Ethical Concerns

The Social and Ethical Issues Raised, excerpted from the BBSRC's policy document: http://www.bbsrc.ac.uk/organisation/policies/reviews/scientific_areas/0806_synthetic_biology.pdf Synthetic Biology Social and Ethical Challenges, written by Andrew Balmer & Paul Martin, Institute for Science and Society, University of Nottingham.

Uncontrolled Release

The main concerns in this area are centred on the development of synthetic organisms that are either intentionally or accidentally released into the environment. The ETC Group raises this as a major issue that parallels the debates about GM crops. Their report was spurred by the widely publicised patent application for a minimal bacterial genome, a list of genes, submitted by the Venter Institute, detailing the least number of genes that the bacterium M. genitalium requires for survival and reproduction. Further concerns were expressed following the announcement of Venter’s bacterial genome swap. Generally the media reports quickly dismiss certain concerns, celebrate the research, and present a rather balanced approach, e.g.: Would a synthetic bug cause havoc if it escaped from the lab? No, because it's too weak to survive in the wild. Could synthetic biology be used to build bioweapons? Yes. … By the way, isn't it mindblowing that "life" can range from a gaggle of 400 genes mooching about in a Petri dish, to a free-thinking assortment of 30,000 genes, with sparkling eyes and heartstopping dimples? Anjana Ahuja, ‘Life is Just a Bowl of Petri’ The Times July 2nd 2007 Scientists have converted an organism into an entirely different species by performing the world's first genome transplant, a breakthrough that paves the way for the creation of synthetic forms of life. … The work is at the cutting edge of synthetic biology … But critics fear the field is progressing too fast for society to grasp. Some are concerned that artificial organisms could escape and damage the environment, or that maverick scientists or terrorist groups could create powerful new bioweapons. Ian Sample, ‘First genome transplant turns one species into another’ June 29th 2007 The ETC however were very critical and wrote to Venter and the patent authority asking that it be withdrawn or rejected on the basis that it was contrary to the public morality and safety. They claim that the patent application represents a “high-stakes commercial race to synthesize and privatize synthetic life forms” [ETC Group 2007c]. They raise many other fears such as potential misuse of the organism, including creating a biological weapon and also ask, “How could their accidental release into the environment be prevented or the effects of their intentional release be evaluated?” [ETC Group 2007c]. They draw comparisons to other controversies including the Dolly clone and are sceptical about the promise of synthetic biology: Synthia may not be as cuddly as a cloned lamb, but we believe this is a much bigger deal. … It's purely speculation and hype that syns [synthetic living organisms] will be used to ameliorate climate change by producing cheap ethanol or hydrogen … The same minimal microbe could be harnessed to build a virulent pathogen that could pose grave threats to people and the planet. Jim Thomas, ETC Group ‘Patenting Pandora’s Bug’ June 7th 2007 [ETC Group 2007c]. A major issue raised by the critics of this technology is that by their very nature biological machines are evolutionary machines; they are subject to natural selection and potentially gene flow [Benner and Sismour 2005]. This means that mutations in the genome of the synthetic organisms could produce unexpected interactions with the environment and other living, natural organisms. Considering the myriad unusual functions enabled by BioBricks that could be integrated in synthetic genomes, a concern is that functions upon which nature has never operated may provide advantages over natural organisms leading to unexpected proliferation of a synthetic biology product, thereby radically altering the ecosystem. Microorganisms intended for clean up of one particular chemical may interact with others, potentially passing synthetic genes to natural species thereby “contaminating” the gene pool [Tucker and Zilinskas 2006]. It’s also claimed that even without such evolutionary intervention the released species may interact with naturally existing substances and cause unexpected side-effects [Bhuktar 2005]. These fears are reminiscent of the concerns voiced by anti-nano groups and individuals such as Prince Charles, who famously envisaged a world reduced to “grey goo” by out of control nano machines[1]. In this context questions have been asked about the adequacy of existing regulatory regimes for the control of GMOs, which are based on assessing relatively simple genetic changes to bacteria [Schmidt, 2008]. In particular, established risk assessment methods may not be adequate to deal with the much more complex changes brought about by synthetic biology, which involves the engineering of entire biochemical pathways. This challenge may require important changes to the methods and procedures used to assess the environmental risks posed by the novel organisms created by synthetic biology.

