In the year 67 B.C. the Roman general Pompey set out to conquer King Mithridates of Pontus. Mithridates had an insatiable curiosity, having mastered, among other things, twenty-two languages, the use of many weapons, and the art of magic. This wily and courageous ruler was unable, however, to prevent the advance of Pompey's superior forces. He and his men slowly retreated over the course of a year until the two armies confronted each other near Trabzon, on the Black Sea coast of Turkey. Although the retreat looked unplanned, it may have been a strategy suggested by Mithridates' chief adviser, the Greek physician Kateuas.

Kateuas is known to historians as the first herbalist of record—an expert on the medicinal uses of plants. During his extensive studies of herbal medicines he had apparently read Xenophon's account of another battle that had occurred at Trabzon, some 300 years earlier. In 401 B.C. Xenophon had led his Greek soldiers in a hasty retreat from Babylon. To the Greeks, the campsite near Trabzon looked very much like heaven. Fish were available from the nearby sea, the hills were covered with beautiful rhododendrons, and the woods harbored rich beehives. The soldiers feasted on honeycombs. The result was unpleasant. As Xenophon later wrote,

All the soldiers who ate of the honeycombs lost their senses, and were seized with vomiting and purging, none of them being able to stand on their legs. Those who ate but a little were like men very drunk, and those who ate much, like madmen, and some like dying persons. In this condition great numbers lay on the ground, as if there had been a defeat, and the sorrow was general. The next day, none of them died, but recovered their senses about the same hour they were seized; and the third and fourth day, they got up as if they had taken a strong potion.

Kateuas apparently recognized from this passage that a significant strategic opportunity was present in the hills of Trabzon.

Modern science calls the poison in Trabzon's honey a grayanotoxin. Grayanotoxins are produced by various species of rhododendrons and laurels and are present in the nectar of these plants, which is collected by bees for making honey. The toxins selectively bind to sodium channels in cell membranes. When excitable cells such as those in nerves or muscles start pumping sodium out through their membranes, grayanotoxins prevent the pumps from turning off, and so the cells remain in an exited state. People who ingest "mad honey," as it is called, develop symptoms that include excessive salivation, vomiting, loss of coordination, tingling and burning sensations in the mouth and extremities, low blood pressure, decreased heart rate, muscular weakness, and sometimes convulsions. Some cases mimic heart attacks. Although few attacks are fatal, even a small amount of mad honey can result in total incapacitation, which lasts for about twenty-four hours.

Kateuas urged Mithridates to take advantage of the ready-made trap offered by Trabzon. Xenophon, he knew, had been fortunate. During his army's time of near-impootence the trailing Colchian army had not attacked. Mithridates made sure that Pompey's army was not so fortunate. According to Strabo's Geography, Pompey's troops repeated the honey-feasting of Xenophon's troops, went into drunken convulsions, and were massacred by the waiting army of Mithridates. This is the first recorded instance of a biological poison doing service as a weapon of mass attack.

Accidental cases of mad-honey poisoning still occur regularly in Trabzon and in other areas of the world, such as the Pacific Northwest, where the relevant species of plants are found. "Today, cases of mad honey poisoning should be anticipated everywhere," the toxicologist Kenneth Lampe warned in a 1988 article in JAMA, the journal of the American Medical Association. "Some may be ascribed to a search for exotic tastes that can be realized from imported honey. Others may result from the ingestion of unprocessed honey in the quest for 'natural foods.'" Lampe did not mention another, much more sinister, way in which mad honey could make an appearance: through the sort of premeditated mass poisoning arranged by Mithridates, either to gain advantage in warfare or for purposes of terrorism. Indeed, it may be only a matter of time before terrorists turn to biological agents in their attempts to menace innocent people.

The threat is real. Biological-warfare agents, such as grayanotoxins, exist all around us. To engage in bioterrorism requires only the type of knowledge that Kateuas found in his herbals—that is, a sophisticated understanding of the properties of various edible plants, medicinal herbs, toxins and venoms, and infectious and pharmaceutical agents. The threat of biological warfare garnered significant attention in recent months from both the military and the press—owing, of course, to the war in the Gulf—but the possibility that terrorists might employ similar means of attack against civilians has received much less attention. Although no overt acts of bioterrorism are yet on record, a number of suspicious cases have recently come to light which suggest that the possibility of bioterrorism is more than just science fiction.

One of the best-documented, and probably the oldest, uses of biological agents as weapons is the purposeful spread of contagion. The contamination of enemy wells with excrement and diseased bodies is likely as old as warfare itself. The Tartars are reported to have catapulted the bodies of plague victims into the besieged city of Kaffa during the fourteenth century; during the French and Indian Wars the British spread smallpox among American Indians by means of contaminated blankets. It was therefore with foreboding that I read a recent article in The Lancet, a British medical journal, titled, "Giardiasis due to deliberate contamination of water supply."

