Robert E. Chapin
Pfizer, Groton, Connecticut

The goal of the In Vitro Toxicology Lecture series is to feature important research using in vitro and alternative techniques to study basic mechanisms and to illustrate how these test methods benefit animal welfare by refining, reducing, and replacing animal use whenever it is feasible. Graduate students, undergraduates, postdoctoral scholars, and recipients of Colgate-Palmolive awards are among the guests at the In Vitro Toxicology Lecture and Luncheon.
 

The “Toxicity Testing in the 21st Century” vision promulgates an in vitro approach to safety assessment based heavily on knowing the pathways responding in a cell and then correctly relating that to an in vivo exposure and response to predict the likely health outcome. But we are now much like Galileo was with our Moon: seeing the goal is many, many times easier than actually getting there. However, given that animal models correctly predict only 40–70% of human responses, in vitro models won’t actually have to do that well to be better than the current in vivo models. Thus, for both animal-use issues and for correct-predictivity issues, an in vitro future is a worthy and achievable goal. Meanwhile, there is much trial and error to pursue. This talk will quickly reprise an in vitro testing vision, and then put it into an industry perspective. It will soon become clear that we’re a long way from where we want to be. After this stage-setting, the audience will be asked to discuss and then present their answers to a set of related questions.
 

• What are the limitations (and “costs”) of the current approach using animals?
• What are the limitations of the proposed safety assessments using cell cultures and predictive models?
• What are some possible explanations for the less-than-hoped-for predictivity? Which is most likely, and why?
• How long will it take to implement this new paradigm? Why will it take longer than that?
• What role might stem cells play in this future? What are the assumptions (and thus, possible pitfalls) in their playing that role?
• List the benefits and drawbacks of having multiple cell types in the culture vs. having one cell type.
• What would be the motivations of industry to embrace this new toxicity testing vision? What conditions need to be met for that marriage to happen?
• Why might one solution to the predictivity problem be to use multiple predictive models? How would those models have to differ from each other to make that work?