ORCH grouped in WSJ CELERA article as major in next phase of genomics!
June 26, 2000
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New Race Heats Up to Turn Gene
Information Into Drug Discoveries
By SCOTT HENSLEY
Staff Reporter of THE WALL STREET JOURNAL
Monday's expected announcement that Celera Genomics Group and a consortium of public researchers have finished sequencing much of the human genome is what some scientists are calling "the end of the beginning" in genomic research.
Painstaking putting into proper order the roughly three billion chemical letters that make up human DNA will have little practical value until scientists can use that information to find and understand the more than 60,000 human genes.
The real race, now heating up at biotechnology and drug companies around the world, is to be the first to find and patent the key disease-related genes.
"Genomics to me is not an end. It's a means to get better medicines out," says Dr. Goran Ando, president of research and development at Pharmacia Corp. in Peapack, N.J. The torrent of genetic information brings a bounty of new targets for drug development, he says, yet the sheer volume of data presents a daunting challenge. That's where "very sophisticated bioinformatics" comes in, Dr. Ando says.
A host of companies specializing in bioinformatics -- that is, the analysis and management of genetic data -- are jostling to take the raw genetic information and turn it into practical knowledge for drug discovery and development. Some are specialists serving drug companies; others are using the information to develop drugs themselves.
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Genetic Translators
Companies helping turn DNA data into drugs:
Company Approach Customers
Celera Genomics Group (Rockville, Md.) Sequencing champion and developer of genetic libraries plus software tools to analyze them Amgen, Novartis, Pfizer
CuraGen (New Haven, Conn.) Pinpoints genetic variations, function and level of activity to aid drug development Biogen, Hoffman-LaRoche, GlaxoWellcom
DoubleTwist (Oakland, Calif.) An Internet portal for genetics reasearchers with an assortment of databases and information management tools Chiron, Corp., Genaissance Pharmaceuticals, Tularik
Exelixis (South San Francisco, Calif.) Links human genes and disease by comparing genetic information from the fruit fly, round worm, yeast and man Bayer AG, Bristol-Myers Squibb and Pharmacia
GeneLogic (Gaithersburg, Md.) Combines software tools and genomic databases to determine the activity of genes in normal, diseased and treated conditions Merck & Co., Pfizer, Schering-Plough
Orchid BioSciences (Princeton, N.J.) Combines computerized databases and automated chemical analysis to analyze genetic diversity SmithKline Beecham, Millennium Pharmaceuticals, SNP Consortium
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Celera, a unit of PE Corp., has ambitions to become the premier provider of genetic information. But other companies are already busily analyzing human DNA, using public data from the consortium coordinated by the National Institutes of Health and sometimes their own sequences, to create competing services.
Making sense of the genome is "a decathlon, and the sequence was just one event," says John Couch, president and chief executive officer of DoubleTwist, a closely held Oakland, Calif. firm that is developing an Internet-based information service for genetics researchers. "The real work starts now," he says, "and it will take years."
"In a few years all the genes that are useful for treating diabetes, Alzheimer's and cancer will be known," says George Scangos, president and CEO of Exelixis, Inc., a genetic-information company in South San Francisco, Calif. For most diseases, he says, only 15 or 20 genes will turn out to be most important. "Whoever gets them first will get significant intellectual-property rights and a significant competitive advantage."
To stay ahead of its rivals, Celera is also expected to announce Monday that it has developed a "secret weapon" that will help make its proprietary DNA sequencing data more valuable to potential clients. Celera's chief executive, Craig Venter, plans to unveil a new method for rapidly assembling DNA that he claims will make Celera's data available more quickly and with higher accuracy than the data being produced by the public project -- so much so that drug makers and other clients will be willing to pay hefty annual subscription rates to access the company's map. The advance is the latest in a series of technical coups by Dr. Venter and his colleagues that has allowed Celera to become a major force in the human genome mapping enterprise.
But Celera already has stiff competition. From the 85% of the genome that the public group has already made available, DoubleTwist, for instance, has identified about 65,000 genes thus far and flagged 40,000 that merit closer examination.
CuraGen Corp., which is trying to develop gene-based drugs of its own as well as sell information services, claims that it has more scientists actively annotating the human genome than Celera even does.
"Genomics has taught us that it's right to do things on a big scale and systematically," says Dr. Jonathan M. Rothberg, chairman and CEO of CuraGen, based in New Haven, Conn. "We do not have laboratories. We have assembly lines." In less than two years, he predicts Curagen will have organized all the genes from the human genome into "functional pathways." Genes make proteins, he explains, and they work in complicated networks. Curagen aims to characterize those networks as a way to quickly develop drugs and antibody therapies.
Others are more niche players. Founded in 1995 by fruit-fly researchers, Exelixis has been building an infrastructure of databases on species favored by scientists for genetic research. Now the company can quickly determine the function of human genes by comparing them to well-studied animal models.
"We've positioned ourselves to be here waiting for the sequence," Dr. Scangos says.
Scientists say that comparing the human genome to those already completed for other creatures, including fruit flies, mice and even yeasts, will be particularly useful in teasing out meaningful genes. If a stretch of DNA is "important enough for evolution to conserve, then it's important enough for you to think about" as a researcher, says Dr. Richard Gibbs, who leads the sequencing center that is part of the public project at Baylor College of Medicine in Houston.
That's why Celera believes its new "secret weapon" will help keep it ahead of the competition. Already Celera is using its rapid DNA assembly system to produce the mouse genome. Celera expects that map, which scientists believe will be especially useful in identifying hidden genes involved in disease, to be completed by year end.
As with other techniques developed by Dr. Venter and Dr. Hamilton Smith, a Celera scientist and Nobel laureate, that have helped Celera speed up the sequencing effort, the new method defies conventional scientific wisdom. "It's the best secret we've had," says Dr. Venter.
Even so, finding a gene and even figuring out what it does are no guarantee for a quick disease cure.
"We've had our gene since 1989," says Dr. Robert Beall, president of the Cystic Fibrosis Foundation. Despite high hopes for a gene therapy that would repair the lung tissues of the 30,000 cystic fibrosis sufferers, none has emerged. Even drugs based on that genetic knowledge have so far not progressed beyond early clinical trials. Be excited, he says, but be mindful that cures take time.
"This has been tougher than we ever thought," Dr. Beall says.
Write to Scott Hensley at scott.hensley@wsj.com
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