Which Ounces of Prevention? Predictive Toxicology Using Organotypic Models

By Shane Hutson

VPROMPT team members (left-to-right) Shane Hutson, Dmitry Markov, John Wikswo and Lisa McCawley. Photo courtesy of Vanessa Allwardt.

VPROMPT team members (left-to-right) Shane Hutson, Dmitry Markov, John Wikswo and Lisa McCawley. Photo courtesy of Vanessa Allwardt.

Everyone knows that “an ounce of prevention is worth a pound of cure,” but think about that saying’s application to environmental chemical exposure. There are tens of thousands of chemicals in common use. If we don’t prioritize that list, it quickly adds up to a few tons of prevention.

There is no doubt that prevention is the best medicine when you know exactly what needs to be prevented, but how do we know? How do we predict which chemicals are toxic – and at which exposure levels? Those questions are why I became involved in toxicology research.

For 40+ years, the gold standard for those questions has been expensive, time consuming, animal-based (primarily mice and rats) laboratory exposure studies where results are not clearly predictive of effects in humans. Are we stuck with such studies? A large number of scientists are working to answer that question with “No, we can do better.”

I became involved in this effort during a year at EPA’s National Center for Computational Toxicology. My interests lie in developmental toxicity – understanding how chemical exposures affect the developing fetus – so I worked with EPA researchers on the Virtual Embryo Project to build computational models of specific developmental events and how they go awry during chemical exposure. When combined with high-throughput screening efforts such as ToxCast, computational models do have some predictive ability. But we still have a lot to learn.

That brings me to my current efforts. I’ve teamed up with a talented group of colleagues at Vanderbilt and the University of Pittsburgh to found VPROMPT – Vanderbilt-Pittsburgh Resource for Organotypic Models for Predictive Toxicology.

The word “models” pops up again here, but these are not computational. VPROMPT is using diverse expertise in biology, chemistry, physics and engineering to grow “models” that are three dimensional assemblies of multiple human cell types in carefully perfused microfluidic chambers. Such models are designed to be “organotypic,” that is, matching the microenvironment that cells experience in a living organ. This will enable our model to more closely mimic human responses to chemical exposure.

Our plans focus on developmental toxicity with models for liver, mammary gland, developing limb, and fetal membrane. The latter is a key model for investigating chemicals’ links to preterm birth.

VPROMPT is just getting started. We have lots to do in terms of engineering, fabricating and validating our models, but we also have high hopes for their predictivity. Will they help us make sure we only need that reasonable ounce of prevention? Stay tuned and let’s see where the science takes us!

About the Author: Shane Hutson is an Associate Professor of Physics at Vanderbilt University and Deputy Director of the Vanderbilt Institute for Integrative Biosystems Research & Education.

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