The Growing Threat of Biological Weapons

A reprint from American Scientist the magazine of Sigma Xi, The Scientific Research Society

This reprint is provided for personal and noncommercial use. For any other use, please send a request to Permissions, American Scientist, P.O. Box 13975, Research Triangle Park, NC, 27709, U.S.A., or by electronic mail to [email protected]. ©Sigma Xi, The Scientific Research Society and other rightsholders The Growing Threat of Biological Weapons

The terrorist threat is very real, and it’s about to get worse. Scientists should concern themselves before it’s too late

Steven M. Block

or half a century, America has par- cal development and use of biological um (Bacillus anthracis). Pasteur devel- F ticipated with the world’s nuclear weapons, as well as some recent trends oped the first animal vaccine against powers in an uneasy standoff of mutu- in their evolution and the prospects for anthrax, which, together with Lister’s ally assured destruction. Despite the containing their proliferation. ideas about antiseptic precautions, seemingly relentless proliferation of nu- helped turn the tide against outbreaks clear arms, there’s reason to hope that The Plague and Anthrax of the disease. some version of the current stalemate Biological warfare is not a new phe- Anthrax is only weakly communica- will continue to hold. Against this back- nomenon. The ancient Romans, and ble in humans and rarely causes dis- drop, terrorist factions and “nations of others before them, threw carrion into ease, unless the bacterium comes into concern” (the current government eu- wells to poison their adversaries’ contact with the bloodstream through a phemism for rogue states) have sought drinking water. In the 14th century the wound (causing cutaneous anthrax) or ways to leverage their chances. In the Tatars catapulted the bodies of bubonic- is ingested in contaminated meat (re- jargon of the day, they seek a means to plague victims over the city walls of sulting in intestinal anthrax). However, wage “asymmetric warfare” against a Kaffa, a Black Sea port that served as a Bacillus anthracis has the ability to form more powerful, nuclear-capable adver- gateway to the Silk Road trade route. resistant spores, which can remain vi- sary. Asymmetric warfare concentrates People inside the city soon came down able for over a hundred years if kept on the use of unconventional (and af- with the disease, suggesting that the desiccated and out of direct sunlight. fordable) weapons and tactics, ranging maneuver may have worked—but the Breathing in significant numbers of from traditional guerrilla fighting to the tactic may have exceeded the Tatars’ spores (typically estimated at about deployment of new weapons of mass operational goals. Some of the city’s in- 10,000) can lead to inhalation anthrax destruction. Ironically, the supremacy in habitants escaped in sailing ships, in humans, which was historically conventional weaponry established by which happened to be infested with called “woolsorter’s disease” because the U.S.—and demonstrated to lethal ef- rats, carrying fleas infected with the spores were prevalent in the contami- fect during the 1991 Gulf War—has causative agent of plague, the bacteri- nated wool of sheep in 19th-century made asymmetric warfare all the more um Yersinia pestis. The escaping ships England. Inhalation anthrax is a very attractive. Figuring prominently in the entered various Italian ports that sub- deadly disease in humans. Unless treat- arsenal of asymmetric warfare are both sequently served as foci for the spread ed with large doses of a penicillin-type biological and chemical weapons. Al- of the disease. Over the next three antibiotic within the first day or so of though it may be something of a mis- years, the bubonic plague—the Black exposure it has a mortality rate in ex- nomer to label most current forms of Death—raged northward, wiping out cess of 80 percent. This is to be contrast- these agents as “weapons of mass de- nearly a third of Western Europe. ed with smallpox, which has a mortali- struction,” their power is nevertheless It was not until the 19th century that ty rate of “only” around 30 percent. considerable. Worse still, it is now in- the microbial basis for infectious dis- Only some filoviruses, such as Ebola, creasing, and these weapons are emerg- ease was understood. One of the first which cause hemorrhagic fevers, have ing as a serious threat to peace in the illnesses to be explained by the new comparable rates of mortality. 21st century. Here I explore the histori- germ theory was anthrax, an infectious All of this suggests why Bacillus an- disease common to sheep and cattle. thracis became the agent of choice for Indeed, the primary architects of the most biological warfare programs. Steven M. Block is a professor of biological sciences and of applied physics at Stanford University, and a germ theory—Robert Koch, Louis Pas- Consider the properties of anthrax. It member of JASON. Address: Department of Biolog- teur and Joseph Lister—were instru- is convenient: Variants of the anthrax ical Sciences and Department of Applied Physics, mental in describing anthrax and its bacterium can be isolated worldwide Gilbert Hall, Stanford University, Stanford, CA containment. Koch was the first to iso- (although not all possess equal viru- 94305–5020. Internet: [email protected] late and describe the anthrax bacteri- lence), and great quantities of spores

