Genes mapped at warp speed

J. Craig Venter, the geneticist whose private, for-profit research company put the effort to map the 46 chromosomes that make up the human genome on fast-forward, regaled a packed Irvine Auditorium audience Feb. 28 with the story of his project and its implications for future scientific research.

Venter, the self-described “adrenaline junkie” who founded Celera Genomics after the National Institutes of Health declined to fund his novel genome mapping method, gave an overview of his method and compared it to the one used by the publicly-funded Human Genome Project. “Assembling genomes is very much like doing a jigsaw puzzle,” he said. “The trouble is, there were no corner pieces.”

And with 27 million of these pieces—each of them consisting of a string of 500 to 600 proteins—comparing each piece to each other piece individually would have taken decades. “Some of my colleagues in England proposed doing this in monasteries over the next several centuries,” he said.

Venter noted that his method could not have been attempted were it not for advances in mathematics and computing power that had taken place during the 1980s and 1990s. And even with computers capable of performing 1.5 trillion calculations per second, the calculations required to process the data collected by Venter’s team took several months. These advances, he said, mean that “the future of biology now depends on the future of computing and of math.”

Venter’s team used the computers to take the entire genome, eliminate segments where genetic information was repeated, and focus on the genes in the non-repetitive segments—a process known as whole-genome shotgun sequencing. He likened his method to using Tinkertoys to construct a complex structure, as opposed to the Human Genome Project’s gene-by-gene examination, which, he said, was like building the same structure using Legos, one brick at a time.

What was more interesting, though, in Venter’s view, was what Celera discovered using the same method on other genomes. For example, in taking the shotgun approach to map the genome of the Hemophilus influenzae bacterium, they also found that the genome alters itself at pre-set, regular intervals. “One of the most important things we discovered in sequencing this genome is that evolution is in fact pre-programmed into the genetic code—it’s not just a series of random events,” he said.

The researchers were also able to locate and identify genes that evolved in response to specific events, such as the bubonic plague that swept Europe some 700 years ago. Venter noted that the genes that mutated in response to the plague also provide resistance to HIV, which may help explain why the virus is far more prevalent among Africans, who were never exposed to the plague.

The success of the shotgun sequencing method in mapping the human genome has also led to the rapid mapping of scores of other genomes, including those for the pathogens that cause tuberculosis, malaria, Lyme disease and syphilis. “These are now driving vaccine and therapeutic research quite rapidly,” he said.

That some of this research is being done by private companies like Venter’s, some of which have acted quickly to patent the genes they have identified, has raised some ethical questions. “Most if not all of the gene patenting efforts will be a tremendous waste of time and money,” he said. “Gene patenting is now inhibiting the development of new drugs.”

Venter’s address was delivered as part of the annual Dean’s Forum of the School of Arts and Sciences, which honors outstanding scholarly achievement by SAS students.

Originally published on March 28, 2002