Genie in the Bottle: What Bioterrorism Might Mean

1. The dangers. Though the number of cases reported so far is small and most have been treatable, the anthrax events of the past few weeks have sensitized public and politicians to the threat of bioterrorism. They have also drawn a picture, much in miniature, of what public reaction to a more serious crisis would be. Medical and laboratory facilities would surely be overloaded. Maddening hoaxes would flourish in a climate of mounting anxie‚ty. A significant fraction of the population might attempt to flee the epidemic zone. The ability of local authorities, including police and emergency medical responders, would likely be insufficient and need to be supplemented, first by the National Guard and then by the Army. Government might or might not be able to continue its normal operations.

The way such a grim scenario might play out depends critically on what the real dangers are. Because of the way in which it has been dispersed so far, for anthrax these have so far been minimal. There are, however, other pathogens potentially available to terrorists that pose much greater risks. Some of these will be reviewed later in this article. One on which public attention has already begun to focus is smallpox.

Why would smallpox be so different from anthrax? Anthrax is a bacterial disease and therefore treatable, especially during its period of incubation. Smallpox is a viral disease, which like the common cold is essentially untreatable, although the antiviral drug cidofovir, which has been approved by the F.D.A. for other uses, has shown some promise in animal tests. In general, one can do little but provide supportive care to persons afflicted with smallpox. Anthrax is not contagious while smallpox is highly contagious from the time its characteristic rash breaks out until the disease has run its course, 10 to 40 days later. Anthrax, when treated, is only rarely fatal in its most common, cutaneous form.[1]Smallpox kills up to a third of those it infects and disfigures and may blind its survivors. The main disadvantages of smallpox as a weapon are that it is much less able than anthrax to survive for extended periods outside a host and that the epidemic which its release would produce could spread back to harm populations ìfriendlyî to the party releasing it.

For millennia smallpox was one of mankind's most dreaded scourges, killing king, townsman, and peasant, African and Londoner, man, woman, and child with sublime indifference, erupting occasionally, as in 1614, into mass pandemics. But after the 1798 introduction of vaccination this dread genie was progressively squeezed into smaller and smaller bottles. By official account there are now only two such: one at the Center for Disease control in Atlanta, the other at the Russian State Research Center of Virology and Biotechnology, in Koltsovo, Novosibirsk Region. When caps were put on these bottles and they were lowered into liquid nitrogen for preservation, a great victory for humanity was signalled. Two decades of intense activity by the World Health Organization had eliminated smallpox. Or so it was hoped.

In this optimistic spirit, vaccination of American children, a common practice for almost two hundred years, was halted in 1972. Vaccination for travelers was halted in 1978. Currently no one under 29 years of age has any protection at all, and those over 29 have only some residual resistance. The immunity conferred by vaccination is thought to decline after about 10 years, so most of those previously vaccinated are now susceptible to the disease. This leaves the world population, like the Hindenburg passengers, floating along serenely in the confident expectation that there will be no spark.

But can we be sure? Past Soviet behavior and the chaotic situation that developed during and immediately after the collapse of the Soviet Union give cause for concern. Ken Alibek, a former deputy director of the Soviet bioweapons program, has alleged that in 1980 the Soviet government embarked on a program to produce large quantities of virus for use in bombs and intercontinental ballistic missiles. Reflecting on this program, he has remarked ominously: "There were plenty of chances for somebody to walk off with an ampule." In an allegation supported by Alibek, Jonathan Tucker of the Monterey Institute of International Studies writes in his new book Scourge: The Once and Future Threat of Smallpox that ìSmallpox biological weapons were intended for use against U.S. cities in a war of total mutual annihilation, with the aim of killing the survivors in the aftermath of a nuclear exchange. A 1998 U.S. intelligence assessment concluded that Russia, Iraq and North Korea were probably concealing undeclared stocks of smallpox virus. In the North Korean case, the evidence was the presence of antibodies suggesting recent smallpox vaccination in the blood of a North Korean soldier (by contrast, vaccination of American military personnel stopped in 1989). This assessment reportedly fixated President Clinton on the emerging germ threat, prompting him to issue Presidential Decision Directive 62, "Protection Against Unconventional Threats to the Homeland and Americans Overseas," which ordered federal agencies to take significantly expanded and better-coordinated steps to protect against bioterrorism directed at civilian populations, and to push for increases in spending on bioterrorism preparedness.

