By M. Shane Hutson, PhD, SOT 2013 Translational/Bridging Travel Award Recipient
Let me start by saying that I am honored to have received a Translational/Bridging Travel Award and it was a real pleasure to attend the Society of Toxicology Annual Meeting. This truly is a bridging “award”—by training, I am a biological physicist—so I only hope that I can make substantial future contributions in a new field. At this point, you might be wondering, “What on earth is a physicist doing at the Annual Meeting of the Society of Toxicology?” I’ll try to explain, try to give you some insight into what I learned from this meeting, and try to encourage other physical scientists that there are research questions in toxicology that could spur their interest and use their expertise.
As for why I joined in with a merry band of toxicologists in San Antonio, it’s a fairly short story. I am an Associate Professor of Physics and Biological Sciences at Vanderbilt University with a long-time interest in the interplay of mechanical and biochemical cues during embryonic development. I am currently on an ORISE-sponsored research leave for the 2012–2013 academic year and working with Thomas B. Knudsen and his vEmbryo team in the US Environmental Protection Agency’s (EPA) National Center for Computational Toxicology (NCCT). This is a collaboration in which I am trying to combine my experience in systems–level modeling—particularly the role of cell- and tissue-level mechanics—with NCCT’s expertise in predictive toxicology and high-throughput screening. Our initial work in this area is the development of cell-level models of secondary palate fusion and its disruption by chemical exposure. This model is a prototype for a variety of human disease conditions involving the dysregulation of epithelial-mesenchymal behavior at discrete tissue interfaces. I was very pleased to present my work on this model in one of this year’s platform sessions.
That’s why I came to the meeting in San Antonio, so what did I learn from the experience? First of all, the highlights. Monday was chock full of good science and debate. It started with Bruce A. Beutler’s Plenary Opening Lecture on “Genetic Analysis of Innate Immune Sensing.” He provided an amazing history lesson on the study of infectious disease leading to the identification and study of bacterial endotoxins. The program on Monday ended with what I found to be a very intriguing SOT/EUROTOX debate on the premise: “In the Near Foreseeable Future, Much of Toxicity Testing Can be Replaced by Computational Approaches.” Given my own interest in computational toxicology, I am almost certainly biased, but I felt the debate went to the affirmative—defended ably by Rory B. Conolly, and ably opposed by George Loizou—with the critically important caveat of what “near foreseeable future” meant. If we are talking only five years from now, then the challenge is daunting, but in 10-20 years or longer, perhaps computational approaches really can significantly reduce our dependence on animal testing. Tuesday’s science was just as good, starting on a related theme with Don Ingber’s impressive Leading Edge in Basic Science Award Lecture on “Human Organs on Chips as Replacements for Animal Testing” and including the Frontiers for Toxicology Symposium Session on “Systems and Computational Biology as Foundations for Toxicology Research.” In light of all the great talks I saw that day, I wonder if modifying the SOT/EUROTOX debate premise to: “In the near foreseeable future, much of toxicity testing on animals can be replaced by computational approaches and advanced in vitro assays” might shorten the timeline for “near foreseeable future.”
On the other end of the lab-to-clinic spectrum, I also found opportunities at this meeting to think about how computational toxicology could find its way into clinical practice. My thoughts on this subject were stimulated by a talk given by Marcello Lotti on “Translational Toxicology and its Many Facets” at the Clinical and Translational Toxicology Specialty Section Reception. He made the very salient point that “translational toxicology” means different things to different people. I take this as a positive; there are lots of different ways in which foundational research in toxicology can be used (i.e., translated) to improve patient care. This is an aspect of my own research to which I will certainly pay more attention in the future.
Even though I mention the above as highlights, the most important interactions for me took place in the poster sessions. These direct interactions helped me see first-hand how toxicologists think about scientific problems. One of my primary goals during this meeting was participating in such interdisciplinary discussions. I was not disappointed. There was plenty of exciting work being done under a wide range of topics that fit into computational toxicology, from approaches that model chemical structure, those that estimate chemical exposures, to those that model chemical perturbation of normal biology.
This wide range of topics and the fact that SOT would even ask whether computational approaches might replace toxicity testing brings me to my final point—there is a place and a need for physical scientists in toxicology research. As with any aspect of biology, responses to potential toxicants are highly variable and complicated. This complexity frankly scares away a lot of physical scientists, but it shouldn’t. The questions toxicology poses are important, they require modeling probabilistic nonlinear systems, and the answers can be relevant even when limited to orders of magnitude. Who better to take on such problems than physicists and mathematicians? I found the SOT Annual Meeting to be a welcoming place for this sort of approach and plan to return in the future. I hope SOT continues to value the interdisciplinary nature of toxicology and seeks to attract students from a wide range of STEM backgrounds—biology, chemistry, physics, and mathematics—and I hope to see you all at the next meeting!