© 2001 Sigma Xi, The Scientific Research Society. Reproduction 28 American Scientist, Volume 89 with permission only. Contact [email protected]. Leif Skoogfors/Corbis Figure 1. Biohazard suits are the first line of defense against contamination for response teams entering a “hot zone”—the site of a biological- weapon release. A number of civil and military organizations—including the Department of Defense, the Centers for Disease Control and Prevention, the Federal Emergency Management Agency as well as local emergency medical services, fire and hazardous material experts and law enforcement specialists—now hold workshops and training sessions throughout the United States as part of a “Domestic Preparedness” program in case of a terrorist attack with a bioweapon. The challenge is to integrate these forces to mount an effective response under various attack scenarios. Here Marines prepare for a military exercise in Jacksonville, North Carolina. can be readily prepared from liquid edged sword, of course, since the vac- The World Wars cultures. It is robust: Once desiccated cine may be available to the target pop- The First World War saw one of the and stabilized, hardy spores have a ulation as well. For this reason alone, first attempts to use anthrax during long shelf life and are well suited to anthrax doesn’t quite qualify as the warfare, directed—ineffectively— weaponization in a device that can de- perfect bioweapon. against animal populations. Instead, liver a widespread aerosol. It is self-ter- There are certain other drawbacks to WWI became infamous for its intro- minating: Airborne spores remain in- anthrax as a weapon. The number of duction of poisonous mustard gas, fectious until they fall to the ground, spores that must be delivered to the which was used effectively against hu- where most become inactivated by lungs to produce the disease is quite mans. (By odd coincidence, WWI also sunlight. It is effective: After inhalation high compared with some other infec- overlapped with a deadly outbreak of the spores produce disease with a high tious agents—it has been estimated influenza, the Great Pandemic of 1918, mortality and morbidity. It can be con- that certain viruses and rickettsiae may which eventually killed more people tained: Anthrax is not very communi- communicate disease with just a single than the Great War itself.) International cable, thereby reducing the risk that it particle. Finally, for conventional an- revulsion at the horrors of WWI led to will spread beyond the intended tar- thrax, antibiotic treatment can be effec- the signing of the Geneva Protocol of get. Moreover, a well-established vac- tive if administered quickly. Even so, 1925, which went into force on Febru- cine exists that can prevent the onset of all the natural biowarfare agents, an- ary 8, 1928, with 29 participating na- of the disease, allowing it to be used thrax traditionally ranks near the top tions, including the U.S. The treaty safely by the aggressor. This is a two- of everyone’s short list. contained “A Protocol for the Prohibi-

© 2001 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 2001 January–February 29 Sverdlovsk 1979 accidental release of anthrax from bioweapons facility Ping Fan, Manchuria 1936–45 Stalingrad 1942 Japanese Military Unit 731 Soviets infect German Panzer experiments on Chinese troops with tularemia Soviet Union 1972–92 Biopreparat (major Kaffa 1347 bioweapons program) Tatars catapult plague The Dalles 1984 victims over city walls salmonella release Tokyo 1990–95 by cult followers of Aum Shinrikyo makes several Baghwan Sri Rajneesh Iraq 1980s–1990s bioweapons program unsuccessful attempts to use bioweapons

Figure 2. Historical incidents involving biological weapons span the globe and range from relatively modest events, such as salmonella poisoning of salad bars in The Dalles, Oregon in 1984, to the notorious experiments by the Japanese military during the 1930s and 1940s, in which many thousands of Chinese were killed with infectious agents. Not all historical events are listed here. tion of the Use in War of Asphyxiating al occasions by dropping from air- A good deal of effort on both sides gas, and of Bacteriological Methods of planes laboratory-grown fleas fed on went into attacking the problem of Warfare.” infected rats. The Soviets may have weaponization. Biowarfare agents may Although the Geneva Protocol didn’t deliberately infected German Panzer be deadly, but they are also labile and expressly forbid the production and de- troops with tularemia during the Bat- difficult to deliver to the intended tar- velopment of biological weaponry, it tle of Stalingrad in 1942, by far the get. It took years of experimentation did ban all use during war. Disappoint- costliest battle of WWII, but the ensu- before the U.S. and Soviet programs ingly, neither the U.S. nor Japan ratified ing outbreak soon spread to both eventually succeeded in developing ef- the treaty before the advent of World sides and resulted in more than 100,000 fective means of stabilization and dis- War II, when anthrax and other cases of the disease. tribution—in the form of explosive bioweapons were secretly being devel- Unlike the years following WWI, the bomblets or aerosol-spray weapons oped by both countries—as well as by post-WWII period heard little public that could be delivered by aircraft or Germany, the U.S.S.R. and Great Britain. debate concerning the need to limit ballistic missiles. Today, the operating The Japanese and British bioweapons bioweapons—perhaps owing to the principles of such delivery devices are programs were particularly extensive, global preoccupation with nuclear arms among the most closely held national but no documented use of agents ever that began in 1945. With the advent of secrets. This is entirely appropriate, occurred during combat. This may the Cold War, the U.S. biowarfare pro- given the relative ease with which have been due to residual respect for gram (begun in 1942 and aided by post- most other aspects of the bioweapons the 1925 treaty or, what seems more war intelligence from the Japanese) problem are tackled. likely, from the relative immaturity and went into overdrive. Over the course of associated imperfections of bioweapons the next 25 years, the U.S. would quiet- Modern-Day Transgressions technology. ly develop, test and weaponize at least On November 25, 1969, under Presi- There were some notorious in- 10 different biowarfare agents, includ- dent Nixon, the U.S. announced that it stances of biological warfare during ing bacteria, viruses and microbe-de- would unilaterally and unconditional- this period, however. The Japanese rived toxins. The U.S. not only experi- ly renounce all biological weapons. Military Unit 731 at Ping Fan, Man- mented with human disease, but also Following executive order, the U.S. churia, experimented extensively targeted economically vital agriculture program was summarily terminated, with bioweapons, killing thousands with fungal weapons such as wheat and the Department of Defense was in- of prisoners of war with anthrax, rust and rice blast. The Soviets had a structed to destroy all remaining stock- cholera, plague, dysentery and other program that was every bit a match for piles of weapons based on biological infectious agents. They also released the American one, but concentrated on agents. This order was extended the plague on the Chinese civilian popu- a different subset of diseases. Both following year to cover toxin weapons, lation of Chekiang Province on sever- countries stockpiled plenty of anthrax. including biologically produced toxins.