One great fear is that small amounts of virus could have escaped from supposedly secure facilities during the chaotic period following the collapse of the Soviet Union, when its scientific laboratories were catastrophically underfunded. The relaxation of security that resulted is shown by the following incident, which seems to have passed largely unnoticed in the United States:

Reuters, 19 June 2000 [edited] The World Health Organization expressed concern Monday over the careless way a Russian clinic discarded smallpox vaccine ampoules, causing the infection of eight children. The children aged six to 12 were diagnosed with a mild form of smallpox [generalized vaccinia] when doctors discovered that they had played with glass ampoules they found in a dustbin of a local epidemiological center in Russia's Far East, Russian officials said Monday. The children had been taken to hospital with fever and severe rashes. . . . Spokesman Valery Abramov of the Geneva-based WHO said that although the infections were not life-threatening, the vaccine ampoules should have been incinerated before being discarded. Smallpox has been eradicated but the virus has not been destroyed completely due to the remaining stocks in Russia and the United States. The stocks are there because of fears about terrorist use of smallpox virus, The concern is how these vaccines are disposed of. Throwing them away is against the rules. They need to be incinerated.

2. What a spark would do. What if there is a spark, as our government now clearly fears there might be? As with fire spreading into a combustible material, the events that this would trigger are in principle predictable. Flame applied to nitroglycerine produces an immediate explosion, to gasoline a wildfire, and to dry wood a blaze that can spread fast enough to be very dangerous. Flame set to damp paper may simply flicker out. What would smallpox, once loose in the US population, do?

The answer to this question depends in part on how an outbreak is contained. Vaccination of large segments of the population is one means of containing an epidemic, confinement and quarantine of the sick and exposed another. In previously unexposed populations unused to dealing with the disease, smallpox outbreaks have been devastating. For example, the fact that today's Caribbean population is principally Black and Hispanic is largely because of smallpox: in 1507 and 1518 two epidemics of smallpox killed from a third to more than half of the native populations of Cuba, Haiti, and Puerto Rico. Absent vaccine, even a population familiar with smallpox can be hard hit: during the 1721-22 smallpox epidemic in Boston, more than half the population of 11,000 was affected, and 844 persons, about 15% of those affected, died.

To translate such historical accounts into predictions of what would happen if smallpox reemerged in today's America, one must understand the epidemiology and course of the disease. For the first 12 days or so after infection, smallpox patients-to-be may have no symptoms whatsoever. Fortunately, during this period the patient is not infectious. Then a fever develops, followed about two days later by a rash marking the onset of infectivity. About four days later the initial rash evolves into the characteristic 'pocks' or pustules that give the disease its name. Death usually occurs within five or six days of the development of the rash. In patients who survive, these pustules gradually dry up, and the scabs, which themselves are infectious, fall off over the following 2 to 4 weeks. Pitted scarring of the face and blindness are common in survivors. Infected individuals are most dangerous to others in the days immediately following the onset of the rash. Subsequently, their rapidly worsening condition usually forces them to seek medical assistance and in any case reduces the risk of casual exposures.

