Mammalian synthetic biology holds the promise of providing novel therapeutic strategies, and the first success stories are beginning to be reported. Here we focus on the latest generation of mammalian transgene control devices, highlight state‐of‐the‐art synthetic gene network design, and cover prototype therapeutic circuits. These will have an impact on future gene‐ and cell‐based therapies and help bring drug discovery into a new era. The inventory of biological parts that are essential for life on this planet is becoming increasingly complete. (...) The postgenomic era has provided encyclopedic information on gene‐function correlations and systems biology is now delivering comprehensive details on the dynamics of biochemical reaction networks in living organisms. The time has come to reassemble these catalogued items and design new biological devices and systems with novel and useful functionality in a rational and systematic manner. This is the premise of synthetic biology, a constructive systems biology discipline likely to become the life science revolution of the 21st century. (shrink)

Scientists and policy‐makers have long understood that the products of research can often be used for good or evil. Nuclear fission research can be used to generate electricity or create a powerful bomb. Studies on the genetics of human populations can be used to understand relationships between different groups or to perpetuate racist ideologies. While the notion that scientific research often has beneficial and harmful uses has been discussed before, the threat of bioterrorism—a concern that has only grown since 2001—has (...) led to increased awareness about the need to prevent the misuse of biomedical research, particularly when it involves dangerous pathogens or toxins. In 2012, the concern was ratcheted up another notch by two papers reporting the results of research on genetically engineered strains of the H5N1 avian influenza virus. Although the H5N1 papers have potential scientific and social value, some scientists and policy‐makers opposed their publication because they feared that terrorists (or others with nefarious motives) could use the research to create a bioweapon that could trigger a global pandemic. The H5N1 papers raise difficult questions concerning the ethics of knowledge. Should scientific research with dangerous applications be published? Should some types of research be kept secret or not be conducted at all? What type of government oversight of dangerous research is appropriate? In this essay, I will develop a framework for thinking about the ethics of knowledge and apply it to the H5N1 controversy, focusing on issues related to publication. I will argue that redacted publication would have been a reasonable response to the dilemmas posed by the H5N1 papers if not for practical and legal problems with this option. Given these problems, full publication seems appropriate. (shrink)

Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into (...) two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. (shrink)

Synthetic biologists aim to generate biological organisms according to rational design principles. Their work may have many beneficial applications, but it also raises potentially serious ethical concerns. In this article, we consider what attention the discipline demands from bioethicists. We argue that the most important issue for ethicists to examine is the risk that knowledge from synthetic biology will be misused, for example, in biological terrorism or warfare. To adequately address this concern, bioethics will need to broaden its scope, contemplating (...) not just the means by which scientific knowledge is produced, but also what kinds of knowledge should be sought and disseminated. (shrink)

The precautionary principle (“the Principle”) has been widely embraced as the new paradigm for contending with biological and environmental risk in the context of emerging technologies. Increasingly, it is being incorporated into domestic, supranational, and international legal regimes as part of a general overhaul of health and environmental regulation.1 Codifications of the Principle typically are vague, with their content intentionally left for scholars to debate, decision makers to interpret, and the courts to flesh out through case law. Generally speaking, the (...) Principle holds that scientific uncertainty will not be a bar to preventive regulatory action, and that decision makers should err on the side of .. (shrink)

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

This article examines criticisms of cost-benefit analysis and the contingent valuation method from methodological and moral philosophical perspectives. Both perspectives argue that what should be elicited for public decisions are attitudes or values, not preferences, and that respondents should be treated as citizens and not consumers. The moral philosophical criticism argues in favour of deliberative approaches over cost-benefit analysis. The methodological perspective is here criticized for overemphasizing the importance of protest responses and anomalies and biases in contingent valuation, and for (...) failing to provide the necessary information needed to make public decisions over the allocation of scarce goods. The moral philosophical perspective is criticized for: failing to provide criteria for distinguishing between values and preferences, assuming impartiality requires expression of values and not preferences; failing to recognize the diversity of forms of expression of values, including expression of values through monetary evaluation; and assuming that cost-benefit analysis is necessarily an implementation of a utilitarian political philosophy. The article concludes by showing that deliberative decision-making mechanisms can be overly demanding on citizens, and argues for greater openness in the potential moral justifications of cost-benefit analysis. Key Words: cost-benefit analysis • values • preference aggregation • democracy • willingness to pay. (shrink)

The precautionary principle is a useful strategy for decision-making when physicians and patients lack evidence relating to the potential outcomes associated with various choices. According to a version of the principle defended here, one should take reasonable measures to avoid threats that are serious and plausible. The reasonableness of a response to a threat depends on several factors, including benefit vs. harm, realism, proportionality, and consistency. Since a concept of reasonableness plays an essential role in applying the precautionary principle, this (...) principle gives physicians and patients a decision-making strategy that encourages the careful weighing and balancing of different values that one finds in humanistic approaches to clinical reasoning. Properly understood, the principle presents a worthwhile alternative to approaches to clinical reasoning that apply expected utility theory to decision problems. (shrink)

