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Growing Together: Biological and Chemical Threats

The Convergence of Biology and Chemistry and its Implications for Arms Control

SOURCE: AP Photo/Ken Cedeno Many nations have developed chemical and biological weapons and the means to deliver them. But rapid technological change is resulting in gaps in the treaties that protect us from them, giving rise to the need for new measures to address these developments.

Technology is beginning to outgrow the treaties that keep us safe from biological and chemical weapons. Biological and chemical production methods, once distinct, are converging. On the one hand, it is possible to produce organic chemicals with biologically mediated processes; on the other hand, biological molecules such as DNA and proteins can be made by strictly chemical means. This technological crossover is creating risks of misuse for warfare and terrorism that were not anticipated by the treaties banning biological and chemical weapons, posing a major challenge to the nonproliferation regime.

Biological production of chemicals

Three biologically mediated methods of chemical production are currently under development. The first is “biocatalysis,” or the use of purified enzymes to catalyze, or accelerate, chemical reactions. This approach offers several benefits: enzymes make precise changes to target molecules and yield only biologically active products; they function optimally at body temperature and thus require less energy than standard catalysts; and they are environmentally friendly because they employ renewable starting materials and produce fewer toxic byproducts.  Given these advantages, the chemical and pharmaceutical industries will make greater use of biocatalysis in the coming years. When this technology becomes widespread, however, enzymes called halogenases might be misused to produce highly toxic chemicals containing chlorine or fluorine, including known chemical warfare agents.

A second biologically mediated production method involves inserting clusters of animal or plant genes into bacteria in order to coax them into producing medically useful compounds. This technique, known as “metabolic engineering,” or “synthetic biology,” has the potential to mass-produce molecules that are difficult and costly to extract from their natural sources and are too complex to synthesize chemically on an industrial scale. The antimalarial drug artemisinin, for example, is currently extracted from the sweet wormwood plant. But researchers at the University of California, Berkeley, have used the genes coding for the biosynthesis of a closely related compound to produce artemisinin in bacteria. Synthetic biology is also central to efforts to manufacture ethanol from cellulosic material such as cornstalks and to make diesel fuel from genetically modified algae.  Nevertheless, synthetic biology techniques might be misused to mass-produce highly poisonous natural products such as saxitoxin, which is made by a species of marine algae responsible for the toxic algal blooms called “red tides.” During the 1960s, the CIA sought a supply of saxitoxin to use in suicide pills for captured spies. In order to acquire the deadly poison, the agency secretly spent millions of dollars to harvest tons of clams contaminated by a red tide and process them to extract a few grams of pure saxitoxin. Using synthetic biology techniques, it might be possible to isolate the algal genes responsible for the biosynthesis of saxitoxin and transfer them to bacteria, which would then produce the toxin relatively cheaply. If this scenario were realized, saxitoxin might become a serious chemical warfare threat.

A third biologically mediated process, known as “biopharming,” involves the production of protein-based pharmaceuticals such as vaccines, microbicides, and therapeutic antibodies in transgenic plants and animals. Foreign genes coding for the therapeutic proteins are inserted into crops such as corn and tomatoes, which are then harvested and the desired proteins extracted. Biopharming has a potential dark side, however, because it might be used to mass-produce toxic proteins for hostile purposes.

Chemical production of biological molecules

In parallel with the use of biological processes to manufacture drugs and other chemicals, companies are using chemical methods to synthesize biological molecules such as DNA and proteins from scratch. The invention of advanced DNA synthesizers, for example, has made it possible to construct genes and even entire microbial genomes by stringing together the four chemical units of DNA in any desired sequence. Over the past decade, scientists have recreated several pathogenic viruses by chemical means, including poliovirus, a SARS-like virus, and the formerly extinct “Spanish” strain of influenza, which was responsible for a global pandemic in 1918-19 that killed as many as 50 million people worldwide.

The size and accuracy of the DNA molecules that be created with automated chemical synthesis is increasing and the cost is declining. Moreover, commercial suppliers around the world now produce custom DNA sequences to order. A customer simply enters the desired sequence on an Internet web site, provides a credit card number, and a few weeks later receives a vial in the mail containing the requested DNA molecules in a biologically usable form. The synthesized sequence can then be copied and used for various scientific or industrial purposes. In October 2010, the U.S. government, fearing that outlaw states or sophisticated terrorists might order DNA coding for dangerous viruses and protein toxins of bioterrorism concern, issued voluntary guidelines for the gene-synthesis industry that call for the screening of customers and DNA sequence orders.

Chemical methods are also being applied to produce biological molecules called  peptides: short protein chains made up of 20 possible amino-acid building blocks. Worldwide, pharmaceutical companies are marketing about 40 peptide-based drugs, including the anti-HIV therapeutic Fuzeon and the potent painkiller Prialt, and hundreds more are under development. The human body also produces myriad biologically active peptides called “bioregulators” that control temperature, blood pressure, sleep, immunity, and other vital physiological functions. Although at low concentrations bioregulators are essential for life, they can be toxic at higher levels or if their molecular structure is modified. For example, a bioactive peptide called Substance P, consisting of a chain of 11 amino acids, serves as a messenger chemical in the central and peripheral nervous systems. In 1999, scientists at the Swedish Defense Research Establishment administered low doses of Substance P to guinea pigs the form of an aerosol, an airborne suspension of microscopic particles that can be absorbed in the deep region of the lungs. Under these circumstances, the peptide was acutely toxic, leading the Swedish researchers to warn that Substance P was “a possible future warfare agent.”

