Gilbert Plans New Company

Sporting hiking boots and a rumpled red flannel shirt, Walter Gilbert '53 looks like a scholar who spends more of his time out of the laboratory than in it. But any time that the maverick. Nobel Laureate spends outside Harvard's ivy walls is more likely to be in the boardroom than the great outdoors.

Venturing into an untapped scientific field, Gilbert plans to start a company this fall aimed at mapping every single gene in the human body. Scientists say the project to decipher the human genome--the 100,000 to 300,000 genes that shape every detail of our bodies--represents an extraordinary effort comparable to the Apollo space program in the 1960s.

Seen by many as the most ambitious biology research effort ever conceived, sequencing the human genome has sparked an intense controversy among scientists about how it should be done and who should do it. Some believe that the federal government should undertake the project, while others argue that no massive, directed effort is necessary.

"The knowledge is obviously of great social value, the only question is what's the easiest way to get there," says Gilbert, who last week was awarded one of Harvard's prestigious University professorships.

Gilbert, who left Harvard in 1981 to head one of the first biotechnology firms to exploit genetic engineering techniques, claims his company can do the job and turn a profit at the same time. He estimates that his "moderately sized bio firm" would require 300 scientists working over a period of 10 years at a cost of $300 million. The only problem, Gilbert says, is "how to make money while the research is going on."

Scientists have traditionally reaped rewards for their discoveries by patenting their research and licensing the results to industry. However, it is generally agreed that a researcher can't "own" knowledge about the human body.

So to recoup his investment and time, Gilbert has proposed a novel way to sell scientific work which has important ramifications for university research; he believes he has the legal right to copyright his discoveries and sell them. Much like Dow Jones sells its stock quoting service to stockbrokers, Gilbert would place his genetic map in a large computer database and charge pharmaceutical and biotechnology companies an access fee to use it.

"They can use the information, they just can't turn around and sell it again," Gilbert says. However clients could sift through Genome's DNA map to discover the genetic cause for a disorder and develop a cure for it, he says.

Critics say that Gilbert's copyright ideas could transform campus-based research by increasing the profit motive for professors. The free exchange of information would be restricted as scholars worry about protecting their discoveries from competitors. And connections between professors and the companies that develop their finds would tighten the ties between universities and industries, which critics fear will threaten academic freedom.

Officials in the nation's capital have also noticed the potential benefits a genome map could reap, and are currently debating whether to fund a full-scale sequencing effort. Sen. Peter Domenici (D.N.M.) has introduced a bill that would establish a national gene mapping "initiative" and the Department of Energy has designated three national laboratories to conduct work on the project. The National Institutes of Health (NIH), the federal agency which funds most biomedical research in the nation, also plans to send more resources to a genome mapping effort.

However, some scientists do not welcome Washington's sudden interest. Pointing to the example in physics of the superconducting supercollider project, they fear that such a large project will draw money away from smaller researchers.

Gilbert believes such fears are unfounded. "NIH spends $7 billion a year. This project is still small compared to the research done in this country," he says.

"It would cost as much as city hospital," Gilbert says.

Although scientists disagree over whether a large government push in gene sequencing is necessary, no one doubts the great social benefits such a map could bring. Researchers up to now have translated only a few human gene sequences. And almost all of this little information has been put to practical use.

Physicians studying cancer, for example, have related the role of specific genes to tumor development in some cancers. Doctors can also use human genetic markers to test mothers for the possibility of giving birth to a seriously diseased child.

With further discovery and decoding of the rest of the human genome, such medical advances could be significantly enhanced. In the very long term, researchers have suggested that most genetically based disorders in humans could be corrected before birth, using molecular biology techniques.

"Once we have the sequence, human biology can shift from the qestion of how to find the genes to the question of what genes do," Gilbert wrote recently.

Washington "Too Slow"

Impatient for Washington--which Gilbert believes "is too slow" to lead the way--the professor has been raising funds for his own sequencing efforts and plans to start operations this fall.

"We have the technology available to explore the field much more rapidly than we do now," says Gilbert. "If we start now that research will proceed much faster than if we just go along with science as usual."

Some scientists are skeptical that the government, not to mention a private company, could undertake such a large project as tracking all the genes. Gilbert's reputation causes others to shed their doubts.

"There are only one or two in the field of molecular biology who could propose doing something like this and be taken seriously," says Assistant Professor of Biological Chemistry Allen M. Maxam. "Walter Gilbert is one of them."

"It's a tremendous undertaking," says another Harvard gene expert. "It's crazy what Gilbert's doing but he's not crazy."

Graduating summa cum laude in both Chemistry and Physics in 1953, Gilbert received a Ph.D. from Cambridge University in 1957 before returning to Harvard as a lecturer the following year. Ten years later he was tenured after climbing from assistant and associate professorships. In 1980 Gilbert won the Nobel Prize for chemistry and in 1982 he resigned from Harvard so he could assume his full-time duties as head of Biogen, a biotechnology firm.

Gilbert Returns to Harvard

In 1985 left his Biogen post and returned to Harvard, whereupon his tenure was restored and upgraded this year to a University professorship. Earlier this year Gilbert also assumed the chairmanship of the Department of Cellular and Developmental Biology.

Gilbert developed the first technique to sequence DNA, the chemical blueprint by which genes are encoded. His methods are the principal theories underlying today's genetic engineering techniques.

Under a long-standing Harvard rule that professors could only spend one day of the week on outside work, Gilbert had to resign his professorship to head the Cambridge-based Biogen. He says that nothing of the sort will happen with his new company.

"I will have nothing to do with Genome's day-to-day operations," Gilbert says. "I will act in an advisory capacity once it starts."

The sequencing project will complement Gilbert's other work which is considered to be some of the most promising and far-reaching in the genetics field. One of his current laboratory projects is using gene sequencing techniques to analyze how DNA interacts with other chemicals inside cells.

He is also investigating the chemical evolution of human genes' structure, which is divided into two types of sequeces--exons and introns. Such work is integral to understanding the very mechanism by which genes encode hereditary information. In addition, Gilbert's work includes an analysis of how the human imune system operates, as well as discovering the molecular basis for central nervous system's development.

Unlike such research, which is on the cutting edge of genetics, sequencing holds little intellectual interest for the gene expert. He characterize genome mapping as "boring, assembly line work," and says that social good and the profit motive have led him to form Genome.

"I am interested in the final outcome. I think its a good thing to do," says Gilbert. "I am also interested in personal profit."