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BY: BILL SNYDER

Nobel laureate Sydney Brenner, D.Phil., delivers the inaugural Vanderbilt Discovery Lecture. 
Photo by Anne Rayner

9/22/2006 - Nobel laureate Sydney Brenner, D.Phil., delivers the inaugural Vanderbilt Discovery Lecture. Photo by Anne Rayner

Sydney Brenner, D.Phil., talks with Justin Glenn, Vanderbilt sophomore and Biology major, at last week’s lecture.
Photo by Anne Rayner

Sydney Brenner, D.Phil., talks with Justin Glenn, Vanderbilt sophomore and Biology major, at last week’s lecture. Photo by Anne Rayner

Wearing sunglasses because recent eye surgery had made him sensitive to bright light, Nobel laureate Sydney Brenner, D.Phil., launched the new Vanderbilt Discovery Lecture series last week with equal doses of gravitas and wit.

Speaking to a Medical Center audience that approached 1,000, Brenner, over the course of an hour, managed to impale several of biomedicine's sacred cows, including high-throughput technology and translational research.

The title of his talk was “The Next 100 Years of Biology,” but Brenner, whose scientific triumphs include establishing the existence of messenger RNA, shied away from speculation. Instead, he asked, “What should we do over the next 100 years?”

“I think a lot of (biology) is going in absolutely the wrong direction,” he said.

The Human Genome Project, for example, has led to what Brenner called “factory science” — heavy investment in expensive gene sequencers that begin to drive the direction of research.

“You have 100 machines; you're looking at about $100 million of investment,” he said. “And you've just got to keep that going all the time in order to get the use from them.”

This, he said, and the “Genburo, the Politburo of Genetics, in which everything is decided … stultifies” research, and discourages young people from entering the field.

“They think, 'How can I work in a field where this guy has a lab of 300 people and all the tools and lots of money?' And I tell you something; one good idea is worth more than all of that.

“Because what we're looking for is innovation, something new,” Brenner said. “And you won't get something new if you work within a completely established mode of work. We need some people to stray off of the standard path and ask new questions.”

Brenner, a distinguished professor at the Salk Institute for Biological Studies in La Jolla, Calif., shared the 2002 Nobel Prize in Physiology or Medicine with Robert Horvitz and John Sulston for their discoveries regarding the genetic regulation of organ development and programmed cell death.

His talk concluded a symposium that celebrated the 100th birthday of another Nobel laureate and genetics pioneer, Max Delbrück, who taught at Vanderbilt during World War II.

The venue — 208 Light Hall — quickly filled to capacity for Brenner's talk, which was piped into four additional lecture halls and via live Webcast on the VUMC Web site to accommodate the crowd.

Speaking in the crackling cadence of his native South Africa, Brenner took delight in piercing the latest biological trends, including the proliferation of “omic sciences.”

“I was asked by a business journal in England, The Economist, which was the most important omic science for biotechnology, and I gave them the obvious answer: it was that science called econ-omics,” he chuckled.

“So we now have a culture which is based on everything must be high-throughput,” Brenner continued. “I like to call it low-input, high-throughput, no-output biology.

“I'm not taking advantage of my advanced years in order to make cracks about this. But … this is not the way to solve problems,” he said.

The discovery of a gene, for example, doesn't necessarily mean that the protein it encodes has an important function. “You've got to have a theory on how the cell works,” Brenner said.

The same goes for translational research.

“The promise of the human genome is that we will have millions of targets … and we can take all the chemicals, and we can just do high-throughput analysis on all of these and find all the drugs for everything for the future … from bench to bedside.

“I think this is totally wrong.”

For one thing, this approach requires a “therapeutic hypothesis,” that blocking a particular target could affect a physiological function or prevent a disease.

“It is very rare that I have seen coming out of basic labs hypotheses of these kinds,” Brenner argued, “mostly because most people in basic labs don't know anything about human physiology and pathology.

“So I believe that the process should be the other way around. I think what we can do very well now is to go from bedside to bench.”

Skip the mouse models, Brenner said. Go directly to humans.

“We should explore as much as we can this vast range of genetic diversity that exists among human beings, because then we'll come to understand much more about complex function.

“So I think we should have a moratorium on mice,” Brenner concluded, “until 2053, which is the 100th anniversary of the DNA model.

“After that, when we have used our knowledge to solve many of the human and social problems that we have, we will encourage people then to study diseases of mice.”

For a complete schedule of the Discovery Lecture series, go to www.mc.vanderbilt.edu-/discoveryseries.

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