2014, pp 811-826
Date: 30 Aug 2013

Synthetic Biology

Abstract

Synthetic biology aims to bring to biology the principles of engineering, standardizing and modularizing the design of biological systems to make possible the development of biological systems that perform specified tasks. Several distinct lines of research fall under the general heading of synthetic biology. Examples of synthetic biology to date include the development of microorganisms that can produce a precursor to artemisinin (a drug for treating malaria) and fuels. The technology poses ethical and policy challenges concerning its risks and potential benefits, its socioeconomic impact and the implications for social justice, and the very idea of engineering living organisms. Many commentators have recommended that these questions should be addressed in a manner that engages the public, raising additional questions about how that is best done.

Henk A.M.J. ten Have and Bert GordijnHandbook of Global Bioethics201410.1007/978-94-007-2512-6_135
© Springer Science+Business Media Dordrecht 2014

48. Synthetic Biology

Gregory E. Kaebnick 
(1)
The Hastings Center, 21 Malcolm Gordon Rd., Garrison, NY 10524, USA
 
 
Gregory E. Kaebnick
Abstract
Synthetic biology aims to bring to biology the principles of engineering, standardizing and modularizing the design of biological systems to make possible the development of biological systems that perform specified tasks. Several distinct lines of research fall under the general heading of synthetic biology. Examples of synthetic biology to date include the development of microorganisms that can produce a precursor to artemisinin (a drug for treating malaria) and fuels. The technology poses ethical and policy challenges concerning its risks and potential benefits, its socioeconomic impact and the implications for social justice, and the very idea of engineering living organisms. Many commentators have recommended that these questions should be addressed in a manner that engages the public, raising additional questions about how that is best done.

Introduction

Synthetic biology is a collection of lines of biological research linked by the common goal of engineering novel biological systems, designing and building them to human specification. The basic idea of altering biological systems has been part of genetic research for several decades, and it has been an explicit part of traditional breeding programs for much longer than that; indeed, the very phrase “synthetic biology” was coined a century ago (Campos, 2009). Contemporary synthetic biology seeks to bring this goal to fruition through the application of new technologies – especially technologies for reading and producing genetic sequences – ideally in a structured way that allows design inputs to be well understood and standardized so that design outcomes can be predictable and efficiently achieved. It has potentially transformative benefits, but it also poses a variety of questions that will be a challenge to evaluate fully and to address in public policies. What is the right balance between risks and potential benefits? How can the risks be managed in light of the complexity of microorganisms and ecosystems? Can a society ensure that the changes wrought by the field are just and environmentally beneficial? Is the idea of engineering living organisms intrinsically troubling? And how are these questions most usefully discussed – how do we ensure that deliberation reflects the global import of synthetic biology, for example? This chapter provides an overview of synthetic biology and then delves into four broad ethical concerns that encompass the questions above.

Overview of the Technology

The overall goal of synthetic biology is to make possible the engineering of novel biological systems that can be used like machines or miniature factories to make products or provide services. Such industrial analogies are inescapable when talking about synthetic biology, and while they may deflect attention from the fact that synthetic biology is about living systems, they capture several key aspects of synthetic biology, including the focus on engineering those systems and on altering them in ways that making engineering easier – standardizing and simplifying them.
Since synthetic biology is fundamentally about bringing the principles of engineering to bear on biology, it is, in principle, not defined in terms of and not limited to any particular kind of biological research or category of organism. In practice, however, the main lines of work in synthetic biology are on microorganisms and have to do with the synthesis and alteration of their genomes.

