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'Concerns Are Very Real'
Expert Panel Discusses Bioterrorism Threat,
Preparedness in U.S.

By Rich McManus

Photos: Bill Branson

On the Front Page...

The thought of adapting biological agents to do harm instead of good seems anathema at NIH. But the campus played host Mar. 23 to a sober discussion of how the United States must prepare nonetheless for the possibility, once regarded as taboo, that some group may use viruses, bacteria or toxins to sicken or kill unsuspecting thousands of citizens. Because this threat has become more plausible in recent years, NIH's role in both disease prevention and therapy has broadened.

Continued...

"This is a subject we would as soon not have to talk about at all," admitted Dr. Donald A. Henderson, director of the Center for Civilian Biodefense Studies at Johns Hopkins University, who was the keynote speaker at a STEP Science for All session titled, "Bioterrorism: Ready or Not?" Widely regarded as the architect, while at the World Health Organization, of the plan that has eradicated smallpox worldwide, Henderson said he "didn't expect to be discussing smallpox again as a weapon, but I'm afraid this is where we are."

Smallpox authority Dr. Donald A. Henderson of Johns Hopkins said the virus could be used eventually as a weapon of bioterrorism.

Arguing that the threat of bioterrorism is neither hype concocted by scientists in search of fatter research budgets nor the result of sensational reporting by irresponsible media, he said, "I'm afraid the concerns are very real. The consensus is that a bioterrorist event is likely in the next decade, and that it could be a catastrophic one. We've only just begun to prepare."

Like nuclear and chemical warfare, biological weaponry is intended for mass destruction. While the world has some experience with nuclear war (Japan in World War II) and chemical warfare (during WW I, the Iraq/Iran conflict, and in 1995 when a religious cult in Tokyo poisoned thousands with sarin gas), biological warfare has been little used, said Henderson. During the French and Indian War, the British gave smallpox-infected blankets to Indians to transmit the deadly virus, Henderson recounted, and the Germans tried to "weaponize" anthrax during WW I. He said the Japanese "undertook extensive work that is very little known" to wage biological warfare against mainland China during WW II.

As science grew more sophisticated in the postwar period, "the negative side of developments in biology— like the dark side of nuclear power — resulted in a bioweapons race among the world powers," continued Henderson. In 1969, President Nixon tried to end the offensive use of biological warfare, an effort that resulted in the Biological and Toxin Weapons Convention of 1972. "Iraq and Russia signed on," noted Henderson, "and so did the U.S."

The result was an evolving complacency. "That was the hallmark for many years," Henderson said. "It was a taboo subject at academic institutions." Four characteristics kept biological warfare in the background of world affairs: it was historically uncommon, morally repugnant, technologically difficult (not only hard to produce, but also tough to deliver via aerosol), and, lastly, unthinkable.

Breaking the Taboo

Since 1995, however, the taboo's potency has eroded. That was the year an Iraqi defector, Saddam Hussein's son-in-law, produced the so-called "chicken coop documents" showing a biological warfare program far more extensive than anyone had imagined. "It was a log greater in sophistication than anyone had given them credit for," Henderson said, and included schemes to deliver aerosolized anthrax and botulism toxin by drone aircraft. Nineteen-ninety-five was also the year the Japanese religious cult Aum Shinrikyo spread sarin gas at 5 stops in Tokyo's subway system, hoping to kill hundreds of thousands of people (12 people died and there were some 4,000 casualties — probably because the group used only 30 percent pure sarin, said another panelist). "They had tried to use anthrax and botulism toxin before the sarin event," reported Henderson. "They had trucks with aerosolizers ready, but they had the wrong strain of anthrax and the nozzles on their spray guns got plugged up. What they released was something more like an anthrax vaccine than anthrax," he said. Aum Shinrikyo failed in eight previous attempts to effect mass destruction before the sarin incident, he said, adding that the group is still legal, has many devotees worldwide (including some in what used to be Russia) and conducts businesses earning revenues of $20 million to $30 million a year.

"We haven't heard the end of Aum Shinrikyo," he predicted. Also, in 1992, Soviet scientist Ken Alibek defected to the West, revealing "quite a remarkable story of what Russia had been engaged in. They had a very extensive complex of facilities in eight cities, employing some 60,000 people engaged solely in biological warfare work," reported Henderson.

"They took advantage of the eradication of smallpox by 'weaponizing' the virus — putting it on multiple re-entry warheads. These were strategic weapons for use in lands far distant, such as the United States."

This evidence led to a Presidential Decision Directive in June 1995 to coordinate national preparedness measures among a variety of federal agencies including the FBI, HHS and Defense Department.

