Future Perspectives on Nucleic Acid testing

The molecular structure of DNA was established in 1953, and the genetic code was deciphered in 1966. There followed a rapid surge in both fundamental and applied nucleic acid research that laid the foundation for in vitro nucleic acid-based diagnostic tests, and culminated in the draft sequence of the 3.2 gigabase human genome in 2000 (1, 2) (see also the Smithsonian Institute Archives, DNA sequencing and video history collection; http://siris-archives.si.edu). During this period the regulatory approval of in vitro nucleic acid tests has proceeded at a relatively cautious pace. In 1985 the Food and Drug Administration (FDA) granted the first clearance for a clinical diagnostic based on nucleic acid probe technology to Gen-Probe Inc. (San Diego, CA) for a culture confirmation test for Legionnaire’s disease, and in 1988 approved a test for detecting infection by the human papilloma virus (ViraPap assay, Life Technologies Inc., Rockville, MD) as an indicator of risk for the development of cervical cancer. The FDA approved the first viral load test in 1999 (the Roche Amplicor HIV-1 Monitor Test), and the first DNA-based laboratory test for an inherited disorder in 2003, when they approved a test for blood clotting abnormalities arising from the Factor V Leiden and the Factor II genetic abnormalities. The issues confronting nucleic acid testing are diverse and incompletely resolved. For example, the medical significance of DNA sequence variation is as yet, not fully understood. Also, none of the current sequencing or testing methods is either simple or direct, and this drives continuing innovation in sample preparation and testing technology. Finally, the advent of nucleic acid testing has generated legal and ethical issues over access and dissemination of an individual’s DNA sequence. This chapter reviews key issues in nucleic acid testing, and surveys selected advances and new directions in nucleic acid assay technology since 2000, and also explores some of the continuing challenges to the implementation of nucleic acid tests.