Once a toxic peptide has been identified, it could be manufactured in large quantities by chemical means. Peptide synthesis is now a thriving commercial business involving some 80 companies worldwide. These firms produce peptides to order according to customer specifications and in quantities ranging from a few milligrams for research use to thousands of kilograms for the pharmaceutical industry. Although natural peptides are generally unstable in aerosol form and are rapidly broken down in the body, limiting their potential utility as lethal or incapacitating warfare agents, structural variants of these molecules might be developed that resist rapid degradation and can enter the brain from the bloodstream. In addition, engineered nanoparticles might be used to facilitate the delivery of bioactive peptides in aerosol form or to target specific body tissues or organs.

Gaps in the disarmament regime

In 1925, the League of Nations (the forerunner to the United Nations) negotiated the Geneva Protocol prohibiting the use in war of toxic chemicals and bacteriological agents, but not restricting their production and stockpiling. In 1971, seeking to extend the ban to cover development and production, the UN disarmament conference in Geneva agreed to separate biological from chemical weapons because the former had been used only rarely in warfare and were assessed to have little military utility, while the latter had been employed extensively in World War I and other conflicts. The culmination of this negotiating strategy was two separate treaties: the 1972 Biological and Toxin Weapons Convention (BWC) and, two decades later, the 1993 Chemical Weapons Convention (CWC).

Although the two accords each prohibit the development, production, and possession of an entire category of arms, they have distinct provisions and sets of member states. The CWC, for example, has extensive verification measures, whereas the BWC has none. Because both treaties ban the acquisition for hostile purposes of toxic chemicals of biological origin, such as natural toxins and bioregulators, one would expect that the controls in this area would be particularly effective. In practice, however, the overlap has allowed the members of each treaty to deemphasize this category of agents, in the expectation that the other treaty will cover them. As a result, as the British analyst Julian Perry Robinson has pointed out, the overlap between the BWC and the CWC with respect to toxins and bioregulators “risks becoming a gulf into which things disappear.”

Today convergence is creating three gaps in the biological and chemical disarmament regime. The first concerns the biological production of toxic chemicals. At present, the CWC verification system does not cover facilities that make treaty-relevant chemicals by biologically mediated processes, such as biocatalysis or synthetic biology. Although the use of such methods for the large-scale production of chemical warfare agents is not economically viable, that situation could well change as the techniques become cheaper and more widespread.

The second gap in the arms control regime concerns the chemical synthesis of pathogenic viruses from scratch. Although the BWC prohibits the production of viruses for hostile purposes, the treaty does not have any formal mechanisms to verify compliance. Conversely, the CWC has extensive verification measures but does not ban the chemical synthesis of viruses because they do not cause harm through “toxic effects on living systems.” As a result, there is no verification in this area.

The third gap in the regime concerns the synthesis of bioactive peptides like Substance P. Such production is not subject to routine verification under the CWC because no peptides are listed in the treaty’s Schedules of Chemicals, which determine which production facilities must be declared and opened for inspection. At the same time, bioactive peptides are manufactured in quantities too small to be covered by a second CWC verification mechanism covering “other chemical production facilities” (OCPFs) that do not currently produce scheduled chemicals but have the potential to do so. The OCPF regime is based on quantitative production thresholds rather than on specific chemicals.

If nothing is done to close these three gaps, it may become possible for countries to exploit convergent technologies to break out of the BWC and the CWC without risk of detection. In sum, as biological and chemical production methods continue to converge, the traditional strategy of pursuing biological and chemical arms control on separate tracks has become obsolete, and the two treaties will have to become better integrated.

Policy recommendations

Finding concrete ways to prevent the misuse of convergent biological and chemical technologies for weapons purposes will require innovative thinking and political will on the part of the United States and other like-minded countries. The following three steps would help to address the problem of convergence:

  1. The international implementing body for the CWC, the Organization for the Prohibition of Chemical Weapons, or OPCW, in The Hague, should convene a panel of scientific and technical experts to assess the biologically mediated production of chemical warfare agents and their precursors, including its feasibility and likely timeframe, to help policymakers determine the level of attention this issue deserves.
  2. The member states of the CWC should add a toxic peptide such as Substance P to the Schedules of Chemicals subject to routine verification, using the technical-change procedure provided in the treaty. At present, the CWC Schedules include only two toxins (ricin and saxitoxin) and no bioregulators. Because of its known toxicity, Substance P would be a good placeholder to represent the entire class of bioactive peptides.
  3. To better coordinate the implementation of the two treaties in response to convergence, the member states of the CWC should establish a liaison position in the Verification Division of the OPCW for a representative from the BWC Implementation Support Unit, or ISU, in Geneva. Although the ISU currently has only three full-time staff members, the upcoming five-year review conference of the BWC in December 2011 is expected to expand the size of the unit, in which case it may be possible to send an ISU representative to The Hague.

In conclusion, the growing convergence of biological and chemical production methods is outstripping the ability of the CWC and the BWC to prevent the misuse of these technologies for hostile purposes. Although the risks have not yet fully materialized, the rapid pace of technological progress in the biological and chemical fields and the political hurdles facing efforts to strengthen the two treaties suggest that the time to begin is now.

Jonathan B. Tucker, Ph.D., is a policy analyst specializing in biological and chemical arms control and nonproliferation issues. He is the author of Scourge: The Once and Future Threat of Smallpox and War of Nerves: Chemical Warfare from World War I to Al-Qaeda, and the editor of Toxic Terror: Assessing Terrorist Use of Chemical and Biological Weapons. For a more technical discussion of this issue, see: Jonathan B. Tucker, “The convergence of biology and chemistry: implications for arms control verification,” Bulletin of the Atomic Scientists, vol. 66, no. 6 (November/December 2010), pp. 56-66.

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