Johns Hopkins Magazine -- February 1999
Johns Hopkins 
     Magazine Home




Biological weapons exist today that could kill thousands, if not millions, of people. Medical personnel are alarmingly ill-prepared to meet the threat, warns the man credited with eradicating smallpox.

P U B L I C    P O L I C Y    A N D    I N T E R N A T I O N A L

Rx Against Terror
By Melissa Hendricks

This past October, a worker at a Planned Parenthood clinic in Indianapolis opened an envelope to find inside a brown powder and a note that claimed the substance was anthrax. Emergency workers quickly evacuated the clinic. The 31 staff members and patients who had been in the clinic were hosed down and scrubbed off in the parking lot, and rushed to a hospital where again they were decontaminated. These allegedly exposed people also received the antibiotic ciprofloxacin, which is effective against anthrax.

Apparently, hospital personnel also dosed themselves with ciprofloxacin, probably to prevent contracting the disease. Sometime during this incident, extra samples of the drug were removed from hospital shelves.

Afterward, labs concluded that the brown powder was not anthrax. The threat had been a hoax. The emergency and hospital teams were commended for responding so quickly to a crisis that could have led to fatalities.

But was it the right response?

Donald Ainslie (D.A.) Henderson sees several things wrong.

Decontaminating people is the proper procedure to follow if a victim has been exposed to a chemical; chemicals can

penetrate the skin, says Henderson, University Distinguished Service Professor and former longtime dean of Hopkins's School of Public Health. But in Indianapolis, the alleged agent was dried spores of a bacterium. The risk would come from inhaling the organism, probably not from skin contact. It is unlikely the worker who opened the envelope would have disturbed its contents enough to disseminate them throughout the clinic, or even a few feet.

Furthermore, hospital personnel were not at risk of contracting anthrax from their patients. The disease is not spread from person to person. Taking ciprofloxacin would have been unnecessary.

"We treated it as a chemical response because everyone knew how that system worked," says Mark Kirk, the associate medical director of Indiana's Poison Center.

And that is the problem, says Henderson. Medical, public health, and emergency personnel throughout the nation are simply not adequately prepared to respond to an incident of biological terrorism.

The threat is real
In 1985, hundreds of Americans were sickened when followers of the Bhagwan Shree Rajneesh planted salmonella in Oregon salad bars. A decade later, the Aum Shinrikyo cult released the nerve gas sarin on a Tokyo subway (above), killing 12 people. Investigators later discovered that the cult was also producing a variety of biological agents and had allegedly launched botulinum toxin and anthrax, in ultimately unsuccessful attempts to kill large numbers of people. The cult had also attempted to procure Ebola virus from the former Zaire for use as a weapon.

The time has come to prepare, says Henderson. To date, most bioterrorist incidents have involved individuals or fringe groups rather than rogue nations. But the potential exists for far more illness, death, and psychological trauma. Several countries have produced biological weapons that could sicken and kill hundreds, thousands, even millions of people, says Henderson. Iraq, for instance, fitted SCUD missiles with warheads containing botulinum toxin, aflatoxin, and anthrax. Iraq's continuing evasiveness and the Desert Fox operation only underscore the uncertainties about Iraq's germ weapons capabilities.

Despite the very real potential for disaster, says Henderson, "there's been no involvement yet of the hospitals or the public health people.

Alarmed by the nation's lack of preparation, Henderson established the Center for Civilian Biodefense Studies at the School of Public Health last August. The center is working to alert and inform medical and public health professionals about the threat of bioterrorism, and to serve as a sort of public health think tank for responding to bioweapons use, says Henderson, who is the center's director. Their work, he notes, complements other efforts to reduce the risk of bioterrorism through improved intelligence and diplomacy.

Top names in the field have signed on as center members and collaborators, including the former and current directors of the U.S. Army Medical Research Institute of Infectious Diseases, USAMRIID. The center is due to receive a $1 million appropriation from Congress. And this month, it is sponsoring a national symposium on the medical and public health response to bioterrorism. Featured speakers include U.S. Health and Human Services Secretary Donna Shalala, terrorism experts from the FBI, infectious disease specialists, and city and state health officials.

HENDERSON, 70, IS BEST KNOWN for his leading role in eradicating smallpox. Once the world's most dreaded disease, smallpox covers the body with painful sores and causes muscle pain and fever. It is incurable, kills a third of the people it infects, and usually leaves survivors covered with pockmarks. As director of the World Health Organization's global smallpox eradication campaign in the 1970s, Henderson and his force of vaccinators swept across India, Bangladesh, other parts of Asia, and Africa, vaccinating millions of people against the disfiguring disease. By 1980, the WHO declared that smallpox was officially vanquished.

"I never thought smallpox would return," states Henderson. "Ever."