Types of Synthetic Biology

Exactly what the term “synthetic biology” refers to is contested (Brent, 2004), and various taxonomies can be found to explain the term (Presidential Commission for the Study of Bioethical Issues, 2010), but one or more of three broad lines of work are usually in mind when it is used.
One line, and arguably the line that aims most directly at the goal of integrating biology and engineering, is what Maureen O’Malley et al. have called “DNA-based device construction” (O’Malley, Powell, Davies, & Calvert, 2008). It is exemplified by the construction of “biobricks,” made from DNA and other molecules, that can function as standardized and interchangeable parts or tools to perform very specific functions – turning gene production on or off, say, or measuring the concentration of a particular gene product (BioBricks Foundation, 2011). Assembled in sequences and installed in “platform” organisms, these parts would, as proponents describe it, turn that organism into a very specialized tool of sorts. Some proponents would add that the parts should also be well characterized and available to the public. Some other synthetic biologists have expressed doubts, however, about whether standardized genetic sequences are achievable (Kwok, 2010).
In a second line of research, Craig Venter and colleagues at the J. Craig Venter Institute are engaged in what O’Malley et al. have called genome-driven cell engineering. For example, they hope to use synthetic DNA to build a “minimal genome” that contains only the genetic material needed to sustain bacterial life (Gibson et al., 2008). Such a minimal genome might provide a standardized platform that could then be equipped with DNA-based devices. In May 2010, researchers at the J. Craig Venter Institute announced that they had taken a step toward creating a minimal genome by successfully synthesizing the entire genome of the bacterium Mycoplasma mycoides (Gibson et al., 2010 To prove that the synthesis was successful, they inserted the genome into a cell of a closely related species, Mycoplasma capricolum, resulting in a fully functioning M. mycoides.
The development of interchangeable biological parts and of general purpose platform organisms into which the parts could be installed are ideal goals. They are certainly not yet realized, and in practice, they tail off into what is sometimes called “metabolic engineering” – the study and alteration of metabolic processes within existing organisms (Nielsen & Kiesling, 2011). Metabolic engineering frequently resembles a more advanced form of older lines of gene transfer research, differing in that it can be done faster, on a larger scale, potentially combining genetic sequences from three or more organisms, and with more information about the genetic sequences and the organism into which they are put, and therefore with greater ability to design the resulting organism. Given the links and differences with gene transfer, critics sometimes refer to synthetic biology simply as “extreme genetic engineering” (ETC Group, 2007).
A third line might be cobbled together from what are really distinct lines of research, but are united in that they seek to reinvent the basic mechanisms and materials found in living things. For example, in what is known as minimal cell creation or protocell creation (also the creation of “chemical cells,” or “chells”), the goal is to design and build organisms from the ground up, first identifying the basic functions necessary for the simplest forms of life (for example, mechanisms for metabolism, for control, for replication, for organization) and then constructing them from basic parts (Presidential Commission, 2010). The new cells might use chemicals not found in naturally occurring organisms. In principle, the development of protocells could lead to an entirely new biochemistry – a biochemistry that was nonorganic, in that it would not be carbon-based. Additionally, mechanisms for control and replication need not depend on DNA.
Two particularly high-profile examples of new products to which synthetic biology might lead are worth describing in greater detail. The examples both illustrate the science and help ground a discussion of the ethical issues synthetic biology raises.

The Case of Artemisinin

What is sometimes considered the flagship example of synthetic biology is the production of artemisinin, a highly effective but to date comparatively expensive treatment for malaria. Up until now, artemisinin has been extracted from the wormwood plant (Artemisia annua), which can be grown in plantations but according to some commentators is not easily grown in the quantities necessary to make artemisinin affordable for widespread treatment. An alternative strategy, developed by a partnership formed between Amyris Biotechnologies, the Institute for One World Health, and the University of California, Berkeley, is to construct a new metabolic pathway, comprised of genes from bacteria, yeast, and wormwood, that allows microorganisms equipped with the pathway to synthesize artemisinic acid, an artemisinin precursor, through a fermentation process (Hale et al., 2007). The pathway was first developed in Escherichia coli and then in baker’s yeast (Saccharomyces cerevisiae). The artemisinic acid produced by the organism can then be processed in the laboratory into artemisinin. (This final step in the production of artemisinin is performed by the wormwood plant, but it has not been recreated in microorganisms.)
As malaria affects hundreds of millions of people globally each year and kills up to one million, the potential health benefits of this application are considerable. The work was initially funded by the Bill and Melinda Gates Foundation, and it has now been licensed to and further developed by the pharmaceutical company Sanofi-Aventis. Synthetically produced artemisinin is expected to be available in 2012 (Specter, 2009).

