Technology Transfer 
Legislation 
Technology transfer involves converting scientific knowledge into commercially useful products. Through the 1980s, a series of laws was enacted to encourage the development of commercial applications of federally funded research at universities and federal laboratories. Such laws [chiefly the Bayh-Dole Act of 1980, Stevenson-Wydler Act of 1980, and Federal Technology Transfer Act of 1986 (Public Laws 96-517, 96-480, and 99-502, respectively)] were not aimed specifically at genome or even biomedical research. However, such research and the surrounding commercial biotechnology enterprises clearly have benefited from them. The biotechnology sector's success owes much to federal policies on technology transfer and intellectual property. [Source: U.S. Congress, Office of Technology Assessment, Federal Technology Transfer and the Human Genome Project, OTA-BP-EHR-162 (Washington, D.C.: U.S. Government Printing Office, September 1995)]

Transferring technology to the private sector, a primary mission of DOE, is strongly encouraged in the Human Genome Program to enhance the nation's investment in research and technological competitiveness. Human genome centers at Lawrence Berkeley National Laboratory (LBNL), Lawrence Livermore National Laboratory (LLNL), and Los Alamos National Laboratory (LANL) provide opportunities for private companies to collaborate on joint projects or use laboratory resources. These opportunities include access to information (including databases), personnel, and special facilities; informal research collaborations; Cooperative Research and Development Agreements (CRADAs); and patent and software licensing. For information on recently developed resources, contact individual genome research centers or see Research Highlights. Many universities have their own licensing and technology transfer offices. 

Some collaborations and technology-transfer highlights from FY 1994 through FY 1996 are described below. 

Collaborations 

Involvement of the private sector in research and development can facilitate successful transfer of technology to the marketplace, and collaborations can speed production of essential tools for genome research. A number of interactive projects are now under way, and others are in preliminary stages. 

CRADAs 
One technology-transfer mechanism used by DOE national laboratories is the CRADA, a legal agreement with a nongovernmental organization to collaborate on a defined research project. Under a CRADA, the two entities share scientific and technological expertise, with the governmental organization providing personnel, services, facilities, equipment, or other resources. Funds must come from the nongovernmental partner. A benefit to participating companies is the opportunity to negotiate exclusive licenses for inventions arising from these collaborations. For periods through 1996, the CRADAs in place in the DOE Human Genome Program included the following: 
 

• LLNL with Applied Biosystems Division of Perkin-Elmer Corporation to develop analytical instrumentation for faster DNA sequencing instrumentation; 
• LANL with Amgen, Inc., to develop bioassays for cell growth factors; 
• Oak Ridge National Laboratory (ORNL) with Darwin Molecular, Inc., for mouse models of human immunologic disease; 
• ORNL with Proctor & Gamble, Inc., for analyses of liver regeneration in a mouse model; and 
• Brookhaven National Laboratory with U.S. Biochemical Corporation to identify proteins useful for primer-walking methods and large-scale sequencing. 
Work for Others 
In other collaborations, the LBNL genome center is participating in a Work for Others agreement with Amgen to automate the isolation and characterization of large numbers of mouse cDNAs. The center group is focusing on adapting LBNL's automated colony-picking system to cDNA protocols and applying methods to generate large numbers of filter replicas for colony filter hybridization and subsequent analysis. ["Work for Others" projects supported by an agency or organization other than DOE (e.g., NIH, National Cancer Institute, or a private company) can be conducted at a DOE installation because this work is complementary to DOE research missions and usually requires multidisciplinary DOE facilities and technologies.] 

NIST Advanced 
Technology Program 

Several commercial applications of research sponsored by the U.S. Human Genome Project have been furthered by the Advanced Technology Program (ATP) of the U.S. National Institute of Standards and Technology. ATP's mission is to stimulate economic growth and industrial competitiveness by encouraging high-risk but powerful new technologies. Its Tools for DNA Diagnostics program uses collaborations among researchers and industry to develop (1) cost-effective methods for determining, analyzing, and storing DNA sequences for a wide variety of diagnostic applications ranging from healthcare to agriculture to the environment and (2) a new and potentially very large market for DNA diagnostic systems. 

Awardees have included companies developing DNA diagnostic chips, more powerful cytogenetic diagnostic techniques based on comparative genomic hybridization, DNA sequencing instrumentation, and DNA analysis technology. Eventually, commercialization of these underlying technologies is expected to generate hundreds of thousands of jobs. [800/287-3863, Fax: 301/926-9524, atp@micf.nist.gov]

The Resource for Molecular Cytogenetics was established at LBNL and the University of California (UC), San Francisco, with the support of the Office of Biological and Environmental Research and Vysis, Inc. (formerly Imagenetics). The Resource aims to apply fluorescent in situ hybridization (FISH) techniques to genetic analysis of human tissue samples; produce probe reagents; design and develop digital-imaging microscopy; distribute probes, analysis technology, and educational materials in the molecular cytogenetic community; and transfer useful reagents, processes, and instruments to the private sector for commercialization. 

