The way pharmaceutical companies test drugs is broken, and Donald Ingber has an idea for how to fix it.
Scientists typically test potential pharmaceuticals on animals, but more often than not, “the predictions from animals fail when a compound is tested in humans,” says Ingber, director of Harvard University’s Wyss Institute. Performing initial tests on people, of course, is too dangerous. “Our proposed solution is to do studies with human cells,” he says, “but not just cells in a dish—cells that exhibit organlike structures and functions.”
To achieve this, Ingber and his team are developing a menagerie of microscale devices that replicate the structures and environments of actual human organs more closely than a simple culture dish.
The Wyss Institute’s first organ was a breathing lung on a microchip. The transparent, thumb-size device is made of cell-friendly materials and serves as a platform for growing human lung cells. Tiny channels cut through the device. Air and liquid flow through the central channels, where the lung cells are grown, and because the device is flexible, scientists can apply vacuum pressure to the side channels so that the central channels expand and contract—much like human lungs. The team has shown that such mechanical forces affect the behavior of the cells. In the case of the lung cells, the mechanical breathing helps them absorb particles flowing in the air chamber.
More recently, the institute has developed a human gut on a microchip. The central channel of the device, which is lined with human cells, can be subjected to wavelike motions that mimic the movement of the intestines during digestion. In the chip, the cells form fingerlike structures known as villi that are important for absorption of nutrients and other compounds. These structures do not form when cells are grown in a dish, suggesting that the cells feel more at home in the device. Scientists can also grow common intestinal bacteria along with the gut cells in the channel. In a culture dish, the bacteria usually overtake the human cells, says Ingber; “now we can study much more complex interactions.”
Individually, each organlike chip gives researchers a chance to study human cells in a more natural environment and to test how they respond to drugs and toxins. But Ingber is working toward a grander vision in which several of the chips are linked together. By connecting the microfluidic versions of a heart, lung, gut, kidney, and more, Ingber and his coworkers believe, they will be able to better study how the body processes and responds to various compounds.
One project under way with Wyss faculty member Kevin Kit Parker is to test inhaled drugs for negative effects on the heart—a long-standing problem in drug discovery. “Cardiac toxicity is actually the biggest cause of failure of drugs, regardless of what they target,” says Ingber.
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