Genomics Giants Receive Awards for Research

Things don't always turn out as planned.

Eric Lander admits to having no formal biology training, yet he is involved in one of today's leading biology research projects, sequencing the human genome, as director of the Whitehead Institute/MIT Center for Genome Research.

An open mind and a keen interest in current events led him from teaching business at Harvard to MIT's genomics research center. He followed the trail to biology backward from mathematics, starting with the multi-piece puzzle of mathematical neurobiololgy and then focusing on its individual pieces, genetic building blocks.

At a ceremony November 27, 2001, Lander was one of three scientists honored for their achievements in genetics. Sydney Brenner and J. Craig Venter were also honored. Since its creation in 1977, the Novartis/Drew Award in Biomedical Research has been presented to 75 scientists in recognition of their achievements.

Lander's resume is nothing short of a novel. While in high school, he won the Westinghouse Scholarship. He attended Princeton University as a mathematics student, where he earned his Ph.D., and was also a Rhodes scholar. As both an undergraduate and graduate student, Lander knew nothing about biology. After earning his Ph.D., he spent the next nine years teaching economics at Harvard Business School. A friend introduced him to mathematical neurobiology, and he soon moved to MIT's Whitehead Institute. In 1993, he founded Millennium Pharmaceuticals.

Unlike Lander, Sydney Brenner had an acute interest in science from the very beginning. Brenner grew up in South Africa, and sped through high school, graduating two years early. His achievements would not have been possible without the help of a neighbor, who taught him how to read and fostered his love of learning. His parents were illiterate.

Brenner won a scholarship to a local university where he studied medicine. Upon graduating, he found that he was too young to obtain a medical license and turned to research instead, traveling to Oxford University in England. It was there that he made some of his most important contributions to genetics, including the discovery of messenger RNA and determining the sequence of the worm Caenorhabditis elegans.

According to Brenner, the study of genetics is "the fundamental science of biology." Furthermore, he added, "Your genome is your future."

Brenner noted that two scientific processes, invented in the mid-1970s, propelled research forward at an incredible rate: DNA cloning and DNA sequencing. With the new technology, a piece of DNA may be sequenced in just a few months (if not sooner), whereas it used to take nearly 10 years, Brenner said. It is this type of technology that has allowed the completion of a rough draft of the human genome.

At the awards ceremony last November, Lander elaborated on Brenner's statements, explaining that each quarter of the 20th century saw significant molecular biological advances. In the first quarter, scientists learned that DNA contained genetic information, which is subsequently packaged into chromosomes. James Watson and Francis Crick determined the double helix structure of DNA in the second quarter of the century. In the third, scientists began to understand how to read the information contained in DNA, and how that information instructed protein construction.

During the last 25 years, scientists have continued to piece together the genetic puzzle, using all the techniques of the 20th century. These technologies are what allowed researchers at Whitehead to complete the first full draft of the human genome, Lander said.

Two methods are currently used to sequence genomes. The publicly funded project (involving Lander and his colleagues) employs the "clone-by-clone" approach. This method involves systematically mapping regions of DNA, sequencing each region, and stringing the sequence together.

The other method, know as the "shotgun" approach, is the brainchild of J. Craig Venter and his privately funded company, Celera Genomics. The shotgun method involves randomly sequencing sections of the genome, and then matching the ends of the sections using powerful algorithms. The result is one long sequence, in a relatively short amount of time.

Venter founded Celera Genomics in 1998, following his creation of The Institute for Genomic Research (TIGR) in 1992. Prior to that, Venter studied biochemistry at the University of California San Diego as an undergraduate, and continued at the university for graduate studies, earning his Ph.D. in physiology and pharmacology.

Both the clone-by-clone and shotgun methods of genetic sequencing have led to rough drafts of the human genome. However, Lander said, the work is not complete. "We have the structure but no meaning yet," he said. Scientists have successfully identified the sequence of nucleic acids, but not the location of all the genes or their precise functions. Adding to the complications is the fact that 99% of the human genome is "junk" DNA and does not code for genes. Whether these nucleic acids even have a purpose is still unknown.

Research on the human genome continues to proceed as more scientists become enthusiastic about the project. Both Lander and Venter said they hope to publish a final draft of the human genome April 26, 2003, which marks the 50th anniversary of the publication of the paper in which Watson and Crick detailed the double helix structure of DNA.

An archived webcast of the symposium can be viewed at http://www.novartis.com/media/dates_events.shtml.

More than 100 issues of JYI have been published since the journal was founded in 1997.
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