But in recent conversations with the Soviet defector Ken Alibek, who had helped lead that nation's biological weapons program in the 1980s and early '90s, Henderson learned that the Soviets had stockpiled dozens of tons of smallpox and hundreds of tons of anthrax. According to Alibek, Russian scientists are still conducting research that is suspiciously close to the development of biological weapons. The potential that some vials of smallpox are unaccounted for still worries Henderson, who now finds himself pondering an old enemy.

"In a way, I resent it," he says. "We should not at this time have to worry about smallpox or other biological agents used in terrorism. We should not have to work on the potential of man's inhumanity to man rather than trying to combat natural maladies and diseases."

When Henderson was battling smallpox in the 1970s, his team used brute force public health strategies to rout the germ. At one point in India, patients with smallpox were confined to their homes, and guards were posted at their front and back doors. No one was allowed to enter or leave unless they had been vaccinated against the virus.

But can such an approach be used to respond to illnesses that could be released anywhere, anytime? "It's not like a war where you know when it is going to happen," says Trish Perl, the hospital epidemiologist at Hopkins and a member of the Center for Civilian Biodefense.

The Deadliest Five

Inhalational Anthrax
Bacillus anthracis

Variola Virus

(Pneumonic) Plague
Yersinia Pestis

Viral Hemorrhagic Fever

(Inhalational) Botulism
Clostridium botulinum
The first step is alerting people to the problem. For the past year, Henderson has traveled around the country, lecturing about the threat of biological weapons to medical and scientific organizations ranging from a hospital in Hartford to the Council of the National Academy of Sciences.

Henderson tells these professionals that the nation needs to increase its supply of vaccines and drugs against smallpox and other potential biological weapons agents. The United States currently has only enough smallpox vaccine for about 6 million people--and part of that stock has probably deteriorated, he says. Worse, there are no production facilities anywhere in the world to make more smallpox vaccine.

He also stresses the importance of training health workers to diagnose and treat casualties of bioterrorism. Public health surveillance systems should also be enhanced, he says, so that they can better spot new disease patterns that could alert health workers to bioweapons use.

Henderson has assembled a working group of biodefense experts, which recently drew up a short list of potential biological weapons that would pose the greatest risk. The group includes representatives from the Centers for Disease Control and Prevention, USAMRIID, and the Department of Health and Human Services.

The good news is that the list includes only five microorganisms- -a manageable number anyway, not the infinite variety that some biologists had feared could pose a threat. At the top of the list and potentially far more harmful than any of the others are smallpox and anthrax, followed by plague, hemorrhagic fever viruses (such as Ebola, Marburg, and Lassa), and botulism (see p. 15). Tularemia is a runner-up.

The bad news is that these microrganisms cause horrendous diseases, some incurable, which have the potential to paralyze cities, perhaps entire nations, and wreak physical and psychological trauma.

The bacteria and viruses were chosen because of their ability to cause catastrophic illness and significant loss of life, and because it is believed that a perpetrator could procure and weaponize them, and disseminate them to a large population. The experts also concluded that the aerosol release of these agents would pose the gravest danger. Spreading disease through water or food is technically more difficult.

The working group is now examining each germ in detail: its history, epidemiology, symptoms, and treatment. All this information is being published as a series of white papers. The first, expected to appear early this year in the Journal of the American Medical Association, is on anthrax.

Obstacles to inspection
In a 1994 inspection of Al Hakam, an R&D plant in Iraq, Raymond Zilinskas was told that fermenters and other equipment were being used for benign purposes: to grow yeast as a protein supplement in animal fodder, and produce bacteria for use in pesticides. But to Zilinskas and his fellow inspectors from the United Nations Special Commission (UNSCOM), many things did not wash. "It was very obvious" that Al Hakam was used to produce biological weapons, says Zilinskas, adjunct faculty member at Hopkins's School of Public Health.
   Al Hakam was located in the middle of the desert, away from any city or town, and its operations were divided among three buildings, each separated by a mile. "That's not efficient, but it is if you want biological security," he says. And the equipment was far more extravagant than scientists would need to grow yeast or pesticides. When the inspectors asked about a missing lot of culture media, used for growing bacteria, Iraqi scientists told them it had been destroyed in a recent bombing. But there'd been no bombing. "Oh, well, there was a fire." There was no evidence of a fire. "Well, there were riots." But there were no riots. And on it goes. "It's obvious to everyone that these are lies," Zilinskas says. "They've been carefully coached."
   He ended up feeling sorry for the scientists, whose lives could have quickly been extinguished if they had said the wrong thing: "The scientists are servants of the government, and the government is not forgiving."

