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Research Story of the Week

Smallpox: Threat, Vaccine, and US Policy
Part III of a Six-Part Series

View: Parts I & II | Part III | Part IV | Part V | Part VI

View the entire series as a single PDF file. PDF format, 36 pages, 539 kb.

Illustration showing vaccination for smallpox. [Source: World Health Organization] View the entire series as a single PDF file. PDF format, 36 pages, 539 kb.

By Richard Pilch, M.D.

[The author would like to especially thank Dr. Raymond A. Zilinskas for his extensive editing and review of this segment.]

III. The Disease versus the Vaccine

In determining whether vaccination is appropriate for a given individual or family, the theoretical threat of a smallpox attack must be weighed against the real risks of the vaccine, the complications of which are well-established as discussed in Parts I and II. But what then is the threat of a smallpox attack on the United States?

The formula for a threat assessment is Threat = Vulnerability x Capability x Intent, with threat being the probability that an adversary will inflict injury or damage.[1] Vulnerability is the extent to which a potential target is open to attack. Capability is whether a given adversary has the technical ability to carry out an attack, and with respect to biological weapons (BW) this component of the threat assessment consists of three major hurdles: acquisition of a pathogenic strain, production, and effective delivery. Intent is whether an adversary would actually be likely to carry out an attack, and generally speaking this component of the threat assessment requires that a distinction be made between desired acquisition for deterrence, prestige, or other motivations unrelated to imminent use, and desired use in place of or in conjunction with conventional weapons or other weapons of mass destruction (WMD), namely chemical weapons (CW) and radiological and nuclear weapons.[2]

Vulnerability

In nonspecific terms, it can be stated with some certainty that the United States is in fact vulnerable to BW threats on a number of levels.[3]

With open borders to goods and people and unregulated interstate movement, the transport of key personnel, equipment, and pathogens is possible both into and within the country, despite the concerted efforts of officials and others in the wake of September 11th to tighten physical security along US borders and nationwide. Add to this the fact that the US public health system has essentially been a victim of its own successes. For example, advances in infectious disease management, particularly heralded by the advent of new and improved antibiotics, led to the steadily improving general health of civilians of the middle and upper socioeconomic strata over the past few decades. Neglect in the form of budget cuts followed, leaving the nation largely unguarded against both emerging natural biological threats and deliberate advances (again, in spite of government efforts and great strides in the public health sector to address this problem post 9-11). Along these lines, emergency physicians, nurses, and technicians, as well as family practitioners and other members of the medical community who effectively represent the first line of defense against a biological attack, have virtually no practical experience in the recognition and management of those diseases most likely to be encountered in such an attack. Moreover, at present they have not been extensively trained to overcome this shortfall.

All of these points have their place in a discussion of this nation's vulnerability to smallpox. Most important, however, is simply the fact that without vaccination, the human body is susceptible to the virus. Its inherent risks notwithstanding, the vaccine is effective in preventing the disease.

Capability: Acquisition

In order to attain a smallpox capability, three steps must be taken: a pathogenic strain of the virus must be acquired, the strain must be used to produce an amount of agent sufficient for use, and the agent must be effectively delivered.

As far as is known, US policy-makers do not possess any incontrovertible evidence that any of our perceived enemies, whether state or terrorist organization, has acquired the smallpox virus. Potential sources for such acquisition are largely concentrated in two spheres: (1) the former Soviet BW program, which throughout the 1970s is said to have maintained a 20-ton per year stockpile of the virus;[4] and (2) surviving virus from the pre-eradication era.