30 American Scientist, Volume 89 © 2001 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. The existing American stockpiles of bi- bioweapons effort, the Soviets consid- moved a critical filter that had clogged. ological weapons were destroyed be- ered the best bioweapons agents to be The filter happened to be on the output tween May 1971 and May 1972. those for which there was no preven- of a drying machine used to remove These welcome developments paved tion and no cure. liquid from industrial-scale cultures of the way for the landmark international It was during Biopreparat’s heyday, anthrax spores, which were being pro- treaty of April 10, 1972, the Biological in 1979, that the “Sverdlovsk incident” duced for bioweapons. An aerosol of and Toxin Weapons Convention (or occurred. In April and May of that spores was released from the unit’s ex- BWC)—which has now been signed by year, about 100 people and uncounted haust pipes over a period of several 160 nations and ratified by 143. Among livestock suddenly died of anthrax in hours before the mistake was discov- the countries that have signed and rati- Sverdlovsk (now Yekaterinburg), a city ered. Sverdlovsk suffered the single fied the treaty are the U.S., Great of 1.2 million people. All the victims largest epidemic of inhalation anthrax Britain, China, the Russian Federation, were located within a narrow band di- in history. In 1992, former Russian Pres- Iraq, Iran, Libya and North Korea— rectly downwind of a secure microbio- ident Boris Yeltsin formally acknowl- some of which figure prominently in logical facility run by the military. The edged the true origin of the outbreak. reports of actual or suspected bio- Soviet authorities blamed the deaths The current economic and political cli- weapons programs. Eighteen nations on contaminated meat (intestinal an- mate in the former Soviet Union raises signed the treaty but subsequently thrax), whereas U.S. agencies attrib- the disturbing likelihood that their failed to ratify it—including Egypt, Syr- uted the deaths to inhalation anthrax. bioweapons experts will be forced to ia and Somalia—and 34 nations haven’t The latter explanation would consti- seek employment elsewhere, resulting in even signed it, including Israel. tute prima facie evidence for violation unwelcome proliferation. The analogous The BWC, which went into force in of the BWC. International investiga- problem arises for former Soviet nuclear March 1975, took ambitious steps to tions followed, some involving noted experts, of course, but bioweapons issues ban both biological and chemical Harvard biologist Matthew Meselson. have received comparatively little atten- weapons, including their development, His group’s reports, although some- tion and scant resources. production, procurement or stockpil- what critical, initially seemed to lend The BWC was also clearly violated ing for any hostile purpose or use in credence to the Soviet explanation. by Iraq, which established extensive armed conflict. Unfortunately, the However, subsequent findings and de- programs for the development of both BWC incorporated no provisions to in- tailed witness accounts left little room chemical and biological weapons un- vestigate or follow up on suspicious for doubt. der Saddam Hussein in the early 1980s. activities. It lacked “teeth.” Today, it appears that the deaths Details of these programs only sur- Perhaps the greatest BWC transgres- were precipitated by a shift worker at faced in the wake of the Gulf War, fol- sion of all occurred between 1972 and the microbiological installation who re- lowing investigations conducted by 1992, when a truly massive bioweapons effort was under way in the Soviet bacterial disease causative agent Union. Despite endorsing the BWC anthrax Bacillus anthracis Treaty, the Soviet Union carried out ul- brucellosis Brucella suis, B. melitensis, B. abortus tra-secret bioweapons work right up glanders Burkholderia mallei, B. pseudomallei until it collapsed in 1990. Some experts plague Yersinia pestis contend that a low, but significant, level Q fever Coxiella burnetii of research still exists today. Revelations Rocky Mountain spotted fever Rickettsia rickettsii of the staggering scope of the Soviet tularemia Francisella tularensis program have only recently come to typhus Rickettsia prowazeki light, after the much-publicized defec- viral disease causative agent tion of Ken Alibek—formerly Colonel smallpox variola major Kanatjan Alibekov—the Deputy Direc- viral encephalitis Venezuelan equine, eastern equine, tor of Biopreparat, the Soviet state “phar- tick-borne encephalitis virus maceutical” agency charged with car- African hemorrhagic fever Ebola, Marburg, Congo-Crimean virus rying out bioweapons research. South American hemorrhagic fever Junin, Machupo, Sabia, Flexal, Guanarito virus other Rift Valley, Lassa, yellow fever virus Alibek has called Biopreparat “the fungal disease (of crops) causative agent darkest conspiracy of the cold war” rice blast Magnaporthe grisea and tells a chilling tale. During the hey- rye stem rust Puccinia graminis forma specialis avenae day of the Soviet program, Alibek su- wheat stem rust Puccinia graminis forma specialis tritici pervised as many as 32,000 people (out biological toxin source of 60,000 in the program) at nearly 40 botulinum toxin Clostridium botulinum facilities spread throughout the Soviet enterotoxin B Staphylococcus aureus Union—effectively a “toxic archipel- epsilon toxin Clostridium perfringens ago.” Here the Soviets worked not only ricin Ricinus communis (castor bean) on perfecting “conventional” biologi- shiga toxin Shigella dysenteriae, S. flexneri cal weapons based on anthrax, glanders and plague, but also on weaponiz- Figure 3. Biological agents that could be used in a weapon include various bacteria, viruses, ing deadly (and highly contagious) fungi and toxins. Adapted from the CDC Select List of Agents, U.S. Department of Health viruses such as smallpox, Marburg and and Human Services 42CFR Part 72, RIN 0905–E70. Available at: http://www.cdc.gov/od/ohs/ Ebola. In contrast to the American lrsat/42cfr72.htm#Summary_Changes.

