the spores should both take antibiotics and be vaccinated.

In a 1999 article, two military medical experts at the Army Medical Research Institute of Infectious Diseases, Dr. Theodore J. Cieslak and Col. Edward M. Eitzen, recommended that everyone exposed to anthrax in a bioterrorism attack should be given the antibiotics ciprofloxacin or doxycycline and that in addition, "exposed persons should be immunized." At least three doses of vaccine should be given, they wrote, before stopping the antibiotics.

But the Advisory Committee on Immunization Practices, a group of outside experts that advises the C.D.C. on vaccine use, concluded in December that a sustained course of antibiotics was the best protection for people who might have inhaled spores, and that vaccination was not necessary.

"You can do pretty darn well with antibiotics alone," said Dr. Charles M. Helms of the University of Iowa, a panel member. "Particularly if you have limited doses of vaccine to offer, there is no reason to get hung up on the issue of using both."

But Dr. Helms said there was always the risk that bioterrorists "would recognize the usual antibiotic and may create an antibiotic-resistant strain." He added, "I think we should clearly have more vaccine available."

Health experts also worry that large- scale use of antibiotics will hasten the rise of antibiotic-resistant diseases.

Another advantage of a vaccine is that it would allow people to quit the 60-day course of antibiotics much sooner than otherwise.


Antibiotics and Antitoxins

Even as government and industry are working to increase production of known treatments for potential biological weapons like smallpox and anthrax, scientists are trying to develop additional weapons.

For anthrax in particular, scientists say they have promising ideas. But, they say, the work is in its earliest stages and is far from producing a new drug that could be tested in humans.

One idea is to find an antitoxin, a molecule that neutralizes the toxins produced by anthrax bacteria. Since it is the toxins, not the bacteria themselves, that kill, antitoxins could block the germs' effects.

Dr. R. John Collier, a professor of microbiology and molecular genetics at Harvard Medical School, and his colleagues started on this path several years ago, and now have two possible compounds that might work. They are nowhere near ready to give the compound to people and, as with all new drugs, there is a good possibility that they will either be too toxic or too ineffective for human use.

One antitoxin acts like a decoy, attaching itself to sites on cells where active anthrax toxin binds and then combining with normal active forms of the toxin and inactivating them. The investigators began by testing the decoy toxin in rats, which die in 90 minutes if they are injected with the lethal anthrax toxin. But when Dr. Collier and his colleagues inject the rats with a mixture of one part decoy toxin to four parts active toxin, the rats "survive with no symptoms," Dr. Collier said.

The group also has a compound that blocks the last step in the assembly of the anthrax toxin a seven-sided structure that assembles on the surface of a cell and then delivers the toxins into the cell. This antitoxin sticks to the heptagonal anthrax toxin and prevents it from delving into the cell. The researchers tested it with the same sort of rat tests, with the same results, Dr. Collier said.

Another line of research involves a new type of antibiotic against anthrax bacteria. It was discovered by Dr. Lucy Shapiro, a Stanford microbiologist, and Dr. Stephen J. Benkovic, a chemist at Penn State, and their colleagues, who initially had no intention of going after anthrax. Instead, Dr. Shapiro said, they were designing a drug to inactivate a crucial enzyme used by so-called gram negative bacteria, a class that does not include anthrax. The made six new drugs, and all worked against gram negative bacteria in laboratory experiments, wiping out gram-negative bacteria that cause the diseases brucellosis and tularemia. Both bacteria are considered potential germ warfare weapons.

Then, Dr. Shapiro said, the group tried their antibiotic on gram positive bacteria, which do not have the enzyme the drugs were made to attack. They expected that the bacteria would be impervious. But, she said, "to our astonishment, it hit anthrax and multidrug resistant strep and staph." She said she had no idea why the drugs worked against these microbes.

Dr. Shapiro stressed that the work was just beginning. "If I were to give odds, I would say we have a 10 percent chance of getting all the way to an antibiotic," she said. "We are just now making enough to treat a rat. We are three years from availability if everything worked."


Messages, and Missteps

It is an axiom of public health that sound science and good medical care are essential to controlling outbreaks of disease. But anthrax has demonstrated that other things are equally important: strong leadership, and a clear public relations strategy.

As Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases, said in a recent interview, the anthrax scare, in which relatively few Americans have actually become sick, has been "high on terror, but low on biomedical impact."

Curtailing that terror is essential. In any outbreak, public health officials need people to follow their directions on such issues as, for example, taking antibiotics, being vaccinated or remaining where they are rather than fleeing, possibly spreading deadly germs as they go. The way to obtain the public's cooperation, experts say, is simple: by delivering accurate information, even if it might be scary.

"Leaders may feel that they are under a lot of pressure to deliver the message, `Don't worry,' " said Dr. Monica Schoch- Spana, a medical anthropologist at the Johns Hopkins University Center for Civilian Biodefense Studies. "Quite frankly, we would all love to have the message, don't worry, if we felt it really was grounded in honest to goodness truth. But because we can't have that ideal state, the next best thing is honesty."

In a bioterrorist attack, of course, government leaders must chart a delicate course.

"The main message in bioterrorism is that the government is putting the right programs in place," said Dr. Margaret A. Hamburg, a former New York City health commissioner. "But that is not a message that is very satisfying."

With anthrax, there have been missteps. On the day the public learned that a Florida man had been diagnosed with inhalation anthrax, for instance, Tommy G. Thompson, the secretary of health and human services, suggested that the man may have contracted the disease by drinking water from a stream.

The facts later proved Mr. Thompson wrong, causing some public health experts to fear that the public would lose faith in him and the federal government.

Another problem has been a lack of centralized information; because local public health officials typically control their own outbreak investigations, information and misinformation has come from various corners of the country. Self-proclaimed experts have dominated the airwaves, confusing reporters and, hence, the public.