Since the dissolution of the Soviet Union, fears have persisted that seed stocks of certain BW agents, including the smallpox virus, have been illegally removed from one or more of the many facilities of the former Soviet BW program. Vector, reportedly the central facility of the Soviet civilian smallpox weaponization program from 1987 on, has long been the focus of international threat reduction efforts, and as such has benefited from enhanced physical security and increased wages for its scientists over the past few years.[5] The security measures have essentially served to guard this facility against outside penetration, while the salary hikes are meant to dissuade insiders from stealing and selling strains of the virus, thus addressing the two major concerns with respect to containment at such facilities: poor security and vastly underpaid scientists who might be persuaded to supply agents or expertise to an outsider. This outsider may represent a state of proliferation concern or a terrorist organization. For example, in 1999 a member of al-Jihad, a group associated with Usama bin Ladin, testified that the group had successfully purchased biological and chemical weapons from countries of the former Soviet bloc.[6] More likely, however, the outsider would be a member of one of Russia's estimated 12 to 15 major mafiya groups,[7] which via operations in 60 to 65 countries could then distribute the acquired agent on the black market or to interested parties directly.[8]

The notion of smallpox virus persisting from the pre-eradication era generally refers to blood samples of smallpox patients that for whatever reason were not destroyed following the disease's eradication. In the wake of the World Health Organization's global eradication campaign, the necessity of such destruction was emphasized, and compliance was ultimately reported by all countries without exception. But bits and pieces of evidence to the contrary have come to light suggesting that this may not in fact have been the case. A second possible source of virus from the pre-eradication era is bodies of smallpox victims buried in permafrost ground. The virus is preserved in deep cold (illustrated for example by the fact that it is stored as such at the Center for Disease Control [CDC]), and thus viable virus could theoretically be recovered from smallpox victims buried in Siberia, Alaska, and other permafrost regions. The recovery of viable influenza virus from victims of the 1918 "Spanish flu" pandemic was attempted in this manner, albeit unsuccessfully.[9]

The debate surrounding Iraq's possible smallpox capability reflects in part the potential for acquisition from each of these two major sources. In December 2002, the New York Times published a story that outlined possible links between a certain Soviet scientist and Iraq.[10] The scientist reportedly had access to various Soviet strains of smallpox, most importantly what is believed to have been the former Soviet Union's primary BW strain, "India-1."[11] This strain, procured by KGB agents in India during a particularly severe 1967 outbreak of the disease, was chosen for its extreme virulence (ability to cause disease).[12] Apparently, it was later weaponized (prepared for use in a weapons system such as an aerosol sprayer, missile, or munition) such that the virus maintained infectivity (the ability to cause infection) over a range of 15 kilometers or more in the open air.[13] While this report has not been discredited and such acquisition cannot be ruled out, most analysts believe that the most likely source of an Iraqi stockpile, if one does in fact exist, is retained cultures from a late 1971 through mid-1972 smallpox outbreak in and around Baghdad that led to an estimated 800 cases of the disease.[14]

In spring 2002, the CIA's Weapons Intelligence, Nonproliferation, and Arms Control Center reported to senior US officials that Iraq was among four states it believed to be maintaining undisclosed stocks of the smallpox virus, the others being Russia, France, and North Korea.[15] Confidence level of this assessment was considered "high." Thus, given the potential threat it seems appropriate to review the evidence supporting such possession.

Most importantly, United Nation's Special Committee (UNSCOM) inspections of Iraq's suspected BW facilities--carried out as part of UN Security Council Resolution 687, the conditional cease-fire agreement that effectively ended the Gulf War--revealed that Iraqi scientists of the Foot and Mouth Disease Center at Al Manal had engaged in research on the camelpox virus beginning in 1990.[16] Both the camelpox and smallpox viruses are orthopoxviruses, a family of 11 closely related DNA viruses. The central region of the orthopox virus family's genome is usually conserved from species to species because it houses genes essential for replication, while the outer ends, which contain variable instructions for host targeting, infectiousness, and resistance, tend to vary. The outer regions of the camelpox and smallpox virus genomes, however, are remarkably similar.[17] This close resemblance suggests to some that the Iraqis may have intended to develop an "ethnic weapon" from camelpox as a result of the selective pressures of mass production or even genetic engineering that in theory would affect populations not routinely exposed to camels more than it would the populations of Iraq, where the disease is endemic and where inhabitants presumably have developed or could easily develop antibodies to the virus. Others theorize that camelpox could be used to fill the evolutionary niche vacated by smallpox.[18] The main theory, however, is that in light of this close resemblance, camelpox was used as a simulant for smallpox, offering the Iraqis a model for everything from the formulation, production, and delivery of the virus to the manipulation of its genome.

