Catherine Jefferson; Filippa Lentzos; Claire Marris

“ The idea that synthetic biology could make it easier for non-specialists, including those working outside of institutions, to exploit this powerful technology for both benevolent and malevolent purposes, has to a large extent become a hallmark of the field. ”

“ Of course, it is prudent to take measures to prepare against the possibility of a biological weapons attack and concerted action across a policy continuum that extends from prevention through preparedness to consequence management is necessary. However, as we have demonstrated, any bioterrorism attack will most likely be one using a pathogen strain with less than optimal characteristics disseminated through crude delivery methods under imperfect conditions, and the potential casualties of such an attack are likely to be much lower than the mass casualty scenarios frequently portrayed. ”

“ Researchers from our own field of science and technology studies (STS) are not immune from such processes: we will generally seek to emphasize the complexity of real world situations and the importance of social dimensions of science, in order to justify the need for our expertise. However, at least until now, STS framings have had less influence on the dominant narrative than the discourse mobilized by actors from the fields of synthetic biology and biosecurity. ”

“ For example, scientists such as Rob Carlson, George Church, or Drew Endy, who are heavily engaged in the promotion of synthetic biology, need to portray an optimistic vision of the potential of the engineering approach to biology as part of their endeavors to develop support for a new field of research which they believe has great significance and potential. Actors in the security field (including some policy makers, social scientists, and natural scientists) play a different role and often exaggerate the “dual-use threat” in order to attract attention and resources to their own work. ”

“ Together, the reconstruction of poliovirus and Spanish influenza virus have come to epitomize the threat narrative that DNA synthesis has become faster and cheaper, and that this will make it easier for terrorists to create biological threat agents. This is illustrated by statements from biosecurity experts such as Jonathan Tucker and Raymond Zilinskas7:
One potential misuse of synthetic biology would be to recreate known pathogens (such as the Ebola virus) in the laboratory as a means of circumventing the legal and physical controls on access to “select agents” that pose a bioterrorism risk. ”

“ The effects of naturally occurring pathogens are limited by the evolutionary advantage gained by not eliminating their hosts. Among the many implications of the anticipated progress in biotechnology is the presumption that it may be feasible to create novel biological agents that are far more predictable and dangerous than any of the naturally occurring pathogens that have been developed as biological weapons in the past. It may be difficult to engineer a more successful pathogen than those already present in nature that have been perfected by evolution for their niche in life. ”

“ We show that the importance of tacit knowledge is commonly overlooked in the dominant narrative: the focus is on access to biological materials and digital information, rather than on human practices and institutional dimensions. ”

“ With the spread of synthetic biology, some small scale research groups and even some individuals are now able to make the deadly Ebola and smallpox viruses and even some viruses against which all drugs are ineffective, thus making it much harder to counter bioterrorism. Furthermore, it has become much easier to obtain sensitive information. Using publicly available DNA sequences, terrorists can quickly synthesize pathogenic microbes that had previously been eradicated. ”

“ Specialized expertise, teamwork, large infrastructures, complicated machinery, advanced technology, trouble-shooting, and organizational factors continue to be required when a design and engineering approach develops. Thus, even though the engineering approach of synthetic biology aims to make processes more systematic and more reproducible, this will not make it easier for anybody to engineer biology. ”

“ Underlying the first four myths are certain assumptions about who the terrorists might actually be, what their intentions are, what capabilities they might pursue, and the level of skills and resources available to them. Despite a lack of analysis of the potential adversaries involved in the misuse of life science research, the bioterrorism threat has generally been portrayed in policy circles as an imminent concern, and emphasis is placed on high consequence, mass casualty attacks, performed with “weapons of mass destruction” (WMD) . ”

“ Myth 4 Synthetic biology could be used to design radically new pathogens
In addition to recreating dangerous viruses, concerns have also been expressed that synthetic biology could be used to enhance the virulence or increase the transmissibility of known pathogens in order to create novel threat agents.
The 2001 mousepox experiment is the most widely cited examples of the dual-use potential of life science research and has come to epitomize the potential to create more virulent viruses. In this experiment, researchers inserted the gene for interleukin-4 into the mousepox virus ( [49] ) . ”

“ Ordering short oligos and then assembling them into a genome was the method used in the polio and Spanish flu experiments, but this required specialist expertise, experience, and equipment, which were all available in the academic laboratories involved but would not be easily accessible to an amateur working from home. Obtaining the oligos (as was done by The Guardian journalist for the smallpox virus) is only the first step in a complicated process. This is the first challenge to Myth 3. ”

“ We believe that a better understanding and acknowledgment of the social dynamics at play would help to develop more productive discussions in which the different communities involved could move beyond simply promoting their own interests and perspectives. This is important because in some cases the discourse deployed can have unintended consequences that are detrimental to the interests of the actors themselves, and to the nature of public debate. ”

“ Scaling up fragile microorganisms that are sensitive to environmental conditions and susceptible to change — and viruses are more sensitive than bacteria — has been one of the stiffest challenges for past bioweapons programs to overcome, even with appropriate expertise at hand. Scaling-up requires a gradual approach, moving from laboratory sample, to a larger laboratory quantity, to pilot-scale production, and then to even larger-scale production. During each stage, the production parameters need to be tested and often modified to maintain the lethal qualities of the agent ”

