The Silicon Guinea Pig
Can silicon microchips mimic living organisms? Some researchers believe they can provide a fast, cheap way to screen thousands of drugs for toxic side effects.
At first glance, Michael Shuler's chip could pass for any small silicon slab pried out of a computer or cell phone. Which makes it seem all the more out of place on a bench top in the Cornell University researcher's lab, surrounded by petri dishes, beakers, and other bio-clutter and mounted in a plastic tray like a dissected mouse. The chip appears to be on some sort of life support, with pinkish fluid pumping into it through tubes. Shuler methodically points out the components of the chip with a pencil: here's the liver, the lungs are over here, this is fat. He then injects an experimental drug into the imitation blood coursing through these "organs" and "tissues"-actually tiny mazes of twisting pipes and chambers lined with living cells. The compound will react with other chemicals, accumulate in some of the organs, and pass quickly through others. After several hours, Shuler and his team will be closer to answering a key question: is the compound, when given to an actual human, likely to do more harm than good?
This so-called animal on a chip was designed to help overcome an enormous obstacle to discovering new drugs: there is currently no quick, reliable way to predict if an experimental compound will have toxic side effects-if it will make people sick instead of making them well. Testing in animals is the best drugmakers can do, but it is slow, expensive, often inaccurate, and objectionable to many. To minimize the number of animal tests, drug companies routinely screen drug candidates using cell cultures-essentially clumps of living human or animal cells growing in petri dishes or test tubes. The approach is relatively cheap and easy, but it gives only a hazy prediction of what will happen to a compound on the circuitous trip through the tissues and organs of an animal.
Shuler is among a handful of researchers who are developing more sophisticated cell cultures that simulate the body's complex organs and tissues. MIT tissue engineer Linda Griffith, for one, has built a chip that mimics some of the functions of a liver, while Shuichi Takayama, a biomedical engineer at the University of Michigan, has built one that imitates the behavior of the vasculatory system (see "Other Animal-on-a-Chip Efforts," below). But while such efforts have produced convincing analogues of parts of human or animal bodies, Shuler has gone a step further. Working with colleague Greg Baxter, who launched Beverly Hills, CA-based Hurel to commercialize the technology, Shuler has combined replicas of multiple animal organs on a single chip, creating a rough stand-in for an entire mammal. Other versions of Shuler's chips attempt to go even further, using human cells to more faithfully reproduce the effects of a compound in the body.
Drug companies are interested, and no wonder: they routinely make thousands, even tens of thousands, of compounds in hopes of finding one that is effective against a particular target. Chips such as Shuler and Baxter's could mean a cheap, fast, and accurate way to weed out compounds that would eventually prove toxic, saving companies years and millions of dollars on the development of worthless drugs. According to a recent study by Tufts University's Center for the Study of Drug Development, for each drug that reaches market, the drug industry spends an average of $467 million on human testing-the vast majority of the money going to drugs that fail, either because they aren't effective or because they prove toxic. If more failures could be identified before animal testing even began, companies could focus more of their time and money on the winners. "Everyone in the industry hopes to have surrogates for animals and humans when it comes to testing compounds," says Jack Reynolds, head of safety sciences for Pfizer, the world's largest pharmaceutical firm. "This is the sort of technology we'd want in our toolbox."
OTHER ANIMAL-ON-A-CHIP EFFORTS
(San Diego, CA)
|Chips lined with human liver tissue for drug screening|
|Liver on a chip for drug screening|
|Paul Kosnik||Tissue Genesis
|Chips with vascular and ligament cells for developing tissue replacement|
|Shuichi Takayama||University of Michigan
(Ann Arbor, MI)
|Cell-culture chips with channels that mimic the vasculatory system|
(Iowa City, IA)
|Drug-screening chips that will include cells from the brain and other organs|