February 1, 1997 - Preventing the Misuse of Microorganisms: The Role of the ASM in Protecting Against Biological Weapons

Ronald M. Atlas, Kenneth I. Berns, Gail Cassell, Janet Shoemaker

Abstract

The American Society for Microbiology's (ASM) involvement with issues surrounding biological weapons began during World War II and continues to the present time. The Public and Scientific Affairs Board (PSAB) of the ASM has played an important role in monitoring and responding to legislative and regulatory issues involving biological weapons. As this review makes apparent, there is not consensus of opinion among scientists on their role in biological defense research, nor is it likely that there ever will be complete agreement. There is consensus that steps should be taken to prevent biological warfare and that openness of scientific research and global surveillance of disease outbreaks can significantly increase transparency for detecting development of biological weapons. The ASM recommends increased attention to and efforts directed toward global surveillance of disease outbreaks, not only to aid public health organizations in improving human health, but also to establish baseline data against which unusual disease outbreaks can be assessed. Issues of how best to increase global security and to achieve a scientifically based verification protocol of the Biological Weapons Convention are important and continue to be addressed by the ASM.

Preventing the Misuse of Microorganisms

Foremost among the issues affecting the possible misuses of microorganisms is the potential use of pathogenic microorganisms and microbially produced toxins as weapons of warfare or terrorism. As a major scientific society representing over 43,000 members, the American Society for Microbiology (ASM) has increasingly become involved in public affairs, including issues related to preventing biological warfare and terrorism using biological weapons. Members of the ASM have a considerable history of bringing scientific and technical knowledge to the issue of biological weapons control. Of the 91 Presidents of ASM, 21 have spent some part of their scientific careers at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRID) at Fort Detrick, the main U.S. biological defense research facility. The Society's membership possesses a unique body of knowledge and expertise in microbiology and immunology, and this has given the ASM a strong foundation for its important role in decisions regarding U.S. policy on biological warfare and defense. The ASM has sponsored a series of round tables at its national meetings and other activities through its Public and Scientific Affairs Board (PSAB) aimed at bringing technical information about biological weapons to policy makers and informing the scientific community of the issues being debated among regulators, legislators, and nations. The ASM is very active in offering its expertise in advisory roles to the government in an effort to help protect against the use of biological weapons and to ensure that policy development is scientifically credible.

ASM's involvement with biological weapons issues dates back to the 1940s, when microbiologists served as advisors to the government's Biological Defense Research Program and participated in the Biological Warfare Committee of the U.S. National Academy of Sciences. The ASM governing council in 1970 followed the 1969 unilateral declaration by President Nixon that the United States would not conduct biological warfare by calling for an end to offensive biological weapons programs. "The Council of the Society affirms that the health of science is enhanced by non-secret research and free movement of scientists. Furthermore, the Council affirms support of President Nixon's action on November 25, 1969, and February 14, 1970, to end our involvement in production and use of biological weapons. Because of our concern for humanitarian application of microbiological science, we urge that all nations convert existing offensive biological warfare facilities to peaceful uses." The ASM Council reaffirmed this position in 1993 in a message sent to negotiators in Geneva discussing a verification regime for the Biological Weapons Convention of 1972; the ASM Council further resolved at that time to work to prohibit the possession, development and use of biological and toxin weapons.

Although the ASM has taken a strong stance against the very notion of biological warfare, the subject has long been contentious among its diverse membership. Because infectious diseases have killed more soldiers in some wars than bullets, biomedical research and the development of vaccines and treatments for many diseases, including exotic diseases that do not normally occur in the United States, has been very important to the US Department of Defense. It is sometimes a thin line between such defensive research and generating results that could be misused for biological weapons development. While only a few would argue that biological warfare might be a humane form of war, a more problematic question has been whether microbiologists should engage in national defense efforts involving research in biological weapons. A particularly thorny question has been whether research for defense against biological weapons can ever be truly separated from research that affects offensive capability in this area.

