Sanford-Burnham scientists receive grant to assess potential toxicity of large collections of chemicals

A bicoastal group of scientists at Sanford-Burnham Medical Research Institute (Sanford-Burnham) was recently awarded a three-year grant from the U.S. Department of the Air Force to assess the potential toxicity of large collections of chemicals. The goal of the project is to provide an early and relevant assessment of potential toxicities in a rapid, cost-effective manner.

"The current approach to assessing the health risks of chemical exposure relies extensively on data from animal models. But humans may react very differently to chemicals than animals," said Anne Bang, Ph.D., director, Cell Biology in Sanford-Burnham's Conrad Prebys Center for Chemical Genomics (Prebys Center). "As a way to help solve this problem, we have developed a technology platform that relies on high-throughput, human cell-based assays to analyze processes in a cell when it is exposed to a certain chemical."

For these chemical screens, a team of scientists from Sanford-Burnham's La Jolla, Calif., and Orlando, Fla., campuses uses induced pluripotent stem cells (iPSCs) - stem cells that are genetically reprogrammed adult cells - to test thousands of potential toxins. In a second step, the scientists analyze the iPSC-derived cells to assess mitochondrial function and identify subsets that demonstrate a potential for toxic effects.

"Given the thousands of chemicals humans are exposed to in the course of their lifetime, there is a clear unmet need to find better ways to screen for toxicity," said Darrin K. Ott, Lt. Col., USAF, B.Sc., Ph.D., CIH Chief, Research Section Occupational and Environmental Health Dept., at the USAF School of Aerospace Medicine." Our men and women in the Air Force are no different in this regard - and we need to push the cutting edge of toxicological research because they do spend time in challenging environments, performing complex missions that have unique chemical mixtures present or even advanced materials that are newly developed for the high-tech capabilities they bring. This collaboration with Sanford-Burnham should lay the foundation for a smarter way to determine potential toxicity and better ensure the health of our personnel and environment."

The collaboration is a prime example of how scientists at Sanford-Burnham combine their expertise in stem-cell research with the high-throughput screening capabilities at the Prebys Center to make a tangible impact on human health.

The Challenges of Toxicity Testing

The goal of toxicity testing is to assess the risks posed to human populations at ambient exposure levels. For the past 50 years, this goal has been met by high-dose experimental testing in animals with specific approaches for extrapolation from high to lower doses and from the experimental animals to the human population.

These observational studies remain of great value, but yield little understanding of the molecular mechanisms underlying the toxic response, thereby limiting the ability to predict potential human risk. Adding to the scope of the problem is the exponential increase in the rate of discovery of new chemicals.

It is estimated that there are more than 100,000 new chemicals for which little to no risk assessment has been performed. While animal studies represent the foundation of toxicology, current methodologies, capacities, and budgets of the regulatory agencies tasked with toxicity testing are unable to meet the critical and growing need for testing.