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Writing the genetic code

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Five years ago, biologist J. Craig Venter led a project to map the human genome, a feat celebrated as reading "the book of life."Now, he wants to write his own book.

Mr. Venter has formed a company that will try to manufacture organisms for industrial purposes by piecing together genes, the building blocks of life. The goal is to cobble together single-cell life forms that can perform tasks such as cleaning up hazardous waste, reducing carbon dioxide spewed out by power plants or creating new drugs.

"We are now switching from being able to read the genetic code to being able to write it," said Mr. Venter, who will be the Rockville company's chairman and chief executive officer.

However, much of the science is still unknown -- no one has been able to build something as complex as Mr. Venter envisions. Researchers have constructed viruses, which have fewer genes, but creating the genome of an entire cell is much more difficult.

A host of ethical questions swirl around the science of tinkering with the building blocks of life, including whether it could be used for devious purposes such as creating new strains of anthrax or other lethal bugs.

"Can you control what you are doing?" asked University of Pennsylvania bioethicist Arthur Caplan. "Is what you are doing transparent? Have we set up enough rules to ensure safety and accountability?"

The new company, Synthetic Genomics Inc., is Mr. Venter's first foray into a commercial venture since he left Celera Genomics in 2002. Celera raced scientists at the National Institutes of Health to map the human genome, a project both completed in 2000.

Mr. Venter left Celera after he clashed with the company's parent over how to profit from that work.

He went on to found a research institute in Rockville where scientists work on practical applications for genomic research. That work includes drugs tailored to individual patients or a way to decode a person's genes in seconds at minimal cost.

Synthetic Genomics, which will be based at the J. Craig Venter Institute, is seeded with $30 million from private investors, about half of which comes from Mexican billionaire Alfonso Romo Garza.

The first step is to determine the minimal number of genes needed to sustain life in a single-cell bacterium, which Mr. Venter compares to the operating system of a computer. Once that has been achieved, genes can be added to the cell's chromosomes so the organism can serve a specific function, much like a computer user adds his own programs.

"It is life programming," he said. "We make the synthetic chromosome and the cell actually builds the hardware."

Working in the 1990s with Nobel laureate Hamilton Smith, the co-chief scientific officer of the new company, Mr. Venter and other scientists were able to whittle down that number in a bacterium that causes urinary tract infections in humans. The team found that 265 to 350 were needed for the bacterium to survive, but couldn't determine the role those genes played. That question was put on hold when Mr. Venter became president of Celera.

Scientists have used similar technology to create viruses from scratch. In 2002, researchers at the University of New York at Stony Brook assembled a synthetic polio virus. Mr. Venter's institute built a simple virus in just two weeks in 2003 that infects and kills bacteria cells.

But Mr. Venter said creating a single-cell bacterium would be more complex because it requires more genes than a virus to support life.

The technology, which Mr. Venter hopes to complete in two years, will focus first on production of hydrogen and ethanol. Among the new company's potential business models would be to tailor organisms for the specific needs of its clients, such as germs that could scrub carbon dioxide out of power plant smokestacks or eat up oil spills, said Juan Enriquez, president of Synthetic Genomics.

Drew Endy, a professor at the Massachusetts Institute of Technology who studies synthetic biology, said most scientists agree that these types of organisms can be pieced together. The major question, he said, is whether the parts can be arranged in a way that the organism does its job.

"How do we put it together so that it behaves the way it is predicted to?" he asked.

To help achieve this, Mr. Endy and others at MIT have created the online Standard Registry of Biological Parts. One goal is to store data about specific genes and DNA that scientists know can be inserted into a genome to perform a specific task.

Perhaps anticipating potential ethical pitfalls, Mr. Venter's institute has teamed with Mr. Endy and the Center for Strategic and International Studies, a Washington think tank, to draft a report on synthetic genomics. Funded by a nearly $600,000 grant from the Alfred P. Sloan Foundation, the group will review the effect of the new science and whether it should be regulated, and will issue a report next year.

One major issue is if engineered germs can be used for bioterrorism, said Gerald Epstein, a homeland security expert at CSIS.

Mr. Epstein stressed the study is separate from Mr. Venter's new company, and study results will be independent.

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