| echnologies Catalyze a New, High-Profile Life | | | | repay fundamental public investments. Following |
| Sciences Industry | | | | are a few key public R&D contributions that |
| The deluge of data and related technologies | | | | made some current genomics ventures |
| generated by the Human Genome Project (HGP) | | | | commercially feasible. These examples describe |
| and other genomic research presents a broad | | | | DOE investments, but substantial commitments |
| array of commercial opportunities. Seemingly | | | | by NIH and the Wellcome Trust in the United |
| limitless applications cross boundaries from | | | | Kingdom were equally important. |
| medicine and food to energy and environmental | | | | Scientific Infrastructure. The scientific foundation |
| resources, and predictions are that life sciences | | | | for a human genome initiative existed at the |
| may become the largest sector in the U.S. | | | | national laboratories before DOE established the |
| economy. | | | | first genome project in 1986. Besides expertise in |
| Established companies are scrambling to retool, | | | | a number of areas critical to genomic research, |
| and many new ventures are seeking a role in the | | | | the laboratories had a long history of conducting |
| information revolution with DNA at its core. IBM, | | | | large multidisciplinary projects. |
| Compaq, DuPont, and major pharmaceutical | | | | Genomic Science and Pioneering Technology. |
| companies are among those interested in the | | | | GenBank, the world's DNA sequence repository, |
| potential for targeting and applying genome data. | | | | was developed at Los Alamos National Laboratory |
| In the genomics corner alone, dozens of small | | | | (LANL) and later transferred to the National |
| companies have sprung up to sell information, | | | | Library of Medicine. Chromosome-sorting |
| technologies, and services to facilitate basic | | | | capabilities developed at LANL and Lawrence |
| research into genes and their functions. These | | | | Livermore National Laboratory enabled the |
| new entrepreneurs also offer an abundance of | | | | development of DNA clone libraries representing |
| genomic services and applications, including | | | | the individual chromosomes. These libraries were a |
| additional databases with DNA sequences from | | | | crucial resource in genome sequencing. |
| humans, animals, plants, and microbes. | | | | Sequencing Strategies. When the HGP was |
| Other applications include gene fragments to use | | | | initiated, vital automation tools and high-throughput |
| for drug development and target identification and | | | | sequencing technologies had to be developed or |
| evaluation, identification of candidate genes, and | | | | improved. The cost of sequencing a single DNA |
| RNA expression information revealing gene | | | | base was about $10 then; today, sequencing |
| activity. Products include protein profiles; particular | | | | costs have fallen about 100-fold to $.10 to $.20 a |
| genotypes associated with such specific medically | | | | base and still are dropping rapidly. |
| important phenotypes as disease susceptibility and | | | | DOE-funded enhancements to sequencing |
| drug responsiveness; hardware, software, and | | | | protocols, chemical reagents, and enzymes |
| reagents for DNA sequencing and other | | | | contributed substantially to increasing efficiencies. |
| DNA-based tests; microarrays (DNA chips) | | | | The commercial marketing of these reagents has |
| containing tens of thousands of known DNA and | | | | greatly benefitted basic R&D, genome-scale |
| RNA fragments for research or clinical use; and | | | | sequencing, and lower-cost commercial diagnostic |
| DNA analysis software. | | | | services. |
| Broader applications reaching into many areas of | | | | Sequencing Technologies and Biological Resources. |
| the economy include the following: | | | | Other major factors in cost and time reduction |
| * Clinical medicine. Many more individualized | | | | are greatly improved sequencing instruments and |
| diagnostics and prognostics, drugs, and other | | | | efficient biological resources such as the following: |
| therapies. | | | | * DOE-funded research on capillary- based DNA |
| * Agriculture and livestock. Hardier, more | | | | sequencing contributed to the development of the |
| nutritious, and healthier crops and animals. | | | | two major sequencing -machines now in use. The |
| * Industrial processes. Cleaner and more efficient | | | | core optical system concept of the Perkin-Elmer |
| manufacturing in such sectors as chemicals, pulp | | | | 3700 sequencing machine (used by Celera and |
| and paper, textiles, food, fuels, metals, and | | | | others) was pioneered with DOE support. The |
| minerals. | | | | instrumentation concepts that matured as the |
| * Environmental biotechnology. Biodegradable | | | | MegaBACE sequencer were pioneered by Richard |
| products, new energy resources, environmental | | | | Mathies (University of California, Berkeley). The |
| diagnostics, and less hazardous cleanup of mixed | | | | DOE JGI chose this sequencing hardware platform |
| toxic-waste sites. | | | | after competitive trials. |
| * DNA fingerprinting. Identification of humans and | | | | * DNA sequencing originally was done with |
| other animals, plants, and microbes; evolutionary | | | | radiolabeled DNA fragments. Today, DOE |
| and human anthropological studies; and detection | | | | improvements to fluorescent dyes -decrease the |
| of and resistance to harmful agents that might be | | | | amount of DNA needed and increase the |
| used in biological warfare. | | | | accuracy of sequencing data. |
| From the start, HGP planners anticipated and | | | | * Bacterial artificial chromosome (BAC) clones, |
| promoted the private sector's participation in | | | | developed in the DOE program, became the |
| developing and commercializing genomic resources | | | | preferred starting resource in sequencing |
| and applications. The HGP's successes in | | | | procedures because of their superior stability and |
| establishing an infrastructure and funding | | | | large size. A critical component of public- and |
| high-throughput technology development are | | | | private-sector sequencing, BACs were used to |
| giving rise to commercially viable products and | | | | assemble both the draft and final human DNA |
| services, with the private sector now taking on | | | | reference -sequences. |
| more of the risk. | | | | * Further extending the usefulness of BACs, the |
| A Public Legacy | | | | DOE HGP funded the production of sequence tag |
| Substantial public-sector R&D investment often is | | | | connectors (STCs) from BAC ends. This early |
| needed in feasibility demonstrations before such | | | | information enabled the selection of optimal BACs |
| start-up ventures as those by Celera Genomics, | | | | for complete sequencing, thus saving time and |
| Incyte, and Human Genome Sciences can begin. In | | | | money. STC use for the HGP was advocated by |
| turn, these companies furnish valuable commercial | | | | Craig Venter and Nobelist Hamilton Smith (both at |
| services that the government cannot provide, and | | | | Celera), and Leroy Hood (now at the Institute for |
| the taxes returned by their successes easily | | | | Systems Biology). |