But many knowledgeable observers point to the fact that although biological weapons have been around a long time and are widely known, they have never emerged as an issue. From this they extrapolate that biological weapons are unlikely to be a significant threat in the near term. The sophistry is obvious: applied in the 1950s this logic would have suggested that airline hijacking would never become a problem. Nevertheless—and almost overnight—hijacking became a dominant issue of the 1960s.
Biological agents are not new; militaries have used them for thousands of years. As early as 600 B.C., the Athenian army poisoned the water supply in the city of Kirrha with a biological toxin derived from the Helleborous plant. But biological agents have been slow to migrate into warfare, largely because they make poor weapons for organized combat. To be useful, agents must have several features: they must lend themselves to mass cultivation, be stable in storage for long periods, be easy to weaponize, cause rapid and predictable effects in target populations, and dissipate rapidly and predictably enough to pose no threat to friendly troops. Because biological agents often fall short in several areas, traditional warfare methods generally have proved much more practical.
Recently, however, there has been a growing acceptance of both the threat and the opportunity of biological weapons. As the attack on a Tokyo subway last spring suggests, weapons that can cause terror and damage of strategic dimensions already are available to small states, not to mention small groups. We know, for example, that the Rajneesh cult in Oregon used salmonella, and the Aum Shinrikyo cult experimented with terrorist applications for botulinum toxin. Reportedly, Aum also was attempting to locate ebola virus cultures for weaponization.
In addition to attacks on civilians, some commentators have noted the possibility of agricultural, ecological, or economic bioterrorism. No one has claimed that the cases of mad cow disease in Great Britain were deliberate, but this outbreak is ample illustration of the loss of revenue and disruption of commerce that can result from the hysteria created by a perceived danger.
Nonproliferation treaties that intend to restrict or prevent the use of biological agents have had little effect, in part because they are so difficult to verify. When mass chemical warfare was introduced during World War I, various international regimes were promulgated to deter the use of biological weapons. The most significant of these, the Geneva Protocol, was signed in 1925 and was viewed at that time as a resolution of the problem. That view soon proved flawed, however, when several breaches of the agreement—most notably Italy's use of mustard gas in Ethiopia during the Abyssinian War—affirmed international apathy and the ineffectiveness of the Protocol.
After World War II, nuclear technology and policy overshadowed concerns about chemical and biological weapons. In fact, until the 1970s, arms control and nonproliferation measures virtually ignored what previously had been the only weapons of mass destruction. A breakthrough occurred in 1969, when the Nixon administration decided that the United States would renounce its long-held policy to respond in kind to biological-weapon attacks. The U.S. position that biological weapons were an unacceptable form of warfare, and our decision to destroy our own stockpiles, resulted in a rash of ratifications of the Geneva Protocol and the creation of the Bacteriological and Toxin Weapons Convention of 1972.
But the biggest problem has been—and still is—verification. During the Gulf War, for example, Coalition aircraft sought to destroy the Iraqi biological-weapon infrastructure. After the conflict, U.N. inspectors with complete access to Iraqi facilities and documents—a level of access that never would have been attained through an international inspection regime—sought to uncover concrete evidence of an active biological weapon program. To date, relatively little has been found, and virtually every breakthrough has been the result of personnel defections. Perhaps most troublesome is the ambiguity of the treaty and the inherent dual-use nature of biological weapon technology. How does one differentiate between production or development of biological agents as weapons versus production or development for "prophylactic, protective, or other peaceful purposes?" To complicate matters further, even well-known biological warfare agents have few explicit proliferation markers. Anthrax, for example, is endemic to most of the world, and samples may be obtained from stockyards or soil. The existence of indigenous anthrax cultures is what enabled the Soviet Union to offer the somewhat plausible explanation that tainted meat caused the Sverdlovsk outbreak of 1979.