Bioterrorism

Though researchers in the field are quick to point out the potential ethical dilemmas and social implications, or at least acknowledge that they need to be investigated [2], the media has continued to see this as a major issue. In 2006 a Guardian reporter ordered part of the DNA sequence of the smallpox virus and had it sent to his home [Randerson 2006], which raised questions about the regulation of DNA sequence supply. An article in the New Scientist [Aldhous 2005] on the sequence suppliers found that, “Of the 12 companies that replied [to their communications], just five said they screen every sequence received. Four said they screen some sequences, and three admitted not screening sequences at all”. The Guardian article [Randerson 2006] also found that of three UK sequencing companies, “one did not screen customers or sequences, one carried out checks on customers only and a third checked customers and had carried out a pilot study on screening DNA orders but is not currently doing so.” The major question raised by these reports is that if a Guardian or New Scientist journalist can order and be supplied with genetic sequences from dangerous pathogens then who else may have, or may be able to do so? Whilst the academic community continues debating regulation and ethics, biohacking or ‘garage biology’ is, according to some media reports [Rowan 2006], being established as a home hobby. As DNA sequencing becomes cheaper and quicker and second hand equipment becomes available on eBay the power to create synthetic sequences may be dispersed to many individuals and groups. Biohackers have also become known by the portmanteau ‘biopunk’ (biotech punk)[3] , that has its origins as a science fiction genre. The most recent, and significant addition to this movement has been the online publication of a ‘Primer for Synthetic Biology’, a manual, written in simple, non-technical language, for those wishing to engage themselves in some bio hacking [Mohr 2007]. Interestingly Mohr, a student at Boston University at the time of writing, includes in his 72 page draft a notice of intent to provide an outline of the key ethical issues facing synthetic biology titled ‘ethics for everyone’. Though biohacking is beginning to develop a web presence, and is certainly becoming quite prominent in the blogosphere there is little evidence, as yet, that it has any active/practising following. Tucker and Zilinskas identify two potential terrorist categories: the ‘lone operator’ and ‘the biohacker’. The lone operator is a rogue synthetic biologist and the biohacker is, as above, a college kid eager to demonstrate their technological prowess. If indeed second hand tools for genome assembly are becoming available to the public at affordable costs then this would seem to add weight to the concerns over possible terrorist use of synthetic biology research. However, Tucker and Zilinskas [2006] argue that ‘At present, the primary threat of misuse appears to come from state-level biological warfare programs’. They suggest that the construction of an entirely new pathogen using synthetic sequences is unlikely given the present state of the art and that the more likely threat is from the creation of already known pathogens, such as polio, as discussed above. The technological obstacles to producing either pathogen are seen as a limiting factor that renders synthetic biology no more concerning that previous debates about genetic engineering [Tucker and Zilinskas 2006]. Furthermore, even if such organisms could be produced, they are hard to ‘weaponise’ – something which would be essential for their role as offensive weapons or instruments of terror. Whilst the prospects for the creation of biological weapons based on synthetic biology remain contentious and uncertain, a more fundamental problem has been raised about the level of awareness within the scientific community of the potential military uses of the technology. Most proposals for governance and oversight depend on scientists being aware of and reporting potential misuses. However, this in turn will critically depend on researchers being aware of the possible applications and risks of synthetic biology. A recent study carried out by Alexander Kelle found a low level of awareness of the key policy documents and debates about biosecurity amongst synthetic biology researchers in Europe [Kelle 2007]. This raises major questions about how easy it will be to implement any such measures in this area.

