Prof. Jacob T. Schwartz
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.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.
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
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.
can we be sure? Past Soviet behavior and
the chaotic situation that developed during and immediately after the collapse
great fear is that small amounts of virus could have escaped from supposedly
secure facilities during the chaotic period following the collapse of the
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
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
translate such historical accounts into predictions of what would happen if
smallpox reemerged in today's
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
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
series of epidemics in late 19th-century
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
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%.  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.
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
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.
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
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.
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
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.
1985 and 1992, an average of 171 tularemia cases per year showing varios symptoms, were reported in the
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. 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.
 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.
uptake of varicella vaccine and the epidemiological
effect on varicella disease in 11 day-care centers in
 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.