Image: NIH MICE ARE OFTEN MODELS for human diseases. A technique called gene knockout allows researchers to delete any of their genes at will. The mouse genome is next in line once the human genome is finished

The good news is that because the genes of these organisms are so similar to our own, they can help reveal new cures for genetic diseases. As much as 60 percent of the 289 known human disease genes have counterparts in Drosophila. Says Kevin Fitzgerald, a worm researcher at Bristol-Myers Squibb, "Some of the same genes and components that are responsible for cancer, breast cancer for instance, or Alzheimer's disease, are actually found, and they seem to function very similarly, in both worms and flies."

Even simple baker's yeast, which consists of only one cell to our billions, is playing a role in studies of how cancer treatments work. To date, yeast has taught scientists a lot about cell division and DNA repair, processes that go wrong in cancer. And researchers at the "Seattle project", an effort funded by the National Cancer Institute to find new anticancer drugs, are mutating genes in yeast cells--such as the ATM gene or the mismatch repair genes--that often lead to cancer in humans. Then they expose these mutated yeast cells to a whole range of chemical compounds used in cancer therapy to find which ones will kill them. The results give clues as to how these drugs work and how they can be improved.

Image: ZFIN THE ZEBRAFISH is the simplest vertebrate animal studied by researchers in depth. While it develops, it is completely transparent.

Multicellular organisms lend themselves better to the study of other diseases, like Alzheimer's or diabetes. Drugs that help these and other conditions often interfere with so-called signaling pathways within cells. Along these pathways, many different messages--each of them taking the form of a protein--are passed, and each protein is a potential drug target. To find more of these targets--places where a medication might change the message or block the signal--researchers are looking for mutations in worms and flies.

"Let's say we want to find a new antidiabetic compound," explains Geoffrey Duyk, CEO of Exelixis, a California-based company that specializes in model organisms. "We know that in type II diabetes, most patients are essentially resistant to the action of insulin. So what you do in the model systems is you create one mutation, or a series of mutations, which makes those organisms resistant to the action of insulin. Then essentially what you are looking for is suppressor mutations, things which alter other genes, which change the sensitivity of the organism for insulin. And then you find the corresponding vertebrate genes and ask whether they do the same thing." And drugs acting on the products of these genes might have the same effect as the mutations--change the insulin response back to normal.

In the end, of course, understanding how the genes of a worm or fly work can never fully explain the human genome. "There is a second phase of any project, which is it needs to be extrapolated into mammalian cells. And that's independent of whether you are in yeast, in flies or in C. elegans," says Stephen Friend, president of Rosetta Inpharmatics in Seattle and formerly one of the coordinators of the Seattle project. But studying the genomes of other organisms stands to offer valuable, if indirect, lessons in understanding our own genes, once the race to read them is closed.

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