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BWC Biological Weapons Convention

CSynBI Centre for Synthetic Biology and Innovation

DIY biology/DIYbio Do-it-yourself biology

EPSRC Engineering and Physical Sciences Research Council

ESRC Economic and Social Research Council

FBI The Federal Bureau of Investigation, US Department of Justice

GOF Gain of function

iGEM International Genetically Engineered Machine Competition

IL-4 Interleukin 4

ISU Implementation Support Unit (of the BWC)

NSABB National Science Advisory Board for Biosecurity, US

SSHM Department of Social Science, Health & Medicine, King’s College London

STS Science and Technology Studies

WHO World Health Organisation

Appendix 1: Synthetic Biology and Biosecurity: Challenging the ‘Myths’

Scoping Report for the Workshop on ‘Synthetic Biology and Biosecurity’ held at King’s College London on 28th February 2014. Prepared by Catherine Jefferson, Filippa Lentzos and Claire Marris, Department of Social Science, Health and Medicine, King’s College London and distributed to all participants in advance of the workshop. Please note that a revised version of this document will be published in the Journal

Frontiers in Health and wherever possible that article should be cited in preference to this version.

Introduction

A common narrative has emerged in the media and in policy arenas, in which advances in biosciences are seen to make biology easier and more accessible, and this is presumed to increase the ‘dual use’ threat, i.e. the potential for legitimate peaceful research to be misused for the production of biological weapons. Developments in synthetic biology, a field that emerged at the start of the 21st century with the stated aim of ‘making biology easier to engineer’, have further fuelled these concerns. One school of synthetic biology aims to build a set of standard biological parts whose functions have been well characterised and which can be assembled in a modular fashion into devices to produce liv- ing organisms that predictably perform human-designed functions. Concerns have been expressed that this, combined with open online ac- cess to DNA sequences of living organisms (including viruses and other pathogens) and the reduction in price for DNA synthesis, could make biology increasingly accessible to non-biologists and amateurs. The emergence of ‘do-it-yourself’ (DIY) biology communities have come to epitomise this supposed trend towards greater ease of access and the associated potential threat from rogue actors.

However, these dual use concerns are largely based on promissory constructions of synthetic biology and speculative assumptions about the field’s ability to produce well-characterised biological parts that function predictably in living organisms; assumptions that may not accurately reflect current scientific realities. Furthermore, there remain a number of tangible and intangible barriers to the production of biological weap- ons using synthetic biology. There are considerable challenges involved in successfully creating a viable biological threat agent, and further challenges to turn these into weapons. Amateurs lack the necessary specialist ‘tacit’ knowledge and institutional support to overcome these challenges; and rogue actors have other means at their disposal that are less onerous. In discussions about biosecurity, it is also important to distinguish between weapons designed to generate terror from weapons designed to cause mass destruction: terror weapons do not need to cause extensive physical harm and thus do not require sophisticated weaponisation.

This Scoping Report identifies five recurring ‘myths’ about the dual use threat of synthetic biology that dominate discussions in policy arenas and the media. It highlights some key challenges to this narrative and suggests that the biosecurity threat may be exaggerated. This is not to argue that there is no threat, but rather to draw out some of the subtleties that frequently disappear from these discussions. Moreover, it is important to note that these ‘myths’ have power and perform real functions by mobilising support, resources and action. Emphasising the potential biosecurity threats of synthetic biology serves to bolster the speculative promises of the field. These myths also serve to attribute roles and influence to particular actors: they define who is legitimate to speak on these topics, what they can say, and where. They influence who gets funded, for what. Contrasting the ‘promises and perils’ of a field such as synthetic biology also aligns particularly well with the way in which science and technology is typically framed in mass media, and this serves to further fuel these myths.

The aim of the Flowers Consortium Workshop on ‘Synthetic Biology and Biosecurity’ is to examine the assumptions that underlie these ‘myths’ and to explore the implications for policy.

2001 Mousepox Experiment

Australian researchers used genetic engineering techniques to insert the gene for interleukin-4 into the mousepox virus. They aimed to produce an altered virus that would induce infertility in mice and serve as an infectious contraceptive for pest control. However, the altered virus was found to be lethal to both mice that were naturally resistant to mousepox and mice that had been recently immunised against ordinary mousepox. The publication of these findings led to concerns that this could provide instructions to terrorists to produce novel biological weapons.

Jackson, RJ, Ramsay, AJ, et al. (2001) Expression of mouse interleukin-4 a recombinant ectromelia virus sup- presses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox, Journal of Virology, 75(3): 1205-10.

2002 Poliovirus Experiment

Researchers at the State University of New York at Stony Brook synthesised the poliovirus without using any natural virus or viral components. They obtained published poliovirus RNA genome sequence information and converted this into DNA se- quence data, which they then ordered from a commercial DNA synthesis company and assembled into a viral genome. En- zymes were used to convert the DNA back into RNA and to translate the RNA into a functional virus. Publication of the re- search article raised concerns that terrorists could synthesise viruses ‘from scratch’.

Cello, J, Paul, AV & Wimmer PE (2002) Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template, Science, 297 (1016): 1016-18.

2005 Spanish Influenza Virus Experiment

Researchers at the US Centers for Disease Control and Prevention reconstructed the Spanish flu virus, which is thought to have killed around 50 million people during the 1918 pandemic, using a recently recovered genomic RNA. Concerns were expressed that publication of the full genome sequence could give bioterrorists the information necessary to make their own version of the virus.

Tumpey, TM, Basler, CF, et al. (2005) Characterisation of the reconstructed 1918 Spanish influenza pandemic vi- rus, Science, 310: 77-80.

2011 H5N1 Virus Experiment

Researchers in the Netherlands and the USA developed a novel, contagious strain of the H5N1 ‘bird flu’ virus. They infected ferrets with genetically modified H5N1 and found that the modified H5N1 acquired small mutations during passage in fer- rets, ultimately becoming airborne transmissible. When two papers relating to the research were submitted for publication to

Myth 1: DNA synthesis has become faster and cheaper and this will make it easier for terrorists

to create biological threat agents.

DNA synthesis is one of the key enabling technologies of synthetic biology and the increasing speed and reduced costs of DNA synthesis have raised concerns that this technology could make it easier for bioterrorists to recreate dangerous viruses from scratch, especially when com- plete DNA or RNA sequences for viruses and other pathogenic agents are increasingly freely available online. Reconstruction of poliovirus (2002) and Spanish influenza virus (2005) have come to epitomise this threat narrative (see Box 1).

‘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 biot- errorism.’ (China 2011)

‘in the near future... the risk of nefarious use will rise because of the increasing speed and capacity [of synthetic genomics].’ ... ‘ten years from now, it may be easier to synthesize almost any pathogenic virus than to obtain it through other means.’(Garfinkel, Endy et al. 2007, pp. 12-13)

‘Synthetic biologists have already shown how terrorists could obtain life forms that now exist only in carefully guarded facilities, such as polio and 1918 influenza samples.’ (Maurer and Zoloth 2007, p. 16)

‘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. Indeed, the feasibility of assembling an entire, infectious viral genome from a set of synthetic oligonucleotides has already been demonstrated for poliovirus and the Spanish influenza virus.’ (Tucker and Zilinskas 2006, p. 37)

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