APR 03, 2014 12:00 AM PDT

Human-Like System May Improve Drug and Chemical Toxicity Screening

Animal testing is a distasteful part of chemical and drug development, and some have argued that it is unnecessary and/or immoral. Nevertheless, we must have some method of testing toxicity and side effects on living organisms...or must we?

A group of scientists, led by the Los Alamos National Laboratory, has taken on the ambitious project of creating a desktop-sized replica of major components of the human body in interconnected form-liver, heart, lung and kidneys-along with analytical capabilities provided by an ion mobility mass spectrometer (IMS-MS).

The intent is to create a rapid screening tool for drug and chemical development, which could also be a potential alternative to animal testing. Named ATHENA, for Advanced Tissue-engineered Human Ectypal Network Analyzer, the proposed system would connect constructs of a beating heart, a metabolizing liver, an excreting kidney and a breathing lung to provide a dynamic and rapid feedback system for chemical exposure. The project has received funding from the DTRA (Defense Threat Reduction Agency).

It is believed that by testing exposures in a dynamically interconnected system modeled to respond as human organs do to toxins, we can receive better and more relevant toxicity information than extrapolating effects from simple Petri dish testing or animal exposure testing.

For such a massive undertaking, the team has subdivided into work on the individual organs, calling on an impressive network of university colleagues.

A group at Vanderbilt University has already begun work on the liver, and has described a construct that can react to toxic chemical exposures in the same manner as a real liver. This presentation will be made at the upcoming meeting of the Society of Toxicology.

The Vanderbilt group is working on the underlying hardware platform to operate and monitor ATHENA, while a separate group of scientists at Charité Universitätsmedizin in Berlin are developing the physical liver construct. The first generation of liver construct was demonstrated recently and was successfully integrated into the ATHENA platform.

A separate group at Vanderbilt in conjunction with the University of California-San Francisco is working on the kidney constructs, while a group at Harvard is addressing the heart construction. The team hopes to connect the heart construct sometime this winter.

CFD Research Corporation in Huntsville, Alabama, is running models to help design the output and feedback systems necessary for useful drug exposure data and analysis. Along with Vanderbilt and Los Alamos, CFD will also be working on a suitable "blood" to drive all four organs.

Finally, Los Alamos scientists will contribute the analytical capability component and integrate the entire system.
Can the team pull this off? It seems unlikely that ATHENA could replace all traditional toxicity and drug testing, but it certainly could have a meaningful place in the chemical and drug development process.

At the very least, any system that can allow for rapid, cost-effective initial screening of the thousands of chemicals with unknown effects on humans is a significant step forward. We wish the ATHENA team good luck in their quest.
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