Patenting and the Creation of Monopolies

One of the main issued raised is that synthetic biology falls into US intellectual property ‘at the confluence of biotechnology and computing’ [Rai and Boyle 2007]. Rai and Boyle highlight that patenting appeals have proven a rather problematic case for the Federal Circuit Court of Appeals, which has consistently ignored the ‘obviousness’ clause of patent legitimacy, relying instead on per se rules developed for 20th century chemical inventions. Coupled to this are the problems that software caused by neither fitting into the intellectual property regime of patents or copyrights; an issue that was hardly resolved by forcing it under both. Rai and Boyle suggest that difficulty with the way in which the law handles software and biotechnology individually could come together to form ‘a perfect storm’. There are two major concerns about the intellectual property puzzle of synthetic biology, namely patents that are too broad and those that are too narrow. The difficulty is that broad patents may restrict collaboration and stifle development in the field, and narrow patents may over-complicate the process, meaning that hundreds of patents have to be negotiated to produce a system from standardized parts. The spur for debate on the IP problems surrounding synthetic biology has come from Venter’s patenting of Synthia. He hasn’t only sought a patent for the minimal living cell in the US, but also at the international level through the World IntellectualProperty Organisation (number WO2007047148). More recently Venter has filed patent applications for making synthetic genomes (UPSTO no. 20070264688) and putting them into cells (20070269862). The ETC Group claims that Venter’s ‘enterprises are positioning themselves to be the Microsoft of synthetic biology’ [ETC Group 2007b], or what they called Microbesoft [Anjana Ahuja 2007]. ETC argues that the landmark ruling of Diamond vs. Chakrabarty [4] opened the door to patent all biological products and processes, and that synthetic biology easily fits into its scope. Other than the detraction to potential research on synthetic biology the ETC Group doesn’t expand on why such a monopoly on synthetic life forms should be avoided.

Trade and Global Justice

The ETC Group [2007] claims that the development of artemisinin has ‘become the raison d’être of synthetic biology and given the field a philanthropic sheen’. They draw a comparison to the poster child of the agricultural biotech industry ‘Golden Rice’ which was designed to feed the poor and tackle vitamin deficiencies. The ETC group suggests that the scale of the success has been drastically inflated to ensure continued funding of Keasling’s lab and that ongoing research on synthetic biology for such social and economic problems diverts resources from other more effective approaches. It is recommended by the WHO that artemisinin should be mixed with other malaria drugs, Artemisinin Combination Therapies (ACTs), to ensure thatresistance does not build up. However, ETC argues that Novartis has a virtual monopoly on ACTs and quote the Royal Tropical Institute of the Netherlands ‘This monopoly-like situation has created an imperfect market defined by scarcity of raw materials, speculation and extremely high retail prices’. Critics contend that synthetic artemisinin would ensure that no local production of natural Artemisia could be stimulated or sustained, thereby maintaining the discrepancy of wealth and health. The Gates foundation has been applauded for its charitable and practical aim, but it is not clear that producing a drug of this sort in developed countries is the best way of either eradicating malaria in the long term or supporting sustainable development in the poorest countries. As with many other advanced technologies, such as GM crops, when applied to issues of economic development, public health and global justice, a number of important questions are raised about the extent to which these innovations help tackle these problems or make them worse.