Sergiev Posad Kirov Omutninsk Reutov Moscow Strizhi Koltsovo Minsk Serpukhov Novocheboksarsk Yekaterinburg Belarus Golitsino Lubychany Pokrov Berdsk Vladimir Miass Obolensk Ufa Kurgan Kiev Penza Pushchino Stepnogorsk Ukraine Saratov Moldova Kharkiv Oziorsk Kazakhstan Shikhany Volgograd Rostov Otar Black Sea Aralsk Almaty Aral Vozrozhdeniye biological weapons sites Sea production facilities Island Kyrgyzstan Georgia Tashkent storage facilities Tbilisi Caspian Nukus Uzbekistan research facilities Armenia Sea Azerbaijan testing grounds Abovian Tajikistan mobilization facilities Turkmenistan (activated in time of war)

Figure 4. Institutes and facilities constituting the Soviet Union’s enormous bioweapons program—Biopreparat—involved nearly 60,000 people at 40 sites during the 1970s and 1980s. The ultra-secret program violated the 1972 Biological and Toxin Weapons Convention, which the Soviet Union signed, and it was not dismantled until 1992. The egregious transgression is a testament to the weakness of biological-weapons treaties and conventions that cannot be enforced. The current economic and political situations in the former republics of the disbanded Soviet Union also raise the question of how out-of-work bioweapons scientists are finding gainful employment. (Adapted from Smithson 1999). the United Nations Special Commis- struction. Relevant portions of the fa- hance and strengthen the provisions sion (UNSCOM) in charge of Iraqi dis- cilities at Salman Pak and Al Manal of the BWC—giving it some “teeth.” armament. As a result of these investi- were also destroyed, either by the This would include verification mea- gations, more is known today about Iraqis themselves or under direct UN- sures that monitor treaty compliance, the once-secret bioweapons program SCOM supervision. including reciprocal inspection visits in Iraq than that of almost any other In the aftermath of the Gulf War, to suspected bioweapons facilities. nation. Iraq maintained several dis- Iraq officially acknowledged that it had This is an essential component of tinct facilities, including those at the worked with several species of bacteri- modern arms-control regimes, similar Muthanna State Establishment (the al pathogen—including Bacillus an- to those implemented for nuclear principal chemical weapons plant), thracis, Clostridium botulinum and weapons treaties. Salman Pak (the main biowarfare re- Clostridium perfringens (which causes An international group of BWC par- search center, just south of Baghdad), gas gangrene)—and several viruses— ticipants has been convened since Jan- the “Single-Cell Protein Production including enterovirus 17 (human con- uary 1995 to accomplish just that, un- Plant” at Al Hakam (the main bio- junctivitis), rotavirus and camel pox. der the chairmanship of Ambassador weapons production facility, allegedly They also purified biological toxins, in- Tibor Tóth of Hungary. It carries the built to produce animal feed) and the cluding botulinum toxin, ricin and ponderous name of “The Ad Hoc Foot and Mouth Disease Center at Al aflatoxin. In total, a half million liters of Group of the States Parties to the Con- Manal (a site for biowarfare research biological agents were grown. vention on the Prohibition of the De- on viruses). velopment, Prohibition, and Stockpil- The Al Hakam facility began mass A Meaningful Bioweapons Treaty ing of Bacteriological (Biological) and production of weapons-grade anthrax All told, it’s suspected that more than Toxin Weapons and on Their Destruc- in 1989 and eventually generated at a dozen sovereign nations possess tion”—or simply the “Ad Hoc Group.” least 8,000 liters (based on declared some form of offensive bioweapons By now the Ad Hoc Group has met for amounts). This plant was not bombed program, assuming one includes more than 50 weeks in Geneva. The during the Gulf War in 1991, and its some republics of the former Soviet draft treaty they have prepared is as true role in Iraq’s bioweapons program Union. How can this proliferation be ponderous as the group’s name: It cur- was not established until 1995, at controlled? One approach is to rently weighs in at several hundred which point the U.N. ordered its de- muster international resources to en- pages, including an astonishing 1,500

