Air Date: Week of June 16, 2000

Researchers are using a breakthrough technology to understand how toxins cause illness. Gene chips are letting scientists actually see, in an instant, how a toxin disrupts thousands of our genes. Living On Earth’s Diane Toomey reports.

Transcript

CURWOOD: It's Living on Earth. I'm Steve Curwood. Any time now, scientists will finish decoding the billions of building blocks that make up our genes. One expected payoff for this work will be new ways to treat or even prevent disease. But another project already has a head start on that. The government’s Environmental Genome Project is trying to discover how interactions between our genes and pollutants can lead to illness. Living On Earth’s Diane Toomey reports.

TOOMEY: When researchers study how a toxin affects the body, they're limited to looking at just a few genes at a time. But a new microchip technology is changing that. It's letting scientists see a toxin's effect on thousands of genes at once. Rick Paules is a biologist with the National Institute of Environmental Health Sciences, the federal agency that's in charge of the Environmental Genome Project.

PAULES: This holds potential for our being able to study the responses of cells to exposures from our environment, and to look how genes are turned on or turned off.

TOOMEY: There may be up to 140,000 genes in the human body. At any given moment some are off. Others are on, or active. Environmental toxins like dioxin or heavy metals can cause illness by disrupting this on-off mechanism. But often, scientists don't know which genes have gone haywire. By using microchip technology, Dr. Paules is able to figure that out. When a gene is turned on it produces a substance called RNA. Each gene has its own distinctive RNA. Using this information, Dr. Paules exposes a batch of genes to a toxin. Then he scoops up the resulting RNA and tags it with a fluorescent red color.

PAULES: And we take another set of cells that are normal cells, that have not been exposed to anything, prepare the RNA from that, and then label that with a different chemical that under a laser will glow a certain color, but it's a different color.

TOOMEY: Usually green. So researcher have two color-coded clumps of RNA that represent the genes that are turned on in each group. To tease out the toxin's effect, they need to compare the two. To do that, they take a simple glass slide and use microchip technology to place 12,000 human genes on it. At that point, the slide is transformed into a gene chip.

PAULES: We will then allow these labeled or colored RNAs to float over the face of the chip.

TOOMEY: Conveniently, RNA sticks to the type of gene it came from. So if the toxic turns a gene on, the RNA from that gene finds its mate on the chip and makes that spot glow red. If the toxin turns a gene off, the spot that corresponds to that gene would glow green.

PAULES: So we have a slide, then, that has a collection of spots that are glowing either red or green. And the pattern, then, gives us a wealth of information as to the toxic mechanisms, what's going on in the cell. What genes are turned on and turned off.

TOOMEY: Each toxin creates a distinctive fluorescent pattern. Its own signature, so to speak.

PAULES: it should be able to give us some insight into some of the mechanisms of the disease processes underlying the genetic changes and the disease processes that occur as a result to an exposure. And when you can understand those mechanisms, then that holds the potential for an intervention and a therapy.

TOOMEY: Gene chips might also offer a way to pin down the effects of combinations of toxins, and they could be used to screen chemicals for their potential to cause illness.

PAULES: Once we've established a basis of information, then the expectation is that we will be able to use what we know to look at a new compound and say, well, that looks very similar to something we've seen before. We hope that this technology will allow us to do this very rapidly, and minimize the use of animals in these long-term studies.

TOOMEY: Dr. Paules says as more and more human genes are discovered, they'll be added to his gene chip. He hopes it may one day be possible to fit the entire human genome on a single chip. This would let scientists see, in a single moment, the complete picture of how a toxin affects our bodies. For Living on Earth, I'm Diane Toomey.