The ASM has faced the philosophical dilemma of whether a scientific society can appropriately tell its members what types of research not to do, so long as that research is legal; that is, can scientific societies provide real moral direction to their memberships. In this regard the Society's code of ethics, published in 1985, contains two relevant sections that seek to discourage ASM members from participating in biological weapons development: (I) AMicrobiologists...will discourage any use of microbiology contrary to the welfare of human kind. and (ii) Microbiologists are expected to communicate knowledge obtained through their research through discussions with their peers and through publications in the scientific literature. This code of ethics clearly establishes that it is the individual responsibility of every microbiologist to conduct research that is beneficial to humankind. It further holds that openness of research activities collectively provides the transparency necessary to help prevent activities that could result in the misuse of microorganisms as biological weapons.

Preventing Biological Warfare -- Verification of the Biological Weapons Convention

The ASM and its members, like scientists and policy makers from around the world, have struggled with the question of how the Biological Weapons Convention of 1972 can be strengthened through a verification regime. When the BWC was enacted it provided for periodic reviews but no specific verification regime was designed to detect violators who continued to develop biological weapons. Revelations that biological weapons development continued in the former Soviet Union past the signing of the BWC and that Iraq had an active biological weapons development program at the time of the Gulf War have made the implementation of a legally binding verification regime imperative in the views of some nations and groups of concerned scientists, such as the Federation of American Scientists. Other groups, such as the Pharmaceutical Manufacturers Association (PhRMA), have expressed concern that an invasive verification regime could result in the loss of proprietary information and should be approached with extreme caution. Others have pointed to the experience of inspection teams of the United Nations Special Commission (UNSCOM) in Iraq following the Gulf War as showing that even the most invasive inspections may be unable to detect specific evidence of biological weapons development.

Based upon extensive reviews of the risks and benefits of a mandatory verification regime for the BWC, the ASM has advised the US government and other negotiating parties in Geneva that detecting offensive biological weapons development activities is very complex and should be based upon scientific principles that would permit differentiation of legitimate biomedical activities from those activities related to biological warfare that are prohibited under the BWC. The ASM pointed out that microorganisms which can be used as biological weapons may be the same as naturally occurring pathogens or microorganisms used for beneficial purposes such as vaccine production. The same fermentors that are used for the production of pharmaceuticals could be used to grow large numbers of microorganisms for use as biological warfare agents, as could flasks and other cell culture systems found in academic research laboratories. Natural occurrences of diseases such as anthrax can be mistaken for accidental or deliberate releases of biological warfare agents. Likewise, accidental or deliberate releases of such agents could be misinterpreted as outbreaks of naturally occurring diseases. Finding spores of the anthrax bacillus may very well be an isolated natural occurrence or it may be associated with a contrived outbreak of the disease from biological weapons. A system of verification that does not enable differentiation of legitimate activities and natural occurrences from offensive biological weapons development would be ineffective and would produce a false sense of world security. An effective verification regime must be able to differentiate between legitimate biomedical activities and biological weapons development prohibited by the BWC. It is the effective, efficient, and timely determination of this difference that must form the critical, scientifically based underpinning for a justifiable verification regime of the BWC.

The ASM offered the following points for use as a framework of scientific principles for consideration of proposals for verifying compliance with the Biological Weapons Convention: (1) Detection of accidental releases or deliberate use of biological weapons requires comparison with the natural occurrences of disease; (2) inspections to confirm compliance with the Biological Weapons Convention should be conducted when there is adequate cause; (3) measures that increase transparency should be taken to ensure compliance with the Biological Weapons Convention; (4) proprietary information must be protected; (5) incentives for scientific discovery must not be removed; and (6) lists of equipment and organisms cannot adequately define the scope of appropriate surveillance for compliance with the Biological Weapons Convention. These points are aimed at enhancing global security by limiting the potential development of biological weapons while simultaneously allowing the development of pharmaceuticals, vaccines, and diagnostic procedures aimed at reducing the incidence of infectious diseases.