3. The shape of epidemics. The pattern of epidemics in unvaccinated populations exposed to smallpox year after year differs significantly from the catastrophic explosions seen in the native American populations. The epidemiologist's rule of thumb is that in previously unexposed populations each infected person will infect 10 to 20 others, so that every generation of infection results in a tenfold expansion of the epidemic. Thirty days after the a first patient becomes symptomatic, the disease can have spread to as many as a thousand individuals, and thirty days after that to almost a million. Such epidemics do not recede until the population of immune survivors greatly exceeds the number of susceptible persons in the population. This is roughly the scenario that confronted former Senator Sam Nunn and the other participants in the 'Dark Winter' bioterrorism simulation organized in late June by the Center for Strategic and International Studies, the Johns Hopkins Center for Civilian Biodefense Studies, the ANSER Institute for Homeland Security, and the Oklahoma National Memorial Institute for the Prevention Terrorism. Basing its calculations on the quarantines and vaccination programs that could have been implemented (given the current stock of 14 million doses of vaccine), the Johns Hopkins group predicted 3 million cases and 1 million deaths by day 90. It was this simulation, reported to Congress in late July and subsequently to Vice President Dick Cheney, that prompted HHS to order 300 million doses of vaccine.

The survivors of such an epidemic, approximately two-thirds of those infected, are left fully immune to the disease for at least 10 years. For this reason, smallpox outbreaks have different shapes in populations exposed to smallpox year after year. Immediately after a universal contagion the whole population is immune. Seven years later, children under seven, who account for about 10% of most populations, are susceptible, but their elders, for the most part, are still immune. Fourteen years after an outbreak, the susceptible fraction of the population will have increased to about 30%, as children continue to be born and previously infected individuals begin to lose their immunity.Over time, such a populationís drying biological Ýëtimberí becomes increasingly combustible. As mentioned above, each victim of smallpox has the potential to infect about ten others.But if 19 of every 20 persons in a population is immune, then the second generation of an outbreak will only be half as large as the first and the outbreak will be self-contained.If 8 of every 10 persons are immune, then the disease spreads to 2 rather then 10 new victims every generation, and thus grows at a lower rate (aabout 3 times more slowly) than it would in a population with no immunity.The maximum mortality in such a population will not exceed 7% of the total population, and the epidemic will affect the young disproportionately. These effects give smallpox outbreaks their historical form: in Europe, Africa, and the East they appeared, not as single overwhelming catastrophes, but as periodic smaller epidemics that (along with diphtheria and scarlet fever) contributed to high child mortality rates.

A series of epidemics in late 19^th-century Chicago illustrates this pattern.Smallpox epidemics occurred in 1872 (with mortality rates of 1.8 individuals per thousand population); 1873 (1.4 per thousand); 1881 (2.2 per thousand); and 1882 (2.3 per thousand.) We can surmise that the 1881 and 1882 epidemics together attacked that part of the population, arriving since 1873 by birth and immigration, that was unvaccinated.If the unvaccinated fraction of the public accounted for 10% to 20% of the total population then the death rate in a wholly unvaccinated population might have been 5 to 10 times the cumulative death rate of the 1881/1882 epidemics, potentially reaching 45 per thousand or 4.5%. Applying this figure to todayís wholly unresistant US population gives us a premonition of what would happen if stocks of vaccine were to run short: 8 to 15 million deaths in the worst case. And the world as a whole is no better protected (there are only about 50 million doses of vaccine worldwide). We could anticipate as many as 300 million deaths, with countries lacking public health infrastructures being hit the hardest.

4. Containing an epidemic.The ability to vaccinate, and a sufficient supply of vaccine, greatly relieves this hideous picture. If the whole population, or a large fraction of it, was vaccinated in advance, any outbreak would peter out after a scattering of cases. Since the rare but predictable complications of vaccination kill about 1 in a million persons vaccinated (about 300 in the whole US population), a crucial issue arises.Is it best to vaccinate in advance, or only following an actual outbreak? If an outbreak is feared but does not actually occur, the second policy is clearly best, since it spares the unknown 300 whom vaccination would kill.If an outbreak seems certain, it is best to vaccinate immediately, since this will be necessary in any case, and vaccination prevents the fatalities certain to occur once the outbreak begins. So making the proper policy choice depends on the probability of an attack with smallpox (which we can guess but not really know), and on the number likely to be lost in spite of a vaccination campaign mounted only after an outbreak is identified.Though there are many uncertainties involved, we can at least try to estimate this second number.