“ There are two dimensions to Myth 5. The first is about the intention of would-be terrorists, and the assumption is that terrorists would seek to produce mass casualty weapons and pursue capabilities on the scale of twentieth century state-level bioweapons programs. While most leading biological disarmament and non-proliferation experts believe that the risk of a small-scale bioterrorism attack is very real and very present, they consider the risk of sophisticated large-scale bioterrorism attacks to be very small ( [64] ) . ”

“ The mousepox and H5N1 experiments are frequently cited to demonstrate how dangerous new pathogens could be designed. However, assessments of this threat tend to overlook the fact that, in both these experiments, the researchers did not actually design the pathogens. With respect to H5N1, researchers had indeed been trying to design an air-transmissible virus variant for some time, without success. The ferret experiment was set up as an alternative approach, to see whether “natural” mutations could generate an air-transmissible variant. ”

“ The research team, led by Eckard Wimmer, obtained published poliovirus RNA genome sequence information and converted this into DNA sequence data, which they then ordered from a commercial DNA synthesis company and assembled into a viral genome. The DNA was converted back into RNA and the RNA was used to produce a functional virus. Publication of this research in a scientific journal article immediately raised concerns that terrorists could use it as a recipe to synthesize dangerous viruses without needing access to biological material. ”

“ Naturally occurring disease remains a serious biological threat; however, a thinking enemy armed with these same pathogens — or with multi-drug-resistant or synthetically engineered pathogens — could produce catastrophic consequences. A small team of individuals with graduate training in several key disciplines, using equipment readily available for purchase on the Internet could produce the type of bioweapons created by nation-states in the 1960s. ”

“ The price of gene synthesis has declined greatly over the last 20 years, and the policy discourse that underlies biosecurity fears often implies that it will naturally become even cheaper over time, and thus widely affordable. ”

“ We see here how the myths we previously discussed, about de-skilling and increased access, and about the ease of designing new dangerous pathogens, underlie concerns about terrorists’ potential ability to launch a mass attack, and how these are connected, by actors, with the advent of synthetic biology. ”

“ Such concerns became prevalent at the NSABB, an organization established in 2005 to provide advice to the US government on biosecurity issues:
As synthetic biology techniques become easier and less expensive and the applications become more widely relevant, the range of practitioners expands to include scientists from a variety of disciplines; students at all levels, including high school; and amateur scientists and hobbyists who may lack any formal affiliations with universities or research institutions. ”

“ Using such technologies, which have been utilized to investigate Ebola, pandemic flu, influenza, hanta viruses, lassa, rabies, and Marburg viruses, there is no need for a bioweaponeer to isolate the virus from an infected patient, acquire it from a germ bank, or culture it from nature. ”

“ Large urban reservoirs are usually unguarded, but unless terrorists added massive quantities of biological agent, the dilution effect would be so great that no healthy person drinking the water would receive an infectious dose ( [65] ) . Moreover, modern sanitary techniques such as chlorination and filtration are designed to kill pathogens from natural sources and would probably be equally effective against a deliberately released agent. Bacterial contamination of the food supply is also unlikely to inflict mass casualties. ”

“ Terrorists would therefore have to develop or acquire a sophisticated delivery system capable of generating an aerosol cloud with the necessary particle size range and a high enough agent concentration to cover a broad area. Overall, an important trade-off exists between ease of production and effectiveness of dissemination. The easiest way to produce microbial agents is in a liquid form, yet when such a “slurry” is sprayed into the air, it forms heavy droplets that fall to the ground so that only a small percentage of the agent is aerosolized. ”

“ Results Myth 1 Synthetic biology is de-skilling biology and making it easier for terrorists to exploit advances in the biosciences
Founding leaders in synthetic biology have argued that developments in the field would lead to a situation where biology would not only become “easier to engineer,” but that it would become easier for anyone to engineer biology. ”

“ The dissemination of biological agents also poses difficult technical challenges. Whereas persistent chemical agents such as sulfur mustard and VX nerve gas are readily absorbed through the intact skin, no bacteria and viruses can enter the body via that route unless the skin has already been broken. Biological agents must either be ingested or inhaled to cause infection. To expose large numbers of people through the gastrointestinal tract, possible means of delivery are contamination of food and drinking water, yet neither of these scenarios would be easy to accomplish. ”

“ Members of DIYbio communities who are involved in more sophisticated experiments tend to be trained biologists, not amateurs and, as noted in the previous section, the experiences of amateur members of the DIYbio community demonstrate the challenges posed by tacit knowledge to successfully conduct even rudimentary biological experiments. ”

“ Synthetic biology’s efforts to reprogram life have raised concerns in some quarters that the technology could one day be used to make radically new weapons, such as pathogens that could be narrowly targeted towards populations with known genetic susceptibilities [ ( [36] ) , p. ”

“ Producing viral particles in a laboratory is, moreover, not the same as creating and deploying an effective biological weapon. Challenges to the processes of scaling up, storage, and developing a suitable dissemination method are discussed under Myth 5. ”

“ Moreover, most microorganisms are sensitive to ultraviolet radiation and cannot survive more than 30 min in bright sunlight, limiting their use to night-time attacks. One major exception is anthrax, which can be induced to form spores with tough outer coats that enable them to survive for several hours in sunlight. Terrorists could, of course, stage a biological attack inside an enclosed space such as a building, a subway station, a shopping mall, or a sports arena. ”

“ A useful analogy to aeronautical engineering was used at the workshop to illustrate this. Planes are built from a large number of well-characterized parts in a systematic way, but this does not mean that any member of the general public can build a plane, make it fly, and use it for commercial transportation. ”