32 American Scientist, Volume 89 © 2001 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. “bracketed” paragraphs—which de- in the way of equipment and infra- Between 1990 and 1995, the well-fi- note passages where there continues to structure. The materials themselves nanced Japanese apocalyptic cult Aum be disagreement. are less rare. And less is required in Shinrikyo launched a repeated series of For the moment, progress of the Ad the way of specialized knowledge for attacks on civilians using both biologi- Hoc Group seems depressingly stalled. the biological aspects, since much of cal and chemical weapons. These cul- Embarrassingly, the United States itself the information can be found in the minated in the infamous sarin gas re- bears a direct responsibility for many public domain. Worldwide, trained lease inside the Tokyo subway system brackets, as it has steadfastly resisted microbiologists overwhelmingly out- in March 1995, which left 13 people certain attempts to establish provisions number nuclear physicists. All these dead and sent more than 5,000 to the for inspections. The U.S. position is aspects tempt not only nations of con- hospital. Before resorting to toxic gas, motivated by a desire to protect the in- cern, but also non-state actors. In fact, the group had reportedly attempted, terests of the powerful American it seems far more likely that biological unsuccessfully, to mount attacks with biotechnology sector, which fears that agents will be used by terrorists than biological weapons on at least nine oc- inspection visits may be intrusive, or by warring nations. Although the ter- casions over a five-year period. Aum used as a pretext for industrial espi- rorist use of bioweapons is likely to oc- Shinrikyo boasted a dozen or so mem- onage. There has been limited progress cur on a reduced scale, it could have bers with biological training and had on this front with the release last May worldwide ramifications under unfa- even gone so far as to buy a 500,000- of a joint statement by the Pharmaceu- vorable circumstances. acre sheep station in Banjawarn, Aus- tical Research and Manufacturers of Little of real consequence has oc- tralia to serve as a site for operations America and the Federation of Ameri- curred along these lines, but shots have and to carry out tests. can Scientists who agreed on “man- been fired across the bow. In a bizarre The cult worked to develop biologi- aged-access” measures in support of episode that took place in September cal weapons based mainly on botu- verification. 1984, more than 750 people fell ill with linum toxin and anthrax, although Another sticking point rests on a food poisoning in The Dalles, Oregon. some members made an unsuccessful constitutional issue: It is one thing for Thankfully, no one died. The cause of trip to Zaire to obtain Ebola virus. They the U.S. government to authorize visits the epidemic was not uncovered by also attempted, but failed, to acquire to its own labs and bases, but can it health authorities at the time. But in the rickettsia Coxiella burnetii, which mandate visits to privately held facili- 1986, Ma Anand Sheela confessed at causes Q fever. In their earliest at- ties? Some have argued that such in- trial that she and other followers of the tempts to carry out biological attacks, spections may require warrants. How- Baghwan Sri Rajneesh had spread sal- members of the cult sprayed home- ever, under the Fourth Amendment, monella bacteria, grown on the cult’s brewed botulinum toxin on Tokyo warrants are necessary only if actions Oregon ranch, in salad bars in four streets, near two American airbases in rise to the level of a “search.” Federal restaurants, all in an effort to keep vot- Japan and at the Narita International courts have generally held that the ers from the polls so as to influence a Airport. All of these attacks failed— subject of a search must enjoy an ex- local election. After serving two and a most likely because they worked with pectation of privacy—but this standard half years in federal prison, Sheela was the wrong strain of C. botulinum (not is stricter for individuals than it is for released and deported to Europe. all natural variants yield equal toxicity) corporate entities, particularly for in- dustries that are highly regulated. Moreover, the Supreme Court has already recognized that valid exceptions exist to the warrant requirement—for example, for drunk driving, contra- band and immigration documenta- tion—and compliance with a vital international treaty certainly should qualify as a valid exception. As the world’s remaining superpow- er, the United States bears a unique responsibility to take the moral high ground in this process, assuming a leadership role in support of meaningful weapons treaties that establish international norms. A way must be found before a singular opportunity is lost.

Assessing the Terrorist Threat Biological weapons have been called

“the poor man’s atom bomb.” By any AP Photo/Henry Arvidsson/United Nations measure, the economic outlay required Figure 5. Scud missiles were destroyed by the United Nations weapons inspectors in Iraq to develop offensive bioweapons ca- during the investigation of the country’s bioweapons program after the 1991 Gulf War. Israel pabilities is significantly less than that was purported to be a target for the long-range Iraqi Al Hussein Scud missiles armed with of a nuclear program. Less is needed “non-conventional” warheads, including biological weapons.