The Case of Fuel Production

Research is under way on several fronts to develop organisms that would produce fuel. One line of research is aimed at the development of organisms that can more efficiently process biomass, typically crops such as corn, into biofuels such as ethanol. The organisms considered candidates for ethanol production include S. cerevisiae and Zymomonas mobilis, which naturally produce ethanol out of glucose, and E. coli, which naturally produces a small amount of ethanol but can process a broad variety of substrates (Jang et al., 2012). The research aims to eliminate metabolic pathways that compete with ethanol production, allow the organisms to tolerate higher levels of ethanol, and broaden the range of substrates that the organisms can process. An organism that processed cellulose, which is abundant and cheap, would be especially desirable. Butanol production is also desirable, because butanol has a higher energy density than ethanol, allowing for better gas mileage, and because it has properties similar to gasoline, so that it can replace gasoline in existing engines and in the existing systems for fuel storage and transport. Research on butanol production is under way with Clostridium, which produces butanol naturally, and E. coli modified with clostridial genes (Jang et al.).
Research is also under way on the development of organisms that produce alkanes (which, depending on the number of carbon atoms, can be used either as gasoline or as diesel or aviation fuel), isoprenoids, and hydrogen (which has an extremely high energy density and produces only water when it burns) (Jang et al.).
Another line of research is on organisms such as algae and cyanobacteria that could produce some of these same kinds of fuel photosynthetically. Biomass from feedstocks would be unnecessary; the inputs might only be carbon dioxide, water, and sunlight. In principle, then, this method of producing fuel could avoid or limit the environmental harms of drilling and transporting oil and of growing feedstocks to produce biomass and also serve as a carbon-fixing process, thereby helping to offset the environmental costs of burning fuel. However, some methods of producing fuels photosynthetically would require a significant investment in equipment (such as greenhouses), land, and water.
Some of these methods are expected to be commercially viable in the next few years; others are longer-term propositions (Presidential Commission, 2010).

Where Synthetic Biology Occurs

The research described above is undertaken primarily by laboratories in major research universities and private industry. As noted, research on the production of artemisinic acid is a collaborative effort involving a major research university, nonprofit funders, and private companies. Research on biofuels is conducted by the Joint BioEnergy Institute (a public-private research partnership that brings together Lawrence Berkeley, Sandia, and Lawrence Livermore national laboratories along with the University of California campuses of Berkeley and Davis and the Carnegie Institution for Science), the J. Craig Venter Institute (with $600 million in funding from ExxonMobil Corporation), Amyris Biotechnologies (with funding from Crystalsev, a large Brazilian ethanol distributor), and an assortment of start-ups and smaller biotechnology companies.
Some synthetic biologists believe, however, that the spirit of synthetic biology is in the research and development that occurs outside established academic and commercial facilities – in so-called “garage biology,” “outlaw biology,” “bio-hacking,” or “DIY bio.” These terms embrace more than synthetic biology, but synthetic biology is in some ways the most striking example of what can be accomplished in a garage setting, and if synthetic biology is defined as the application to biology of engineering principles, then the goals of synthetic biology are closely affiliated with DIY bio: both aim at the democratization of skills.
Research in DIY bio could veer off in unpredictable and entrepreneurial ways, following the inclinations of the practitioner. Although DIY biologists often aim to develop serious, marketable products–in recent years, projects at the International Genetically Engineered Machines competition, which is structured to imitate and advance amateur biology, have included bacteria that could break down plastic waste in landfills and a form of E. coli that could function as a drug delivery system (iGEM, 2010) – they can also experiment with toys, gadgets, and lifestyle products. Amateur biology will be greatly facilitated if extensive catalogs of well-characterized, standard “biobricks” become available, allowing people to order off-the-shelf parts.

Overview of the Ethical Issues

The ethical issues raised by synthetic biology will be familiar, in outline form, to those who have thought about the ethical implications of earlier waves of technology. As with any emerging technology, the ethical issues can be crudely divided into several general categories, having to do, respectively, with the tangible benefits and harms of the technology, with the implications for equality and justice (i.e., the distribution of benefits and harms), with the intrinsic value of limiting human intrusion into nature (aside from any questions about benefits and harms), and with deliberation about the science and its ethical issues. While these issues are already familiar in broad outline, however, they sometimes take particularly interesting and challenging forms with synthetic biology. The potential benefits and harms are uncommonly great, for example, and the issue of human intrusion into nature amounts, with synthetic biology, to concerns about the very idea of synthesizing living organisms.

