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Clinical Chemistry 51: 661-671, 2005. First published January 13, 2005; 10.1373/clinchem.2004.045336
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(Clinical Chemistry. 2005;51:661-671.)
© 2005 American Association for Clinical Chemistry, Inc.

History

Fifty Years of Molecular (DNA/RNA) Diagnostics

Thomas R. Gingeras1, Russell Higuchi2, Larry J. Kricka3, Y.M. Dennis Lo4 and Carl T. Wittwer5,6,a

1 Affymetrix, Inc., Santa Clara, CA.
2 Roche Molecular Systems, Alemada, CA.
3 Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA.
4 Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, China.
5 Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT.
6 Associated Regional and University Pathologists (ARUP), Salt Lake City, UT.

aAddress correspondence to this author at: Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132. Fax 801-581-4517; e-mail carl.wittwer@path.utah.edu.

The first 300 words of the full text of this article appear below.

As the journal Clinical Chemistry celebrates its 50th birthday and enters its 51st year, we reflect on recent advances in nucleic acid diagnostics. Although the structure of DNA was also described ~50 years ago, only 20 years have past since a practical method of amplifying DNA for the clinical laboratory appeared, well known today as the PCR. Since the advent of PCR, growth in nucleic acid diagnostics has been extraordinary and is the fastest growing segment of many clinical laboratories. Clinical Chemistry is now subtitled The International Journal of Molecular Diagnostics and Laboratory Medicine in recognition of the importance of DNA/RNA diagnostics.

In this review, we offer personal perspectives on five key advances in molecular diagnostics by some of the pioneers in the field. Russ Higuchi reviews real-time PCR, which is an elegant solution for nucleic acid quantification in research and the clinical laboratory. Carl Wittwer describes DNA melting analysis as a simple and surprisingly powerful tool that can be seamlessly appended to PCR. Tom Gingeras reviews the increasing power of array technology, with feature density rivaling microelectronics miniaturization. Progress on integrated devices that combine cell separation, sample preparation, amplification, and analysis is described by Larry Kricka. Finally, the field of circulating nucleic acids is reviewed by Dennis Lo, with a myriad of clinical applications enabled by a new understanding of the biology of extracellular DNA and RNA.

Many early advances in molecular diagnostics have been highlighted in Clinical Chemistry. With DNA/RNA diagnostics becoming ever more important in the 21st century, the Journal serves as an advanced window into the future of molecular clinical chemistry.


Real-Time PCR

—Russ Higuchi

When late in 1986 I joined Cetus, the birthplace of PCR, "closed-tube" PCR using a thermostable DNA polymerase had just been achieved (1)(2). Before this, the thermolabile polymerase . . . [Full Text of this Article]


Melting Curve Analysis


Array Technology


Integration of Molecular Diagnostics on a Microchip


Circulating Nucleic Acids




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Copyright © 2005 by the American Association for Clinical Chemistry.