© 2001 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 2001 January–February 33 and because their misting device may must overcome two significant prob- that would ensue might alone bring not have been up to the task. They later lems, one biological and the other about the intended effect. Our public switched to anthrax, releasing spores physical. First, it must acquire and pro- health system simply isn’t geared up in Tokyo near the Imperial Palace, the duce stable quantities of a suitably po- to handle an outbreak of this kind, legislature and a foreign embassy. tent agent. For a variety of reasons this which would, for a time, flood emer- These tactics again failed, almost cer- is not the trivial task that it is some- gency rooms. A terrorist group might tainly because they used a vaccine times made out to be. Second, it must also be tempted to finesse the dispersal strain of B. anthracis. And again, their have an effective means of delivering problem and release some contagious spraying device may not have worked the agent to the intended target. For disease, with the aim of starting an epi- as intended. most, but not all, bioweapon agents, demic or even a worldwide pandemic. Does this mean that we should all re- this translates into solving problems of Or it might choose to act covertly, per- lax, because using bioweapons turns dispersal. Programs in both the U.S. haps attacking an economic target, out to be harder than the perpetrators and the U.S.S.R. devoted years of effort such as crops or livestock, rather than a thought? Is the terrorist threat therefore to perfecting these aspects. human population. There are many exaggerated, as some have maintained? But who is to say that a terrorist different options. Those who claim that biowarfare agents group might not find its own way to In my opinion, the terrorist threat is can be brewed in a garage by practically imperfect solutions? After all, a terror- very real, and it’s about to get worse. anyone with a modicum of training ist works under entirely different con- And opinions do count here, because may be guilty of overstating the case, straints. For one thing, there’s no re- quantitative risk assessment is a practi- but although there has been no short- quirement for the dispersal to be very cal impossibility. As with nuclear war, age of exaggeration, that doesn’t mean efficient, because bioweapons terror at- successful bioweapons attacks are char- we’re off the hook. tacks are highly leveraged. If anthrax acteristically “low probability, high con- A lesson from the Aum Shinrikyo were released haphazardly in a major sequence” events. The expectation val- case is that any group bent on develop- U.S. city and produced only a handful ue of the risk is the product of a very ing offensive bioweapons capabilities of cases, the public fear and disruption small and a very large number, and such numbers carry great uncertainty. AP Photo/Joe Marquette The Smallpox Wildcard All of which brings us to smallpox, the bête noire of bioweapons. Smallpox is a frequently lethal, highly contagious disease caused by the variola major virus. By the end of the second millen- nium, it had killed, crippled, blinded or disfigured one-tenth of all hu- mankind who ever lived. In one of the greatest achievements of the 20th century, smallpox was finally eliminated after a decade-long, worldwide health campaign, which was launched in 1967 under the auspices of the World Health Organization (WHO), under the direc- tion of Donald A. Henderson (now the director of the Center for Civilian Biodefense Studies at Johns Hopkins University). The last recorded case of smallpox occurred in Somalia in 1977, and the disease was officially declared eradicated in 1980. Although there is no cure for smallpox, it can be prevented with a vaccine

Figure 6. Simple spraying device might be employed by a terrorist to deliver deadly biological agents in a crowd of people. Despite the apparent ease of such delivery methods, attempts by the Japanese cult Aum Shinrikyo evidently failed, in part, because of their spraying device. Here William C. Patrick, one-time chief of product development for the (now-defunct) U.S. bioweapons program, provides a demonstration to the House Select Committee on Intelligence in Washington on March 3, 1999.

© 2001 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. derived from the vaccinia virus. The U.S. Public Health Service recom- isolate nonvirulent isolate virulence mends re-vaccination every 10 years, host (harmless) plasmid (harmless) but since routine vaccination of the U.S. population ended nearly 25 years pathogenic bacterium ago, few Americans retain immunity today. The current stocks of the vaccine are negligible. Fortunately, there has introduce an been some recent action to correct this antibiotic-resistance state of affairs. As of last September, gene the U.S. Centers for Disease Control clone and Prevention (CDC) have contracted amplify for a 40-million-dose stockpile of the vaccine. The first batches of the vaccine are slated to be ready by 2004. Howev- er, some public-health scientists have questioned whether such a “small” stockpile is adequate. In the event of a binary weapon simultaneous terrorist attack on several (with separated components) major cities, hundreds of millions of doses might be required to prevent the disease from spreading. Whether terrorists could get access to the smallpox virus is still an open activate question. At the end of the heroic WHO campaign frozen stocks of the variola virus were maintained in trust by two organizations: the CDC and Vector, the Russian State Research Center of Virol- deadly bacteria ogy and Biotechnology in Koltsovo, Novosibirsk, Russia. These stocks were Figure 7. “Black biology” is the colorful name given to the dark art of employing modern originally scheduled to be destroyed on techniques in molecular biology to create “new and improved” varieties of bioweapons. December 31, 1993, but this date has One such possibility includes the creation of a binary bioweapon, in which, for example, a been repeatedly postponed as politi- virulence plasmid is separated from its bacterial host, thus allowing weapons manufactur- cians and health officials debate the ers to work safely with the components (which are harmless on their own). The cloned bacteria and amplified plasmids can be placed into separate chambers within a device. When wisdom of retaining or destroying the the contents of the chambers are mingled together with certain drugs or chemicals, a small remaining virus, given the growing fraction of the bacteria are induced to take up the plasmid, which confers antibiotic resis- bioweapons threat. For now, the deci- tance. Subsequent regrowth of the bacteria in the presence of the antibiotic ensures that sion has been deferred by the WHO un- only recombinant, infectious cells carrying the virulence plasmid are produced. til 2002. A concern shared by many is Unfortunately, there are many ways to use advances in biotechnology to create particularly whether the Russian stocks are securely effective bioweapons. held. Ken Alibek has reported that Bio- preparat secretly prepared smallpox- pathogen (Vibrio cholerae) was recently now accomplished. Back in the summer based bioweapons up until at least published, and the genomes of more of 1997, JASON (a group of primarily aca- 1992, leading one to wonder how much than 100 other microorganisms are now demic scientists, which consults on tech- viable smallpox virus might exist out- being sequenced—including the bacte- nical matters for the U.S. government and side the official Koltsovo depository. ria that cause anthrax, plague, dysen- its agencies) addressed the problem of If any weaponized material or viral tery and typhoid. Of course, the new next-generation bioweapons threats. The stocks found their way to terrorist or- information is critical for answering JASON study explored a wide range of ganizations, the consequences could be fundamental and practical questions in future possibilities open to genetically en- disastrous. Simply put, smallpox repre- biology and medicine, and will be put gineered pathogens, including some that sents a direct threat to the entire world. to direct, practical use in a myriad of could be achieved with the current state of health-related applications. But what the art and others that are—happily—still “Black Biology” about “black biology”? Could biotech- some way off. The prospects are sober- Beyond the smallpox scenario, what nology be used to produce a new gen- ing. Both bacteria and viruses may now has people worried is the impact of eration of biowarfare agents with un- be engineered to be qualitatively differ- modern biotechnology. For better or precedented power to destroy? Or is ent from conventional bioweapon agents. worse, the world is in the midst of a this just alarmist hype? No one can say In terms of bioweaponry, this includes stunning revolution in the life sciences. for sure, but many molecular biologists imbuing them with such “desirable” at- Scientists have already determined the familiar with the relevant technologies tributes as safer handling, increased vir- complete genomic sequences for more seem inclined to a pessimistic view. ulence, improved ability to target the than 30 microbes and even more virus- A key reason for pessimism is the ease host, greater difficulty of detection and es. The DNA code for the cholera with which genetic manipulations are easier distribution.

