Shaping DNA data into tools

By JOSHUA L. KWAN

June 27, 2000 Web posted at: 2:52 PM EDT (1852 GMT)

SAN JOSE, California (San Jose Mercury News) -- Champagne bottles may still be popping in laboratories to celebrate the mapping of the human genome, but in Silicon Valley, Hugh Reinhoff is already off and running in the next race: turning that data into tools for diagnosing and attacking diseases.

Reinhoff and many others in the private sector have been charging ahead to find uses for the chunks of DNA sequence that the government has dribbled out along the way. Those bits of information are just part of the entire sequence of the human genome -- all the genes in a cell that together define the makeup of the human body.

Even with this latest scientific achievement, the book of instructions that tells a cell its function in life is still a raw, nearly incomprehensible jumble of roughly three billion letters. An onslaught of companies -- from those that manufacture machines analyzing genetic data to ones that write software for dissecting DNA to drug firms hoping to make more effective medications -- are rushing to fill in the punctuation, figure out the words and find meaning in the roughly 100,000 or so paragraphs that represent genes.

``The gene sequence success is as important to health care as Einstein's theory of relativity is to the development of technology,'' said Paul Knight, a genomics analyst at Thomas Weisel Partners in New York, calling the achievement ``the single biggest breakthrough in health care history.''

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And there's plenty of money to be made in the coming revolution in medicine. The 21st-century genomic Gold Rush reprises many of the same characters as the original version of 1849. There are companies that make the pickaxes and shovels like the DNA-sequencing and -analyzing machines of PE Biosystems and Agilent Technologies. Just as in the California Gold Rush, these companies are enjoying the early fruits of the discovery.

There are the middlemen, too. Bioinformatics companies such as Celera, Incyte Genomics and DoubleTwist are the information go-betweens that analyze data for the drug manufacturers. And then there are the armies of lab scientists at huge pharmaceutical companies and young biotech firms, sifting through thousands of automated drug trials that test chemicals' impact on gene expression and protein production.

At Reinhoff's start-up, DNA Sciences in Mountain View, the company hopes that deciphering the variations between genes of healthy and sick people will yield clues about a person's predisposition to diseases and reactions to medications.

The Johns Hopkins-trained doctor is the chief executive at DNA Sciences, which he founded in May 1998. Reinhoff is recruiting 5,000 patients in each of six categories of disease, including asthma, diabetes and breast cancer. The goal: to pinpoint the slight differences in a person's code of life that might show a higher probability for developing the disease.

If it works, the battle between doctor and disease could radically shift. Today, physicians are essentially in a defensive position, reacting to disease and trying to fend off its blows. Tomorrow, it may be possible to know if a patient is likely to develop an illness and the physician can then attack the problem before it surfaces, Reinhoff said.

``In 10 years, every dialogue with a doctor will begin with an assessment of a person's genome,'' he said. ``He'll want to know what my susceptibilities (to various diseases) are, what protective genes I may have, and then base his diagnosis and treatment plan on how my genetics determines how I metabolize drugs.''

Perhaps one of the first fruits of genomics to reach consumers will come from the joint venture formed by genetic information analyzer Incyte Genomics of Palo Alto and British pharmaceutical giant SmithKline Beecham. The two companies started DiaDexus Inc. in 1997 to develop diagnostic tools that detect the most prevalent forms of cancer and heart disease.

``We're focusing on simple blood tests to screen for major cancers,'' said Mohan Iyer, vice president of research and development at Santa Clara-based DiaDexus.

With the sequences of a large number of known genes already published, DiaDexus has delved into studying a portfolio of cancers: colon and rectal, breast, ovary, prostate and lung. The mapping announcement will only widen the spectrum of genes available to companies like DiaDexus.

The next stage after diagnostics -- tailoring medications to a person's unique genetic sequence -- is still years away. But pharmaceutical and biotech companies are plunging hundreds of millions of dollars into the creation of a whole new era of medication.

Much of the transformation of healthy cells to disease can be traced to how genes are expressed -- certain ones are turned on and off, producing proteins in too great or too little a quantity at inappropriate times. Drugs that interrupt this downward spiral, being developed by companies like Human Genome Sciences and Millennium Pharmaceuticals, might be able to prevent disease from even taking hold.

Another sector in genomics has been spawned: the providing of data to these genetic medicine men. Companies in this field, like Incyte, gather information on genes and assemble the analysis into databases for subscription to drug makers. While Incyte focuses only on the segments of DNA that comprise genes, Celera has gone toe-to-toe with government scientists mapping the entire human genome. Its plan is also to identify potential targets and sell that data to drug companies that have the resources and expertise to shepherd drugs down the laborious regulatory pipeline.

The government and Celera's achievement in sequencing the entire genome is quite a milestone, to be sure. But the race to decipher it all has kept plenty of others preoccupied with bringing that achievement into the hands of patients.

The promise and perils of the human genome
Genome announcement 'technological triumph'
Genome announcement a milestone, but only a beginning

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