This joint effort will include experts from the NIH National Toxicology Program (NTP), high-speed, automated screening robots at the NIH Chemical Genomics Center and computational toxicology capabilities available at the EPA Office of Research and Development's National Center for Computational Toxicology (NCCT).
"Today we want to report to you this remarkable collaboration," Elias Zerhouni, director of the NIH, said during a teleconference with reporters held to announce the groundbreaking agreement. He added that the effort—designed to expand the use of in vitro testing of human cells and cellular components to identify chemicals with toxic effects—represents the "birth of a new approach to a crucial problem in public health."
The agencies are hoping to coordinate their resources to better identify toxicity pathways, select chemicals for testing, analyze and interpret data, and promote their findings to scientific and regulatory communities. This is expected to generate data more relevant to humans, expand the number of chemicals tested and reduce the time, money and number of animals involved in current lab studies. The collective budget is yet to be determined, the agencies say.
Animal testing has always been a sore point for scientists and animal-rights advocates, following some high-profile cases of mistreatment of lab animals, such as monkeys discovered in 1981 at the Institute for Behavioral Research in Silver Spring, Md., in deplorable conditions. One of the primary ways to test the toxicology of a compound has been to inject it into a lab animal, see if the animal gets sick, and then conduct an autopsy to observe the damage done to their internal organs. (For more on this, click here. Additional information on animal rights legislation can be found here.)
Scientists present at the news conference agreed that animal testing has yielded some important medical breakthroughs. But Robert Kavlock, director of the NCCT, said that it also is expensive, inefficient and is not always an accurate indicator of how a substance will affect humans.
"The desire here is to see if we could do better," said Francis Collins, director of the NIH's National Human Genome Research Institute. He said the federal government is exploring the feasibility of using high-throughput assays to allow scientists to "look at toxicology in a totally new way."
"The news here is the capacity to test many thousands of compounds, something we haven't had until this collaboration," Samuel Wilson, acting director of the NIH National Institute of Environmental Health Sciences and NTP, said at the press conference. The new research model would allow scientists to test 100,000 compounds in 1,500 different concentrations in about two days compared with years if the testing was done on animals. This sort of "high-throughput" testing will enable researchers to generate more data relevant to humans, and at the same time reduce the amount of animal experimentation. The cross-species extrapolation from animals to humans is "not always as precise as it should be," Wilson said. "This collaboration is a milestone because it gives us the ability to apply a new generation of approaches to determining toxicities."
The scientists were unable to provide a specific time frame for when the technology might produce significant results or predict how many fewer animals would be used in testing if their effort is a success. They stressed that they plan to move quickly to test the new technology and reduce animal testing as soon and as much as possible.
But they acknowledged that some animal testing will continue at least until the technology proves its mettle in large-scale studies or until Congress passes a substance regulation act similar to the European Union's (E.U.) Registration, Evaluation, Authorization and Restriction of Chemicals, or (REACH), which regulates chemicals and their safe use. It is set to take effect in March 2009 and bans such testing.
The officials noted that despite the E.U.'s pending ban, it is unclear whether scientists in Europe have access alternative methods of toxicology testing. Wilson noted that the technology being tested by the EPA and NIH is not yet available in the E.U.
For now, NIH chief Zerhouni said, animal testing will continue in the U.S. in conjunction with the new high-speed, automated screening technology. There are several other approaches under development that would also allow relatively quick, inexpensive testing of a large number of compounds and cells simultaneously. "We plan to use all of these," Christopher Austin, director of the NIH's Chemical Genomics Center, said at the news conference.
As ScientificAmerican.com reported in December, 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) have developed biochips—called MetaChip and DataChip—that 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; DataChip is a slide lined with droplets containing cell cultures from the bladder, kidney or liver. Scientists can test the safety of a chemical by putting drops of it onto these slides and measuring the culture's growth or shrinkage over time.
These biochips are used with a high-throughput microarray spotter machine that places the liquid enzyme dots on the slides. The next step involves an optical assay system consisting of a camera connected to a fluorescent light source to take a digital image of the cell culture and highlight living and dead cells. Austin noted, however, that MetaChip and DataChip are not currently capable of handling the volume of testing that the government wants to conduct.