The ASM also affirmed the principles highlighted in these points when it opposed the development by the US Department of Commerce of a list of equipment used in biological research that would be prohibited from shipment to countries which have not signed the Biological Weapons Convention. Consideration for establishing this list arose shortly after the Gulf War when it was learned that the American Type Culture Collection had shipped cultures of Bacillus anthracis to Iraq. Even though these shipments had been in conformity with U.S. law and had been approved explicitly by the Department of Commerce, the unfavorable publicity generated by the shipments because of concern about the potential use of biological warfare agents by Iraq led the Commerce Department to start to generate a list of items whose export would be restricted. Many of the items proposed for the list, such as laminar flow hoods, were equipment commonly used in medical laboratories and were likely to be able to be obtained from many sources outside the United States. The advice of the ASM to the Commerce Department was that the list was unlikely to serve any useful purpose in terms of limiting research on biological weapons, but would open the U.S. for criticism for inhibiting medical care and research in developing countries.

Throughout its deliberations about biological weapons, the PSAB and other bodies of the ASM have considered it essential that efforts aimed at protecting against the misuse of microorganisms as biological weapons not inhibit efforts to control and to prevent infectious diseases. In late 1994, the PSAB convened a task force of expert scientists to assist the U.S. government in developing scientifically sound approaches to biological arms control that would seek scientifically sound ways of enhancing global security by limiting the likelihood of the misuse of microorganisms as biological weapons. The task force comprised of members from academe, industry and government reflects the breadth of expertise on biological weapons found within the ASM. The task force has struggled with the issue of how to help ensure compliance with the BWC while protecting incentives for advancing biomedical research.

The ASM Task Force on Biological Weapons has been debating the various proposed components of a verification regime with regard to their scientific merits, likelihood of achieving the goal of preventing the development of offensive biological weapons, and potential impact on biomedical research, public health, academia, and the biotechnological industry. Perhaps the most critical questions under current discussion are how can one recognize a biological weapons facility, how can one detect an unusual outbreak of disease, and can an inspection regime be developed that has a high probability of detecting illicit activity and a negligible probability of negatively impacting biomedical research and the private biotechnology/pharmaceutical sector. Being able to define the signature of an offensive biological weapons development program and its components has a direct bearing on the declaration process that is being considered for the BWC verification regime.

Possessing a microorganism on a proscribed list of pathogens has been considered as a possible trigger for requiring the filing of a declaration. The ASM Biological Weapons Task Force has discussed the value of lists in a verification regime. Such an approach is relatively simple because it sets easily defined objective criteria but is fraught with problems if one considers the full breadth of pathogens that could be used as biological weapons against humans, non-human animals, and plants and the facts that virtually all the pathogens on such a list are naturally occurring disease-causing agents that are detected in clinical laboratories and studied at biomedical research facilities around the world whose aim is to control the diseases caused by those microorganisms, and that many of those pathogens are grown in the pharmaceutical industry to produce vaccines which prevent diseases of humans and other animals and in the biological control industry to limit plant pests that threaten world food supplies. Establishing specific lists of controlled microorganisms could serve as a prescription for which organisms to choose for illicit biological weapons programs-either the ones on the list because they are considered by the world to be the best candidates for use as biological weapons or those not on the list because they are not explicitly prohibited and their detection wuld not constitute a violation of the declaration process.

Producing large volumes of pathogens, presumably in well-contained reactors, is another possible criterion that could help define a facility producing biological weapons. Relying on such a criterion could exempt all clinical laboratories and most academic laboratories but would certainly place a burden for filing declarations on the fermentation industry and vaccine manufacturers. Further the Task Force has recognized that microorganisms can be stored in one facility and grown in another. Also, while extreme containment would characterize the production of large volumes of a deadly pathogen in a facility following good manufacturing procedures, production could be carried out under conditions of poor containment if the surrounding population were vaccinated or if little care was given to possible disease spread into the populations surrounding the production facility.

