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
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."