One of the most challenging aspects of drug development is testing. Scientists are forced to either experiment on whole animals (which is expensive, raises ethical issues and may not predict effects in humans) or to perform tests on microscopic human cells found in tissue cultures, which have been altered to live forever and bear little resemblance to actual living, breathing people.
Nowadays researchers are working on a new technique to help bridge the gap: microchips that stimulate the activities and mechanics of entire organs and organ systems.
These “organs on a chip”, as they are called, are typically glass slides coated with human cells that have been configured to mimic a particular tissue or interface between tissues. Developers hope they could bring drugs to market more quickly and, in some circumstances, perhaps even eliminate the need for animal testing.
The chips are still in their early stages but investigators are translating more and more body parts to the interface. Last summer bioengineers at Harvard University wrote in the Journal Science that they had created a device that mimics a human lung: a porous membrane surrounded by human lung tissue cells, which breathes, distributed nutrients to cells and imitates immune responses.
In November 2010 Japanese researchers announced online in Analytical Chemistry that they had built a chip that simultaneously tests how liver, intestine and breast cancer cells respond to cancer drugs.
In March 2011 scientists developed a microscale replica of the human liver that allowed them to observe the entire cycle life of hepatitis C, a virus that is difficult to observe in cultured cells.
Pharmaceutical companies have expressed interest in the chips but are proceeding with caution. The main drawback is that the chips may not capture certain crucial aspects of living physiology the way whole animal tests do. Harvard researchers say the chips can provide hints about toxicity: for instance, the lung-on-a chip initiated an immune response against silica nanoparticles, which are under investigation as possible drug-delivery vehicles.
Ultimately, the goal is to make chips that mimic more complex systems – perhaps even entire humans, says Donald Ingber, director of Harvard’s Wyss Institute for Biologically Inspired Engineering and co-creator of lung-on-a-chip. Scientists could build chips containing cells from patients with specific genetic mutations, which could predict drug responses in specific populations, as well as personalized chips that predicts an individual’s drug response.