There are multiple points corroborating this final idea, all of which are circumstantial.[19] In 1994, UNSCOM inspectors discovered a large freeze-dryer, used to make biological products stable over long periods of time (and also to convert wet products to dry form, a process discussed below), labeled with the Arabic word for "smallpox." The discovery was made at the maintenance shop of the State Establishment for Medical Appliances on the outskirts of Baghdad. Iraqi officials ensured the inspectors that the freeze-dryer was used for lyophilization (the technical term for freeze-drying) of vaccinia, in other words for preparation of the vaccine virus and not smallpox itself. This explanation was accepted at the time but later called into question when after close to four years of steadfast denial, Iraq finally admitted to the existence of an extensive BW program. That same year, the Defense Intelligence Agency reported that according to an unidentified scientist of the former Soviet BW program, Russia had provided both Iraq and North Korea with smallpox technology in the early 1990s. In the wake of Iraq's disclosure, the state relinquished a number of documents related to BW, among which were at least three papers on smallpox. Later, another document was recovered listing smallpox as one of the diseases against which Iraqi troops were being vaccinated in 1997. This information correlated with a 1991 report issued by the Armed Forces Medical Intelligence Center that the bloodwork of 8 out of 69 Iraqi enemy prisoners of war (EPWs) had revealed neutralizing antibodies against smallpox, indicating that they may have been vaccinated against the disease in recent years (these same blood samples had revealed protective antibodies against anthrax as well). This information, along with whatever intelligence had been amassed in the classified realm, led the CIA in 1998 to inform White House officials that Iraq was most likely in possession of the smallpox virus, and that stockpiles of this agent had probably been effectively hidden from UNSCOM inspectors throughout the nineties.

Capability: Production

Like vaccinia vaccine production in embryonated cells or cell culture, production of the smallpox virus requires the insertion of a pathogenic seed strain into a living host. Presumably, this requirement limits potential perpetrators to well-funded state-level programs. For example, throughout the 1970s, the former Soviet Union's BW program reportedly collected hundreds of thousands of eggs monthly for its smallpox production process, which took the form of an extended laboratory assembly line.[20] The capability of Iraq (and North Korea as well) in this regard is uncertain. It is important to point out, however, that contagious agents such as smallpox do not necessarily require any additional production measures upon acquisition of a pathogenic strain, a point which will be addressed further in the analysis of delivery mechanisms. Also, it should be noted that the handling of contagious agents, whether bacteria or viruses, requires a high level of expertise because of demanding isolation techniques.

The endpoint of the above-described production process is the puncture and drainage of each egg, the liquid of which contains virtually limitless copies of the virus. This initial product is considered a basic wet preparation. As with most BW agents, the initial wet preparation of smallpox can be taken a step further in two separate ways.[21] It can either be suspended in a "formulation" of adjuvants, preservatives, and other chemicals, or dried and then milled to attain the proper-sized particles. Either of these processes demands much more technical ability but generally yields a far better agent in terms of ease of dissemination and overall effect. In addition, the resulting agent can usually be stored for much longer periods of time in either case. Dry agents can be taken an additional step further and specially formulated as well, as was the case for example in the "anthrax letters" of 2001, to prevent clumping due to electrostatic forces.[22] This clumping results in large, ineffective particles that are either blocked by the mucociliary response of the respiratory tract or fall harmlessly to the ground. Though largely preferring dry formulations of their BW agents, the Soviets chose only to produce smallpox in a wet formulation because the virus remained virulent for up to a year in such a state and was highly stable when aerosolized.[23]

Capability: Delivery

Little is known about the current delivery capability of any state thought to possess smallpox. Conceivably, the virus can be delivered in a number of ways. In the past, for example, the former Soviet Union's Strategic Rocket Forces deployed intercontinental ballistic missiles (ICBMs) armed with single warheads containing smallpox-laden bomblets near the Arctic Circle, where they were maintained in silos on a launch-ready status.[24] Soviet wartime (i.e., World War Three) strategy also called for the dropping of cluster bombs by long-range strategic bombers to deliver the virus.[25]

