Biochip Implants

A Shift From Detection to Prediction


Biochips to Transform Treatment of Disease
by Lawrence M. Fisher
New York Times

Source: San Jose Mercury News

December 21, 1999

Coming soon, to a chip near you, your own genes.

The biotechnology industry, which has long lived in the shadow of Silicon Valley and envied its many overnight successes, is now tapping into that same technology in a bid to speed up its own growth significantly.

These biochips look like the integrated circuits in a personal computer, but instead of containing tiny semiconductors, they are loaded with bits of actual DNA that make up genes or fragments of genes. Inserted in a PC-size analytical instrument, the chips allow scientists to perform thousands of biochemical experiments at a fraction of the cost and time required for traditional tests.

``This is a basic tool for change in the laboratory,'' said Michael R. Knapp, vice president for science and technology at Caliper Technologies in Mountain View. ``We have been operating with the test-tube paradigm for basically as long as anybody has been doing anything.''

Biochips, or microarrays, as they are also known, will bring genomics, the study of all the genes in a living organism, out of the research laboratory and into the daily practice of medicine. If genomics delivers on its promise, health care will shift from a focus on detection and treatment to a process of prediction and prevention. Fortunes will be made.

The initial market for the biochips has been in drug dis covery, and the major customers have been the large drug companies. By analyzing the subtle changes that occur in genes when a cell becomes cancerous or is infiltrated by a virus, scientists at these companies search for new molecular targets for drugs. This needle-in-a-haystack process could take many years using test tubes and petri dishes but is accelerated a thousandfold by biochip technology.

The market for biochemical research instruments is in the billions, and the transformational power of biochips has not gone unnoticed by the stock market. Shares in Affymetrix, of Santa Clara, the pioneering company in biochips, have risen more than fivefold the last year, giving the company a market value of about $3.08 billion. Other public companies in the field have had similar gains.

Genomics on a desktop

But the biochip makers are now chasing a bigger opportunity: personal genomics. Even as the public and private efforts to spell out the 3 billion biochemical letters that make up the human genetic code race to a conclusion, the biochip companies say they will bring genomics to an affordable desktop system that could be deployed in clinics and physicians' offices. Sophisticated genetic analysis could be performed at the individual level, making possible early prediction or detection of disease, more accurate diagnosis and customized therapy.

Originally the province of a handful of start-ups backed by venture capital and operating in a sort of gray area between Silicon Valley and the biotech world, the biochip market has lately attracted the attention of major electronics companies like Motorola, Hewlett-Packard, Texas Instruments and IBM, all of which have chips in development. Motorola's recent advertisements promote the company's ``digital DNA,'' while those of Hewlett-Packard proclaim the ``DNA of Silicon Valley.'' The message may be metaphoric, but the market is very real.

`A big business'

``The biochip space lies at the intersection between high-technology chip manufacturing, signal processing, software skills and more traditional molecular biology and genomics,'' said Nick Naclerio, vice president and general manager for Motorola's biochip systems division. ``So it seemed right for Motorola to get involved in what we think will ultimately be a big business.''

The biochip companies are one of three new industries that piggybacked on the human genome project, the multinational, decade-old effort to identify the 100,000 or more genes -- made from the 3 billion letters or base pairs of nucleotides -- that inform every aspect of human biology. That project is expected to be completed within a year or two, either by the national labs or private companies or, as seems most likely, a combination of the two.

Genomics companies like Human Genome Sciences, Millennium Pharmaceuticals, Incyte Pharmaceuticals and the Celera Genomics Group of PE Corp. rushed to beat the public effort by finding and patenting genes of medical utility. Bioinformatics companies, like and Informax, offer software to interpret genomic data. The chip companies, led by Affymetrix, offer a tool to automate the arduous lab work of biochemical research -- and maybe to do much more.

Fodor's paper

``We're going to burn a set of chips with the whole human genome,'' said Stephen P.A. Fodor, president and chief executive of Affymetrix. Fodor headed a group that pioneered the field of biochips, with a 1991 paper in the journal Science describing how photolithography, the standard process by which semiconductor companies etch circuits in silicon, could also be used to synthesize biological materials on a chip.

Companies like Eli Lilly, SmithKline Beecham and American Home Products have been eagerly buying Affymetrix's GeneChip arrays, helping to increase the company's revenues in the first nine months of this year to $65.7 million, from $35.8 million in the comparable period a year earlier.

Often lost in the excitement about the completion of the genome project is that the first human genome will be a consensus, culled from the DNA samples of dozens of anonymous donors. The sequence of each gene will be arrived at only after billions of taxpayer dollars and a decade of study in laboratories lined with $300,000 gene-sequencing machines and other elaborate devices. What the makers of biochips promise is to offer that same depth of information at the individual level and at low cost.

``As soon as the reference DNA is out there, this will move in a thousand different directions,'' Fodor said.

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