NATURALLY OCCURRING ANTHRAX generally causes a cutaneous disease, which is easily cured by antibiotics. But a biological weapon would most likely be used in aerosol form, leading to inhalational anthrax, a far more deadly disease. It is caused by inhaling minute spores of Bacillus anthracis, which form when the bacterium is exposed to air. The tiny particles penetrate into the very depth of the lung, where they germinate into bacteria that secrete toxins causing swelling and bleeding in the chest cavity. The infection can spread to the blood, causing septic shock, and infect the brain.

Once the organism begins to grow, death occurs quickly--on average in two to three days, Henderson says. "There is some question of whether any treatment at all is of value once the symptoms begin," he says. "It goes that fast. In animals that have died, 25 percent of the dry weight of the blood is made up of organisms."

There have only been a handful of cases of inhalation anthrax in the U.S. in the past century, most occurring among workers in hide-processing plants. (Grazing animals can inhale anthrax spores that are deposited naturally in the soil.) But in 1979, anthrax spores were accidentally released from a biological weapons plant in Sverdlovsk, Soviet Union. The germ sprayed out into the atmosphere, infecting people within a three-mile corridor. At least 66 people eventually died from inhaling it.

Sverdlovsk provided valuable information for Henderson's working group and highlighted the daunting challenges of responding to such a crisis. One task, they concluded, would be figuring out where anthrax exposure took place and how many people were infected. Suppose a quarter of the people in a town of 100,000 were exposed. Says Henderson, "You can't smell [the aerosol]. You can't see it. Nobody would know it was there. So you'd wind up having to deal with the whole population in that area"--all 100,000 people.

How to treat them? While studies in monkeys have shown antibiotics to be successful in preventing onset of the disease, Russian scientists have reportedly produced antibiotic-resistant anthrax. "It's jolly," says Henderson, grimly. Fortunately, the center's experts came upon one class of antibiotics that would be difficult to resist against: the quinolones, including ciprofloxacin (normally not prescribed for children or pregnant women because it apparently inhibits bone growth). The scientists recommend that an exposed population start taking ciprofloxacin and then, if tests indicate the germ is sensitive to penicillin, to shift to that drug or one of its relatives, which are less expensive and have fewer side effects.

A vaccine, currently used by the U.S. Army, could also be employed--at day zero and two weeks later. At this point, though, "there is no vaccine for civilian use," Henderson reports. Even if one becomes more widely available, most likely there will be only limited quantities. So who should receive it--medical personnel, firefighters, police? "That's a decision that will have to be made," he says.

The center's experts did find one ray of light in their study of the literature on anthrax. Once the spores settle to the ground, they do not easily resuspend. No cleanup was conducted at Sverdlovsk, but after the initial rash of anthrax cases, no further infections occurred. "So our assumption here is that once the aerosol settled out, the risk would be very, very small," Henderson says. Nonetheless, "I think it would be impossible to say to the public, 'Look, just go back in. Don't worry about it. The risk is very small.' This is not going to go over very well."

IF SOMEONE DUMPED ANTHRAX on Baltimore, no one would be in charge," says John Bartlett, director of the Division of Infectious Diseases at the Johns Hopkins School of Medicine and a member of the Biodefense Center. "There has been no planning at the city or state level. I doubt there is a physician in Maryland who has ever seen a patient with inhalation anthrax. There probably is not a lab technician who has identified anthrax."

Diagnosing and treating a disease in one person is relatively straightforward medicine. But when the number of patients is multiplied by 1, 10, or 1,000 orders of magnitude, the task becomes one of complex logistics.

If anthrax were released at a Denver shopping mall, for instance, 9,000 people might be exposed. Of those, 2,600 would require intensive care. But Denver has only 300 ICU beds.

When Hopkins's Trish Perl heard a speaker describe this hypothetical scenario during a recent meeting in Denver of infectious disease specialists, she thought: The same thing could happen in Baltimore or any number of cities across the U.S. "The hospital infrastructure would probably be overwhelmed," she says.

Henderson recently learned that the Soviets had stockpiled dozens of tons of smallpox and hundreds of tons of anthrax. He now finds himself pondering an old enemy. "I never thought smallpox would return, he says. "Ever."
Photo by Stephen Spartana
So Perl, whose responsibility is to prevent the spread of infectious diseases within the hospital, is crafting a bioweapons response plan for Johns Hopkins Hospital. As a starting point, she is working from the hospital's existing "Outbreak Management Plan," and systems set up to respond to bombing or civil disobedience. Obviously, she says, a bioweapons policy will have to be far more detailed. Unlike a conventional bomb or a nuclear attack, says Perl, "with a communicable disease, you would have ongoing cases."

Some strategies are obvious: Stop elective surgery at the hospital. Isolate infectious patients. "I'll identify a dedicated group of healthcare workers who will come in contact with the patients," says Perl. Each would have to receive appropriate vaccinations or prophylactic antibiotics, if these existed and were available.

