Response to review by Trevor Charles re: Precautionary Principle

Thank you for the review of our paper. We will provide a point by point response below to your comments. Since you have focused on biological questions, it is important for us to emphasize that we did not perform a “statistical analysis” (which is inherently evidentiary and data based and anchored in biological experiments). Instead, we are engaged in a rigorous analysis of risk as it is derived from mathematical probability theory. Many of the citations you are asking for fall within the “carpenter fallacy” that we present in the text, i.e. that discussions about carpentry are not relevant to and distract from identifying the risks associated with gambling, even though the construction of a roulette wheel involves carpentry. Mathematical, probabilityrelated arguments do not require biological citations. At the same time we have striven to explain how the biological context maps onto the risk analysis so that the connection between the two is more apparent to those who are focused on biology. For this reason we are providing the responses below. As a general comment, it would be very helpful for biologists who are contemplating or engaging in engineering strategies to read about the failures of systems engineering discussed in the text (Section VIII). This should lead to a better understanding about why the issue is not biological per se, but about the nature of engineering complex systems in cases that carry high potential harm, as has been found in the modernization of the Air Traffic Control system, for example. Reading that discussion should establish a better context for a conversation about the risks in biological engineering.