Minimal controversy

Craig Venter's "minimal genome" project announced Wednesday is not about creating a new life form and probably doesn't pose much of a biowarfare threat, researchers say. The high-profile project was just funded by the US Department of Energy (DOE) with $3 million going to the Institute for Biological Energy Alternatives (IBEA), one of the non-profit research institutes Venter founded after leaving the newly profit-minded Celera Genomics early this year. According to some scientists, the new project won't even define the minimal genome—the basic gene set required for life—because there can be no single minimal genome."The question of the minimal genome for an organism is always 'minimal in which environment,'" said Francisco J. Silva of the University of Valencia in Spain. Silva and colleagues at the university's Cavanilles Institute for Biodiversity and Evolutionary Biology are studying the genome of the insect endosymbiont Buchnera aphidicola, which appears to have an even smaller genome than that of the parasite Mycoplasma genitalium, Venter's organism of choice. M. genitalium grows well in the human genital tract, but will not grow in milk, Silva pointed out. "The basic set of genes are those required for producing the basic set of proteins and RNAs that a bacterium needs for growing and multiplying in the best environment," he said. Each environment requires a different minimal gene set, although, Silva noted, scientists can identify a minimal set of functions that are essential for life in every kind of environment.The IBEA scientists "are definitely not creating a new form of life," Eckard Wimmer, of the State University of New York at Stony Brook, told The Scientist. Wimmer and colleagues recently synthesized a polio virus from information in public genome databases. Science published their paper in August; among those who criticized its potential biowarfare applications was Venter. IBEA scientists "will strip an existing microorganism of genes until it chokes to death—making a minimalist organism much like it has been done with large complicated viruses, such as herpes viruses," Wimmer explained. Adding new genes to this organism is a strategy already being pursued with other, non-minimal, organisms, he noted. "Whether there is an advantage in the Venter approach cannot be predicted at present. At this stage, the project is interesting and should be carried forward."Venter has speculated that restrictions on publication might be required because of the remodeled minimalist organism's biowarfare potential. Other researchers don't see why. "I don't get the connection with terrorist activity," said Monica Riley, of the Marine Biological Laboratory in Woods Hole, Massachusetts. She co-authored a 2000 review of Escherichia coli genomics that showed how the definition of a minimal genome was variable and linked to an organism's life style. Pathogenic bacteria usually have more genes than their harmless relatives do, Riley pointed out. But the disease-related genes are not essential to life, so they would be the first category of genes a scientist would jettison from a minimal genome organism, she argued.Others note that a more pragmatic approach to biological terrorism is to make use of existing organisms rather than devise new ones. "Synthetic viruses are not an issue at the present time in biowarfare because evildoers can obtain the real viruses in laboratories and from human specimens. Everybody, except Venter, seems to agree on this," Wimmer commented.In developing biological weapons, it is more efficient to add toxic or poisonous genes to an already-successful microorganism, Silva added. "A minimal genome organism," he said, "will be a prisoner of the laboratory dish where it lives, and will be unable to compete with the outer world." Thus, Silva argued, "it would be an error to restrict the accession to this information to the scientific community."Venter and his colleagues at The Institute for Genomic Research (TIGR) in Rockville, Maryland began the Mycoplasma genitalium project some years ago because it had the smallest amount of genetic material then known for any organism, about 500 genes. In a 1999 paper in Science, the researchers reported that about 300 of those genes appeared to be essential for its survival in the lab. Venter also commissioned a bioethics working group to examine the ethical issues in devising a minimal genome organism. In the same issue of the journal, this group declared that the project posed few ethical dilemmas except perhaps the risks posed by any escapees and a biowarfare potential. Their paper also underscored the lack of regulation and oversight governing such work.The minimal genome organism now being planned, already fragile and fastidious, will be further crippled so that it cannot survive without laboratory coddling. The strategy is to synthesize an artificial chromosome containing the presumptive minimal gene set, remove all existing genetic material from M. genitalium, and then insert the synthetic chromosome into the vacant cell. The work will be directed by Hamilton O. Smith, who won the Nobel Prize in 1978 for co-discovering restriction enzymes, and is a long-time colleague of Venter's. Ten scientists are presently at work on the project, which will eventually employ about 25.The short-term aim will be to get the artificial bug to survive and reproduce. The long-term goal, besides answering central questions about basic biology, will be to help the world solve some of its environmental problems. That's why the funding is coming from DOE, where recent genetics projects have focused on bioremediation and other environmental topics. Venter said this week that he is hoping eventually to make microbes that can generate hydrogen for fuel and sequester carbon in order to reduce greenhouse gases in Earth's atmosphere.

Minimal controversy

Scientists see new Venter genome project as interesting, but hardly dangerous.

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