ATP Working Paper Series—Working Paper 04-01
Catalyzing the Genomics Revolution: ATP's Tools for DNA Diagnostics Focused Program

IMPACTS AND DIRECTION

Impact on Genomics Technology

The Tools for DNA Diagnostics focused program met the overall technical and business goals of accelerating the commercialization of high-risk technology that would enable lower cost, more rapid DNA analysis for diagnostic purposes. It also contributed to accelerating the time line for completion of the Human Genome Project by three years. The ATP focused program helped revolutionize the field of medicine by encouraging companies to develop technologies they would probably have put on the back burner or abandoned had they not received government funding. Projects funded under this program resulted in the following accomplishments:

• Development of a "Lab-on-a-Chip" a microfluidic device that efficiently separates, purifies, and analyzes DNA samples in very small assay volumes resulting in higher throughput and reduced costs.
• Production of a new enzyme for use in DNA analyses (PCR) that enables efficient DNA sequencing and has become the "gold standard" for this technique.
• Building of a novel mass spectrometry system for rapidly sequenc-ing DNA (this is currently undergoing early stage commercial testing).
• Demonstration of a novel method of detecting single nuclear polymorphisms (SNPs) for use in a variety of clinical applications (products based on this technology are currently on the market).
• Development of a rapid, automated DNA karyotyping system for clinical use in analyzing chromosomes for genetic disorders (a prototype system is currently undergoing early stage testing).
• Commercialization of a new diagnostic test that identifies breast cancer patients eligible for treatment with a novel anticancer drug.
• Commercialization of a portable genetic analysis system for use in molecular diagnostics.
• Development of a system that enables direct detection of bacteria or cells from blood.

Broad-Based Impact of Technical Achievements

Not only have the Tools for DNA Diagnostics projects successfully accelerated lower cost DNA diagnostic technologies toward commercial-ization, but many spillover benefits have also been realized. These benefits have resulted in new technical achievements as well as broader benefits to the emerging industry sector. According to Dr. Michael Knapp, CEO of Caliper Technologies, "the Tools for DNA Diagnostics program had a huge impact on the industry. It put advanced technolo-gies for life sciences on the map." This created critical mass for the industry, which "validated genomic technologies" and set the stage for "market expansion and enhanced competitiveness," explains Dr. Robert Lipshutz, vice president of corporate development at Affymetrix. Other significant benefits of the program include the following:

• By the year 1999, the cost of performing an SNP analysis had fallen to under $1.00.¹
• In the late 1980s, the cost of sequencing a base pair of DNA was approximately $5.00. As of November, 2002, this sequencing cost has fallen to $0.09.²
• Various technologies developed during ATP projects have led to the establishment of an entirely new market-the study of gene expression using DNA arrays. Project participants Affymetrix, Molecular Dynamics, and Combion all played a role in this emerging market by demonstrating the ability to perform DNA expression analysis with DNA microarrays (gene-chips), developing new methods for producing arrays, and improving data management.

All major pharmaceutical and biotechnology companies now use DNA microarrays as part of their drug discovery and development efforts. Insights into the mechanism of various cancers and the discovery of improved treatment regimens have resulted from the application of this technology.

Some observers credit ATP as the "godfather" of the U.S. biochip industry. Some examples supporting ATP's role in establishment of this industry include the following:³

• Affymetrix (Santa Clara, CA) started independent operations in 1993 and received an ATP award in 1994. It had 512 employees in 1999, with sales totaling $201 million in 2000.
• PE Biosystems (Foster City, CA) received ATP awards in 1994, 1995, and 1998. The company had 3,504 employees in 1999 with $1.4 billion in sales in 2000.
• Vysis ( Downers Grove , Illinois ) was incorporated in 1991 and received its first ATP award in 1994. By 1999, Vysis had 138 employees and in 2000 reached $21 million in sales. Notes Uwe Miller, the company's director of advanced technology, "Two-thirds of all of Vysis's current technology, and all of our future technology, can be traced back to ATP funding."
• Nanogen (San Diego, CA) was founded in 1993 and received an ATP award in 1995. By 1999, the company had 142 employees; by 2000, it had reached $11 million in sales. The ATP funding award was "like a godsend" in "getting us going as a company," says James O'Connell, Nanogen's vice president of research.

As part of a project to develop a fully integrated DNA assay system, Molecular Dynamics created a 96-array capillary electrophoresis system (a high-efficiency method to separate DNA fragments so they can be analyzed after being cut and stained). This system formed the basis for a new DNA sequencing instrument that enabled high-throughput sequencing at a significantly lower cost. Commercialization of this instrument sparked an intense competi-tion among manufacturers that spurred the development of technological improvements and expanded the use of these instruments.

U.S. Biochemical (since acquired by Amersham Biosciences) received funding to develop new enzymes that operate at high temperatures. Notably, the company produced a modified DNA synthesis enzyme, or polymerase, that could be used at high temperatures making it ideally suited for use in PCR (PCR repeatedly heats and cools the DNA in order to promote gene multiplica-tion). This enzyme became a significant success in the DNA analysis market. Soon, other researchers and manufacturers entered the field and contributed to the growth of this innovative and competitive marketplace.

The $138 million total investment by ATP on all projects supporting DNA diagnostic technologies not only spurred the development of cutting-edge biotechnology but also enabled companies to grow and contribute to sustaining this new industry sector. Thirteen of the funded companies are now public companies, adding jobs and fostering new businesses. And, further enhancing U.S. competitiveness, 179 new patents have been filed as a result of projects funded by the ATP in this area (see appendix A). One technology that was significantly advanced under the program, DNA-chips, is fast becoming a multibillion-dollar market.

Future Directions in DNA

The technical innovations funded by ATP accelerated the analysis, understanding, and application of DNA information. Industry-led research emphatically shows that there is room for further refinement and expansion of the technology in various applications such as pharmacogenomics, proteomics, and homeland security. Additionally, the evolution of the technology has created new scientific and manufacturing challenges that will require future high-risk and innovative solutions.

Return to Table of Contents or go to next section of working paper.

Date created: August 1, 2005
Last updated: August 5, 2005