New York's 1947 experience can serve as a model. In late March 1947, a certain Mr E. LaBar, infected in Mexico, developed hemorrhagic smallpox (a uniformly fatal but atypical form of the disease) shortly after arriving in New York City. His disease was not recognized as such until two new typical cases of smallpox occurred in individuals in the hospital where he was treated. The public was informed on April 5, when City Health Commissioner Weinstein reported on the three cases and announced Mr. LaBarís death.An intense search for other contacts of LaBar began.The entire medical staffs of Bellevue and Willard Parker Hospitals were vaccinated, and everyone living in the city was urged to seek vaccination, which was provided free of charge by the city.On April 8, two more cases appeared in Willard Parker Hospital. On April 12, a case was reported in Millbrook, New York, and the next day two more cases were reported at the Cardinal Hayes Convalescent Home for Children there. On April 15, another case was diagnosed in New York City. At this point, the cityís stocks of vaccine were starting to run out, but extra vaccine was quickly obtained from the military and from medical supply outlets. Simultaneously, the Westchester County Health Commissioner reported that he had been unable to acquire vaccine because New York City had cornered the supply. The Federal government allowed drug manufacturers to package vaccine in 50-dose tubes to speed their distribution, and on April 18, 1947, the same day a death from smallpox was reported in Camden, New Jersey, over 500,000 persons were vaccinated in New York City in one day. By April 24, 4 1/2 million people had been vaccinated. By May 3, when the campaign ended, a total of 6,350,000 people had been vaccinated in New York City and Westchester.

In spite of the many medical advances since 1947, contemporary Americans are worse off than the New Yorkers of 1947 in two ways. In 1947, a substantial fraction of the population was either fully immune or had substantial residual immunity from childhood vaccination, so that a powerful herd effect protected the unvaccinated. The effects of herd immunity can be great. Clements and colleagues at Duke recently observed a greater than 90% decline in varicella (chicken pox), which is far more infectious than smallpox, among unvaccinated children in daycare centers over a period in which the vaccination rate of enrolled children increased from 4.4% to 63.1%. [2] Today, no one under 29 is protected at all, and the average time since vaccination among the rest of the population is 50 years. As a result, today's population is considerably more 'combustible' than that of 1947:an outbreak would spread exponentiallyfaster and will menace the whole population rather than merely a fraction of it. A second and not negligible factor promoting the rapid evolution of an epidemic is the great increase in air travel and general mobility since 1947.

Once an outbreak was detected, everything would hinge on the speed of containment efforts relative to the spread of infection. If a vaccination program began immediately and 5 million persons per day (ten times New York's best effort during the 1947 outbreak) could be vaccinated, it would take 40 days to vaccinate two thirds of the population, which should be sufficient to slow the spread of infection substantially. The ëDark Winterí scenario estimated that about 1700 people would have been infected by that time, with about 200 fatalities recorded, not counting those related to vaccination. If taken seriously, this scenario, which assumes that full stocks of vaccine are available and that the government is poised and able to organize an immediate national response at the 5 million vaccinations per day level, indicates that pre-vaccination of the entire US population makes sense if the probability of an attack is somewhere around 50%. A policy alternative would be to vaccinate groups critical to any organized response immediately.These would include medical and social-work staffs, mortuary workers, police, firemen and other emergency workers, and members of the National Guard and military services. But all of these cool-headed calculations are likely to be swept aside by rapidly mounting public pressure, which may soon force the government to permit voluntary vaccination. This became quite clear in a recent SenateAppropriations Committee hearing on smallpox preparedness, in which Senator Arlen Spector stated insistently that he would prefer to have his own grandchildren vaccinated immediately, and Dr. Anthony S. Fauci, Director of the National Institute of Infectious Diseases, testified that he would wish this for his own children as well.

