Recently announced grants by the National Institutes of Health and the Defense Advanced Research Projects Agency aim to allow scientist to test the safety of drugs in humans without using human subjects. The effort focuses on the development of 3-D chips with living cells and tissues that model the structure and function of human organs such as the lung, liver, intestines, and heart.

More than 30 percent of promising drugs have failed in human clinical trials because they are determined to be toxic despite promising pre-clinical studies in animal models. Tissue chips, which are a newer human cell-based approach, may enable scientists to predict more accurately how effective a therapeutic candidate would be in clinical studies.

“Serious adverse effects and toxicity are major obstacles in the drug development process,” says Thomas Insel, acting director of the National Center for Advancing Translational Sciences. “With innovative tools and methodologies, such as those developed by the tissue chip program, we may be able to accelerate the process by which we identify compounds likely to be safe in humans, saving time and money, and ultimately increasing the quality and number of therapies available for patients.”

The aim is to use the new chips to test drugs known to be safe or toxic in humans to help identify the most reliable drug safety signals and ultimately advance research to help predict the safety of potential drugs in a faster, more cost-effective way. It is the first interagency collaboration launched by the NIH’s newly created National Center for Advancing Translational Sciences.

Tissue chips merge techniques from the computer industry with modern tissue engineering by combining miniature models of living organ tissues on a transparent microchip. Ranging in size from a quarter to a house key, the chips are lined with living cells and contain features designed to replicate the complex biological functions of specific organs.

NIH’s newly funded Tissue Chip for Drug Screening initiative is the result of collaborations that incorporate the resources and ingenuity of the NIH, DARPA, and U.S. Food and Drug Administration. NIH’s Common Fund and National Institute of Neurological Disorders and Stroke led the trans-NIH efforts to establish the program.

NIH announced 17 grants and plans to commit up to $70 million over five years to the program, while DARPA has committed up to $63 million in cooperative agreements with two of the NIH recipients, the Wyss Institute at Harvard University and MIT, to develop engineering platforms capable of integrating 10 or more organ systems. The FDA will help explore how this new technology might be utilized to assess drug safety, prior to approval for first-in-human studies.

Wyss Institute researchers have already developed a human Lung-on-a-Chip and human Gut-on-a-Chip. Both are the size of a computer memory stick and contain hollow microfluidic channels lined by living human cells. They are translucent, allowing researchers to see the inner-workings of a human organ non-invasively. The cooperative agreement with DARPA, worth up to $37 million, is for the development of 10 different human organs-on-a-chip that are linked together to more closely mimic whole body physiology, and to engineer an instrument that will make it all work and permit real-time analysis of complex biochemical functions.

DARPA also entered into a cooperative agreement with researchers in the Department of Biological Engineering at MIT, worth up to $32 million over the next five years to develop a similar technology platform that will mimic human physiological systems in the laboratory. Called “Barrier-Immune-Organ: Microphysiology, Microenvironment Engineered Tissue Construct Systems,” or BIO-MIMETICS, the program will combine technologies developed at MIT, the Charles Stark Draper Laboratory, MatTek Corp., and Zyoxel, to develop a microfluidic platform that can incorporate up to 10 individual engineered human organs-on-a-chip and be used to accurately predict drug and vaccine efficacy, toxicity, and pharmacokinetics in pre-clinical testing.