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Contending with Ambiguity

The negotiators have their work cut out for them. The equipment and facilities used to cultivate biological-warfare agents are essentially the same as those used for the commercial production of vaccines, antibiotics, vitamins, biopesticides, feed supplements-even beer and yogurt. The spread of these “dual-capable” technologies for industrial microbiology has given rise to a burgeoning global potential for biological warfare, since countries can easily cloak their acquisition of illicit agents under the guise of legitimate research and production. Moreover, it takes only an extremely small quantity of a microbial pathogen-on the order of a few kilograms-to produce a militarily effective weapon. A deadly arsenal could therefore be made over a period of weeks, eliminating the need for long-term stockpiling.

Cultivation of disease-causing microbes cannot be banned outright because the same organisms that can kill thousands of people also have legitimate medical and industrial uses. Pharmaceutical companies, in particular, routinely grow large quantities of dangerous pathogens for the production of vaccines. Similarly, potent toxins such as ricin and botulinum play an increasingly important role in the treatment of cancer and neurological diseases.

Recognizing these peaceful applications, the BWC specifically prohibits the development and production of biological and toxin agents only “in types and quantities that have no justification for prophylactic, protective, or other peaceful purposes.” As a practical matter, however, it is difficult to distinguish between offensive activities and benign ones. Merely looking at a fermentation tank reveals little about its contents. Only the analysis of an actual sample can tell which microbes are present, and that will require on-site inspections of dual-capable facilities such as vaccine plants. Inspectors of a suspicious facility might take samples from various steps in the production process, ranging from seed cultures to finished products. Samples might also be swabbed from the surface of production equipment, benches, walls, or floors, or collected from soil, water, air, plants, and animals outside the buildings. These samples would then be analyzed, using some combination of techniques now common in the biotechnology industry and medical diagnostics.

Three sophisticated analytical methods are routinely employed to identify disease-causing bacteria and viruses. In classical bioassay, scientists cultivate a sample to grow live microorganisms; these microbes can then be identified using a variety of chemical or physiological tests. Immunoassay techniques employ specific antibodies to detect unique molecular markers on the surface of target microorganisms, as well as protein toxins. Genetic analysis involves the use of “gene probes”-short strands of synthetic DNA that bind to complementary DNA sequences unique to each microbial species.

Gene probes are often employed in conjunction with a powerful technique called the polymerase chain reaction (PCR), which multiplies a given DNA sequence more than a million-fold. With the aid of PCR, scientists can identify a species of bacteria even if only a few dozen cells are present in the sample-avoiding the need to culture them into large colonies over a period of days or weeks.

In some cases, sampling and analysis can yield compelling evidence of illicit activities. When Japanese police raided the Aum Shinrikyo cult’s headquarters near Mount Fuji, they found an advanced microbiology lab producing anthrax bacteria and botulinum toxin, apparently intended for terror attacks.

Generally, however, the results of sampling and analysis are less clear. Analytical techniques occasionally produce “false positives” by appearing to recognize a biological-warfare agent that isn’t actually present. This problem may arise when the target DNA sequence or molecular marker is present in both a pathogenic agent and a harmless microorganism. To avoid false positives, inspectors should confirm a positive result obtained by one analytical technique with another method based on different scientific principles.

Samples may also be contaminated with pathogenic microbes naturally present in the environment. Anthrax spores, for example, are often found in sheep and cattle grazing areas in concentrations of 100 to 500 spores per 100 grams of soil. These levels, though well below the 10,000 or so spores that must be inhaled to cause infection, are easily detectable with PCR. The pharmaceutical industry therefore worries that anthrax spores naturally present in the environment might be tracked into a vaccine plant on the bottom of workers’ shoes and detected by international inspectors-raising suspicion of a BWC violation where none is warranted and damaging a firm’s hard-won reputation. “The release of erroneous information implying serious wrongdoing could cause irreparable harm to a company’s relationship with its shareholders and the general public,” observes William Muth, a scientist at Lilly Research Laboratories in Indianapolis.

Thus in the absence of a “smoking gun,” such as a rack of bombs or warheads filled with biological agents, sampling and analysis would not provide unequivocal proof of a treaty violation. Detecting anthrax would not necessarily be incriminating, for example, if the facility in question were culturing the agent for a legitimate purpose, such as the production of a protective vaccine, or if anthrax were endemic to the surrounding region. Moreover, highly sensitive detection technologies such as PCR could find minute traces of anthrax DNA, while revealing little about the total amount of agent produced at the site.

On the other side of the coin, since it is not possible to sample everywhere, inspectors may fail to detect actual violations of the BWC. Thus the inability to find an illicit biological-warfare agent at a suspected facility does not necessarily mean that the plant is treaty-compliant. A covert proliferator might exploit a series of negative findings to claim a clean bill of health. Because of the possibilility of false positives or false negatives, evidence of BWC violations obtained by sampling and analysis must be interpreted in the light of other types of information.

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