METACHIP: A MetaChip is a glass slide dotted with 20-nanoliter droplets of a solution containing human liver enzymes; researchers can test toxicity of compounds by introducing these chemicals into the solution droplets and seeing how they react. Image: Courtesy of the University of California, Berkeley
The journey of a drug from lab to pharmacy is usually long and pricey, typically taking a decade or more and gobbling up hundreds of millions of dollars. Pharmaceutical and chemical companies are willing to make these major investments in time and money on chemical compounds that promise to become the next Viagra, Prozac or other blockbuster medication. Often, however, these experiments are scuttled late in the game because toxic side effects surface.
Drugmakers may soon have a new tool to assess safety much earlier in the process, saving them money and time and negating the need to test early-stage compounds on live animals. Researchers at Rensselaer Polytechnic Institute in Troy, N.Y., the University of California, Berkeley, and Solidus Biosciences, Inc. (a biotech company located at the Rensselaer Incubator Program for start-up businesses), report in Proceedings of the National Academy of Sciences USA that they have developed biochip technology that promises to reveal the potential toxicity of chemicals and drug candidates during early experiments.
These biochips—called MetaChip and DataChip—mimic what the body does when it ingests a drug. MetaChip is actually a glass slide dotted with 20-nanoliter droplets—each 20 billionths of a liter—of a solution containing human liver enzymes; researchers can test toxicity of compounds by introducing these chemicals into the solution droplets and seeing how they react. DataChip is also glass slide, but it is lined with droplets containing cell cultures from the bladder, kidney or liver; scientists can test a chemical's safeness by putting drops of it onto the slide and measuring the culture's growth or shrinkage over time. The two biochips can also be used in tandem—a MetaChip can be turned over and applied directly to a DataChip to see how the materials interact.
"We started with the aim of reducing the cost of developing new drugs by enabling toxicity assays much earlier in the drug development process," says Douglas Clark, a U.C. Berkeley professor of chemical engineering and a Solidus Biosciences co-founder. "We wanted drug candidates to be screened for toxicity at the same time they are screened for efficacy. Ultimately, that will lower the cost of failure and that will lower the cost of drugs brought to market."
MetaChip and DataChip are now a reality because scientists are able to isolate and generate p450 liver enzymes as well as make three-dimensional cell cultures in droplets. It is difficult to quantify how much biochips will speed up development and cut costs, says Solidus co-founder Jonathan Dordick, a Rensselaer professor of chemical and biological engineering. "The safest thing to say is that about 70 percent of drug failures occur due to toxicity. If we can catch these sooner, those drug compounds would never make it to clinical trials. It costs hundreds of millions of dollars per chemical compound to take a drug through the discovery process."
And these costs do not take into account the large number of animals needlessly subjected to potentially toxic substances even though humans may respond differently. "There's always a question you have to ask," Dordick says, "and that is whether testing on an animal is predictive of how a human will react."
Demand for biochip technology will no doubt rise in response to a European Union ban on testing on animals set to take effect in March 2009. "I'm not suggesting that we'll eliminate animal testing in the pharmaceuticals industry, but it can be done later in the testing process," Dordick says, after MetaChips and DataChips identify which chemical compounds are safe enough to make it to the stage where such testing might be useful. Solidus is working to commercialize its chips and is close to signing a contract with a "large cosmetics company," Clark says, declining to name the firm.