In sum, it seems unrealistic to expect to gain control of biological weapons through purely political mechanisms. Ironically, our success in inhibiting the proliferation of nuclear weapons might be the greatest stimulant for the development of biological alternatives in Second and Third World states. Frustrated in their attempts to acquire traditional weapons of mass destruction, these nations could be turning to biological weapons, which seem easy to produce and employ when compared with the inordinate cost and technical sophistication required to develop nuclear or even traditional chemical weapons.
In 1975, four nations were suspected of having offensive biological weapons in their arsenals. At present, 10 to 12 nations are reported to have illegal offensive biological warfare weapons. In addition, U.S. government sources suggest that roughly 100 countries possess the indigenous technological capacity to launch such programs.
In addition to ease of production, biological agents have other attractions. Unlike traditional chemical or nuclear weapons, which require meticulous manufacturing and storage procedures, lethal bacteria and viruses replicate and replenish themselves naturally. Biological toxins, which are the products of living organisms, are "mid-spectrum" agents that can be considered biochemical chimeras. They are not alive and are unable to reproduce, but they have extraordinary specificity for living creatures and are vastly more lethal per weight than chemical weapons. As a result, biological weapons may become the poor man's atomic bomb—the weapon of choice for states that do not have conventional strength adequate to meet future security challenges.
Finally, the knowledge required to produce and use biological agents is not sophisticated. Prospective users of biological weapons need only to possess the technical skills of an undergraduate biologist and a physical facility with the sophistication of a microbrewery. Biological weapon production, in fact, is much like brewing, in that it uses a culture placed in nutrient media within a fermentor to be grown en masse. The only significant differences are the selection of culture and the end use. Even more sophisticated production methods such as DNA splicing are well within the grasp of graduate-level microbiologists. The equipment for manufacturing biological weapons can be found in a multitude of universities, industrial research labs, vaccine production plants, pharmaceutical plants, biotechnology facilities, and food production sites around the globe.
Biological warfare agents typically are deployed in aerosols and enter the body through either inhalation or open wounds. The bad news is that general-purpose aerosol delivery systems (e.g., agricultural sprayers) generate invisible clouds of droplets that are the optimal size for reaching distal airways and lodging in terminal bronchioles and alveoli, to be picked up by the systemic circulation. When laced with an agent, each droplet may contain several bacteria (less than a micron in dimension) or many, many viruses (about a hundredth of a micron).
The good news is that even straightforward protective filters can be very effective. Surgical masks and cloth collectors can filter particles smaller than one tenth of a micron reliably, providing effective physical barriers to a biological attack. Mission-oriented protective posture (MOPP) gear is overprotection for biological aerosols, though it is indispensable for filtering chemical vapors. But even simple masks are cumbersome and expensive, and outfitting an entire population in anticipation of a terrorist attack is impractical.
Aerosols also can be neutralized by chemical or physical measures early in their deployment. For example, clouds from missiles or generated as collateral damage from attacks on biological or chemical weapon facilities can be denatured by heat from extremely hot explosives, such as thermites, which burn several times hotter than high explosives and have low blasts that preclude increasing the dispersion. Ozone also is an excellent neutralizer of biological agents and is tolerated by humans. Ultraviolet light, produced by the sun or by artificial sources such as lamps or UV lasers, is another excellent decontaminant. None of these technologies is well-developed enough for large-scale decontamination, however.
A critical element of biological defense is real-time, preexposure detection, discrimination, and identification of biological attack. Especially vital are biological weapon sensors that provide not only dependable advanced warning of specific exposure but also accurate "all clear" assessments after the application of countermeasures. There is a panoply of biosensor investigations now under way, but several major developments deserve mention:
- For detectors, the singular technical challenge of the past was sensitivity. Because just a few particles can cause devastating infection, detectors must sense individual microorganisms or even single molecules to be effective. But the ambient environment contains a great deal of harmless, dust-borne biomatter, such as pollen and nonpathogenic bacteria, that can trigger detectors designed to detect microbe-related compounds such as amino acids.
