Scientifically speaking, the ideal test subject for medical research is the human being. But, for obvious reasons, we resort to the next best option: experimenting on animals. A relatively new trend in research labs, however, seeks to bridge the divide between the ideal human subject and ethical barriers. Researchers are using human tissue to create devices that mimic the three-dimensional realities of organs. These "organ-on-a-chip" technologies could not only do away with animal models that have proven disappointingly unreliable, but their ease of use and affordability could speed up the drug discovery process.
The newest of these, gut-on-a-chip, attempts to mimic the physiology, structure, and mechanics of the human intestines. It is roughly the size of a thumb drive and contains a central chamber that houses a pliant, porous membrane lined with human intestinal epithelial cells, producing an artificial intestinal barrier. It can even harbor the microbes normally abundant in our gut’s luminal space. Not only does the 3D chip mimic organ anatomy, the membrane is controlled with a vacuum pump to produce the peristaltic motions that occur during digestion.
Although the gut-on-a-chip is not yet ready widespread for use, it could potentially provide a relatively cheap way to study intestinal disorders such as ulcerative colitis and Crohn’s disease. And the safety and efficacy of any treatment for gut disorders could be tested on the chip.
Using animal models to look for new drug targets or measure the effects of existing drugs can be costly and time-consuming. Even worse, as the FDA reported nine out of ten clinical trials fail as results from animal models translate poorly during human testing. The other major practice, experimenting with human cell cultures, is far from ideal as many cell lines have been turned cancerous so that they proliferate indefinitely. What you get is a convenient and abundant cell resource, but those cells have a markedly different physiology than cells in the human body.
Creating a more physiologically representative – not to mention cheaper – system is exactly what motivated Dr. Donald Ingber, the founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard, to make the gut-on-a-chip.
The effort to improve upon imperfect and expensive animal models has driven other researchers to seek a biochip-based solution. Stanford University’s Stephen Quake recently won the coveted Lemelson-MIT prize – aka the “Oscar for inventors” – for a chip packed with microfluidic channels, pumps and valves that can perform 10,000 simultaneous measurements each minute. Dr. Fearghal Morgan and others at the National University of Ireland, Galway have come up with the EMBRACE chip that electronically mimics the operation and structure of brain function.
Others are trying to make their own chip-sized organs as well. Dr. Kevin Parker, also at Wyss, has developed a heart-on-a-chip with engineered heart muscle cells to study heart function and drug responses, and Kahp-Yang Suh’s group at Seoul National University made a kidney-on-a-chip that combines kidney tubular cell cultures and microfluidics to study how fluidic pressures and stresses affect kidney function, and how hormones regulate that function.
And Ingber’s gut-on-a-chip is not his first foray into organ-mimicking technologies that you can stick in your pocket. The group has produced a lung-on-a-chip that uses a stretchable membrane coated with epithelial tissue from the lung to simulate a lung. If all goes well, scientists will use the system to study the lung’s immune response against silica nanoparticles, which are currently being considered as a drug-delivery system.
But research scientists and drug makers aren’t the only ones who stand to benefit from the organ-on-a-chip strategy. Last October the Wyss Institute was awarded a $12.3 M grant from DARPA to develop a spleen-on-a-chip that could be used to treat sepsis, an infection of the bloodstream that often proves fatal for soldiers on the battlefield and in intensive care units. The hope is to create a small, portable, dialysis device that can be inserted into the blood vessels of a septic soldier and rid the blood of pathogens in much the same way a normal spleen does.
Of course, try as they might, their organ-on-a-chip is still an artificial system that won’t completely replicate the function of real organs. But given that they allow researchers to study disease or screen molecules with human cells, it will be interesting to see if the chips can improve on animal models’ paltry 10 percent success rate of producing clinical trial candidates. Only time will tell.
In the meantime, places like the Wyss Institute will continue to develop organ-on-a-chip technologies. One could imagine that it is possible, at least in principle, to develop a chip for every organ in the body. Piece them all together and you have a, well, human-on-a-chip. Sound crazy? That’s exactly where Ingber and others in the field think the technology is headed. At any rate, moving toward medical experimentation that does not involve sacrificing animals would be great. As the narrator mentions in the following video, the ultimate hope is that “the chips will replace animal studies altogether.” In the meantime, the organ/human-on-a-chip could drastically speed up research on human physiology and drug discovery, and save researchers a lot of money.