On April 11, 2017, the FDA made the groundbreaking announcement that they would be partnering with Emulate, a company that makes organs-on-chips, to use the devices in food safety testing. This multi-year research and development agreement marks the first time that a regulatory agency is actively pursuing the use of organs-on-chips as animal testing alternatives.
But what exactly do organs-on-chips do? And how are they helping to advance smarter, more humane science?
The Future of Biomedical Research…and Beyond
Organs-on-chips are engineered microsystems designed to replicate the structure and function of human organs. The devices offer the potential for making the process of drug development and toxicology testing more accurate and human-relevant than is currently seen with animal models. These models could also be designed to mimic specific disease states and to study tissue development and organ physiology, potentially reducing the need for animal testing in these and other areas of research.
Tissue chips, small devices that range from the size of a coin to a thumb drive, contain cells grown on platforms in 3-D, and contain features intended to mimic the biological functions of specific organs.
The lung-on-a-chip, for instance, has lung and blood vessel cells grown on opposite sides of a flexible, porous platform that can expand and contract like a breathing lung. This approach enables cells to change shape and respond to physical cues in ways not possible with traditional 2-D or 3-D cultures.
Several other microengineered tissue chips have been generated and continue to be optimized, including models of the liver, kidney, gut, bone, brain and heart, among others. Tissue chips are also being developed that mimic hallmark characteristics of human disease, like cancer cell metastasis, to help researchers better understand the conditions and develop new, more effective therapies.
Because tissue chips are modular devices, it is possible to link individual organs-on-chips together to create a human-relevant, multi-organ model system. In fact, the goal of the Human-on-a-Chip project, which represents a collaboration between the Food and Drug Administration (FDA), the Defense Advanced Research Projects Agency (DARPA) and the National Institutes of Health (NIH), is to generate a miniature 3-D model which includes ten different human mini-organs linked together to form a physiological system. This system would mimic the activities and biological processes of the human body. First attempts to connect different organs together on the same chip have already been made and have provided a strong proof of concept that functional interactions between different organs can be analyzed in these devices.
There have been several other recent notable developments with tissue chips as the validation process for organs-on-chips begins. Models are now being tested—through both government-led and private efforts—not only to see if they are functioning as intended, but also to ensure that the data produced from them is reproducible, accurate and reliable.
The Beginning of the End of the Animal Model?
The use of animals as stand-ins for humans has historically given rise to misleading results because of the intrinsic differences between humans and other species. Nearly 30% of drugs that show promise in preclinical animal models fail in human clinical trials because they are toxic in people, and 60% of drugs fail because of lack of efficacy.
Research into drug development for nervous system disorders such as Parkinson’s and Alzheimer’s disease, for example, has seen some of the highest failure rates, leading pharmaceutical companies to retract their investment in this area of study. Stevin Zorn, president and chief executive officer at MindImmune Therapeutics, notes that there are not currently—and there may, in his view, never be-predictive animal models of complicated human diseases such as nervous system disorders. Experts in the field seem to agree that using human-relevant, innovative modeling approaches—possibly technology such as organs-on-chips—as well as efforts to better utilize data coming from human clinical studies, are more promising approaches.
Lack of efficacy and reliability—compounded by the inherent ethical concerns with the animal model—makes the need for innovations like the organ-on-a-chip both critical and urgent. Simply put, animal models fail to mimic the diseases they were meant to model. As a result, they may actually be screening out drugs that would have been effective in people, thereby keeping us from developing the very treatments and cures these models are meant to be facilitating. Humane innovation like organs-on-chips, therefore, hold life-saving promise for humans and animals alike.