An alternative to creating novel organisms through the traditional ''top-down'' approach to synthetic biology involves creating them from the ''bottom up'' by assembling them from non-living components; the products of this approach are called ''protocells.'' In this paper we describe how bottom-up and top-down synthetic biology differ, review the current state of protocell research and development, and examine the unique ethical, social, and regulatory issues raised by bottom-up synthetic biology. Protocells have not yet been developed, but many expect this to happen within the next five to ten years. Accordingly, we identify six key checkpoints in protocell development at which particular attention should be given to specific ethical, social and regulatory issues concerning bottom-up synthetic biology, and make ten recommendations for responsible protocell science that are tied to the achievement of these checkpoints. Unfortunately, the 'top-down' vs. 'bottom-up' terminology has been used in many different ways in the synthetic biology literature. In this paper we follow the terminological conventions of Rasmussen et al. (2009a), but a variety of alternative conventions exist. A superficial survey of the synthetic biology literature turned up at least five different distinctions that have been marked with the 'top-down' vs. 'bottom-up' terminology: (1) the distinction between building a minimal living cell by using extant nucleic acids and enzymes vs. synthesizing all components from very simple molecules under

Human microbiome research makes causal connections between entire microbial communities and a wide array of traits that range from physiological diseases to psychological states. To evaluate these causal claims, we first examine a well-known single-microbe causal explanation: of Helicobacter pylori causing ulcers. This apparently straightforward causal explanation is not so simple, however. It does not achieve a key explanatory standard in microbiology, of Koch's postulates, which rely on manipulations of single-microorganism cultures to infer causal relationships to disease. When Koch's postulates are framed by an interventionist causal framework, it is clearer what the H. pylori explanation achieves and where its explanatory strengths lie. After assessing this 'simple', single-microbe case, we apply the interventionist framework to two key areas of microbiome research, in which obesity and mental health states are purportedly explained by microbiomes. Despite the experimental data available, interventionist criteria for explanation show that many of the causal claims generated by microbiome research are weak or misleading. We focus on the stability, specificity and proportionality of proposed microbiome causal explanations, and evaluate how effectively these dimensions of causal explanation are achieved in some promising avenues of research. We suggest some conceptual and explanatory strategies to improve how causal claims about microbiomes are made.

Experiments are commonly thought to have epistemic privilege over simulations. Two ideas underpin this belief: First, experiments generate greater inferential power than simulations, and second, simulations cannot surprise us the way experiments can. In this paper I argue that neither of these claims is true of experiments versus simulations in general. We should give up the common practice of resting in-principle judgments about the epistemic value of cases of scientific inquiry on whether we classify those cases as experiments or simulations, per se. To the extent that either methodology puts researchers in a privileged epistemic position, this is contextsensitive.

No abstract