- The development of polymerase chain reaction (PCR) technology greatly reduced this problem. If one knows to search for a particular threat or can obtain a specific DNA sequence from a sample, PCR can multiply a single encountered particle thousands of times. At present, this process takes hours, and the apparatus is elaborate, but there is an urgent effort under way to simplify and accelerate PCR-to sound alarms in minutes, if not seconds. Greater capability is certain to emerge in the near future.
- Less sensitive, but more mature, are enzyme-linked immunoassay and mass spectrometry based tests. These probably have not yet reached their fundamental limits in practical applications. Add the breakthrough fabrication technologies of micro-electromechanical systems and microfluidics, and very sensitive detectors of extraordinarily small size (palm-sized and smaller) and low cost (a few hundred dollars per sensor) are possible.
The future challenge is one of almost excess selectivity. For the most part, detectors are effective only for specific agents (e.g., individual strains). Knowing this, an adversary can exploit that specificity by modifying pathogens or toxins genetically, so they will not be recognized.
New approaches to detection are based on knowledge of toxicity rather than on the specific causative agent. These pragmatic detectors, also called "canaries," do not detect the specific threat itself. Rather—like the real canaries used by coal miners—they monitor the health of actual cells for any abnormal response when exposed to potentially hostile environments. They are only able to warn of general danger, but such devices can supplement more specific schemes to determine the specific nature of the danger.
Once infected by a biological agent, the human immune system is a natural and vigorous combatant. It is even more effective when aided by immunization. We can develop vaccines, one by one, for almost any defined biological agent. Even now we have an almost-good-enough vaccine for the currently weaponized forms of anthrax, one of the most feared diseases used as a weapon. For toxins, when we can identify and anticipate specific ones, vaccines should in be excellent in principle. In truth, our ability to protect against biological weapons is much more positive than against mainstream chemical warfare agents, where prophylaxis is primitive. For example, we have no immune protection from mustard gas, and only a 10- to 100-fold blunting of acute symptoms can be attained for nerve gas.
Unfortunately, immunization is limited by the same factor as detectors—extreme selectivity. Immunization stimulates a person's immune system to produce antibodies against a specific foreign agent by exposing it to a portion or a nonfunctioning version of that agent. It may not be effective against organisms or toxins that are only slightly different from the original, for example, against natural or engineered new strains of even well-known organisms (such as the flu). Thus, conventional immunization requires development and deployment of vaccines for every plausible strain of every threat agent. It is not known how many vaccines can be functional concurrently within the body without compromise to the immune system, but it is unlikely that polyvalent immunization can protect against more than 10-20 antigens simultaneously.
A larger problem is time. It takes months—even years—to develop and test a vaccine, even after the antigen has been isolated. After immunization it takes weeks for the body to build up an effective concentration of antibody. In biological warfare, therefore, the offense usually has a great advantage. This places an unrealistic burden on the depth and reliability of intelligence and advanced reconnaissance. Unless a universal inoculant can be developed that is more broadly effective in much less time, immunization will not be a long-term strategy of biodefense.
Given the rapid advances in biotechnology, it is inevitable that the threat will become far more sophisticated and insidious. It easy to imagine a technologically advanced adversary genetically manipulating an organism to the point where no flaws or projections exist. Antibioticresistant bacteria, airborne and highly contagious viruses, pathogens that do not readily degrade under exposure to ultraviolet light or intense heat, and agents modified to resist immunization could appear. Rejuvenation and modification of organisms such as smallpox, the plague, or typhus could bring back devastating diseases thought to have been overcome centuries ago.
Perhaps more likely is the development of new compounds that are between chemical and biological agents. These might include derivatives of naturally occurring toxins that would be fast acting and create symptoms for which no treatments exist. One can imagine highly potent, synthetic toxins patterned after natural bioregulatory compounds. Death would occur by disrupting both physiological and psychological functions in the body, stimulating intense pain, high blood pressure, or alterations in mood. Theoretically, agents could be designed to be both controllable and predictable enough for organized military conflict.