Maintaining the coherence of the distinction between nature and artefact has long been central to environmental thinking. By building genomes from scratch out of 'bio-bricks', synthetic biology promises to create biotic artefacts markedly different from anything created thus far in biotechnology. These new biotic artefacts depart from a core principle of Darwinian natural selection – descent through modification – leaving them with no causal connection to historical evolutionary processes. This departure from the core principle of Darwinism presents a challenge to (...) the normative foundation of a number of leading positions in environmental ethics. As a result, environmental ethicists with a commitment to the normative significance of the historical evolutionary process may see synthetic biology as a moral 'line in the sand'. (shrink)

Ideas about the presence, absence, and growth of democracy in global politics take different forms. After surveying the basic justifications for global democracy, three frames for making sense of the significance of particular developments and proposals are canvassed. “Soup” involves the proliferation of democratic practices, though the consequences of this proliferation for the overall shape of international politics remain open. “Society” stresses the democratization of processes that affect constitutive norms and discourses. “System” identifies differentiated yet ordered parts, geared to the (...) production of collective outcomes. The soup framing is undemanding yet limited. System provides a way to pinpoint democratic deficiencies and possibilities, but its requirements can be highly demanding, and it leaves open the question of normative integration. Understanding global democratization requires both society and system framings. (shrink)

Societal evaluation of new technologies, specifically nanotechnology and genetically engineered organisms, challenges current practices of governance and science. When a governing body is confronted by a technology whose use has potential environmental risks, some form of risk analysis is typically conducted to help decision makers consider the range of possible benefits and harms posed by the technology. Environmental risk assessment is a critical component in the governance of nanotechnology and genetically engineered organisms because the uncertainties and complexities surrounding these technologies (...) pose such risk potential. However, GEOs are unique technologies, and there is widespread, international recognition that many traditional forms of ERA are not well-suited for evaluating them. Nanotechnology products are also likely to need different models of risk assessment, as there is very little information on their fate, transport, and impacts in the environment. (shrink)

The Commission's recentinterpretation of the Precautionary Principleis used as starting point for an analysis ofthe moral foundation of this principle. ThePrecautionary Principle is shown to have theethical status of an amendment to a liberalprinciple to the effect that a state only mayrestrict a person's actions in order to preventunacceptable harm to others. The amendmentallows for restrictions being justified even incases where there is no conclusive scientificevidence for the risk of harmful effects.However, the liberal tradition has seriousproblems in determining when a (...) risk of harm isunacceptable. Nevertheless, reasonable liberalarguments in favor of precaution can be basedon considerations of irreversible harm andgeneral fear of harm. But it is unclear whenthere considerations can be overridden.Within the liberal framework, the Commissionadvocates a so-called proportional version ofthe Precautionary Principle. This should beclearly distinguished from a welfare-basedapproach to precaution based on risk-aversiveweighing up of expected costs and benefits.However, in the last resort, the Commissiondoes seem to make a covert appeal to suchconsiderations. (shrink)

Critics of a politics of difference have misidentified these social movements as asserting an identity politics of recognition. Most of these movements are better understood as resisting unjust structural inequalities. Inclusive democratic process involves paying specific attention to group differences in order to transform preferences and maximize social knowledge.

As a member of the National Science Advisory Board for Biosecurity, I was involved in early deliberations about the appropriateness of publishing this avian influenza research when manuscripts were referred to us from two scientific journals during their review process, via the U.S. government. As described by David Resnik in this issue, we grappled with benefits and risks, and in our initial, unanimous decision recommended limited publication, alerting the world to the possibility of evolved transmissibility in these viruses but with (...) redaction of the exact genetic mutations that would enable anyone skilled in the art to synthesize these potentially dangerous viruses. However, after additional discussion, both internal and external to the board, we were asked to reconsider the situation, and this time a majority voted in favor of full publication. I was one of the minority that opposed full publication. Resnik points to the difficulties of performing a formal risk‐benefit assessment without the means of quantifying these two terms and suggests application of reasoning based on the precautionary principle instead. This makes sense. But there are three other issues that should be highlighted. (shrink)

The social fact of disease means the ethical dimensions of H5N1 research are not only fraught but empirical. Any account of the reality of research that leaves out its ethical dimensions leaves out reality. For this reason alone—and quite apart from his carefully reasoned analysis—David Resnik deserves our thanks: his attention in this issue to the ethics of knowledge focuses our attention on the fact that the possible harms and benefits of H5N1 turn as much on the “politics of truth”—how (...) work is conducted and talked about—as the biology itself. Sufficient discussion of this ethical dimension, as Resnik points out, requires attending to all stages of research, its premises and its ramifications. Resnik focuses on questions of publication and risk, offering philosophical, legal, and political insight. For my part, I would like to bolster (if complicate) Resnik's assessment by offering a few anthropological notes. (shrink)

Cost-benefit analysis--applying economic reasoning to increasingly complex health policy decisions--continues to be a source of vehement disagreement among its practitioners. re than merely technical issues in measurement and accounting are involved; basic social values embedded in different intellectual traditions are coming into conflict. The "human capital" and "willingness-to-pay" approaches can each aid policy formulation, but neither can substitute for open political process.