But other decisions are more difficult. If city residents were exposed to aerosolized anthrax, for example, there would be a limited supply of antibiotics to treat them. Who should receive them? "I imagine there is going to be total hysteria," says Perl. "I'm going to be forced to ration it."

Then there is the matter of where to house patients. Suppose 200 patients who potentially have been exposed to a germ weapon are brought to the hospital. Perl's first thought was to place them in the Turner concourse, a large lobby at the School of Medicine used for conferences and classes. "Then I learned the ventilation system couldn't handle them. It would recirculate the germs," says Perl. She plans to search for a better arrangement.

If the germ were smallpox, which is transmissible from person to person, then ideally the patients should be placed in negative-pressure rooms, designed to prevent germs from leaving the room, Perl notes. But Hopkins has only 19 or 20 such rooms. So here again, she must come up with an alternative solution.

Other questions arise. Should equipment be disinfected with bleach (plentiful but potentially damaging to equipment), or with quaternary ammonia (milder but more expensive)? Probably bleach, she's concluded. How should the hospital dispose of corpses of infected patients? Probably through cremation, sighs Perl. The questions, it seems, are endless.

ACROSS THE COUNTRY, public health officials are just beginning to ponder a response to bioterrorism, says Henderson. New York City is probably farther along than any other municipality.

If bioterrorists sprayed anthrax in a New York subway or dumped smallpox in the city's waterworks system, Jerry Hauer would be on the front lines of the response team. Hauer (MPH '78) is director of the mayor's office of emergency management for New York City. If a bomb explodes in the Empire State Building or a water main breaks on Fifth Avenue, Hauer is one of the first people to know. He is on call 24 hours a day, seven days a week, a responsibility he undertakes with aplomb.

Hauer and a small staff are creating a bioterrorism response plan. Though he won't go into details for obvious security reasons, the plan's bottom line is vigilance.

"In all likelihood the first indication of bioterrorism will be through public health reporting," says Hauer. He receives daily updates on health indicators through a surveillance system. If there is a case of equine encephalitis virus in Manhattan, which happens once or twice a year, Hauer is notified. Similarly, the system could alert him to an act of bioterrorism by identifying blips in the data of reported illness. As examples, he cites "a disease we don't usually see, such as anthrax, or unusual clusters of illnesses."

Both Hauer and Perl note that a major part of their task will involve managing the psychological trauma that any biological weapons incident would spawn. A tiny amount of a germ weapon, or even a mere rumor of such a weapon, would scare the bejesus out of people, leading some to rob pharmacies for vaccines and antibiotics, and potentially causing mass exodus.

"We have to be careful not to create hysteria," says Hauer. "We don't talk about it in the general media. There is very little citizens can do to prepare. You have to have a balance; you can never completely prepare."

"If someone dumped anthrax on Baltimore, no one would be in charge," says Hopkins's John Bartlett. "I doubt there is a physician in Maryland who has ever seen a case of inhalation anthrax."
To be sure, there are those who contend that the threat of bioterrorism is vastly overblown. In the fall 1998 issue of Foreign Affairs, Ehud Sprinzak, a political science professor at Hebrew University in Jerusalem, argues that the political and physical risks of using germ weapons are strong deterrents to would-be terroritsts. Fear-tainted rhetoric only fuels the "superterrorism craze" and feeds terrorists' desire to cause panic, according to Sprinzak.

Responds Hauer: "There are people who don't take a hurricane threat seriously."

Even if bioterrorists never strike again, adds Henderson, the work that he and his colleagues are doing will not go to waste. The tools they develop can also be used to find and manage new and emerging diseases that are arising naturally. These include Lyme disease, AIDS, and infections caused by antibiotic-resistant bacteria.

Whatever the infrastructure is finally used for, "it is a good investment to the country," says Colonel Gerald Parker, director of USAMRIID and a member of the Hopkins Civilian Biodefense team.

So the public health strategists speak a language that is all about probability rather than certainty. Terrorists are more likely to use one lethal germ than another. They are more likely to strike certain cities than others. But which germs? And which cities?

Hypothetical scenarios easily frighten people. "That's why education is important, and the proper education," says Parker. It is useful to know that anthrax spores cannot become aerosolized if you simply open an envelope, for instance. "You know, sometimes you fear the unknown. We don't need to be frightened of [bioterrorism], but we do need to be prepared," Parker says.

The release of smallpox, he adds, is a low-probability event. "But the problem is that there are very high consequences. If we ignore it and that low probability event occurs, then shame on us."

The author wishes to thank Thomas Inglesby, of the Hopkins Center for Civilian Biodefense Studies, for providing information for this article.