On the other hand, as DNA sequencing techniques become faster and more economical, entire new classes of antibiotic and antiviral compounds will emerge that exploit specific genomic features of an infectious agent directly. Advances in computational methods almost certainly will identify fundamental and common DNA sequences involved in virulence of different pathogens. Knowledge of such common sequences will enable T-cell immunization and DNA vaccines—approaches currently in early stages of development—to be made generic to many pathogens. Structure-based, rational drug-design techniques could yield new proteins and enzymes that will inhibit an agent's signal transduction, suppressing its virulent expression by tricking the organism into thinking that it had not yet found a suitable host. Apoptosins, natural proteins that stimulate programmed cell death, could signal pathogenic organisms to commit suicide.
Ultimately, it should be possible to attack pathogenicity (i.e., the lethal effect) without ever having to deal with the actual virus or bacterium. For example, anthrax kills partly by eliciting cytotoxins from target macrophages, a process that in principle could be blocked by receptor antagonists. Experiments conducted on certain disease-causing bacteria have reduced body damage by 100%, even though they had no effect on colonization of the organism in the body. This would save lives while other defenses were being elicited and antibiotics administered to clean out the bacteria.
Overall, we must learn to defend against biological weapons, to reduce their effectiveness to the point that they are no longer worthwhile for an enemy to develop. Some immediate actions seem clear.
First, our policymakers must resist the temptation to view and manage the biological weapon problem as an extension of nuclear proliferation. Most Cold War arms control strategies are obsolete even for nuclear proliferation and are inappropriate for biological weapons. Of course, there are prudent exceptions. In the Gulf War, we implied that we might respond to any use of chemical or biological weapons by Iraq with tactical nuclear weapons—and it worked. We may choose, in general, to blur the separations among nuclear, chemical, and biological means, especially when the belligerent use of one against us may lead to in-kind retaliation, using another.
Second, we must discard any notion that the development of biological weapons can be impeded by attempts to restrict the flow of biotechnology information. The emergence of .the electronic media, personal computers, and the World Wide Web make efforts to restrict the flow of information inconsequential.
Third, the technological community must be drawn fully into the formulation of both policy and strategy. It is not enough to recruit practicing technologists as consultants or advisors; the nuances and permutations of the threat are just too numerous for casual accounting—and no policy will be embraced by the scientific community without full representation and vetting.
Fourth, the military must recognize that the best technical talent in this field resides within the commercial sector. This is one of the clearest illustrations of a dual-use technology, in which the commercial sector is too far ahead for the defense community to catch. The government must forge active links to leverage outside expertise, rather than attempting to grow its own.
Finally, we must pursue a technological agenda that enables our defense capabilities to outperform our adversary's offense capability. Fortunately, there is a host of technology to be exploited, and great synergy exists between the national security problem and the larger public health problem of infectious disease. Here is a place where the military must fight its tendency to go it alone. The commercial biotech industry has the resources and the talent to move quickly and decisively, once they recognize some advantage. Perhaps all that is missing is recognition of the opportunity.
Biological agents are one of the most fearsome dimensions of modern warfare. Should they be used in future conflict, we can expect a near panic from anyone even marginally exposed. Continuing to ignore the possibility brings us no closer to removing this threat. Biological weapon defense is possible, and technologies with very high potential already exist. Success will require a concentration of effort, in both government and industry, and an extended commitment.
Captain Buchanan is a reservist with the Naval Reserve Space Program and currently is assigned to the CNO Executive Panel. As a civilian, Dr. Buchanan is the Deputy Director of the Defense Advanced Research Projects Agency in Arlington, Virginia. This article is a result, in part, of his participation in the 1996 summer session of the Aspen Strategy Group, Aspen, Colorado.