Expansionary Institute

Michael Zey
futurist3000@aol.com

By Ben Hirschler, European pharmaceuticals correspondent

 
HINXTON, England (Reuters) - The gene machines at the Sanger Center near Cambridge, responsible for mapping a third of the human genome, are still whirring night and day.

Never mind that a working draft of the 3.1 billion letters in the "book of life" was completed on June 26. That is just the start of a coming tidal wave of genetic information.

Managing and interpreting the trillions of bits of data, or terabytes, generated by the genomics revolution is the biggest task facing biologists -- and a major business opportunity for computer companies.

"Informatics is going to be the key challenge in the future," said Richard Durbin, Sanger's deputy head and the man in charge of making the number-crunching work.

Sequencing the repeats of the four letters A, C, T and G, representing the nucleotides that make up DNA in humans and other species, has already piled up more than 22 terabytes of data on the Sanger Center's hard disk drives -- equivalent to more than twice the contents of the Library of Congress.

Durbin expects it to rise to 50-100 terabytes within two or three years as researchers investigate how a 3-billion-piece "parts list" embedded in our chromosomes determines the way we develop, age and fall victim to disease.

Both hardware and software companies are lining up to service this exploding market, which is providing business opportunities well beyond academic institutions like the Sanger Center, which is backed by the Wellcome Trust medical charity.

9 BILLION MARKET BY 2003

Biotechnology, pharmaceutical and agrochemical companies share the same requirement for supercomputing power, data storage and specialized software programs as they strive to apply genomic discoveries to new products.

That makes life science an increasingly enticing prospect for information technology companies, especially when sales of computers to other firms are showing signs of slowing down.

International Business Machines Corp. estimates the IT market for life sciences will surge from $3.5 billion this year to more than $9 billion by 2003 as the volume of life science data doubles every six months. "Big Blue" is designing products specifically for this new market, including a $100 million investment in a supercomputer known as "Blue Gene," designed to simulate protein folding.

Calculating the way a single human protein folds -- a key determinant in its interaction with other molecules -- is deceptively simple. But the possible permutations are so vast it will take the monster computer a year to do the calculation, even though it will be 1,000 times more powerful than "Deep Blue," the IBM machine that beat world chess champion Gary Kasparov in 1997.

Other computer firms have also awakened to the potential of the market unleashed by the genome. IBM's archrival Compaq Computer Corp., the world's biggest personal computer maker, is already a big supplier of servers to the life science sector -- including the Sanger Center.

In a bid to cultivate a new generation of clients, Compaq plans to invest $100 million in start-up biotech companies. Martin Walker, head of high performance computing for Compaq in Europe, sees a huge opportunity for his firm's top-of-the-range servers, which sell at substantially higher margins than PCs.
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SPENDING TO INCREASE

Nearly 10 percent of the aggregate research and development budget of the world's 12 biggest life science companies is already being spent on IT, and the figure is set to rise exponentially, Walker predicts. "Biology is going to become the dominant application in all of computational science."

Alongside the computer industry's big guns are a growing number of specialist bioinformatics companies springing up to service the booming market with customized software.

They include Germany's Lion Bioscience AG, whose Sequence Retrieval System is starting to establish itself as a new industry standard. Shares in Lion have surged 50 percent since their August debut.

"It's incredible how fast data is being put out in the public domain alone, and on top of that companies have proprietary databases which are also producing an incredible amount of data each day," Lion's chief scientific officer, Jan  Mous, said.

"The big challenge is to speed up analysis of that data so that you don't have to wait half an hour to get the result back from a query."

Other bioinformatics boutiques include U.S. firms Doubletwist, Genomica, Synomics and Inpharmatica, while integrated genomics companies like Incyte Genomics, Celera Genomics and Genaissance all offer differing levels of capability in the field.

11:04 12-01-00

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Tularik Discovers Genes Involved in Cholesterol Regulation
 
Researchers Link Mutations to Sitosterolemia, a Rare Genetic Disease  

SOUTH SAN FRANCISCO, Calif., Dec. 1 /PRNewswire/ -- Tularik Inc. (Nasdaq: TLRK) today announced the discovery of two genes responsible for a rare human genetic disorder. Tularik's researchers, working in collaboration with scientists from the University of Texas Southwestern Medical Center, have identified the genes that cause sitosterolemia. Patients with sitosterolemia have high cholesterol levels and typically develop life-threatening coronary artery disease. The discovery was published in the December 1 issue of Science.

The genes discovered encode two previously unknown protein molecules that are members of the class of ATP-binding cassette (ABC) transporter proteins. The newly discovered proteins, ABCG5 and ABCG8, latch onto cholesterol in the liver and small intestine. In the intestines, the proteins are responsible for blocking absorption of dietary cholesterol. In the liver, the proteins help excrete cholesterol into bile.

"While sitosterolemia is a rare disease, these findings represent a significant breakthrough for understanding the common forms of hypercholesterolemia. The genes we've discovered have very important functions. Essentially, they are gatekeepers of cholesterol absorption and secretion in the body," said David V. Goeddel, Ph.D., Tularik's Chief Executive Officer. "Our research has opened a path to the development of novel small molecule therapeutics that may be of use to a wide patient population."

In healthy individuals, cholesterol levels are maintained, in part, by the coordinate regulation of dietary cholesterol absorption in the intestine and excretion in the bile.  Patients with sitosterolemia have excessive absorption and inadequate excretion into the bile, which results in dangerously high cholesterol levels.  High cholesterol, in turn, can lead to plaque build-up in the arteries and coronary artery disease.

The Tularik team has succeeded in linking the disease to a molecular mechanism of action. "In addition, we've shown that the two genes in question are regulated by transcription factors called liver X receptors (LXRs)," said Bei Shan, Ph.D., Program Director of Lipid Disorders at Tularik. "Tularik has identified several synthetic compounds that bind to LXRs, and we're now evaluating these compounds in various animal models of hypercholesterolemia," he added.

Tularik's work with ABC proteins and LXRs is part of a larger research agenda focused on several biochemical targets, all of which may be important in the regulation of cholesterol levels in patients.

Tularik is engaged in the discovery and development of a broad range of novel and superior orally available drugs based on gene regulation. Tularik programs address cancer, CMV, diabetes, obesity, inflammation, immune disorders, lipid disorders and bacterial diseases, and a class of targets known as orphan nuclear receptors.  Tularik has established strategic partnerships with Japan Tobacco Inc., Roche Bioscience and Knoll AG. For additional information, visit Tularik's Internet website at www.tularik.com.

Statements in this press release that are not strictly historical are "forward-looking" statements as defined in the Private Securities Litigation Reform Act of 1995.  There can be no assurance that Tularik will obtain necessary regulatory approvals for its drug candidates or be able to develop a commercially viable pharmaceutical product.  These and other risks are more fully discussed in Tularik's SEC reports, including the report on Form 10-Q for the quarter ended September 30, 2000.


2/01/2000 07:00 EST www.prnewswire.com