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Genomics

Evolution, the original Xerox machine...

Incyte's DNA databases are valuable because nature is thrifty. As single cells evolved to make mice and then men, many genes were kept on to do their old jobs. Incyte can line up the genes and recognize the similarities in the DNA sequences. (A DNA sequence is the order of the several thousand A, C, G and T nucleotides that make up a single gene.) If the function of a yeast gene is known, the function of the related human gene is, by implication, similar. And yeast genes are easier to study. "We don't put humans in Waring blenders and do experiments," says Smith, "but we do put yeast in Waring blenders."


"People have been blown away in recent years by the sequence comparisons," says Smith. "For example, in the fly the homeobox genes control what end is the mouth and what end is the ass, which apparently is very important. The same genes are used in mice, in exactly the same order. Once biology found a way to get a front and a back, she never did it again."


Pharmaceutical companies are worried about drugs not evolution. But drugs for complex diseases do not spring forth fully formed. Modern drug hunting means finding a chemical that jams a specific protein, and the first step is to find that protein target. Only then can you look through thousands of chemicals to find the one that turns the protein off. If the protein is needed for the virus to invade the cell, or for the cancer cell to multiply, then the chemical is your new drug. "In the past it might have taken a long time to find one drug target, but now you can quickly get multiple targets," says Klingler. "The priming of the pump is no longer a problem."

The most important proteins, like those that tell a cell when and how to grow, are often remarkably similar from yeast to man. In fact a number of human genes can replace their yeast counterparts and keep the yeast alive (some of these genes are listed on the Web). A drug company that searches the Incyte database and finds the human version of a yeast growth protein would count itself lucky: Chemicals that can turn off that protein might have anti-cancer activity.

The immune system has no counterpart in yeast cells, but targets for anti-inflammatory drugs can also be found in the Incyte databases. These searches rely on another result of nature's thriftiness: proteins come in families. Immune cells, for example, must send countless messages to each other. Rather than invent a completely new protein for each message, evolution has Xeroxed its first effort and made minor changes. Even if one of these messengers is useless as a drug target (perhaps turning it off shuts down the whole immune system), it may allow you to find its cousin, which is specific to the auto-immune disease lupus.

The power of DNA databases mushrooms with their size. Every new piece of DNA sequence means not only one more possible drug target, but also one more sequence to compare all the old sequences against. "The sequence comparison method is not new," says Smith. "What is new is how much data we have."

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