Benefits and Harms

One tangible benefit of synthetic biology is nonetheless not immediately obvious, as the benefit may be indirect and deferred: synthetic biology provides further insight into the nature of cells and their genetic machinery, which may prove useful years later, and perhaps in ways that cannot be anticipated at the time the research is performed. The work at JCVI on the minimal genome, for example, which is aimed at determining which genes are essential to the cell, also provides insight into what different genes do. Other lines of research in synthetic biology provide insight into the mechanism of basic metabolic processes. Synthetic biology is a way of testing hypotheses: scientists can find out about organisms by designing and actually building systems that are capable of testing those hypotheses.
More obvious tangible benefits have to do with products and services that synthetic organisms could provide. The two examples above give a concrete sense of these benefits, but most in the field believe they are only a beginning and that the practical benefits will be very heterogeneous. Other possible applications include solvents and other industrial materials, high-yield or disease-resistant crops, new kinds of insecticides, food additives, sensors to detect food spoilage, more efficient vaccine production, and environmental remediation.
The primary concerns about synthetic biology are about the risks of deliberate misuse – bioterrorism, that is – and accidental threats to public health and the environment – dubbed “bioerrorism” by some commentators (Caruso, 2008). The risks of deliberate misuse center on the possibility that the technology used to synthesize and engineer useful microorganisms could be used instead to produce pathogens (Garfinkel et al., 2007). Some virus pathogens have already been synthesized. The 1918 Spanish flu virus has been briefly recreated in the laboratory, and in 2002, polio (an RNA virus) was created from a string of DNA that had been produced in a lab (Cello, Paul, & Wimmer, 2002; Tumpey et al., 2005). Eventually, as the synthesis of M. mycoides makes clear, it should also be possible to create bacterial pathogens in the laboratory. Further, it should be possible not merely to recreate pathogens but to augment them – not just to bring smallpox back from extinction, for example, but to make it even more virulent. In theory, at least, entirely new pathogens could also be created. Also, in addition to human targets, pathogens could be created to target a nation’s crops, livestock, or natural resources.
Merely creating a pathogen is not the only technical hurdle that would have to be overcome to misuse synthetic biology (Mukunda, Oye, & Mohr, 2009). It would also be necessary to grow the pathogen in quantity and then to “weaponize” it. To use a human pathogen against a target, for example, one would need to develop ways of disseminating it so that it is capable of infecting targets in large enough numbers to overcome public health systems. Proponents of the technology argue that terrorists have much better ways of attacking their enemies than with bioweapons, which are still comparatively hard to make and are very hard to control. Once released, they might be expected to hurt those who have released them, and their allies and countries, just as much as or even more than the intended targets. But of course terrorists are not always rational. For some pathogens, such as flu, the weaponization challenge could be overcome merely by sending infected people–suicide bombers of sorts--into crowded public places.
Public health concerns might be raised by some applications that do not initially appear to have any implications for human health. In principle, for example, modified E. coli might escape the environment for which they are intended, display unexpected properties in the new environment, or mutate to acquire them, or either acquire new properties or impart new properties to other microorganisms by means of lateral gene transfer between organisms, developing eventually into an organism that poses a health risk.
Another source of public health concerns is that microorganisms created for use in the human body could turn out to have unintended effects. For example, synthetic biology could be used to engineer the human “microbiome” – the ecosystem of microbes residing in and on the human body. These applications range from medical treatments – transgenic probiotics to treat Crohn’s disease and bacteria modified to serve as vaccines, for example – to early examples of human enhancement – bacteria that eliminate body odor, allow people to take up nutrients more efficiently, or maybe even promote good mental health (exploiting the recently discovered connection between mental health and intestinal function), for example (Sachs, 2007). These applications raise questions not only about risks to the particular recipient but also, because bacteria in the microbiome can be passed from one person to another, about public health.
Concerns about possible harms to the environment follow a similar pattern. In principle, just as public health concerns could be raised by applications not intended for use in humans, environmental hazards might be posed by applications that are not intended for release into the environment. Applications that involve algae engineered to produce fuel, for example, might be designed so that the algae were contained inside sealed equipment. Nonetheless, the risk that some would eventually escape into the environment is very high, and then the question is whether they would display unexpected properties or somehow acquire them and pose a threat to other organisms in the environment.