Patenting and Licensing Highlights, FY 1994­96 
 

• A development license for single-molecule DNA sequencing replaced the 1991­94 CRADA (the first CRADA to be established in the U.S. Human Genome Project) between LANL and Life Technologies, Inc. (LTI). 
• In 1995, a broad patent was awarded to UC for chromosome painting. This technology uses FISH to stain specific locations in cells and chromosomes for diagnosing, imaging, and studying chromosomal abnormalities and cancer. Resulting from a 1989 CRADA between LLNL and UC, FISH was licensed exclusively to Vysis. 
• Hyseq, Inc., was founded in 1993 by former Argonne National Laboratory researchers Radoje Drmanac and Radomir Crkvenjakov to commercialize the sequencing by hybridization (SBH) technology. Hyseq has exclusive patent rights to a variation known as format 3 of SBH or the "super chip." Hyseq later won an Advanced Technology Program award from the U.S. National Institute of Standards and Technology to develop the technology further. 
•  Oligomers--short, single-stranded DNAs--are crucial reagents for genome research and biomedical diagnostics. ProtoGene Laboratories, Inc., was founded to commercialize new DNA synthesis technology (developed initially at LBNL with completed prototypes at Stanford University) and to offer the first lower-cost custom oligomer synthesis. The Parallel Array Synthesis system, which independently synthesizes 96 oligomers per run in a standard 96-well microtiter plate format, shows great promise for significant cost reductions. ProtoGene first licensed sales and distribution to LTI and, later, production rights as well. LTI operates production centers in the United States, Europe, and Japan. 
• The GRAIL-genQuest sequence-analysis software developed at ORNL was licensed by Martin Marietta Energy Systems (now Lockheed Martin Energy Research) to ApoCom, Inc., for pharmaceutical and biotechnology company researchers who cannot use the Internet because of data-security concerns. The public GRAIL-genQuest service remains freely available on the Internet (see box). 
• In 1995, an exclusive license was granted to U.S. Biochemical Corporation for a genetically engineered, heat-stable, DNA-replicating enzyme with much-improved sequencing properties. The enzyme was developed by Stanley Tabor at Harvard University Medical School. 
• In 1995, an advanced capillary array electrophoresis system for sequencing DNA was patented by Iowa State University. The system was licensed to Premier American Technologies Corporation for commercialization (see sidebar below left and R&D 100 Awards). 
• In 1996, a patent was granted to LANL researchers for DNA fragment sizing and sorting by laser-induced fluorescence. An exclusive license was awarded to Molecular Technology, Inc., for commercialization of the single-molecule detection capability related to DNA sizing (see R&D 100 Awards).

SBIR and STTR 
Small Business Innovation Research (SBIR) Program awards are designed to stimulate commercialization of new technology for the benefit of both the private and public sectors. The highly competitive program emphasizes cutting-edge, high-risk research with potential for high payoff in different areas, including human genome research. Small business firms with fewer than 500 employees are invited to submit applications. SBIR human genome topics concentrate on innovative and experimental approaches for carrying out the goals of the Human Genome Project (see SBIR, in Part 2 of this report). The Small Business Technology Transfer (STTR) Program fosters transfers between research institutions and small businesses. [DOE SBIR and STTR contact: Kay Etzler (301/903-5867, Fax: -5488, email] 

Technology Transfer Award 

A Federal Laboratory Consortium Award for Excellence in Technology Transfer was presented to Edward Yeung and a research team at Iowa State University's Ames Laboratory in 1993. Their laser-based method for indirect fluorescence of biological samples may have applications for routine high-speed DNA sequencing (see above left). Yeung also won the 1994 American Chemical Society Award for Analytical Chemistry. 

1997 R&D 100 Awards 

DOE researchers in 12 facilities across the country won 36 of the R&D 100 Awards given by Research and Development Magazine for 1996 work. DOE award-winning research ranged from advances in supercomputing to the biological recycling of tires. Announced in July 1997, these awards bring DOE's R&D 100 total to 453, the most of any single organization and twice as many as all other government agencies combined. 

Two DOE genome-related research projects received 1997 R&D 100 Awards. One was to Yeung  for "ESY9600 Multiplexed Capillary Electrophoresis DNA Sequencer." 

The other award was to Richard Keller and James Jett (LANL) with Amy Gardner (Molecular Technologies, Inc.) for "Rapid-Size Analysis of Individual DNA Fragments." This technology speeds determination of DNA fragment sizes, making DNA fingerprinting applications in biotechnology and other fields more reliable and practical. 

R&D Magazine began making annual awards in 1963 to recognize the 100 most significant new technologies, products, processes, and materials developed throughout the world during the previous year. Winners are chosen by the magazine's editors and a panel of 75 respected scientific experts in a variety of disciplines. Previous winners of R&D 100 Awards include such well-known products as the flashcube (1965), antilock brakes (1969), automated teller machine (1973), fax machine (1975), digital compact cassette (1993), and Taxol anticancer drug (1993).