Giardiasis is a diarrheal illness caused by the microorganism Giardia lamblia. It can be spread by means of fecal contamination of water or food, or anal-oral contact. It is often diagnosed in travelers to countries having inadequate sanitation, but several waterborne outbreaks appear every year in the United States as well. In the outbreak in question four unrelated people, none of whom had left Britain or had contact with the others, but all of whom lived in the same block of apartments in Edinburgh, developed giardiasis in June of last year. The confluence of cases immediately suggested to C. N. Ramsay, M.D., and J. Marsh, M.D., of the Lothian Health Board, that some common source of infection must exist. Investigation revealed that all the apartments were supplied with water from tanks on the roof, which were accessible through inspection hatches. Analysis of the water and the tanks demonstrated the presence of fecal matter containing Giardia cysts. The contamination, which eventually sickened nine people, was found to have been deliberate.

Fortunately, Giardia infection is rarely serious in otherwise healthy individuals, and it is usually easy to treat. But Ramsay and Marsh were not sanguine in their appraisal of this case. "Had the perpetrator been excreting a more dangerous organism," they warned—typhus or typhoid fever, for example—"the consequences could have been grave." They went on: "This incident highlights a potential danger to public health from malicious interference with communal water supplies." Ramsay and Marsh pointed out that other waterborne epidemics of giardiasis, stemming from accidental contamination of water supplies by sewage or by workers unknowingly infected with the organism, have been documented in the United Kingdom and the United States. Other illnesses, such as cryptosporidiosis and dysentery, can be spread in similar ways, and can be difficult to eliminate from the water supply once introduced. "In view of the potential for deliberate contamination of water at any point in the distribution system," Ramsay and Marsh concluded, "and in order to prevent recurrence of incidents like that described here, we suggest there is a need for relevant authorities to protect supplies from interference."

Not only water supplies are susceptible to premeditated contamination; so too is much of the air we breathe. Skyscrapers, tunnels, subways, and their requisite heating and air-conditioning systems provide targets and also avenues of attack for would-be bioterrorists. This potential was demonstrated by the United States Army during the 1950s, when it released the harmless bacterium Bacillus subtilis into some of the subways in New York City and subterranean passageways in Washington, D.C., and then monitored the spread of the bacteria. The experiments demonstrated that such public spaces are vulnerable to attack with biological agents.

The air-conditioning systems of large building complexes may be just as vulnerable to attack as subways and tunnels. Again, no evidence exists that bioterrorism of this sort has occurred, but the example of legionnaires' disease is instructive. When 221 people, most of them guests at a single hotel in Philadelphia, developed an unusual pneumonia following an American Legion convention in July of 1976, a crash program of research revealed that all of them had been infected by a previously unknown bacterium now called Legionella pneumophila. Intensive investigation eventually showed that the bacteria had contaminated the water source for the air-conditioning system of the hotel, and the air-conditioners had spread the bacteria to the guests. Most outbreaks of legionnaires' disease since then have also been traced to water and cooling systems in hotels, hospitals, and businesses. Clearly, unprotected systems of this sort offer a potential target for the bioterrorist.

People need not be the primary targets of bioterrorism. On December 6, 1989, a panel of scientists led by Roy Cunningham, of the U.S. Department of Agriculture, and including Caroll Calkins, of the department's Insect Behavior Unit, in Gainsville, Florida, met in Los Angeles to discuss possible reasons for a very peculiar pattern emerging in the spread of the Mediterranean fruit fly. The Medfly, as it is commonly known, constitutes a major threat to agriculture in California. The larvae eat fruit voraciously and almost indiscriminately, and the adults breed like, well, flies. Despite heroic attempts to eradicate the California Medfly, new infestations keep appearing in odd and unexpected places. The patterns of infestation are so bizarre that some members of the panel concluded that someone or some group of people must be purposely breeding and releasing Medfly larvae. This scenario might seem farfetched except for the fact that Tom Bradley, the mayor of Los Angeles, and various newspapers received letters during 1989 from a group calling itself the Breeders, which claimed to be spreading Medflies to protest California agricultural practices.

The threat that agricultural bioterrorism would pose is vast and carries with it the potential for severe economic disruption. One historical example illustrates this potential. From 1940 to 1942 the beehives of several European countries, including Germany, were decimated by an infestation of Nosema apis, a one-celled parasite that infects the digestive tracts of honeybees. Nosema apis is usually harmless, but occasionally, for reasons that are not entirely clear, it mutates into forms that are deadly. It was one of these deadly forms that ran rampant during the Second World War, not only severely curtailing honey production but also, because bees are the primary pollinators of many food plants, crippling crop yields. As Karl von Frisch, the great expert on bees, has noted, "During a time when food was in short supply, this failure of the bees was therefore a twofold catastrophe." Starvation has been a weapon of siege for as long as cities and states have existed. It is simply too optimistic to think that military planners and terrorist organizations have suddenly forgotten this fact.