5. How ready are we now?Reflecting on the Dark Winter simulation in testimony to Congress in July, Senator Nunn stated: ìFor the participants, this exercise was filled with many such unhappy discoveries and unpleasant insights. Number one:we have a fragmented and under-funded public health system at the local, state, and federal level that does not allow us to effectively detect and track disease outbreaks in real time.Two: since the disease has not been seen in the United States since 1949, very few health care professionals recognize the smallpox virus, so initial cases could be sent back home infectious, even after appearing at doctorís offices and emergency rooms. Three: lab facilities needed to diagnose the disease are inadequate and out of date.Four: there is insufficient partnership of communication across federal agencies and among local, state, and federal governments.Five: the only way to deal with smallpox is with isolation and vaccination, but we donít have enough vaccines, and we donít have enough room, resources, or information for effective isolation.î

Major General William A. Cugno, Commander of the Connecticut National Guard, testifying at the same Congressional Hearings, said, ìI canít emphasize enough the realities of what occurs in a state during emergencies.I know those who advocate a strong federal role often underestimate these realities. The Governor has the ultimate responsibility to restore normalcy to his or her citizens and should to the greatest extent resist relinquishing control. Dark-Winter proponents of a strong federal role clearly demonstrated a lack of understanding of statehood and political realities.î As the recent anthrax outbreaks demonstrate all too well, the basic lines of authority for response to a major bioterrorist attack have not been well-defined. General Cugnoís testimony makes it all too clear that bureaucratic squabbling has the potential to undermine any response.If flame breaks out it is possible that at first we will not even know what fire department should respond.

Clearly such issues need to be addressed immediately, and the deficiencies listed by Senator Nunn, all well-known to medical professionals, fixed.

6. How ready is the rest of the world? The rest of the world needs to look to its own protection. These are no more than 80 million doses available world-wide (so the present grimly inadequate American stock accounts for almost a fourth of the world total.) If there is reason for the US to fear smallpox, London, Moscow, Delhi, and Hong Kong cannot rest easy.

7. Other possible bioweapons. Smallpox has been called the greatest scourge of mankind and no other agent known combines its properties of transmissibility and lethality so ruthlessly.Chicken pox and measles are more infectious, but they are much less lethal, and the same is true for influenza.Rabies and the hemorrhagic fevers (like Ebola) are more lethal, but they are much less easily transmitted and epidemics of these diseases occur only under very special circumstances.This is what make smallpox so frightening as a biological weapon; but also limits its value to all but the most apocalyptic fanatics. Unlike anthrax, can Ýbe targeted at limited groups or used as a weapon of mass destruction, smallpox has almost no tactical value to a party possessing it.In a world where essentially no one has been vaccinated in the last three decades, smallpox must be regarded, like the cobalt bomb, as a ìdoomsday deviceî. As with the cobalt bomb, there can be no good reason to use it.Its only possible ìutilityî, if one can speak in such terms, would be to a group of vaccinated individuals who regarded everyone else on earth as their enemies. But while we can be certain that sufficiently hateful groups exist (the defunct Japanese group Aum Shinrikyo comes to mind), we have no reason to believe they have access to smallpox.Osama bin Laden, on the other hand, who just might, presents himself as a heroic Muslim, which means he feels attached in some way to more than one billion people.And it is difficult to imagine him consciously willing the deaths of millions or tens of millions of his fellow Muslims, which is what would happen were he to release smallpox.

What other agents could terrorists want and possibly obtain?