The final criterion of weaponization is perhaps the most intriguing in terms of being able to distinguish legitimate biomedical facilities from those involved in biological weapons development. Here, though, is where the members of the ASM Task Force have the least expertise. Past major biological weapons development programs have focused on aerosol dissemination so that the possession of milling equipment and other hardware that could form small enough aerosols for weaponization has been considered for triggering the declaration process. The history of biological warfare, however, points to lower technological delivery systems, such as the Tartars catapulting bodies of victims of plague into the walled city of Kaffa in the fourteenth century and the Japanese attempting to float hot air balloons containing plague infected tick and flea vectors over the western United States during World War II. These past experiences suggest that there is no single criterion that can be used for triggering requirements for filing declarations in a BWC verification regime. Like all aspects of the BWC, there is a need for balance that increases the likelihood of dissuading would be violators from developing offensive biological weapons and the legitimate needs of advancing biomedical research and control of infectious diseases.

Although declarations could have a broad impact on the biomedical community, the greater impact could come from investigations of disease outbreaks and challenge inspections of academic, industrial, and government sites. Accordingly, the topic of investigations and inspections has received a great deal of scrutiny in terms of the ability to detect offensive biological weapons programs and their potential impacts on the biomedical community. The investigation of the 1979 outbreak of anthrax near Sverdlovsk in the former Soviet Union points to the virtues and difficulties in investigating unusual disease outbreaks. Initially it was erroneously concluded that this was a natural outbreak of anthrax but a later epidemiological investigation conclusively showed that it had resulted from an accidental release from a Soviet biological weapons development facility. The initial investigation failed to detect the source.

The unusual nature of the 1979 disease outbreak at Sverdlovsk was the high number of fatal cases of anthrax. Recognizing such unusual outbreaks depends upon having an adequate epidemiological data base and unusually sudden high rates of mortality. The ASM has called for increased disease surveillance and epidemiological investigations in order to increase global security and human welfare within the context of BWC verification and beyond.

Finally, the ASM Task Force has been evaluating how site investigations could be conducted that would detect biological weapons without jeopardizing the loss of confidential business information and proprietary microorganisms. A variety of options have been debated that have focused on sampling and analysis. Managed access has been proposed by PhRMA as the preferred means of preventing loss of proprietary organisms. The ASM Biological Weapons Task Force has also been considering the technological approaches that would lessen the risk of loss of proprietary microorganisms. Using on-site analyses based upon gene probe or serologic detection conducted with killed samples would lower the risks of losing valuable microorganisms compared to off-site analyses conducted using live culture techniques. Such an approach would also lower the risk of inadvertently spreading disease as a result of the transport of pathogens. For the pharmaceutical industry test validation and compatibility with FDA regulations are especially important considerations. For groups of concerned scientists, including those in the pharmaceutical industry, the ability to detect biological weapons and to deter their development is of critical concern. The ASM hopes through its efforts that both national economic security and global security through the elimination of the threat of biological warfare can be achieved.

Preventing the use of biological weapons by terrorists

Beyond its concern about preventing biological warfare, the ASM has become very concerned about the possible usage of biological weapons by terrorists. Several recent incidents, such as the attempts of the Japanese Aum Shinrkyo cult to acquire anthrax bacilli, botulinum toxin, and Ebola viruses, have raised concerns about the illegal use of biological weapons by terrorists. It has been illegal since 1990 to engage in biological weapons development within the United States. The ASM played an important role in developing the final version of the Biological Weapons Anti-Terrorism Act of 1989 which was signed into law by President Bush on May 22, 1990. In particular, the ASM helped Senator Herb Kohl (D-Wisconsin) develop an amendment that removed specific language that would have shifted the burden of proving innocence to an accused scientist and that could have been used to restrict peaceful, humane research. The amended bill specifically stated that nothing in this Act is intended to restrain peaceful scientific research or development. The congressional report included language stating that Congress is aware that many scientists conduct peaceful research with potentially dangerous agents and toxins and that the bill will not interfere with such activities. While protecting legitimate biomedical research, the Biological Weapons Anti-Terrorism Act of 1989 made it a crime to possess a biological weapon or to help a foreign nation acquire one. It authorizes the Attorney General to seek the civil forfeiture of biological weapons before they injure people or harm the environment. It imposes criminal penalties against those who would employ or contribute to the dangerous proliferation of biological weapons.