One of the most important features of a contagious agent, however, is that a potential perpetrator would not necessarily have to create a delivery system. In theory, humans themselves can be effective delivery devices for contagious diseases, obviating the need for missiles, sprayers, letter "bombs," and so on. Such an approach also eliminates the need for mass production of the contagious agent (only a small amount is needed to initiate the chain of events potentially leading to an epidemic) and specific formulation. From this notion has come the concept of the so-called "smallpox suicide bomber," in other words a knowingly infected individual who serves as a delivery device, spreading the disease by secondary transmission. Numerous news reports have suggested that such an attack could be carried out with relative ease. However, conceding intent--in other words whether what is known about conventional suicide bombers would translate to this type of event--for the time being, there is still a large capability issue that must be addressed in order to gain an accurate understanding of this specific threat.[26]

Indeed, even if the agent were somehow acquired, initiating an epidemic would likely be more complicated than simply injecting it, waiting for a rash, and going to a public place. This process is similar to the above-described immunization technique variolation. Although a potential suicide bomber might develop fulminating smallpox from such an injection, he or she would be more likely to develop a mild infection with or without a rash that in most cases would not lead to shedding of the virus and secondary spread.[27] Thus, the bomber would have to know to inhale the virus initially, and would have to possess a means for doing so in terms of aerosolizing the agent and so on. The overall likelihood of success with such a scenario is therefore quite low, especially when the difficulty of acquisition is taken into account.

Intent

If a state does in fact possess the smallpox virus in a deliverable form, under what conditions might that state choose to use it as a weapon? This is, of course, the big question. In the case of Iraq, some say that such use is only likely to occur if Saddam Hussein has nothing left to lose--in other words if US or Coalition forces take Baghdad and Hussein's defeat and death or capture are imminent--because to do so any earlier would prove the US correct in its claim that the state is in possession of weapons of mass destruction.

In this instance, regional delivery, for example in Israel, would ultimately threaten the Iraqi population, but would that matter to those issuing or carrying out the order? More desirable would be remote delivery of the virus, for example in North America, by Iraqi intelligence officers, or even terrorist groups benefiting from Iraqi sponsorship and for whatever reason entrusted with the virus. However, this would require significant advanced preparation and the technical challenges outlined above would have to be overcome.

The point of this back-and-forth is to demonstrate the complexity of any assessment of motivational factors. Many analysts believe that the threat of WMD use throughout the world is escalating, even inevitable. Others in the security community question this interpretation, citing for example the need to better understand a given leader's mindset before making such a determination. While it is of course possible to have a best guess with respect to this issue, there is always some underlying level of uncertainty. It is simply impossible to know for sure what someone like Saddam Hussein might do with such a weapon in any number of circumstances. Thus, from a policy-making standpoint, intent must be assumed: because the motivation to use a weapon like the smallpox virus cannot be ruled out 100 percent, policy-making decisions must be based on the fact that such a devastating attack, however unlikely, is in fact a distinct possibility.

Summary

Essentially, this threat assessment can be summarized by a question mark. While an unvaccinated population is in fact vulnerable to smallpox, based on information in the public domain it is not known with 100 percent confidence that the virus even exists outside the CDC and Vector. Acquisition is the principal hurdle. Establishing a production capability is difficult but not impossible, as is delivering the virus. And whether one might have the intent to do so cannot be determined. Thus, the smallpox threat can only be described as uncertain, while the risks of the vaccine are certain.

However, although the threat is most likely very small for any given individual, from a policy-making standpoint a worst-case scenario must be considered. Therefore, because a limited vaccination plan--properly implemented--will substantially reduce the vulnerability of the US population to the virus (the only true certainty of the above assessment) and minimize the potential impact of its release, it is the opinion of this author that despite the significant risks of vaccination such a plan is indeed advisable. But is the current plan enough? Too much? How far should a nation go to protect itself against an unknown threat?