There are some reasons to think that the threat might not be severe. The modified organisms would be designed to spend their energy on something, such as producing excess quantities of hydrocarbons, that would likely put them at an evolutionary disadvantage if they escaped into the field. Moreover, some of their protective mechanisms could be removed, and the genetic complexity that makes for adaptability might be reduced. Deliberately designed fail-safe mechanisms could also be implemented to hamper their survival in the field. Indeed, keeping the organisms separated from the environment may be more important for protecting the organisms than for protecting the environment.
Applications that involve deliberate environmental exposure might pose significantly greater environmental hazards, since the organism would be designed to survive and perhaps reproduce in the field, and once released could never be fully removed from the field. Examples of these applications include organisms designed for contained but unprotected settings, such as fuel-producing algae grown in open ponds, and organisms intended for uncontained release into the environment. Examples of the latter include bioremediation, such as an engineered form of Pseudomonas putida (a soil bacterium) that degrades an organophosphate compound (commonly used as a pesticide) and E. coli engineered to degrade the herbicide atrazine (Presidential Commission, 2010).
All of these possible harms are hard to assess. For many of these applications, the likelihood of harm may be very low, but the severity of harm could be very great. Moreover, it may be difficult to gauge either likelihood or severity with great confidence. Because of the complexity of living organisms and because of the possibility of evolution, which for microbes can occur very rapidly and can be facilitated by lateral exchange of genes across species, synthetic biology inherently involves a high level of unpredictability. Also, once organisms invade new environments, they can be extremely difficult to eradicate, and invasive microorganisms would likely be ineradicable. Environmental contamination by living organisms would be very different in this respect from contamination by a chemical spill (Snow, 2011).
At the outset, then, extremely careful analyses are needed of the organisms proposed for commercial application. In testimony to the Presidential Commission for the Study of Bioethical Issues, ecologist Allison Snow offered the following recommendations for thinking about the risks posed by synthetic algae designed to produce fuel: “a good start for micro algae would be to publish professional monographs dealing with the biology and ecology of each species and its close relatives including information about how they reproduce, how they spread, whether they exchange genes with other strains, whether they have been bred to be suicidal, whether they could become more abundant or might die out, and whether they produce any kinds of toxins or other side effects” (Snow, 2011).
DIY biology raises special concerns about benefit and harm. If a DIY form of synthetic biology becomes feasible, then DIY synthetic biology could be practiced by people who are not affiliated with major laboratories and could prove to be hard to monitor and regulate. Also, the people who practice DIY bio often view themselves as a countercultural force, challenging boundaries and resisting control. Amateur biologists maintain that “outlaw” biology need not be “criminal” biology, but they display a certain edginess in their approach to biology and develop applications reflecting that attitude. The DIY mindset encourages trying unheard of things, which might have a multiplier effect on the inherent unpredictability of the living systems they are manipulating.
Different views about the acceptability of synthetic biology may well depend as much on different views about the weight to be given to remote risks as about different views of the likelihood of the risks. Some thought should therefore be given to the underlying philosophical and psychological questions about the perception and weighing of risk. Evaluating a technology involves both factual claims and value claims – claims both about potential outcomes and their likelihood and magnitude and claims about the significance of those scenarios. Bringing out these values is what “evaluating” outcomes means. Among these value considerations are questions about what counts as a risk, a cost, or a benefit, how heavily to weigh it, how much to discount a risk or potential benefit that is low probability or would occur only many years later, and how much more heavily to weigh a potentially catastrophic impact.
The tools used to evaluate outcomes, such as risk assessment and cost-benefit analysis, make assumptions about these issues. Unfortunately, though, the assumptions are often buried and unexamined. Also, risk assessments and economic evaluations frequently focus on outcomes that can be measured easily, which may not adequately reflect what people actually care about most. In short, evaluating outcomes requires value assumptions that often go unexamined. One result is that people may feel that important values have been ignored or suppressed. Public discourse and public policy could therefore benefit from a thorough interdisciplinary inquiry into the role of values in evaluating the potential outcomes of synthetic biology and other emerging technologies.

