Another Human Genome Project: A Private Company's Plan Shocks the Genetics Community

Article excerpt

Consider it modern biology's equivalent of the fabled race between the tortoise and the hare--except that the prizes at this finish line are the priceless secrets of the human body and the tortoise may not repeat its legendary victory.

In the role of tortoise is the international Human Genome Project, a $3 billion worldwide effort--funded by U.S. agencies such as the National Institutes of Health and the Department of Energy--to decipher the complete human genetic sequence by 2005. Playing the hare are J. Craig Venter, a maverick scientist with a knack for startling the genetics community, and Perkin-Elmer Corp. of Norwalk, Conn., the leading maker of automated DNA sequencing machines. With a pistol shot signaling the start of a scientific race that few people anticipated, Venter and Perkin-Elmer announced May 9 their intention of creating a new company whose goal is to unravel the human genome in just 3 years--and for a measly $200 million to $300 million.

"This is a private company paying to sequence the human genome and give it to the public," says Venter.

Knowing little about the new effort, many scientists, particularly officials overseeing the worldwide genome project, are still contemplating how to react. Some express skepticism about the strategy, known as whole-genome shotgun sequencing, that the as-yet-unnamed company has embraced. They are also concerned about what the company plans to do with the massive amount of genetics data it will generate and what access other scientists will have to it.

"What we're doing is to produce the complete human genome sequence to a very high accuracy and with nothing missing," says John Sulston, director of the Sanger Centre in Cambridge, England, which plans to sequence one-third of the human genome as part of the now 8-year-old worldwide effort. "I'm sure that the product they're going to produce will be of lower quality, and we consider it inadequate."

Supporters of the shotgun strategy respond that speed is of the essence. "The whole-genome shotgun approach would leave gaps and regions where the sequence is less certain, but I still think it's the best approach," says James L. Weber of the Marshfield (Wis.) Medical Research Foundation, who last year coauthored a paper arguing that the strategy should be applied to human DNA. "The greatest cost of sequencing the genome is the cost of not having the sequence. It's the cost of missed opportunity. Pharmacologists and biochemists need new targets for diabetes, obesity, epilepsy, asthma, etcetera in order to develop better treatments, and it can take 5 to 15 years to develop a new drug. These factors overwhelm concerns about incomplete information and imperfections."

Venter also dismisses criticisms of the shotgun strategy, arguing that the data produced by his new company will equal, if not surpass, that generated by the worldwide effort. "This is going to be an incredibly complete, incredibly accurate genome sequence," he says.

Venter has a record of backing up such forceful claims. While an investigator at NIH, he hit upon a technique to identify quickly most of the 50,000 to 80,000 genes in the human genome. The method used bits of single-stranded DNA, so-called expressed sequence tags (ESTs), which represent part of a gene's sequence, as lures to identify a gene's complete protein-coding sequence. NIH skepticism about the method prompted Venter to leave and establish the Institute for Genomic Research (TIGR) in Rockville, Md., where he pursued the project privately. He and other scientists have since used ESTs to identify an estimated 80 percent of all human genes.

The EST method ignores much of the genome, however, including the regulatory DNA sequences that control the protein-coding portion of a gene. Nor can ESTs identify every gene.

Consequently, ESTs can't provide all the useful information contained in the complete human genome--and sequencing full genomes happens to be another of Venter's talents. …