[1] For the purpose of comparison, a risk assessment follows the formula Risk = Hazard x Exposure, where risk is the magnitude and likelihood of adverse effect, hazard is the harm the agent will cause, and exposure is what population will be exposed to the agent, at what concentration, and for how long. Studies have been done that show that the risk of bioterrorism cannot be accurately assessed due to the imprecision inherent to such an undertaking. Homsy, R. and Zilinskas, R., Draft Report on the "Bioterrorist Threat Assessment and Risk Management Workshop," held at the Monterey Institute of International Studies, November 12-13, 2001.
[2] WMD is a categorical term used to describe the large-scale use of CBRN--chemical, biological, radiological, and nuclear--weapons. Technically, chemical and biological weapons are classified separately as mass casualty weapons (MCW) because they do not cause the physical damage implied by the term "destruction," but for the purposes of this paper WMD will be the representative acronym for the full range of CBRN weapons.
[3] The following review of US vulnerabilities draws extensively from Pate, J., "Anthrax and Mass-Casualty Terrorism: What is the Bioterrorist Threat After September 11?" U.S. Foreign Policy Agenda, November 14, 2001.
[4] Alibek, Biohazard, pg. 112.
[5] See, for example, the Defense Threat Reduction Agency's (DTRA) Biological Weapons Proliferation Prevention projects (Security Enhancements, Dismantlement, and Cooperative Biodefense Research), discussed online at http://www.dtra.mil/ctr/ctr_russia.html.
[6] Tucker, J. and Vogel, K., "Preventing the Proliferation of Chemical and Biological Weapons Materials and Know-How," Nonproliferation Review (Spring 2000), pg. 91.
[7] Galeotti, M., "Inside the Russian Mafiya," Jane's Intelligence Review 12:3 (2000), pp. 8-9; as cited in Zilinskas, R. and Carus, W., "Possible Terrorist Use of Modern Biotechnology Techniques," Chemical and Biological Defense Information Analysis Center (2002), pg. 44.
[8] Galeotti, M., "Russia's criminals go global," Jane's Intelligence Review 12:3 (2000), pp. 10-15, as cited in Zilinskas and Carus, "Possible Terrorist Use of Modern Biotechnology Techniques," pg. 44.
[9] Davies, P., Catching Cold: 1918's Forgotten Tragedy and the Scientific Hunt for the Virus That Caused It (Canada: Michael Joseph, 1999).
[10] Miller, J., "CIA Hunts Iraq Tie to Soviet Smallpox," New York Times, December 3, 2002.
[11] Generally speaking, multiple strains of a given virus exist that possess slightly different genetic information and thus exhibit characteristics unique to each strain.
[12] Alibek, Biohazard, pg. 112.
[13] Zelicoff, A., "An Epidemiological Analysis of the 1971 Smallpox Outbreak in Aralsk, Kazakhstan," in Tucker, J. and Zilinskas, R., ed., The 1971 Smallpox Epidemic in Aralsk, Kazakhstan, and the Soviet Biological Warfare Program, Occasional Paper No. 9, Monterey Institute of International Studies (July 2002).
[14] Fenner, F., et al., Smallpox and its Eradication, WHO, 1988 (ISBN: 92 4 156110 6), pg. 1090; available online at http://www.who.int/emc/diseases/smallpox/Smallpoxeradication.html.
[15] "Smallpox I: United States Fingers Four Countries with Covert Stockpiles," Global Security Newswire, November 5, 2002. While analysis of the evidence with respect to each state named is certainly warranted, in view of mounting tensions in the Middle East only the Iraqi assessment will be addressed in this paper. Further, because no evidence exists that a state has in the past supplied a terrorist organization with a BW capability of any kind--let alone that of a contagious and lethal virus with limited vaccine availability--such organizations will only be discussed in passing.
[16] Zilinskas, R., "Iraq's Biological Weapons: Past as Future?" Journal of the American Medical Association, Vol. 278, No. 5, August 6, 1997. The facility at Al Manal is now more commonly known as the Daura Foot and Mouth Vaccine Facility.
[17] Gubser, C. and Smith, G.L., "The Sequence of Camelpox Virus Shows it is Most Closely Related to Variola Virus, the Cause of Smallpox," Journal of General Virology 83, pgs. 855-872 (2002).