The CDC bioterrorism website (www.bt.cdc.gov) lists 18 biological agents in three categories of priority that possess qualities making them plausible weapons. According to the website, the agents of greatest concern are those ìthat pose a risk to national security because they can be easily disseminated or transmitted person-to-person; cause high mortality, with potential for major public health impact; might cause public panic and social disruption; and require special action for public health preparedness.îThere are six such agents listed, smallpox and anthrax being two such. One, botulinum toxin, the causative agent of botulism, is a microbial product, not an organism. Two others Yersinia pestis (which causes plague) and Francisella tularensis (which causes tularemia, a highly infectious disease found most commonly in rabbits and rodents), are bacteria; and the last, viral hemorrhagic fever, is really a group of illnesses, including Ebola and Marburg fevers, caused by several distinct families of viruses. ÝNot listed but perhaps worth mentioning is the monkeypox virus, which causes a syndrome very similar to smallpox in humans and occurs sporadically in Central African populations (the smallpox and monkeypox viruses are closely related; vaccination for smallpox protects against monkeypox as well).Previously monkeypox was not observed to cause epidemics, but in 1997, a new pattern of disease, suggesting person-to-person transmissions and spreading through many generations, was noted in outbreaks in the Democratic Republic of Congo. Authorities have speculated that the new pattern of disease may reflect the waning of smallpox immunity in the involved populations.Whether monkeypox would be as transmissible or lethal as smallpox in cooler, drier climates has not been determined. Soviet scientists are believed to have investigated its use as a biological weapon, however.

Because of descriptions of the Ebola virus published in such books as Richard Preston's The Hot Zone and Laurie Garrett;s The Coming Plague, not to mention the prominent coverage of a large Ebola outbreak in Kikwit, Zaire in 1995, the viral hemorrhagic fevers have acquired notoriety as dreaded modern plagues, and their use as agents of biological warfare would undoubtedly result, at least initially, in public panic and social disruption. However, even leaving aside the considerable difficulty terrorists would have in dispersing these agents, their potential to have a major public health impact is actually quite limited. Ebola and Marburg fevers are transmitted by direct contact with the skin, blood and body fluids of infected patients, and by the time patients become infectious most are devastated by the symptoms of their illness.As a result, most of the epidemics that we know of have occurred in hospital settings, where an initial sporadic case or two has been amplified through the sharing of needles and the absence of standard precautions.In practice it has been relatively easy, even in the primitive conditions of rural African hospitals, Ýto arrest the chain of transmission by implementing such precautions, monitoring the close contacts of infected patients, and Ýquarantining those showing fever or other signs of infection.However, the strategic value of an attack using these agents should not be underestimated. If the aim were to terrorize the public rather than kill a masses, these are ideal agents.In his memoir Virus Hunter: Thirty Years of Battling Hot Viruses Around the World, C.J. Peters, the former head of the Special Pathogens Branch at the Centers for Disease Control and Prevention, asserts that Aum Shinrikyo cult members actually went to Zaire hoping to collect specimens of Ebola.

The germs of plague and tularemia are worldwide in distribution and thus have the advantage of being easily acquired.As for anthrax, few American physicians are familiar with the look of these diseases. Only 390 cases of plague were reported in the United States from 1947 to 1996, and of these, only 2% developed as pneumonic plague, which is the form of disease that would developmost prominently after an aerosol distribution of Yersinia pestis. An outbreak of pneumonic plague would begin one to six days after such and attack when patients would show severe respiratory symptoms and die quickly following the onset of symptoms.

Between 1985 and 1992, an average of 171 tularemia cases per year showing varios symptoms, were reported in the United States. Release of an aerosol containing Francisella tularensis in a densely populated area would result, three to five days later, in the abrupt development of an acute, nonspecific fever Ýin large numbers of previously healthy individuals, with pneumonia developing in a significant proportion of such patients over subsequent days and weeks. Tularemia would progress more slowly and have a lower case-fatality rate than either inhalational plague or anthrax. Like anthrax, neither plague nor tularemia are transmitted from person to person, so the effects of an attack would depend entirely on where and how these agents are dispersed.Unlike anthrax, neither the plague or tularemia Ýgerms form spores. Therefore because of drying, solar radiation, oxidation and other environmental factors neither would be expected to remain for long after an aerosol dissemination.Nevertheless an outbreak of tularemia might pose more challenges to public authorities than outbreaks of plague or anthrax because of the variety of ways the disease can develop, its longer incubation period and slower evolution. In 1970, in a review of potential biological and chemical weapons, the World Organization estimated that the release of 50 kilograms of either Yersinia pestis or Francisella tularensis over a metropolitan area with five million inhabitants would result in 150,000 cases and 36,000 deaths from plague and 250,000 cases and 19,000 deaths from tularemia.

