The NIST Measurement and Standards Laboratories have a long history of working with the NIH, DOE, and other federal agencies that are leading the Human Genome Project to provide the needed tools and standards required for accurate measurements.

NIST has developed genetic standard reference materials to assure the accuracy and reliability of commercial DNA devices used in federal, state and local forensic laboratories, hospitals, pharmaceutical companies, etc.

Because of the proliferation of new genetic tests, there is a growing national need for standardized materials for assessing the quality and reliability of these tests. Additionally, fundamental measurement science needs to be expanded to understand and improve the capabilities of these new technologies.

Examples of measurement and standards research that NIST is providing for biologically based tests include:

· Development of accurate clinical measurement methods and diagnostic standards are made in collaboration with the College of American Pathologists. The CAP is a professional medical society serving more than 15,000 physician members and the clinical laboratory community throughout the world. The CAP has had several employees working at NIST full time on clinical methods and standards for more than 20 years.

· NIST provides reference materials used in quality assurance programs associated with clinical studies performed by many federal agencies and private professional organizations including FDA, NCI, CDC, and CAP.

· DNA standards are available as Standard Reference Materials for state and local crime laboratories that perform human identity testing to allow instrument calibration and to assure quality measurements. In 1998, the Director of the FBI approved a set of standard practices that prescribe the use of NIST standard materials to calibrate DNA measurement systems in federally-funded forensic testing laboratories.

· NIST performs research on the new area of microfluidics, a critical technology for the movement and control of small amounts of biological liquids to deliver samples on DNA chips.

· We also advance the measurement science of silicon surface interactions with DNA to understand the molecular processes required for the manufacturing of genetic test chips.

In 1999, a NIST DNA sequencing standard is being released to the public in the form of well-characterized mitochondrial DNA from a human cell line developed at NIST. This material will provide the entire mitochondrial DNA sequence of 16,549 nucleotide bases so that any laboratory will be able to check their own laboratory sequencing procedures.

For cancer diagnostics, NIST is completing work on a set of well-characterized DNA standards for calibrating genetic tests that measure mutations in the p53 tumor suppressor gene. Tests for this gene may be important to assess the aggressiveness of certain tumors. P53 mutations are found in about half of all breast and colon cancers.

In the area of genetic diseases, NIST is also preparing standards for tests of Fragile X disease. Fragile X syndrome is the most common genetically-inherited form of mental retardation, affecting approximately 1 in 1,000 males and 1 in 2,500 females. Physicians depend upon accurate test measurements, the deviation from which can make a large difference in the prognosis of the severity of the disease.

The Human Genome Project provides the basic information on the genetic makeup of humans. The logical follow-on is to understand the function of the genes found in the HGP database. The ultimate products that are coded by the genes are a set of proteins that are key parts of virtually every structure and function in the human body. This year, NIST will become a partner with Rutgers and the San Diego Supercomputer Center, in managing the Protein Data Bank (PDB). The PDB, jointly funded by NSF, NIH and DOE, contains annotated data describing the three dimensional structure of more than 8000 proteins and is the only database of its kind in the world. All data are publicly available through several web sites including, http://rcsb.nist.gov. The Protein Data Bank is of great value in relating protein structure and function and is therefore an essential complementary activity to the Human Genome Project.

NIST is intensifying efforts to develop critical standards for the genetic testing community so that they may assure the accuracy of their measurements. NIST will continue and expand collaborations with government agencies, such as the Food and Drug Administration, Health Care Financing Administration, Center for Disease Control and Prevention, National Cancer Institute, private technical organizations such as the College of American Pathologists and the Association of Molecular Pathologists and U.S. industry to perform this function.

Additionally, over the next several years we will focus efforts to develop technical tools for accreditation programs. The College of American Pathologists provides accreditation for clinical laboratories and the Molecular Pathology Committee of CAP is working on establishing accreditation and proficiency assessment programs for genetic testing. Existing accreditation programs using NIST standards for genetic testing in the forensic community are administered by the American Society of Crime Laboratory Directors and can provide the template for our future programs in clinical areas.

We will seek to develop a National Quality Assurance System for genetic testing in conjunction with organizations such as the National Committee for Clinical Laboratory Standards. This involves developing a national traceability system similar to other programs that have been developed for many federal agencies.

NIST will need to continue funding research leading to the development of new DNA technologies through its ATP partnerships. The ATP DNA diagnostics program attributes much of its success to collaborations with other federal agencies. Particular thanks go to Francis Collins, Director of the National Human Genome Research Institute of NIH, and to other leaders of the Human Genome Project who have allowed us to make massive use of their personnel in ATP planning, proposal evaluation, and project assessment. NIST also must continue to meet the burgeoning opportunities afforded by the HGP by further developing and refining the measurement and standards infrastructure that allow industry to assure the quality of their commercial products and improve U.S. global competitiveness. NIST looks forward to continued partnering with NIH, other federal agencies, and U.S. industry in the exciting developments that will undoubtedly come from the Human Genome Project. Thank you and I will be happy to answer any questions.