© 2001 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 2001 January–February 35 Several broad classes of unconventional pathogens were identified by JASON. These include “binary” bioweapons, which, by analogy with chemical weapons, are two-component systems in which each part is relatively safe to handle, but which become deadly in combi- nation, and “designer” variations on genes, viruses and complete life forms, including chimeras that mingle existing components. Once gene therapy becomes a medical reality, the technology that al- lows the repair or replacement of defec- tive genes might be subverted to introduce pathogenic sequences. “Stealth” viruses could be fashioned to infect the host but remain silent, until activated by a trigger. New zoonotic agents (those trans- missible from animals to people) might be developed specifically for bioweapon purposes by modifying existing pathogens to seek human hosts. Finally, de- tailed knowledge of biochemical signal- ing pathways could conceivably be used to create “designer diseases.” Of course, some of these exotic possibilities seem downright superfluous given the dangers posed by the current generation of bioweapon agents. Then AP Photo/Gustavo Ferrari again, fusion-based hydrogen bombs Figure 8. Vaccination against anthrax for military personnel is a controversial issue in the seem superfluous, given the destruc- United States, adding further complications to the process of building a defense against bio- tive power of fission-based weapons. logical weapons. Mired in political scandal, the production of the vaccine has been delayed while existing inventories have dwindled. Here an Army sergeant administers a dose of the For now, even the most rudimentary anthrax vaccine to a military specialist near Kuwait City in 1998. genetic manipulations could be used to enhance a bioweapons threat, for ex- vaccine is prepared from a cell-free fil- tive government contract for the mili- ample by introducing antibiotic resis- trate derived from an avirulent strain tary. The most visible corporate direc- tance into a weaponized bacterial of B. anthracis. By most accounts the tor of Bioport is Admiral William strain. current anthrax vaccine is as safe as, Crowe, former chairman of the Joint perhaps safer than, typical vaccines, al- Chiefs of Staff. Bioport thus became the Vaccination Woes though every vaccine carries residual exclusive purveyor of anthrax vaccine Anyone seeking to “improve” on wild- risk. This is why the oral (Sabin) polio and applied for FDA approval of a type anthrax might begin by introduc- vaccine will soon no longer be given to Michigan plant to manufacture more. ing antibiotic resistance in the form of a children in the U.S. Comprehensive That approval is still at least six gene for β-lactamase, which enzymati- vaccination programs have reduced months out. Meanwhile, existing in- cally destroys penicillin. Such a trans- polio to such an extent that the risk as- ventories have dwindled, and the mili- formation is rather straightforward, sociated with receiving the oral dose, tary is running out of vaccine after ad- and similar to the kind of thing done which leads to paralysis in a minuscule ministering fewer than half a million routinely today in molecular biology fraction of cases, now outweighs the doses (out of 14 million). As a result, labs with non-pathogenic organisms. chance of getting the disease itself. they’ve had to reduce monthly inocu- Disease caused by a multi-drug- resis- Unfortunately, the U.S. military an- lations from 75,000 to 14,000 and sus- tant variant of anthrax would essen- thrax vaccination program has been pend injections for all but front-line tially be impossible to treat. Only those mired in controversy and scandal. Pri- troops considered at greatest risk. with prior immunity, conferred by vac- or to the program, the lone American In Senate hearings held in July 2000, cination, would stand much chance of company licensed by the FDA to pro- Republican Senator Tim Hutchison of survival. duce anthrax vaccine in the U.S. was Arkansas reacted to the situation as Considerations such as this have the state-owned Michigan Biologics follows: “The terms of the contract re- helped to motivate the ongoing cam- Products Institute, and it was in danger lief (between the Department of De- paign to vaccinate all 2.4 million U.S. of losing its license after inspections fense and Bioport) reduced the num- active and reserve troops against an- raised questions about potency and ber of dosages to be produced by one thrax. The vaccination process, licensed sterility of the vaccine. The troubled in- half, charged U.S. taxpayers almost by the Food and Drug Administration stitute was bought out by Bioport, a three times as much as originally ne- (FDA), requires a six-dose regimen company apparently created solely to gotiated, and provided Bioport an in- over an 18-month period. The modern take over its assets and land the lucra- terest-free loan of almost $20 million. I