The Journal of the American Medical Association devoted an entire issue to bioterrorism in 1997; four themes were enunciated: a bioterrorist act is increasingly likely, civilian preparedness had scarcely begun, prevention is extremely difficult, and interdiction is extremely unlikely.

Henderson said evidence of an incident of bioterrorism — the "poor man's nuclear weapon" — would likely first show up in an emergency room. "That's the first we'll know we've had an outbreak," he said. Possible agents of such an attack could be anything that infects man, but "serious damage will likely result from smallpox, plague or anthrax." According to Soviet defector Alibek, Russia at one time had some 30 tons of dried anthrax spores, capable of quick activation, in storage.

Smallpox Outbreaks Hint at Danger

Two outbreaks of smallpox in Europe during the 1970's hint gravely at its danger, said Henderson. The first occurred when a German electrician returned from Pakistan. Treated at Meschede Hospital, the man never left his room but managed to infect others throughout the facility, including patients one and two floors above, and a person who only briefly opened a door some 30 feet from the patient's room to ask directions.

"This is what an aerosol would do," forecast Henderson, who said the man had a cough that helped spread the virus. Appearing first as severe flu and rash, smallpox then raises extremely painful sores and high fever; 30 percent of those infected die — survivors are left with scabs and pitting scars. There is no treatment.

The second outbreak occurred in Yugoslavia in 1972; it was the first case in that country since 1927. In this instance, a pilgrim returned from Mecca, and had been previously vaccinated against smallpox, but came back with a mild case. This patient managed to infect 11 others within a few days; those in turn infected 135 more. By the time the small epidemic had been contained, 175 cases had been found.

"The countries around Yugoslavia closed their borders in response to the outbreak," Henderson said. "This is the type of action this disease engenders. The government decided to vaccinate all 20 million of its citizens in the following weeks. Some 10,000 people ended up in isolation.

"This was not a big epidemic," he cautioned, "but a dramatic one. It occurred in a country where smallpox vaccination was regularly provided to all its citizens."

The United States ended its smallpox vaccination program in 1972, noted Henderson. "But immunity is not lifelong — it drops over time. Only about 10 to 20 percent of the population today is immune. We're a more susceptible population than at any time in history."

He noted that Maryland has only 80 or so negative-pressure hospital beds, which are the kind a smallpox patient would occupy. "If you figure that 10 or 20 people get infected from each person with smallpox, and consider the succeeding generation of cases, the scenario is not a pleasant one."

An accidental release of anthrax in 1979 at a bioweapons plant in Sverdlovsk, Russia, resulted in more than 75 human deaths and many animal deaths as spores drifted as much as 30 miles downwind. "Most of the deaths occurred within 3 or 4 days, but some were as late as 42 days," said Henderson. "It grows very rapidly in the lungs. It's too late to provide antibiotics once the disease is recognized. It's a very ugly disease indeed."

Spores are viable for 40 or 50 years once they settle out of the atmosphere; they are tasteless, odorless and behave like a gas, invading both interior and exterior spaces. "There is no (anthrax) vaccine available for civilian use," Henderson cautioned. "You can give antibiotics, but the patient would need them for 2 months after the disease was diagnosed."

There are only 6 million or 7 million doses of smallpox vaccine in the U.S., said Henderson, and that would "quickly run out after the the first two generations of cases. There is no capacity anywhere in the world to meet the potential need."

The federal government is now providing funds to create a reserve supply of vaccine, and to train "first responders" to a potential terrorist act in which an explosive or chemical agent has been used. "These will be emergency room folks, police and fire fighters. Essentially, nothing has been done so far to train the medical and public health personnel who are the first responders to a bioweapons event," Henderson reported.

He said six policy "white papers" are in preparation; the first one, on anthrax, is due in May, to be followed by papers on smallpox, plague, etc. "Happily, money has recently been allocated to HHS to counter the threat of bioterrorism." He said that $150 million has been appropriated this year, and that the President's request for next year is in the range of $230 million.

"We've only begun to acquaint the medical and public health community that there is a problem," he concluded. "There's a lot to do. There is at least an awareness and concern now on the part of the public health profession."

Prudence of Paranoia

Watchdogs at the federal level include Dr. Ali Khan, deputy director of CDC's Bioterrorism Preparedness and Response Activity, who noted that "civil defense is unlikely territory for public health experts. Nowadays, I talk to the FBI every day."

Dr. Ali S. Khan is deputy director of CDC's Bioterrorism Preparedness and Response Activity. He said the threat of bioterrorism is forcing public health authorities to consult regularly with law enforcement officials.