As a localized weapon of mass destruction, the agent of greatest concern would seem to be botulinum toxin, which is the most poisonous substance known.A single gram of crystalline toxin, evenly dispersed and inhaled, would be sufficient to kill more than 1 million people.[3] After the Persian Gulf War, Iraq admitted having produced 19,000 liters of concentrated botulinum toxin (three times the amount necessary to kill the entire world population), not all of which has been accounted for, but more than half of which was loaded into bombs and specially designed missiles. Saddam had a great interest in botulinum toxin, and invested more money and effort in weaponizing it than any other biological agent. Additionally, the Aum Shinrikyo cult is known to have unsuccessfully released aerosols of botulinum toxin on more than one occasion. Problems of dispersal and aerosolization notwithstanding, it is estimated that an outdoor release of botulinum toxin could incapacitate or kill 10% of persons up to half a kilometer downwind, and C.J. Peters has pointed out that while botulinum toxin has a small area of effect compared with infectious agents, it would be deadly if released into the air conditioning system of a building. A large-scale outbreak of botulinum intoxication would represent a public health catastrophe. Botulism paralyses the nerves which control the bodyís muscles and so has effects like those of a severe case of polio. .In survivors the paralysis of botulism, which cannot be reversed by the antitoxin, can persist for weeks to months. During this time patients may require fluid and nutritional support and mechanical ventilation (the former ëiron lungsí), and such patients would be susceptible to any of the complications of prolonged hospitalization in an intensive care unit. Affected patients would develop symptoms within 72 hours of exposure and would overwhelm emergency rooms. The only antidote is an antitoxin that must be obtained from the CDC via state and local health departments. A generally effective toxoid vaccine is available, but mass immunization poses agonizing public health policy problems because of the scarcity of the toxoid and the fact that vaccination would render medicinal botulinum toxin ineffective for those patients who someday may require it. Neutralizing human antibody, with a half-life of approximately one month, would provide long periods of immunity and have fewer side effects than the current equine antitoxin ñ and the technology to produce such human antibodies in vitro already exists.The main issue would seem to be mobilizing the pharmaceutical industry to produce the stockpiles necessary to deter terrorist attacks.

Attacks using biological weapons, as the level of disruption generated by the miniscule anthrax outbreaks seen so far demonstrate, pose formidable challenges to law enforcement agencies, public health authorities, and the whole system of clinics and hospitals in affected areas. Although civilized nations concur in abominating their use, such weapons will remain attractive to fringe elements and groups of fanatics.They are the poor manís weapon of mass destruction.So long as the worldís nuclear arsenal is secure and rogue states are prevented from developing strategic nuclear weapons, we can such states and the terrorist groups they harbor will be attracted to and invest in biological weaponry as an alternative.Much has been made of the way in which on September 11 the hijackers of the American and United flights turned our own technology against us, and the same is true of those who would use biological weapons. The next time an outbreak of viral hemorrhagic fever or monkeypox occurs, the first team on the spot may not be from the CDC; it may but from some terrorist group or state. This is the kind of world we live in now.

[1] Historically, up to 90% of patients developing the inhalational form of anthrax have perished.Recent experience suggests that the mortality rate has declined, presumably because of todayís more powerful antibiotics and improved methods of diagnosis and supportive care.

[2] ìPartial uptake of varicella vaccine and the epidemiological effect on varicella disease in 11 day-care centers in North Carolina,î by D.A. Clements, J.I. Zaref, C.L. Bland, et al. Archives of Pediatrics & Adolescent Medicine 2001;155:455-461.

[3] See ìBotulinum toxin as a biological weapon. Medical and public health management,î by S.S. Arnon, R. Schechter, T.V. Inglesby, et al. Journal of the American Medical Association (JAMA) 2001;285:1059-1070.