"One of the lessons drawn from Florida is that the first thing Americans need to hear is a voice that speaks from knowledge, not hyperbole," said Amy Smithson, a bioterrorism expert at the Henry L. Stimson Center, a nonprofit research organization in Washington.

"Because so many Americans have now heard conflicting things, they are confused and they are frightened. And that is understandable."


Air Pressure and Fine Filters

Buildings are usually regarded as places of refuge, but under many circumstances, a germ attack indoors is likely to be far more dangerous than one outdoors.

Fortunately, say experts on building design and bioterrorism, many measures are available to make buildings much less susceptible to such attacks. They largely involve ventilation and filtering systems, but also include recommendations on surveillance and emergency planning. Further protections are being intensively studied.

"A terrorist would need far less to have the same effect" in a building than outdoors, said Dr. Anthony Policastro, a mechanical engineer at Argonne National Laboratory with expertise in bioterror. But indoors, he emphasized, the degree of danger can be greatly reduced.

Experts distinguish between attacks that originate outside a building and migrate inside and those that start inside.

When the attack begins outside the building, the experts say, among the most important measures is "positive pressure." That means adjusting the ventilation system so that the interior pressure is slightly higher than in the surroundings.

"This requires only a modest-size blower at the normal air intake to the building that makes sure that any leakage of air in the building is out rather than in," said Dr. Richard Garwin, a physicist and bioterror expert at the Council on Foreign Relations.

But the intake must be monitored so a terrorist does not introduce a biological or chemical agent into it directly. The intake should also be filtered with what are called high-efficiency air, or HEPA, filters, he said.

Related measures are available against an interior attack, although "a release inside the building is more difficult to respond to," said Jan Walker, a spokeswoman for the Defense Advanced Research Projects Agency at the Pentagon.

The research agency, which is in the middle of a three-year project called the immune building program to make military buildings resistant to germ and chemical attacks, is working on technologies to sense and destroy those agents before people in the building are even aware they are present.

But experts also know how to prepare buildings and respond to attacks inside them to reduce their lethality. HEPA filters are available commercially.

If installing those filters is not possible, said James E. Woods, founding director of the HP-Woods Research Institute in Herndon, Va., then filters should at least meet the standards of the American Society of Heating, Refrigerating and Air Conditioning Engineers. Mr. Woods said such filters remove even very small particles, like those that carry anthrax, with up to 90 percent efficiency.


Calling on Germ-Busters

One way to cut the risk of contamination from anthrax or other biological material arriving in a letter is to sterilize it.

This would never be practical for the entire annual flow of hundreds of billions of letters in the United States, postal officials said. But it could easily be done for a company or institution with some basis for concern say, a television network or the White House.

Last week, government health officials began contacting companies that routinely sterilize everything from bandages to the tops on whipped-cream spray cans to see if the equipment could be used to kill bacteria or spores in mail flowing to vulnerable government offices.

One senior health official, speaking only on the condition of anonymity, said the inquiries began at the request of White House officials. The White House itself refused to comment. "We don't discuss any specific security measures," Ann Womack, a spokeswoman, said.

Experts said an iron or microwave oven would not have enough energy to kill the durable spores of anthrax, which can stay dormant for a century or more in the soil.

But various devices can easily do the job, almost all of which use high-energy electrons or cobalt, cesium and other sources of radiation to penetrate material and destroy the DNA of any organisms. Experts noted that electronics or floppy discs could be ruined by the high-energy beams.

Also, most of these systems have not been tested to ensure they can destroy the anthrax bacterium. They do routinely kill other bacteria and spores that are just as hardy, including those that cause botulism, said Dr. James S. Dickson, the chairman of the microbiology department at Iowa State University.

Some manufacturers incorporate the systems on assembly lines making sterile products. Johnson & Johnson, for example, keeps Band-Aids germ-free this way.

There are also dozens of free-standing sterilization centers, including several large ones a short drive from Manhattan in New Jersey, that can handle shipments of mail, company officials said.

Last week, officials at a variety of companies that provide sterilization services or machines said they were assessing whether there might be a new, if unwanted, market.

"I wish I lived in a world where this doesn't happen, but if it does, there is equipment to deal with it," said Yves Jongen, the founder and chief research officer of Ion Beam Applications, based in Belgium with American headquarters in Chicago.


Defending the Travelers

A central challenge facing emergency planners is reducing the risk of a biological attack exploiting the country's web of transportation links.

Airports and subway, train or bus stations with crowds of travelers bound for many destinations provide ready-made dispersal systems for biological agents, terrorism experts say.

Ways to prevent that from happening are keeping the air clean, devising detectors to pick up promptly any hints of a release and having the ability to shut down the system at the first sign of a problem.

On planes, at least, the air is far cleaner than it used to be. Since the early 1980's all commercial aircraft have used extremely fine filters to clean recirculating air with filter pores small enough to capture almost everything 0.3 microns or larger. Individual anthrax spores measure one to three microns across.

Most illnesses caught on planes are caught from an adjacent passenger, not from floating pathogens circulating in the cabin, said Dr. Jolanda N. Janczewski, the president of Consolidated Safety Services, which advises airlines and other businesses on ways to prevent disease transmission.

Strategies for cutting terrorism risks in subways are being tested.

Cheryl Johnson, a spokeswoman for the Washington Metropolitan Area Transit Authority, said officials planned to use some of the new technologies, including chemical sensors and computerized alert systems, in a simulated subway attack later this year.

The last line of defense is to make sure that a transportation system can be quickly shut down to prevent dispersal once a release has been identified. The Sept. 11 attacks showed that the Federal Aviation Administration could rapidly stop air travel, and most subway systems, including the New York City system, can be stopped almost immediately from a central control room.