Creating Artificial Life

The NEST high-level expert report [NEST 2005] indicates that the discussion of artificial life is likely to be prompted by public concerns over scientists ‘playing God’. The same report welcomes the discussion on synthetic life, but cautions ‘that it will be productive only if we can develop a more sophisticated appreciation of what is meant by ‘life’ than is current in popular discourse’. As witnessed by a number of media reports, there is a feeling that the science of synthetic biology may have outstripped our ethical reference points: On the moral front, Mooney [of the ETC Group] says of Venter: "God has competition." To argue that the making of life should remain the province of a divine creator is no argument at all. Anjana Ahuja, ‘Life is Just a Bowl of Petri’ The Times July 2nd 2007Fears have been raised about the dangers of tinkering with life and releasing malignant bugs. "We don't yet know what are the social, ethical and even bioweapons implications of this research," said Hope Shand of the ETC technology pressure group. The most ominous note was struck by a scientist at MIT: "The genetic code is 3.6 billion years old. It's time for a rewrite." Feature, ‘The Scientist Who Wants to put a Microbe in Your Tank’ Sunday Times July 1st 2007 Scientists are a step closer to creating artificial life after transforming one type of bacteria into another. … But the announcement has also triggered unease, with some critics warning that the scientists were 'playing god'. Reporter, ‘Scientists ‘Closer to Creating Artificial Life’’ Daily Mail June 29th 2007 Synthetic biology has been touted as the discipline geared towards ‘engineering life’ [Chopra and Kamma 2006]. It is the notion of artificiality, the unknown quality, of synthetic biology’s products that seems to underlie many of the aforementioned ethical concerns. Furthermore, the living, breeding nature of the synthetic biology output makes the threat of environmental contamination or the development of biological weapons so powerful. In this way, the ascription of the term life gives them agency; as though these microbes might seek to destroy us. It shouldn’t be surprising then that this framing of the potential of biological engineering taps into the concept of risk and that some of the responses, particularly the regulative strategies outlined earlier that are aimed at identifying ‘risky’ engineers, are focussed on minimising potential harms whilst enabling scientific progress. However, such concerns are largely utilitarian, ‘what might happen if this microorganism escaped?’ Whilst these arguments are brought to the fore what have been pushed to the edges of the scientific discourse are potentially more fundamental issues about tampering in natural systems and creating ‘life itself’. It has been suggested by Edward Machery73 , a philosopher of science at the University of Pittsburgh, that a stable definition of ‘life’ is impossible and useless. Machery argues that synthetic biologists (amongst other researchers) are confused over what life is, where it begins and particularly, how complex it must be. This, he suggests, is no surprise and is consistent with a whole programme of ‘life definitionism’ that fails to confine its object. A similar set of issues have been raised in a recent Nature Editorial [Nature 2007] [5], which notes that “Many a technology has at some time or another been deemed an affront to God, but perhaps none invites the accusation as directly as synthetic biology.” It then goes on to argue that ‘It would be a service to more than synthetic biology if we might now be permitted to dismiss the idea that life is a precise scientific concept.’ The final step in Venter’s three step process of creating a synthetic organism involves inserting the synthesised genome into a bacterial cell and waiting to see if it springs to life. The publication of this information in January 2008 resulted in quite extensive media coverage with many articles leading with the life aspect: ‘Scientist Creates Artificial Life – Almost’ [6] ; ‘Synthetic Life: Watch this Space’. The Economist concluded its article on the publication with the lines:

…if Dr Venter can take the final step of kicking the new, wholly synthetic genome into reproductive life, he will not only have made a great technological leap forward,he will also have erased one of the last mythic distinctions in science — that between living and non-living matter.

Anon,‘Nearly There’ The Economist January 24th 2008

Whilst others were less impressed:

But what does doing this really signify? What does it teach us about life that we didn't know before?There was indeed a time when scientists believed there was something fundamentally different about living matter and non living matter. It's called the Middle Ages. Carl Zimmer,‘Artificial Life? OldNews’ Wired.com January 25th 2008

If Machery is right, that the idea of life is highly complex, but can possibly be defined by science, it would require multiple definitions across multiple fields. What implications might this have for an ethics that sought to trouble synthetic biology at the level of life definition? Put another way, if life is not a stable concept how might one argue that it is fundamentally immoral to create it? In contrast, if Zimmer is right that our definition of life, or at least the scientific definition, hasn’t changed since the Enlightenment,then perhaps the claim to be creating life is less about heresy and more about hype. He argues that whilst being expertly technical and scientifically significant, the research doesn’t reveal the mysteries of existence; infact he argues that it doesn’t even reveal the mysteries of genetics [7]and that creating a new living organism will lead to a whole new set of mysteries. In this sense we are a longway from playing God.