One distressing feature of bioterrorism, agricultural or otherwise, is that it need not succeed in actually harming anyone or anything in order to have a painful impact. Consider the 1989 case of the two cyanide-laced Chilean grapes. No one is known to have ingested cyanide, and no one was harmed by it. Indeed, the amount of cyanide found in the grapes was too small to have been lethal. Yet the publicity surrounding these grapes caused a voluntary boycott by American consumers that resulted, according to a recent article by Raymond Zilinskas, of the Center for Public Issues in Biotechnology, in Perspectives in Biology and Medicine, in "several hundred millions of dollars damage, [the bankruptcy of] more than a hundred growers and shippers, and strained relations between the United States and Chile." Imagine, Zilinskas went on, what other kinds of damage a terrorist might do:

About 30 grams of the toxin ricin, easily concealed in a pocket, would be sufficient to lethally poison one batch of 150 pounds of meat, enough to produce 1,500 hot dogs. If Salmonella were used instead of ricin, much less would be needed to cause incapacitation.

Fortunately, cooking destroys most living organisms and most of their toxins, so that even if these agents were used to contaminate food, its proper preparation would render it safe for consumption. Nonetheless, Zilinskas believes that it is only a matter of time before some bioterrorist attempts such a poisoning, perhaps with an agent less easily inactivated.

How worrisome is the prospect of bioterrorism? Could it be effective? Is raising the subject tantamount to planting destructive ideas in someone's head? Everything described here has already been discussed publicly, and the information I have offered is readily available in published sources on biological agents. Some of the cases have even been widely publicized. And I have chosen my examples with care, illustrating possible pathways of infection with accounts that involve relatively harmless pathogens—Giardia, for instance. I have not discussed the truly lethal biological agents that experts worry about privately, or the complex technical procedures that deploying them would involve.

What is frightening is that there is very little one can do to deter a biological attack directly. Many of the "weapons" are available in both urban and agricultural environments. They cannot be revealed by metal detectors, x-ray machines, trained dogs, or neutron bombardment, as can guns, grenades, and plastic explosives. They can certainly be smuggled through airports as easily as the drugs that flood into Western countries. This is the bad news.

The goods news is that proper precautions can lower the potential effectiveness of biological weapons to the point where terrorists would probably not consider their use. Vaccines, anti-toxins, and antibiotics exist to combat almost any biological agent that a terrorist could possibly obtain, and the advances of modern medicine make even the apparently awful prospect of the spread of anthrax, botulism, grayanotoxins, or another scourge of previous ages far less of a threat than people may suppose. Public-health measures can also protect us in myriad unseen ways. For example, public water sources and new cooling systems now employ protective measures, including sufficient chlorination, to prevent the growth and spread of Legionella bacteria. These same protective measures would make the spread of most other bacteria and viruses (but not all of them) through such systems very difficult.

Nonetheless, the purposeful or accidental biological poisonings and infections described above suggest that more ought to be done. For example, there is only one manufacturer of anthrax vaccine in the United States; that manufacturer was unable fully to meet the needs of the Army during the Gulf War. What if the population at large had been threatened? Stocks of vaccines and antitoxins must be widely available. The recent deliberate lacing of Tylenol and Sudafed capsules with cyanide and the several cases in which glass shards have been deliberately placed in baby food similarly warn us that packaging systems in the United States have loopholes that may need to be closed. Certainly those people who have the knowledge and the desire to spread pests among our croplands represent a threat that has hardly begun to be addressed. And no matter how fastidious about security those who design heating and cooling systems attempt to be, the outbreak of Giardia contamination in Scotland demonstrates that built-in safeguards can be undermined by the simple failure to properly restrict access to these systems. Protection may require little more than adequate locks on access doors and hatches, supplemented by regular microbiological analyses.

Knowledge both makes bioterrorism possible and provides a strong defense against it. Preparedness in this respect should take many forms. Pentagon-funded research on defenses against biological warfare, much as it may irk some, not only deters the use of biological agents during wartime but also may be the first line of defense against bioterrorism. Much of what we know about anthrax, for example, and how to protect ourselves from it, has resulted directly from studies by Army physicians and from civilian studies supported by the Department of Defense.

But even this sort of knowledge will be insufficient. Public-health officials, epidemiologists, law-enforcement officers, physicians and pharmacists, microbiologists, health-care workers, agriculturalists, package designers, industrial engineers, and those who oversee food preparation and distribution must all become sensitized to the possibility and the signs of bioterrorism, implement precautionary measures, and know how they should react if something unusual happens to come to their attention.

It takes unusual learning to employ bioterrorism. Time, place, and opportunity must coincide. So far, terrorist organizations have apparently lacked the sophisticated knowledge and training to plan and carry out biological terrorism. People with advanced degrees in microbiology, medicine, pharmacology, and agricultural science seem to be rare if not nonexistent among the membership of identified terrorist groups. But this situation may not last much longer.

Just as society has learned to live with airport security systems to protect us against hijackers, and tamper-resistant packaging to protect us against the one-in-a-million lunatic who wants to poison our pills, it may have to learn to live with new forms of protection designed to safeguard our agriculture, our sanitary systems, our communal air-conditioning and heating facilities, and our water supplies.