Vanderbilt chemist David Cliffel has received a grant from the Alternatives Research & Development Foundation to assess the potential of an advanced cell monitoring system for reducing the use of animals in toxicity testing.
Cliffel’s system, which is called a “multianalyte microphysiometer,” represents a new approach to toxicity testing advocated in a 2007 report by the National Research Council: one that focuses on methods that evaluate chemicals’ effects using human cells and cell cultures instead of relying so heavily on animal studies.
“The fact that we can’t predict what will happen when we inject a chemical into an animal is a reflection of just how crude our scientific knowledge of basic biological processes still is,” said Cliffel, associate professor of chemistry.
Current cell assays used to test for toxicity tend to be one-dimensional: They test for a specific type of biological activity. As a result, they cannot identify unanticipated side effects that a novel chemical compound may produce. Cliffel’s approach, by contrast, is to use human cells as “toxicological sensors” that not only can determine if a given chemical damages them but also can identify the way in which the damage is done.
Cliffel’s microphysiometer is a device that has a number of small chambers that hold about 100,000 cells apiece in conditions that keep them alive for several days. These cells are equipped with a battery of sensors that monitor the metabolism of the cells in each chamber. By putting nerve cells in one chamber, heart cells in another chamber, kidney cells in another chamber and so on, Cliffel can theoretically create a toxicological surrogate for a whole person.
With the $33,000 foundation grant, Cliffel and his colleagues will use his device to analyze a cancer drug that passed all the cell assays but proved to be toxic in chimpanzees. They will put human liver cells and macrophage cells from the immune system into the microphysiometer, expose them to the drug and see how it affects them. They will also run a similar test with nanoparticles.
“This approach has the potential of revealing multiple adverse effects of drugs at much lower levels than other methods,” the chemist said.
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