NIST Industrial ImpactCompany: Affymetrix Inc., Santa Clara, California Company: Molecular Dynamics, Sunnyvale, California In just a few years, proposals for ultrafast, miniaturized DNA analyzers have evolved from conceptual curiosities to valuable hardware that already is being applied to detect genetic variations related to breast cancer, compare human and primate genes, test the purity of food and cosmetics, and improve agricultural crops. The DNA chip, for example, is prized by scientists because it can perform so many tests at once in a small, convenient format. "Everybody's trying to get their hands on it," says Jeff Schloss, technology development coordinator for the National Institutes of Health's National Human Genome Research Institute (NHGRI), part of the international effort to determine the chemical makeup of all 100,000 human genes. The current enthusiasm of scientists, the popular media, and stock market analysts makes it easy to forget the recent skepticism of so many. One of the few early supporters was NIST's Advanced Technology Program (ATP), which is credited with hastening the development of these tools as a means of transforming the diagnosis and treatment of disease and slashing costs in the trillion-dollar U.S. health-care industry The ATP-funded research, which is being performed by two small biotechnology companies in California, will continue into 1999 but already has had a substantial impact:
All this from an idea that just recently was seen as lacking near-term economic viability. "We wouldn't have been able to do it without ATP," says Robert Lipshutz, vice president of corporate development for Affymetrix, the project sponsor. "What's more, the ATP money helped to validate what we were doing for our partners and in the eyes of the investment community." The technical success achieved so far has derived from the joint efforts of Affymetrix and Molecular Dynamics to design a low-cost, handheld DNA diagnostic device that can analyze blood samples quickly, accurately, and inexpensively enough for routine use in doctors' offices. The joint venture also involves five leading research laboratories and universities. The Miniature Integrated Nucleic Acid Diagnostic (MIND) device will feature a combination of three component systems. The ATP funding has enabled advances in sample preparation, data analysis, and chemistry and helped validate these components, which are already being sold separately for research purposes while ATP-funded work continues to combine and miniaturize features and make the resulting devices robust and easy to produce. Affymetrix makes DNA chips (or probe arrays), which borrow a process from semiconductor manufacturing to pack thousands of gene sequences on a keychain-sized unit that detects matches in blood or tissue samples up to 100 times faster than conventional methods. The current system includes a fluidics station that controls the introduction of test samples to the probe array, a scanner to read test results, and software to analyze and manage data; eventually the entire process may be performed on a chip. The initial chip products detect genetic variations related to human cancer, drug metabolism in humans, and drug resistance in the virus that causes AIDS as well as the expression patterns of sets of select genes. After its GeneChip system was first commercialized in April 1996, Affymetrix's product sales grew to $4.7 million in 1997. In addition, Affymetrix has received $5.5 million from NHGRI to develop applications. NHGRI also had awarded Affymetrix $2.1 million over three years to develop the underlying technology. Affymetrix has signed agreements with a number of companies for various projects in drug discovery, linking genetic variations to disease, and disease management. Under one of these agreements, diagnostic tests are being developed to detect microbial contamination of food and cosmetic products, signaling the start of a technology transfer process from the initial biomedical research applications to other industry sectors. For example, DNA diagnostics also might be applied in fields such as forensics, environmental monitoring, toxicology, assessment of biological diversity, bioremediation, industrial processing, and animal husbandry. The future economic value of genomics (the analysis of life's genetic blueprint) is suggested by a comment in the March 31, 1997, issue of Fortune magazine, in which a Lehman Brothers analyst predicts that one or more of the leading companies in this field will have a market value of $40 billion by 2010. Molecular Dynamics has used the ATP funding to build and demonstrate two systems that are expected to contribute to the MIND device. One system sorts and sequences DNA in 96 tiny capillaries (tubes the size of a human hair) instead of the traditional slab of gel. About 20 of these desktop-sized systems have been sold, notes David Barker, vice president of research and business development, who says the ATP funding accelerated the company's research by about two years. These systems, which Barker describes as still in the "late testing" stage, already are used in many HGP laboratories because they can determine the chemical makeup of unknown DNA faster than conventional methods and they eliminate the need to pour gels manually, Schloss says. Molecular Dynamics has received $2 million from the National Human Genome Research Institute to develop an automated sample preparation process. Molecular Dynamics also makes DNA microarrays, chip-like devices containing thousands of test spots. These systems can be customized by users to analyze gene function thousands of times faster than conventional methods for a fraction of the cost, because they can analyze so many genes at the same time, Barker says. "It's a whole new paradigm." Demand for the precommercial microarrays is so strong that, in partnership with a major biotechnology supplier, Molecular Dynamics has signed agreements giving 12 collaborators access to the technology. Under one agreement, the companies are working with a customer to study gene function in plants and accelerate the development of products that promote plant health and disease resistance. While the use of these new technologies spreads across the economy, it is still human health that stands to benefit the most. Lipshutz maintains that the single most promising application of the MIND device is "true therapeutic managed care that understands every patient's unique genetic response to treatment, gauging the impact of treatment, and tailoring it to the individual." April 1998 |