He said CDC's resources are currently strained simply for nonterror outbreaks of illness, to say nothing of such deliberate infections as the 1984 seeding of salad bars with salmonella in The Dalles, Ore., by members of the Rajneeshee cult, or an incident in Dallas in 1994 when a disgruntled worker put shigella bacteria in coworkers' donuts and muffins.

"We need to be prepared for any (biological) agent that might be used against us," he said, "including via food, water, air, insects or the blood supply. The job ahead of us is even bigger than we thought initially."

Unlike conventional warfare, with biological attack there is no "bang" to respond to, said Khan. "It might be 2 or 4 days, depending on the agent, before we recognize a terrorist act." Epidemiologists at CDC must sift through a menu of clues to determine if nature or man is behind any unusual outbreak. Sadly, hoaxes are common at CDC, which handles 5-10 such calls per day. CDC is bolstering its preparedness in two major areas, Khan said: it is expanding capabilities with its traditional allies in state and local health departments ("The rapidity of response at the local scene is more important than ever before," he noted) and beefing up its surveillance, epidemiology and lab diagnostics capability. A multilevel national laboratory network will enable CDC to answer the newest question on its mind: "Could this be bioterrorism?"

CDC is also purchasing $51 million worth of supplies for its National Pharmaceutical Stockpile, and developing a Rapid Response and Advanced Technology Laboratory, since most states don't have labs that can handle biosafety level-3 agents. "The purpose of the rapid diagnostic lab at CDC is not to replace local labs but to serve as a national reference and provide reagents and proficiency testing for local laboratories," Khan said, adding that bioterrorism funding at CDC in FY 1999 is about $121.7 million.

Even if no incidents of bioterrorism occur, "strengthening our public health infrastructure will serve us in good stead for any new and emerging infectious diseases, and food-borne illnesses from abroad," said Henderson. Unlike a group of National Guard units being trained as first responders who would be utilized only if needed, biological warfare first responders will always be on the job, always contributing to public health. "It's a very good investment," Henderson argued. "Broadening our defenses generally is good policy."

The NIH Role in Preparedness

Though bioterrorism didn't surface dramatically in the NIH appropriation until FY 2000, about $13 million of ongoing basic research overlaps with research needs related to bioterrorism (about half that figure, roughly $7 million, is very specifically targeted to likely agents of bioweaponry).

According to Dr. James Meegan, acute viral infections program officer at NIAID, events as far back as the 1982 Tylenol scare alerted public health authorities to the threat of biology-based violence against the citizenry. NIH is focussing on agents that pose the biggest public health threat, including smallpox, anthrax, plague, tularemia, and other agents.

"Protection of the civilian population is a very different challenge than military preparation," he explained. The military is quite homogeneous — mostly young, male, and not immune-depressed. Therefore, "A tool optimum for the military might not be optimum for the civilian population."

Meegan said NIH is working closely with other branches of government to develop a comprehensive research plan, including new diagnostics, therapies and vaccines. "We're also working with FDA to streamline the approval process for therapeutics, but mainly for vaccines."

The current smallpox vaccine is an old preparation based on calf lymph, and is not optimum for many who may need it, he reported. It is also in short supply, and requires special bifurcated needles for delivery; there aren't enough of those, either. Further complicating preparation is a lack of corporate sponsorship for work on a smallpox vaccine, for which there is currently no market, and the fact that smallpox isn't even available as a research tool; scientists must use vaccinia and monkeypox as surrogates.

"A new therapeutic antiviral drug could be of great benefit treating smallpox infections and treating complications that might occur during an immunization campaign," said Meegan. "We don't know which strain of smallpox might be used as a weapon against the U.S., so a broad-based therapy needs to be developed."

Foreseen is a new smallpox vaccine propagated in cell culture, not calf lymph; the Defense Department is working on such a product that would protect both civilians and troops.

Meegan said a federal working group is examining the current 6-shot anthrax vaccine, but noted there is very little research base on this organism. Perhaps only two doses of the current vaccine would be effective, he noted, although a new, recombinant product looks promising in monkeys.

As thorough, reasonable and sophisticated as the NIH contribution to preparedness is, the notion of the evil motivating such readiness is still a stumbling block, Meegan admitted. "As scientists, we have a hard time grasping evil intent." He remains baffled by the motive behind the Oklahoma City bombing of April 1995: "How could anyone park a Ryder truck full of explosives in front of a day care center, then get out and look kids in the eye before leaving the scene?" he asked.

The program wrapped up with presentations by a Montgomery County official who spoke about local readiness which, though fairly meager, still far outdistances most counties in the U.S., according to Henderson, and NIH's community liaison Jan Hedetniemi, who warned of community fears that NIH may eventually be called upon to harbor dangerous viruses or bacteria in the event of a national emergency.