36 American Scientist, Volume 89 © 2001 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. am wondering who negotiated such a that nuclear spending certainly can’t Bibliography contract.” claim to match. Money spent on re- Alibek, K. 1998. “Terrorist and intelligence op- Issues of procurement and safety search to develop new types of sensi- erations: potential impact on the U.S. econ- aside, the most disturbing aspect of the tive detectors and related monitors for omy.” Statement before the Joint Economic anthrax-vaccination program is the un- biowarfare agents will almost certainly Committee, U.S. Congress, May 20, 1998. Available at: http://www/house.gov/jec/ known efficacy of the new vaccine. A carry over to the public-health sector hearings/intell/alibek.htm limited study, completed back in 1962 in the form of rapid, improved diag- Alibek, K., and S. Handelman. 1999. Biohazard. among mill workers handling animal nostics for disease. Money spent on co- New York: Random House. materials, demonstrated protection ordinating and developing emergency Bussey, E. 2000. Senate hears testimony on an- against the cutaneous form of anthrax response teams at federal, state and lo- thrax vaccine shortage, Reuters Health News, for an earlier version of vaccine. How- cal levels will also establish better July 18. Available at: http://www.reuters ever, no one is yet prepared to say mechanisms for dealing with natural health.com/frame2/ arch.html whether the current formulation will outbreaks of emerging diseases. Mon- Drell, S. D., A. D. Sofaer and G. D. Wilson. provide adequate immunity against ey spent on innovative surveillance ap- 1999. The New Terror: Facing the Threat of Bio- acute inhalation anthrax produced by proaches for detecting biowarfare at- logical and Chemical Weapons. Stanford, a bioweapon. We may never really tacks should also improve medical Calif.: Hoover Institution Press. know, given the obvious ethical consid- epidemiology. Money spent on vaccine Guillemin, J. 1999. Anthrax: The Investigation of a Deadly Outbreak. Berkeley: University of erations of experimenting with the vac- research and delivery may help to but- California Press. cine. It also seems possible that a strain tress our limited capacity to protect the Lederberg, J. 1999. Biological Weapons: Limiting of anthrax might be genetically engi- civilian, as well as the military, popula- the Threat. Cambridge: MIT Press. neered to circumvent the immunity tion. And money spent on stockpiling Preston, R. 1998. The bioweaponeers. The New conferred by the present vaccine. Does and positioning depots of smallpox Yorker, March 9, pp. 52–65. it therefore make sense to vaccinate all vaccine may turn out to be the smartest Preston, R. 1998. Taming the biological beast. our military personnel? Well, perhaps hedge-bet of all. New York Times, April 21, 1998. not all, but the risks to frontline troops Since 1945, a great many physicists Regis, E. 1999. The Biology of Doom. New York: are very real, and the long interval re- have taken up the challenges posed by Henry Holt & Co. quired for the full immunization sched- nuclear weaponry, and worked hard at Smithson, A. 1999. Toxic archipelago: pre- ule demands foresight. In the end, one both the national and international lev- venting proliferation from the former So- is left to make informed guesses. el to limit their destructive potential. viet chemical and biological weapons The difficulties with the anthrax vac- But with the notable exception of a few complexes. Henry C. Stimson Center cine highlight an endemic problem: The of the old guard, such as Donald Hen- Report no. 32, Dec. 1999. Available at U.S. has precious little in the way of derson, Joshua Lederberg and Matthew http://www.stimson.org/cwc/toxic.htm. vaccine production capabilities, and ob- Meselson, there has been comparative- Tóth, T. 1999. Time to wrap up. Quarterly Jour- taining FDA approval for a new vac- ly little involvement by biologists in nal of the Harvard Sussex Program on CBW Armament and Arms Limitations 46:1–3. cine protocol requires at least two bioweapons issues. The case was put years, generally more. The vaccine in- best by author Richard Preston, who Tucker, J. B. 2000. Toxic Terror: Assessing Terrorist Use of Chemical and Biological Weapons. Cam- dustry faces serious issues analogous to wrote: bridge: MIT Press. the “orphan drug” situation in the The community of biologists in pharmaceutical industry. If a lot of peo- the United States has maintained ple are not dying of the disease, where a kind of hand-wringing silence is the market for the product? And how on the ethics of creating biowea- does a manufacturer protect itself from pons—a reluctance to talk about ruinous lawsuits? This is a topic that it with the public, even a disbelief might be better addressed by the public that it’s happening. Biological rather than the private sector. weapons are a disgrace to biology. The time has come for top biol- Prospects ogists to assert their leadership The Clinton administration has allocat- and speak out, to take responsi- ed some $1.4 billion during fiscal 2000 bility on behalf of their profession to combat biological and chemical ter- for the existence of these weapons rorism, a figure that has provoked and the means of protecting the sharp criticism in some quarters. But population against them, just as this number absolutely pales in com- leading physicists did a genera- parison with the amount spent annual- tion ago when nuclear weapons ly on maintaining U.S nuclear capabili- came along. Moral pressure costs ty, which is at least 30-fold greater. It nothing and can help; silence is makes eminent sense to develop im- unacceptable now. proved capability against bioweapons threats, and we should not have to wait for the biological equivalent of Hi- Acknowledgments roshima to rally our defenses. The author thanks Jonathan Tucker, Amy There are also indirect benefits asso- Smithson, Jerry Joyce and assorted members of ciated with such an investment—ones JASON for comments and helpful discussions.