In 1996, legislators were prompted to amend the U.S. Criminal Code covering biological agents after learning of a 1995 incident involving the acquisition of bubonic plague cultures through the mail by a suspicious purchaser in Ohio. The ASM along with the CDC and American Type Culture Collection testified before the Senate Judiciary Committee on the interstate transport of human pathogens. On April 24, 1996, President Clinton signed into law anti-terrorism legislation (PL 104-132) which expands federal power to prosecute and punish certain crimes related to terrorism. A bipartisan amendment was included in the new law making it illegal to develop, acquire or attempt to purchase biological agents with the intent to kill or injure or use them as a weapon. The provision on biological agents amends the 1989 Biological Weapons Anti-Terrorism Act. The law directed the Secretary of Health and Human Services, through promulgation of regulations, to provide for (1) the establishment and enforcement of safety procedures for the transfer of listed biological agents, including measures to ensure proper training and appropriate skills for laboratorians who handle and dispose of such agents, and proper laboratory facilities to contain these agents; (2) safeguards to prevent access to such agents for possible use in domestic or international terrorism or for any other criminal purpose; and (3) the establishment of procedures to protect the public safety in the event of a transfer or potential transfer of a biological agent in violation of the safety procedures established under (1) or the safeguard established under (2), while maintaining availability of biological agents for research, education and legitimate purposes.

The task of developing regulations to control the interstate shipment of pathogenic microorganisms that might be used as biological weapons was assigned to the Centers for Disease Control and Prevention (CDC). ASM assisted the CDC in establishing new regulatory requirements for facilities transferring and receiving select agents which have the potential to cause widespread harm. The ASM offered advice in the development of the list of organisms to be subjected to regulation; this advice was based in part on a survey conducted via E-mail of 11,000 ASM members. The regulations that emerged from these consultations and the mandate to reduce the threat of terrorist use of biological weapons focused on controlling exchanges of those microorganisms and their toxins that have the highest potential for use as biological weapons. Under these regulations, which come into force on April 15, 1997, public and private laboratories, commercial companies, academic and research institutions, and other facilities that wish to transfer or receive select agents listed in a schedule published by the CDC will be required to register their facilities with CDC. Those facilities will be subject to inspection to verify the information provided at the time of registration (see List of Select Agents). Only registered facilities will be able to transfer or receive select agents, and documentation of each transfer will be required.

As with other issues related to the potential misuse of microorganisms as biological weapons, the ASM offered advice in the development of these regulations that was consistent with ensuring continuance of essential biomedical research and diagnostic activities. In the final regulations, the list of restricted agents is limited so as not to unduly restrict legitimate biomedical research. Clinical laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) that intend to use and transfer select agents only for diagnostic, reference, verification, or proficiency testing purposes are exempt from the requirements of the regulations. Thus, essential medical diagnostic practices can proceed unimpaired.

In conclusion, the American Society for Microbiology is actively engaged in efforts to ensure that microorganisms are never misused as biological weapons. The ASM's membership has unique knowledge and expertise in microbiology and immunology, and this has given the ASM a particularly important role in decisions regarding the U.S. policy on biological weapons and defense. The Public and Scientific Affairs Board of the ASM attempts to provide advice that permits the deterrence of biological weapons development while permitting and encouraging research activities that will benefit humankind and in particular human health. Given the potential dual uses of microbiological research, providing scientifically based advice for preventing biological warfare and biological terrorism to increase global security is a challenge for the ASM and its members. Biological weapons issues are an important issue for society and the microbiology community and they continue to be addressed by the ASM.

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