Equality and Justice

Another kind of concern about synthetic biology has to do with the social distribution of the benefits and harms. In a nutshell, the worry is that the benefits of synthetic biology will accrue to wealthy nations and especially to those who have secured patents on the relevant technological developments, while those in poorer, undeveloped nations are either excluded from the benefits or are actively exploited and harmed, in terms both of the economic effects of synthetic biology and of damage to the environment or public health.
The production of biofuel with synthetic organisms illustrates these concerns sharply. Methods that rely on the processing of substrates collected from biomass would require the cultivation of vast acreage of feedstock crops, possibly with harmful effects in places where these crops might be grown. The feedstocks might replace crops that produce food for humans, for example. “The most productive and accessible biomass,” writes a civil society organization called the ETC Group, “is in the global South–exactly where, by 2050, there may be another two billion mouths to feed on lands that (thanks to climate chaos) may yield 20–50 % less” (ETC Group, 2010, p. iii). Industrial-scale production of the feedstocks might also have ramifications for land ownership, water use, and soil quality, all of which are already often under pressure in undeveloped countries (ETC Group, 2007). Giving land over to production of feedstocks might also have bad environmental consequences.
Finally, there is a debate about the environmental benefits of producing fuel from raw materials harvested from plants, since growing the plants itself requires a lot of energy. Synthetic biology aims to make this way of producing fuel much more efficient, notably by turning to more common raw materials and more easily grown feedstocks, but the outcome of this work is still in doubt. Reliance on photosynthetic techniques would obviate the need for feedstocks, but they would still be resource-intensive; in particular, they would probably require a huge supply of water. If the production of fuel through photosynthesis were conducted in arid locations (which would be attractive because of their plentiful sunlight and because the land might not be considered valuable for other uses), then providing water might worsen water supply problems.
The US Presidential Commission has suggested that synthetic biology might turn out not to exacerbate social disparities. Indeed, it declared, “Much of the optimism surrounding synthetic biology stems directly from its potential to address some of the longstanding, significant problems associated with these disparities. Synthetic biology offers potential applications that may be particularly beneficial to less advantaged populations, including improved quality and access to vaccines against infectious diseases, medications, and fuel sources” (Presidential Commission, 2010, p. 165). Progress on solving long-term environmental harms such as climate change – on the assumption that synthetic biology can be part of a solution – would clearly benefit less advantaged populations, since it is likely that those populations will be disproportionately harmed by those problems.
The concern about justice is also difficult to assess. Partly this is because of uncertainties about the possible outcomes, which include not only the benefits and harms mentioned above but also the long-range and international social and economic consequences of synthetic biology (should the field be as successful as its proponents believe it will be). Additionally, there are questions of values to complicate the assessment. Unsurprisingly, there are starkly different visions of justice at play in synthetic biology. For example, the goal of promoting welfare equally must be traded off to some degree against the value of protecting individual liberty. Some would hold that justice grants the liberty to experiment with emerging technologies in whatever direction one likes, at least to the extent permitted by public safety. Some would also hold that in any adequate understanding of justice, those who have worked to advance the field should benefit disproportionately. Finally, some would also hold that if the financial rewards are curtailed, none of the benefits will be realized.
A second general value question that complicates the assessment of justice is the question of responsibility for ensuring just outcomes. Possible answers range from governments, acting on behalf of citizens, through various categories of private agents. The US Presidential Commission has suggested a broader rendering: “Manufacturers and others seeking to use synthetic biology for commercial activities should ensure that risks and potential benefits to communities and the environment are assessed and managed so that the most serious risks, including long-term impacts, are not unfairly or unnecessarily borne by certain individuals, subgroups, or populations. These efforts should also aim to ensure that the important advances that may result from this research reach those individuals and populations who could most benefit from them” (Presidential Commission, 2010, p. 164).
The very idea that the development of a new technology should be influenced in order to maximize just outcomes is arguably somewhat novel. Technology development has historically not been constrained with this expectation. Thus, another question arises: Is the goal of achieving just outcomes feasible? Or is it better simply to let innovation proceed and to try to address social injustices through other measures? And what sorts of policy mechanisms might appropriately be employed to advance this goal? Two much-discussed kinds of options include funding decisions, which can influence the directions in which the field advances and therefore the kinds of commercial enterprises it makes possible, and intellectual property policy, which determines control over and access to new developments in the field, and may therefore influence the direction in which the field advances both by affecting the incentive structure for conducting research in the field and by affecting access to the fruits of others’ research.

