Synthetic Bioethics

President Obama’s new panel on bioethics met for the first time earlier this month to consider the implications of the emerging field of synthetic biology. Both the tone and content of its public discussions gave some indication of the way this panel will carry out its mandate to offer policy advice on emerging biotechnologies.

The Presidential Commission for the Study of Bioethical Issues (PCSBI) held its inaugural meeting on July 8 and 9, 2010 at the Ritz-Carlton Hotel in Washington, D.C. Secretary of Health and Human Services Kathleen Sebelius kicked off the meeting by swearing in the thirteen members of the commission, including chairman Amy Gutmann (political scientist and president of the University of Pennsylvania) and vice-chairman James Wagner (an engineer and the president of Emory University).

In her introductory remarks, Gutmann repeatedly emphasized that the commission would be a “deliberative” body, suggesting that it would carefully probe and debate the issues before it. But the PCSBI’s first meeting resembled a congressional hearing: the commission members asked the witnesses technical questions and solicited their opinions, but engaged in no substantive colloquies with the witnesses or with one another. The meeting was informative, perhaps, but could hardly be called deliberative. This is remarkable for two reasons. First, it suggests that the commission seems disinclined to use its meetings to deliberate in the public eye. If this inaugural meeting is any indication of what’s to come, the commission is forgoing the opportunity to use its real-time deliberations, rather than just expert testimony, to help the public understand the ethical stakes and complexities that biotechnology raises. Second, even after this first meeting, we still have very little sense of what most of the commission members believe. That fact, and the fact that the PCSBI still has only the barest skeleton staff, suggest something astonishing: it is impossible even to guess at the shape or direction that the commission’s first report, on the subject of synthetic biology, will take, even though that report is due to the president in just four months.

The PCSBI’s first subject of inquiry, synthetic biology, is best understood in contrast to the genetic engineering techniques much discussed in the 1970s, 80s, and 90s. Those techniques had relied on the cutting and pasting of naturally occurring genes. But in synthetic biology, which has only arisen in the last decade, scientists work with strands of synthetic DNA called oligonucleotides, ranging in length from short fragments to long sequences. This allows scientists to design novel biological systems by arranging standardized, customizable genetic parts like building blocks. (The science behind synthetic biology, and its potential ethical and policy implications, were thoroughly explained in layman’s terms in this 2006 New Atlantis article.)

The reason President Obama asked his bioethics commission to examine this burgeoning field is that the J. Craig Venter Institute recently reported creating a bacterial cell with a genome entirely constructed through the techniques of synthetic biology. The synthesized genome was based on the sequence of an existing bacterial species, Mycoplasma mycoides, which had been slightly modified by the deletion of fourteen genes and the incorporation of a handful of “watermark” sequences, which distinguish Venter’s synthetic genome from anything that occurs in nature. Copies of the synthetic genome were inserted into bacterial cells that had had their original genomes removed, but were otherwise intact; they then proceeded to replicate using their new synthetic genes.

The Venter Institute’s paper announcing its work is called “Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome” — but the extent to which the institute’s bacteria constitute the “creation” of life, and more generally the degree to which synthetic biology can be considered distinct from other methods of genetic engineering, was one of the points debated at the PCSBI meeting. One witness testifying before the commission, Bonnie Bassler, president of the American Society for Microbiology, downplayed the breakthrough on the grounds that “creation” is a misnomer. Bassler reminded the commission that Craig Venter and his team not only copied their synthetic genome from a natural species, they also relied on the complex cellular structures of the bacteria receiving that genome. Without the highly complex and precisely structured cellular membrane, or the set of enzymes and ribosomes for replicating and reading DNA, a synthetic genome would not be able to express itself or “create” a new form of life. In this sense, synthetic biology is continuous with older genetic engineering techniques, since both rely on the natural biology of the microorganisms they manipulate. Synthetic biology still relies on natural cellular structures, as well as naturally occurring genes, although it affords a greater ability to customize, standardize, or optimize these genes’ functions for useful purposes.

Of course, while it is more than a semantic debate, the question of whether Venter’s achievement amounts to creating life has no bearing on the practical applications of synthetic biology. Other witnesses at the PCSBI meeting, including bioengineering advocate Robert Carlson and M.I.T.’s Drew Endy and Kristala Prather, discussed how the metabolic pathways of bacteria could be reengineered via synthetic biology. This could allow scientists to employ bacterial cells as microscopic factories, perhaps producing pharmaceuticals, biofuels, and other useful organic compounds. Venter, who was himself also a witness at the meeting, noted that synthetic biology will make it possible to design vaccines with greater precision and speed than traditional methods allow.

