Synthetic life:
Genome team faces ethical questions in its quest to use $3 million grant from Energy Department to create microbe

Keay Davidson, Chronicle Science Writer
Friday, November 22, 2002
2002 San Francisco Chronicle

URL: http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2002/11/22/MN145471.DTL

A well-known gene scientist and his colleagues plan to create a novel form of single-celled life in the laboratory, drawing skeptical or nervous reactions from some scientists and bioethics experts.

J. Craig Venter, the scientist who led the private effort to decipher the human genome, and his Nobel Prize-winning associate, Hamilton O. Smith, hope to create the extremely simple bacterium, with a $3 million grant from the Energy Department, they announced Thursday.

Their initial goal is to learn how few genes are needed for a bacterium to survive, feed and reproduce. And ultimately they hope to create a microbe that could generate hydrogen for energy, or extract atmospheric carbon dioxide gas that is worsening global warming.

"We believe that building a synthetic chromosome is an important step toward realizing these goals because we could potentially engineer an organism with the ideal qualities to begin to cope with our energy issues," Venter said in a statement.

Venter acknowledged the possible risks to such research and said his research team plans to disable the bacterium in some way, lest it fall into the hands of terrorists or escape and wreak havoc on the environment.

"We will be cautious about how and where we disclose new techniques," Venter, the former head of Celera Genomics, said at a news conference in Rockville, Md. "We don't want a group of crazies to deliberately make something that is harmful."

Venter asked a group of ethicists and scientists to review the ethics of the project. The group, led by bioethicist Mildred Cho, now at Stanford University, concluded that the project had adequate safeguards and could offer real benefits.

Venter's latest organization, the Institute for Biological Energy Alternatives, will conduct the research. Venter recently announced that after years of working to decode the human and other genomes, he was shifting his focus to the problem of global warming.

Venter said the plan is to extend work that he and others started in 1995 at the Institute of Genomic Research. Researchers there sequenced the genes of a bacterium called Mycoplasma genitalium, one of the simplest microbes known with only one chromosome and 517 genes. By contrast, humans have about 30,000 genes and 23 pairs of chromosomes in each cell.

Once the normal gene complement of M. genitalium was identified, the researchers began systematically removing genes to determine how many were essential for life. In 1999, they published a paper that narrowed the minimum needs of M. genitalium to 265 to 350 genes.

Under the new grant, Venter said the researchers will use basic chemicals to synthesize the DNA in M. genitalium's single chromosome. They will then use radiation to kill the chromosome in a normal bacterium and replace it with the lab-made DNA.

"This is true basic science," Venter added. "Even though we've found all those genes in the human genome, we can't understand the most basic simple cell yet. That is what is driving this."

Some scientists questioned whether the proposed project would truly create new "life." Scientists and philosophers have long disagreed on the definition of life, especially at the microscopic scale of viruses, DNA and single-celled organisms.

Instead, skeptics said in interviews, Venter's proposal sounds more like they're planning to strip down existing cells, then reassemble their components into a new, functional microcellular organism -- sort of like cannibalizing an 18-wheel truck for components to use in a lawn mower.

"They're not starting from basic elements in building a cell. They're starting from already pretty well established (biological) building blocks" such as enzymes and proteins, noted Harvard professor Dr. Bruce R. Korf, director of the Harvard Medical School Genetics Training Program.

"There's many things you'd have to get right to create (a brand-new) organism. I hesitate to say it would be impossible, but it would be very tough.

So it doesn't particularly worry me that they would be creating something with dangerous consequences," Korf said.

But others said Venter should pause and consider the ethical and potential safety issues before continuing their research.

San Francisco State University professor Laurie Zoloth, former president of the American Society for Bioethics and Humanities, said such research should be subjected to public overview and perhaps regulation.

Although the project is a "phenomenally interesting idea," and although the scientists may try to prevent the novel organisms from threatening other life, even highly knowledgeable researchers can make terrible mistakes, warned Zoloth, a professor of Jewish Studies.

"Just the day before this (announcement)," she noted, "we had a massive oil spill that threatens to contaminate the Spanish coastline in ways that are perhaps irreparable -- and ship technology is something that we've theoretically refined since the 13th century."

E-mail Keay Davidson at kdavidson@sfchronicle.com.

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