June 2004

The Silicon Guinea Pig

Continued from page 3

By David H. Freedman

Kind of Human

Chips that replicate the functioning of animals will likely be the first versions of the technology to make a commercial impact. But the hope is that once those prove to accurately predict the results of animal tests, human-on-a-chip versions will provide a good indication of how toxic a drug is likely to prove in human trials.

Animal testing plays that role now, but not very well. Four out of five drugs that make it through animal testing end up failing in human clinical trials, usually because of safety concerns. Part of the problem is that mice can't tell you they have headaches, blurred vision, or stomach cramps. But the larger issue is simply that animals' organs, and the processes that take place in them, are not identical to those of humans. No one knows how many drugs that would have been safe in humans were shelved because they sickened some animals. (Penicillin, for instance, is toxic to guinea pigs but fortunately was also tested on mice.)

Chips containing simulated human tissues and organs could also allow researchers to work out complicated multidrug schemes for treating various diseases without putting patients through agonizing rounds of trial and error. Shuler, for instance, is zeroing in on anticancer cocktails. He incorporates human cells from uterine or colon tumors in his chips, setting up a more realistic model of a particular type of cancer. He can then test the ability of various combinations of chemotherapy drugs to kill the cells without sickening the rest of the system. "To find good combination therapies, you need to run a lot of tests to determine the right doses and the order in which the drugs are given," he explains. "It's the sort of problem we can get our hands around with this technology."

Neither Baxter nor Shuler claims that the animal on a chip is any sort of panacea for the complex and deeply challenging drug-development process. For one thing, the chips still have to prove in large-scale tests that they really do a better job than conventional cell cultures of predicting toxicity. But if they measure up, then the pills you take ten years from now may very well arrive thanks to the sacrifices of a silicon lab rat.