The prospect of “Do-It-Yourself” synthetic biology (DIYbio) was a source of both excitement and concern for the witnesses who addressed the bioethics commission. The ability to download a gene sequence from the Internet, modify it on a computer, and then custom-order the modified gene from a DNA synthesis company may allow “garage biologists” to develop novel biological systems with relative ease. Endy and Carlson are both boosters of this democratization of bioengineering — the former as president of the BioBricks Foundation and the latter as a judge in the International Genetically Engineered Machine competition. Both men were optimistic about the prospect of so-called “open-source wetware,” expressing their hopes that the wide distribution of synthetic biology will lead to a vibrant, innovative industry. Carlson, in particular, worried that regulation or licensing might hamper the development of DIYbio. Others, including panelist George Church (a Harvard molecular geneticist), suggested that a licensing or surveillance framework should be established to monitor the kinds of sequences being ordered from DNA synthesis companies.[*] Such a surveillance framework could, in theory, allow those companies or the government to keep track of people who might wish to engineer dangerous pathogens.

The bioethics commission’s session on “Benefits and Risks” was dominated by concerns over safety. Allison Snow, a professor of ecology at Ohio State, discussed the possibility of dangerous organisms escaping from research labs and the potential unintended consequences of employing engineered microbes in the environment. Like other forms of genetic engineering, synthetic biology depends upon the use of self-replicating, evolving organisms — which inherently makes it difficult to predict or control the risks they might pose if released, accidently or deliberately, into the wild. One of the strategies proposed for mitigating these risks is the design of built-in safety features for synthetic microbes. For instance, as George Church suggested to the commission, the microbes might be designed to be dependent upon certain chemicals that are not available in nature, or they might contain “suicide genes” that cause them to die under certain conditions. As Snow pointed out, the unpredictability of living things, particularly of rapidly evolving microorganisms, will keep these safety features from ever being as reliable as those engineered into machines such as cars or airplanes.

Following the discussion of the benefits and risks, the PCSBI dedicated two sessions to discussing broader ethical issues. The first of these sessions included a strident and radical presentation by Allen Buchanan, professor of philosophy at Duke University and research associate at Oxford’s Uehiro Center for Practical Ethics. Buchanan pointedly criticized the former President’s Council on Bioethics and recommended that President Obama’s bioethics commission not make the same “error” of taking a “pre-Darwinian” or “teleological” view of nature. The notion that one might reflect upon human nature to discern the human good is, Buchanan argued, a “fallacious” view that might hold us back from seeing the “severe engineering constraints” imposed by “unassisted evolutionary processes.” Following from his view that nature is simply chaotic and inimical to the human good, Buchanan recommended that the commission consider the “costs” of not changing the natural “status quo.” In response to a question from PCSBI member John Arras as to the degree to which religious views ought to have a place in the commission’s deliberations, Buchanan unequivocally replied that the commission, in formulating its report on synthetic biology, “should not water it down in deference to views that you think are false.” (For an eloquent explanation and defense of how the former bioethics council conducted its work, including the centrality of fundamental questions about human nature and the human good, see Gilbert Meilaender’s New Atlantis essay “On Bioethics in Public.”)

At the outset of the meeting, chairman Amy Gutmann noted that the commission would “begin with the benefits” in its consideration of the implications of synthetic biology. In his own introductory remarks, vice-chairman James Wagner expressed his hope that the commission would not only ask for “cautionary recommendations, but also [ask] how best to stimulate responsibly this exciting field of research and development, so that we discover, create, and apply knowledge here in the service of humanity.” It is worth drawing out the implications of these prefatory remarks, since they hint at the perspective the PCSBI might bring to bear on bioethical issues.

What does it mean for a bioethics commission to “begin with the benefits” in its deliberations? If synthetic biology has useful applications, as it certainly seems to, then it is reasonable to suppose that entrepreneurs and scientists, with eager investment from private industry, will investigate and pursue those benefits. There is certainly a role for the public funding of basic research — and perhaps even for applications of particular importance to the national interest, such as the development of biofuels — but what does it mean for a bioethics commission to “begin” with these potential benefits?

Professor Buchanan claimed in his presentation that the former bioethics council had “stacked the deck” against certain new technologies by failing to give sufficient attention to their benefits. He gave no examples from the work of the former council, and would be hard-pressed to do so, since that body’s publications show a scrupulous attention to the potential benefits of biotechnology. Buchanan further argued that the public is generally more disposed to see harms than benefits in new technologies. This, too, is a rather dubious position to take in light of the history of technological progress in the West and our culture’s intense passion for the new.

For those who join Professor Buchanan in seeing the “status quo” of nature as simply a constraint on human freedom, biotechnology is not just a source of beneficial products but also a form of liberation from the shackles clamped on us by nature. On such an understanding, anything that slows the complete biotechnological mastery of nature will be seen as harmful.

However, the task of bioethics is to consider both the practical policy questions and the deeper human meaning of biotechnology and novel medical techniques. The former bioethics council understood that these tasks are integrally connected; even in weighing the potential benefits and harms of new biotechnologies, we must address the question of how the human good, which we seek to serve, is related to our given nature. President Obama’s bioethics commission has been ordered to offer practical policy options instead of investigating deeper questions. But, as Erik Parens has pointed out, the two tasks are inseparable. If this commission ignores fundamental philosophical and anthropological matters, it cannot judge the extent to which new technologies will be “beneficial” beyond basic considerations of health and profit. Such an approach might serve the political needs of the present administration, but it would offer no insight into how biotechnology can truly serve the human good.