Attitudes Toward “Synthesizing” Living Organisms

A third broad category of concern about synthetic biology is whether the idea of synthesizing organisms raises any intrinsic moral issues. This concern is a recurrent topic for synthetic biology and is probably the most controversial and philosophically difficult of the ethical issues of synthetic biology. Such concerns might tilt in different directions. On the one hand, some will find the idea of synthesizing and engineering organisms, at least in the way done in synthetic biology, intrinsically attractive. They might try to articulate this position by arguing that knowledge and creativity are intrinsically good; synthetic biology, somewhat like astronomy and basic physics, embodies the human drive to understand the world and put one’s intelligence to work in it – activities that are good in themselves, apart from the physical benefits they may make possible. Many also feel, however, that the alteration of nature should have limits of some sort; opposition to genetically modified organisms is connected to this feeling, and more than a little of the concern about the environment is rooted in it; the question for them is whether the engineering of living organisms, at least as done in synthetic biology, is morally troubling.
There are several subtly varying ways of articulating this concern in the context of synthetic biology. Perhaps, the most prominent form of the intrinsic concerns about synthetic biology is that the technology reflects and promotes a troubling attitude toward life. In particular, one might object that synthetic biology undermines the specialness of life by showing that life is a purely material phenomenon – a complex combination of ingredients. In the first scholarly article on the ethical issues of synthetic biology, Mildred Cho and coauthors weighed the possibility that, by defining life in terms of DNA, synthetic biology reduces life to a single biological feature and therefore “may threaten the view that life is special” (Cho, Magnus, Caplan, McGee, & The Ethics of Genomics Group, 1999). More recently, Joachim Boldt and Oliver Müller have argued that synthetic biology represents organisms as machine-like artifacts and thereby challenges “the connection between ‘life’ and ‘value’” (Boldt & Müller, 2008). When scientists synthesized the genome of M. mycoides, the achievement was heralded by Arthur Caplan as debunking the idea that living things are “endowed with some sort of special power, force or property” (Caplan, 2010).
Conversely, some have worried that synthetic biology represents a troubling attitude about human agency. Boldt and Müller suggest, for example, that with the advent of synthetic biology, humans no longer merely manipulate nature; they become creators or reinventors of nature. The creation of nature might, they continue, lead to overconfidence: it “might lead to an overestimation of how well we understand nature’s processes and our own needs and interests and of how best to achieve them” (Boldt & Müller, 2008, p. 388). This kind of worry harks back to a reaction sometimes evoked by earlier forms of genetic engineering, that human beings were “playing God.”
Some ways of formulating these concerns – about the denigration of life or the exaltation of human agency – rely on metaphysical claims that are particular to specific traditions and open to various objections. If so, then one problem with them is that they may depend on acceptance of the underlying religious or metaphysical account within which they make sense, and the more robust this account, the less likely it is to be widely shared, and the less traction it will have in public debate.
Alternatively, these concerns can be formulated as merely moral points – as resting on claims about attitudes toward life and human agency and the role that those attitudes play in moral thinking. Still, they face some significant objections. One is that they treat “life” as a very general moral category, bringing together under one heading a variety of different kinds of living things – complex animals (such as mammals), microorganisms, plants, and fungi. But arguably, people tend not to aggregate all living things together when they think about their moral status. Instead, moral distinctions between different kinds are common. Sacredness might be attributed to some but not to all living things. It is worth noting that religious organizations themselves have by and large not voiced objections to synthetic biology per se. The Catholic Church was moderately enthusiastic about the announcement that JVCI had synthesized the genome of M. mycoides and successfully transplanted it into another cell: the achievement was, said the church, “a further mark of man’s great intelligence, which is God’s gift enabling man to better know the created world and therefore to better order it” (BBC Monitoring Europe, 2010).
Moreover, whether synthetic biology is actually tantamount to the creation or synthesis of life, rather than being merely another form of manipulation, is debatable. Most of the actual applications, as described above, amount to something less than the synthesis of living organisms. JCVI described the M. mycoides cell it created through genome synthesis as a “synthetic cell,” and it also claimed that, because it was slightly altered from wild-type variants, it represented a new species, which they dubbed M. mycoides JCVI-syn1.0, but most commentators regard the JCVI achievement as considerably less than a synthetic cell. They argue that JCVI’s accomplishment was synthesis of a genome, but that because the genome was inserted into a naturally occurring cell body and because the genome itself also occurs in nature (minus the slight alterations), thinking of the product as a “synthetic cell” is overblown.
Research on protocells and chells, which in some cases aims to devise novel mechanisms and use novel materials for basic cellular functions, would come closer to creating life. Successful creation of a protocell that employs novel and entirely synthesized ingredients would prove that a living thing does not acquire a “special power, force, or property” only from a previous generation of living things. It would still not prove, however, that living things have no special, nonphysical property. If one believes that living things have such a property, nothing stops one from believing that the property was acquired in the course of the laboratory synthesis; the property might be said, for example, to have been imbued in it directly by God, who sanctioned the synthesis because He saw it as following naturally from the capacity He has given humans “to better know the created world and therefore to better order it.”
Another way of articulating intrinsic concerns about synthetic biology would be to argue that the alteration of nature is in general morally troubling. One might hold, for example, that there are competing moral ideals for the relationship between humans and nature: an ideal characterized by a discourse of “altering nature to meet human demands” and an ideal of “adjusting human demands to accommodate nature” (Jennings, 2010, p. 78). The former holds that nature is no more than stuff to be put to human use, while the latter calls on a person to cherish the natural world and limit the harm that humans wreak on it.
Which of these discourses synthetic biology best fits is contestable, however. On the one hand, to the extent that synthetic biology is the “creation of life” or “extreme” genetic engineering, it might be said to fit the discourse of altering nature to meet human demands. To the extent that it is used to resolve environmental problems and perhaps to replace environmentally damaging industrial systems, however, it might be said to fit the discourse of adjusting human demands to accommodate nature. Moreover, given the moral distinctions often drawn between different kinds of living things humans, other mammals, other vertebrates, invertebrates, plants, fungi, and microorganisms the fact that synthetic biology is, to date, primarily about the alteration of microorganisms might be reassuring. On the other hand, if synthetic biology turns out to be harmful for the environment, then concerns about the alteration of nature would be strengthened; synthetic biology might then be morally troubling even if it appears to be beneficial for human well-being.
Yet, another kind of intrinsic concern that could be associated with synthetic biology is focused on the prospect of human enhancement that is, on the possibility that some synthetic biology applications might be used to raise human cognition, mood, physical performance, or life span significantly above current species-typical norms. Applications involving human cells could someday raise this kind of concern. As noted above, applications involving the human microbiome could also have an enhancing effect. The objections to these uses would be objections to human enhancement, however, rather than to the genetic manipulation of microorganisms.

