A Possible End To Toxic Testing On Animals

Lab rats may one day get a reprieve.

The government is studying a major overhaul of how to test the safety of chemicals, from household cleaners to pesticides. The goal is to see if robotic machinery can predict what is toxic as well as animals do.

Scientists today test the hazards of chemicals for the environment mainly by injecting large doses into laboratory animals, mostly rodents. Researchers see if the animals get sick and then analyze their tissue.

Aside from concern about the animals' welfare, this process is laborious and does not provide fast answers. The main testing agency, the National Toxicology Program, has fully tested just 2,500 chemicals in 30 years.

Moreover, humans typically are exposed to much lower doses of chemicals than are test animals. On the other hand, animal testing does not always predict the disastrous effect that a chemical can have on people. The most notorious example is the drug thalidomide, marketed as a sleeping aid, that caused birth defects.

On Thursday, the National Institutes of Health and Environmental Protection Agency announced a big study of an alternative approach. It involves mixing chemicals with human cells, then using robotic machinery that can detect in minutes cell death or other early signs of harm that need further investigation.

The program "really has the potential to revolutionize the way that toxic chemicals are identified," said Dr. Francis Collins, head of the NIH's National Human Genome Research Institute.

Those 2,500 chemicals the National Toxicology Program has tested in animals over 30 years? The new approach could screen that many chemicals, at 15 different exposure levels, in a single afternoon, said Christopher Austin of the NIH's Chemical Genomics Center.

Even if the new approach works, it would not eliminate the need for animal testing, the U.S. scientists said. Yet European regulators already are moving to end animal tests of certain chemicals, particularly those used in cosmetics.

"You cannot abandon animal testing overnight," said the NIH's director, Dr. Elias Zerhouni.

If the cell-based testing proves reliable enough, it could minimize the use of animals so they are reserved to study questions most important to public health.

Collins stressed that this is an experiment. Scientists must retest old chemicals with the new cell-based approach and compare the results with years of previous animal research to see if the new testing is as reliable at predicting harm.

"Ultimately what you're looking for is, `Does this compound do damage to cells?' Instead of looking at a whole animal as our first line of analysis, look at individual cells from different organs," he said. "We don't know if that's going to be as good as we would like. Hence the purpose of this collaboration is to test this out."

In the new testing, small glass trays are lined with 1,536 little wells. Scientists pick a kind of cell - human liver cells, for example - and the robotic machines rapidly fill each well with those cells. Then scientists drop in different chemicals, or the same chemical at different concentrations, on top of each spot of cells.

Computers measure what happens to the cells over time, from a few minutes to two days. Do they die outright? Do pathways involved in cellular survival or metabolism become altered?

The approach does not use brand-new machinery. These high-speed cell tests - known scientifically as high-throughput screening - have formed the cornerstone of genetics research, used to help identify different genes and their actions. Drug companies use it every day to screen thousands of chemicals in the search for new drugs.

But in those cases, the tests are hunting for positive reactions in cells.

The new program will track how the tests also spot bad reactions from chemicals that people may be exposed to every day.

The EPA last year began retesting about 300 chemicals, mostly pesticides, to start the process. It means running each chemical through 400 different cell tests, from their effect on an organism's proteins to the impact on development, checked by using cells from zebrafish embryos.

The five-year collaboration with the NIH ultimately will test about 2,800 compounds, for across-the-board toxicity as well as clues about whether some people are more genetically susceptible than others to certain chemicals.