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

INTRODUCTION

With the advent of genetic engineering techniques in the 1980s, scien-tists sought to gain greater insight and understanding into the function of DNA-the material used by living organisms to store genetic information and transmit it to their offspring. Among other things, scientists needed to determine the exact sequence of human DNA in order to unlock the treasure trove of information that could lead to understanding health, development, and disease. In 1990, the U.S. Government embarked on the ambitious road to sequence the entire human genome. The successful completion of the Human Genome Project was originally targeted for 2006.

By 1993, the Human Genome Project was starting to gain momentum, but it became clear that the current technology was slowing progress. The technologies being used were developed in the 1980s, and were slow and laborious, limiting the information that could be generated and applied to solve important biological and medical problems. Even as the technological needs of the project became clearer, the U.S. Department of Commerce's Advanced Technology Program (ATP) was hearing from industry, academic, and government leaders involved in the project that the current technology would not fill the bill. To generate the massive amounts of sequence data involved and to then make good use of all these genetic data, better, faster, and lower cost DNA analytical tools were needed. Although it was clear that development of these new tools could best be accomplished within the private sector, the research and development (R&D) entailed posed both high technological and high business risks to companies. These risks made suffi-cient investment from venture and commercial sources unlikely-which in turn led to concerns that only an accelerated R&D approach would bring the much-needed technologies to the market in a timely manner. The ATP focused program "Tools for DNA Diagnostics" proved to be the catalyst for acceleration by the private sector.

ATP started its Tools for DNA Diagnostics focused program in 1994. Its mission was to accelerate DNA analytical tools R&D that would lead to earlier commercialization of those technologies. This new program would fund the development of high-risk technologies with the aim of producing the low-cost, rapid-throughput tools needed to facilitate an effort like the Human Genome Project and for use in low-cost diagnostics, agriculture, toxicology, food quality, and environmental applications. ATP conducted the Tools for DNA Diagnostics focused competitions in 1994, 1995, and 1998; it also funded DNA tools projects in general/open competitions as well. Through 2002, ATP had committed over $138 million to cooperatively fund 42 R&D projects on DNA tools. In addition, ATP funded several workshops and organized conference sessions involving project participants throughout the program period to enhance creation of synergistic collaborations across the research community and further accelerate dissemination of advancements.

ATP's DNA diagnostics projects, funded through the focused program and ATP general/open competitions, produced many innovative, new technologies including rapid methods of genotyping, fully automated and much faster DNA sequencing, and novel biological reagents. They also provided the critical mass needed to enable the commercialization of these new technologies. As a result of the Tools for DNA Diagnostics focused program, this emerging industrial sector benefited broadly from the resultant intellectual property portfolios of the funded companies, from the growth of new small companies into sustainable private sector contributors, and from the discoveries being made using the technologies they developed.

State-of-the-Art DNA Analysis in the Early 1990s

The early 1990s saw improvements in the techniques developed in the 1980s for extracting, manipulating, and sequencing DNA. Scientists were finding new methods to analyze DNA that were faster, easier, and less expensive to perform. The fields of molecular biology and genome analysis were moving to the forefront of biotechnology research, stimulating the demand for new and better technologies. In the early 1990s, automated methods of sequencing DNA (the determination of the exact order of nucleotides making up the genetic code) were spreading into broad usage. These methods used enzymes to cut huge chromosomes into manageable pieces of DNA and stained the resulting pieces with specialized fluorescent (light-emitting) dyes to tag the segments for detection while being sequenced on automated instruments. Extremely large capacity computers and advanced bioinformatic software was used to place DNA fragments into their original order, enabling scientists to read the DNA sequence. Scientists were thus able to identify genes and gene variants significantly faster than with previous methods. Other techniques were also coming into broader use. The most critical of these techniques included the polymerase chain reaction (PCR)-a method that could rapidly multiply specific gene sequences for further analysis, and gene expression analysis-determining which genes are turned on in different cells, which is critical for understanding the role of genes in health and disease

Despite the advances of the early 1990s, technology was still too costly, time consuming, and laborious to bring widespread application of DNA analysis into mainstream use in diagnostics, agriculture, toxicology, food quality, and environmental applications. Further, the Human Genome Project was just getting started and, as it turned out, would benefit greatly from the significant improvements in DNA analytical technology resulting from the ATP-funded projects.

The Human Genome Project

The Human Genome Project began in 1990 as a multi-participant initiative led by the National Institutes of Health (NIH), U.S. Department of Energy (DOE), and U.S. Department of Agriculture (USDA) to sequence the entire human genome by 2006. The development of a complete map and sequence of the human genome would provide the information needed to better understand the genetic basis of health and disease and open the door to a multitude of new applications of genomic information. The availability of this new genomic information would enable entirely new ways of analyzing and using DNA data, particularly in diagnostic applications. However, with the technology of the day, it was unlikely that the human genome sequence would be completed by the target date.

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

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