Public Deliberation

In addition to substantive questions about benefits and harms, justice, and the intrinsic values connected to synthetic biology are procedural questions about who and how the substantive questions should be addressed. One interesting feature of synthetic biology is that those engaged in the work have also sought to advance – and perhaps influence – the discussion of the ethical, legal, and social issues that their work raises. One of the first and most salient articles about synthetic biology was written by a group of bioethics scholars brought together in the late 1990s at the request of JCVI to consider the ethics of creating a minimal genome organism. Many other organizations and commentators internationally have also weighed in on the ethical, legal, and social issues of synthetic biology.
Still, there is a widespread sense among these commentators that the discussion about synthetic biology should if anything be still broader. Recently, the US Presidential Commission has argued that policy on synthetic biology (and other emerging biotechnologies) should be guided by “a principle of democratic deliberation” – that is, by “an ongoing, public exchange of ideas, particularly regarding the many topics – in science and elsewhere – in which competing views are advocated” (Presidential Commission, 2010, p. 151). Such an approach is held to foster better decisions – “outcomes that are inclusive, thoughtfully considered, and respectful of competing views,” as the Presidential Commission put it. It is also held to be intrinsically attractive – itself a mark of a just society.
Questions remain, however, about how democratic deliberation is best carried out. These include questions about how to ensure that the scientific and economic information that is fed into the deliberative process is accurate and how to ensure that the public’s values are adequately represented and respected. The deliberative process could be hijacked either by corporate interests or by “civil society” organizations whose mission is to advocate for public interests; neither may adequately represent the range of public interests, and both might misrepresent the factual claims at stake and unduly influence the deliberative process.
Part of the problem in adequately representing the public’s values is that the relevant “public” for most deliberative processes is restricted to the nation that conducted the deliberation, but the relevant “public” for thinking about the ethics of synthetic biology is international. Since synthetic organisms that have been released or escaped into the environment cannot be expected to observe national boundaries, the risks are international. The implications for justice are also clearly international since questions about the distribution of potential benefits and harms are rooted in the first place in concerns that the benefits will accrue to wealthy nations while developing nations are either excluded from those benefits or are actively harmed. And questions about the very idea of synthesizing organisms are also international in flavor, in the same way that questions about human enhancement are international: if one nation permits this step, then in some sense, the human relationship to nature is changed for everybody around the globe. Moreover, if one nation permits it, other nations may find it increasingly difficult to ban it, given economic competition among nations.

Conclusion

Synthetic biology is still in its infancy, leading some in the field to wonder whether ethical questions about it are being raised prematurely. Perhaps society should await further technical development, this line of reasoning holds, so that the ethical debate can be grounded on more and better information about the field’s risks and potential benefits.
Some of the ethical issues outlined above do not depend on better knowledge of the field, however. The intrinsic values connected to the science are a threshold question – an issue that, in principle, should be raised and resolved before the field progresses. To go ahead with the research is to assume that the intrinsic values generate no insuperable objections.
Questions about the benefits and harms of synthetic biology could certainly be handled more confidently if more information were in hand about actual applications. Yet, it is precisely because of the lack of confidence about outcomes that the effort to think about risks and potential benefits should start early. Perhaps the likelihood of harm is indeed as low as some proponents argue, but the severity of harm could be great, and given the complexity and adaptability of living systems, gauging either likelihood or severity with great confidence is very difficult. It is therefore important to make sure that the processes for identifying and evaluating risks and potential benefits in synthetic biology are reliable and then that the mechanisms for oversight are trustworthy.
Questions of equality and justice also require early attention. The goal should be, not just to correct distributive mistakes after they have occurred, but to correct existing distributive mistakes and avoid exacerbating them with new mistakes, and this requires trying to anticipate outcomes and, if possible, encourage lines of work that will produce good outcomes.
Synthetic biology is heralded by some of its proponents as the beginning of a new industrial revolution. If that turns out to be correct, then it will inevitably generate harms, benefits, new economic and social patterns, and perhaps new ways of understanding how humans are related to the natural world. It is therefore imperative to think about it now.
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