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March 5 & 12, 2001
Special: Technology and the Genome

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  Automatic sequencing machines


The sequencing of the human genome, described in Science magazine as "the crown jewel of 20th century biology," was led, of course, by life scientists. It will be life science researchers--molecular biologists and geneticists, many of them funded by the U.S. National Institutes of Health (NIH)--who will receive the Nobel Prizes and who will exploit the knowledge gained through this achievement. Sometimes overlooked in the excitement and the bombast, however, is the fact that the scientist who actually launched the Human Genome Initiative in 1986 (Charles DeLisi) was not from NIH but in fact was a staff member at the U.S. Department of Energy's Los Alamos National Laboratory. The DOE initiative began two years before the National Institutes of Health decided to commit to the effort. The DOE role is better understood in light of the fact that the genome project was biology's first major foray into the realm of "big science," large-scale organized, technology-intensive research pioneered by the national laboratories in the fields of atomic energy and high energy physics during and after World War II.

Another aspect that is sometimes forgotten is the fact that none of this would have been possible without modern computers and other advanced electronic technology. There are over 3 billion pairs of bases in human DNA. The automatic sequencing machines in use today (like those pictured above) can sequence 300,000 bases a day. What had been estimated to take 30 years when the project was first discussed in 1986, and 15 years a few years later, when the joint DOE-NIH effort was launched, turned into a race between a private firm (Celera Genomics) and the government-led effort and was actually accomplished in less than 3 years. Robots move the genetic material through a "production line,"analyze it, and record the results. Sophisticated computer programs assemble the staggeringly huge volumes of raw data into a form in which biologists can make sense of it. Electro-mechanical systems, lasers, sensors, and highly-capable computers all play key roles.

Just as defense and space programs drove the frontiers of technology in the 1960s and 1970s, continued work in genomics, and in the related field of proteomics (analysis of the set of proteins encoded by a genome), will push the frontiers of technology in the 21st century. In January 2001, Compaq Computer announced it was teaming up with Celera and DOE's Sandia National Laboratory to develop a 100 teraop (100 trillion operations per second) supercomputer by 2004. "We in the nuclear weapons community felt for many years nothing could be more complex than nuclear physics," observes Paul Robinson, president of Sandia, "I'm now convinced nothing beats the complexity of biological science."

Links:
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The National Human Genome Research Institute, a division of the U.S. National Institutes of Health. NHGRI was founded in 1989 and served as the U.S. partner in the International Genome Consortium, which published its sequence simultaneously with Celera. The Institute is directed by Dr. Francis Collins. Among its noteworthy features is an extensive program of studies of ethical, legal, and social implications of advances in genetics.

Celera Genomics. Based in Rockville, Maryland, this firm was founded by scientist Craig Venter, formerly of NIH, and PE Corporation (now Applera) in May 1998. Its stated mission is "to become the definitive source of genomic and related medical and agricultural information." Its sequence of the human genome was published simultaneously with that of the publicly-funded International Human Genome Consortium in February 2001.

Special issue of Science magazine devoted to the human genome and including the Celera paper, associated news reports, commentaries, analyses, etc. Access to the on-line edition of Science magazine is generally reserved for AAAS members and institutions with site licenses, but is free to all users for this issue.

Primer on Molecular Genetics, created by Denise Casey of the Human Genome Management Information System at Oak Ridge National Laboratory. Although the technology section is somewhat dated (it's from 1992), this is still a pretty good introductory discussion of the subject.

Audio and video clips relating to the genome project, including interviews with Francis Collins and Craig Venter, heads of NHGRI and Celera, respectively.

Stanford University's Genome Technology Center. One of its primary missions is to design technology and instrumentation for DNA sequencing and genomics.

"Gene Sequencing's Industrial Revolution." Summary of an article in IEEE Spectrum (November 2000) discussing advances in gene sequencing technology.

"Gene (DNA) Sequencing." Explanations of key concepts and technologies from Axys Pharmaceuticals.

"Gene Sequencing," from Paradigm Genetics.

"Two Cheers for Human Gene Sequencing," by Walter Gilbert and Walter F. Bodmer, The Scientist (October 20, 1986). Two distinguished scientists, one a Nobel laureate, discuss the prospects of sequencing the human genome in an editorial written around the time DOE effort was begun.

"A Beginners Guide to Genome Science," from the Centre for Integrated Genomics at the University of British Columbia, Canada. A short and easily understood introduction.


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