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Computers Quicken Pace of Race for Cures

Pharmaceutical and Biotech Firms Rely on Sophisticated Software to Identify Origins of Genetic Disease


Responding to an eruption in the science of human genetics, pharmaceutical and biotechnology companies are turning to the computer to mine a mountain of information in their search for new treatments for disease.

These companies are using sophisticated software to identify the genes and proteins responsible for a variety of human ills. One biotech firm found a rare gene defect that causes premature aging and early death. Another found a new way to treat patients in the final stages of heart failure. One company is sifting through human genes to find those that play a role in adult diabetes. Others are searching through catalogs of human enzymes to find promising drug targets to fight cancer and arthritis.

Many of these companies have relied on free, publicly available computer programs for sorting through huge libraries of electronic data, or have developed specialized software of their own. But the pace of discovery has accelerated, and many are looking outside to buy software packages that can make sense of the growing mass of information.

In recent months, that's meant a booming business for software firms that have mastered developments in genetic engineering--with several licensing their programs to major drug companies.

The application of computers to genetics has been spurred by the Human Genome Project--the multibillion-dollar attempt to provide a detailed map of human heredity by 2005. Together with commercial research efforts that may be moving even faster, the federally funded project aims to spell out all 3 billion genetic letters that make up an individual's DNA.

That's enough information to fill a thousand phone books of a thousand pages each. Without computers, the pages would be largely gibberish--page after page written out in the four letters of the genetic code--GCTA--without spaces between the words and little in the way of punctuation. No solitary researcher, working with notebook and pencil at his laboratory bench, could glean much of value from such a genetic labyrinth.

"The goal is to find the genes among a gigantic library of books," said Pierre Baldi, chairman of Net-ID, a small genetics software company with offices in Los Angeles and San Francisco. "With the naked eye, you cannot make any sense out of it."

This melding of biology and computer science has been awkwardly christened "bioinformatics."

Many of the firms that are building the new software look more like high-tech start-upsthan biotech laboratories. Typically they have assembled teams that include biologists and computer programmers, as well as those rare individuals who can move with comfort between the two worlds.

"You need people who are trained across disciplines, who know biology and know computing," said Thomas G. Marr, president and scientific founder of Genomica Corp., in Boulder, Colo., which last month licensed its software to drug giant Glaxo Wellcome. Marr is the prototype of the new computer-geneticist--he has degrees in systems engineering and biology.

A Gargantuan Task

Putting together all the fragmentary knowledge of human genetics "couldn't be done without the computer," he said. "It was too big a job; there were too many things that need to be compared."

Without sophisticated computer software, "it's like emptying the ocean with an eye dropper," said Joel Bellenson, one of the co-founders of Pangea Systems of Oakland, which in July licensed its systems to Eli Lilly & Co. "We're trying to provide [our customers] with aqueducts and pipelines."

At one level, the software provides a convenient way of organizing and retrieving data from a variety of sources--like a computerized catalog that lists the contents of a large number of libraries.

But the software has become much more ambitious than that by using tricks developed for military targeting and voice recognition. To determine a gene's function, it can search out similar genes that have been identified in a variety of species. Or it can identify a series of genes that work together inside specialized human tissues such as the liver, the brain or the pancreas. Or zero in on differences between normal cells and those that have been transformed by cancer.

And the most ambitious software attempts to predict the three-dimensional shape of the proteins produced by genes and then identify potential drugs that could fit into the spaces of the larger molecules and block their action.

At Metabolex Inc., a biotech company in Hayward, scientists are using the Pangea software to seek out the many genes involved in adult diabetes. The plan is to find genes activated in normal cells, compare them with those found in diseased cells and eventually design drugs that will treat the diabetes.

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