Scientists Planning to Make New Form of Life

By Justin Gillis
Washington Post Staff Writer
Thursday, November 21, 2002; Page A01

Scientists in Rockville are to announce this morning that they plan to create a new form of life in a laboratory dish, a project that raises ethical and safety issues but also promises to illuminate the fundamental mechanics of living organisms.

J. Craig Venter, the gene scientist with a history of pulling off unlikely successes, and Hamilton O. Smith, a Nobel laureate, are behind the plan. Their intent is to create a single-celled, partially man-made organism with the minimum number of genes necessary to sustain life. If the experiment works, the microscopic man-made cell will begin feeding and dividing to create a population of cells unlike any previously known to exist.

To ensure safety, Smith and Venter said the cell will be deliberately hobbled to render it incapable of infecting people; it also will be strictly confined, and designed to die if it does manage to escape into the environment.

More worrisome than the risk of escape, they acknowledged, is that the project could lay the scientific groundwork for a new generation of biological weapons, a risk that may force them to be selective about publishing technical details. But they said the project could also help advance the nation's ability to detect and counter existing biological weapons.

The project, funded with a $3 million, three-year grant from the Energy Department, will start as a pure scientific endeavor, but it could eventually have practical applications. If Venter and his collaborators manage to create a minimalist organism of the sort they envision, they will attempt to add new functions to it one at a time -- conferring on it the ability, for instance, to break down the carbon dioxide from power plant emissions or to produce hydrogen for fuel.

The more immediate plan is to try to puzzle out, and eventually model in a computer, every conceivable aspect of the biology of one organism, a feat science has never come close to accomplishing. Because all living cells are based on the same chemistry and bear striking resemblances to one another, that could shed light on all of biology. "We are wondering if we can come up with a molecular definition of life," Venter said. "The goal is to fundamentally understand the components of the most basic living cell."

The project is not entirely new. Venter launched an earlier version of it in the late 1990s while running a Rockville institute he founded called the Institute for Genomic Research. With his collaborators, he got as far as publishing a working list of the genes apparently required to sustain life in a single-celled organism called Mycoplasma genitalium, the self-replicating organism with the smallest known complement of genetic material. That work indicated that under at least some laboratory conditions, the organism could get by with only 300 or so of its 517 genes. People, by contrast, have an estimated 30,000 to 50,000 genes.

The project fell by the wayside when Venter and Smith launched Celera Genomics Corp., the Rockville company that raced publicly funded researchers to a tie two years ago in compiling draft maps of the entire human genetic complement, the genome.

Venter resigned from Celera early this year in a dispute over its future direction. He is financing a series of new initiatives, including the Institute for Biological Energy Alternatives, the entity that will house a revived project to build the artificial organism. The $3 million Energy Department grant, awarded recently, will pay for a staff of about 25 to pursue the project over three years, though Venter and Smith acknowledged it could take longer. Smith, widely considered one of the world's most skilled scientists at manipulating DNA, will direct the laboratory work.

The project will begin with M. genitalium, a minuscule organism that lives in the genital tracts of people and may cause or contribute to some cases of urethritis, an inflammation of the urethra. The scientists will remove all genetic material from the organism, then synthesize an artificial string of genetic material, resembling a naturally occurring chromosome, that they hope will contain the minimum number of M. genitalium genes needed to sustain life. The artificial chromosome will be inserted into the hollowed-out cell, which will then be tested for its ability to survive and reproduce.

Ari Patrinos, a senior Energy Department administrator who will help oversee the project, said the organism was an attractive starting point to create a "minimal genome" because it is so minimal already. "We know even the simplest of cells is incredibly complicated," Patrinos said -- too complicated, at least so far, to understand completely. "This is a case where we're trying to cheat a little bit, to take the smallest and simplest and make it smaller and simpler."

The project raises philosophical, ethical and practical questions. For instance, if a man-made organism proved able to survive and reproduce only under a narrow range of laboratory conditions, could it really be considered life? More broadly, do scientists have any moral right to create new organisms?

A panel of ethicists and religious leaders, convened several years ago at Venter's request, has already wrestled with the latter issue. The group, which included a rabbi and a priest, concluded that if the ultimate goal was to benefit mankind and if all appropriate safeguards were followed, the project could be regarded as ethical.

"I'm less worried about the minimal genome project taking off and creating some kind of monster bug than I would be, partly because I have a sense that the scientists are aware of the possible risks of what they're doing," said Mildred Cho, a bioethicist at Stanford University who was chairwoman of the ethics panel.

Scientists don't usually announce their experiments in advance, but Venter said he felt this one needed to be brought to the attention of policymakers in Washington, since it could create a new set of tools that terrorists or hostile states might exploit to make biological weapons. "We'll have a debate on what should be published and what shouldn't," Venter said. "We may not disclose all the details that would teach somebody else how to do this."

Venter and Smith acknowledged the theoretical risk of creating a new disease-causing germ, but said they would take steps to ensure against that. One of the first genes they'll delete is the one that gives M. genitalium the ability to adhere to human cells. Many of the 200 genes to be deleted will be ones that confer the ability to survive in a hostile environment, so that the end result will be a delicate creature, at home only in the warm nutrient bath of a laboratory dish.

Even if the organism were to escape stringent confinement and enter the environment, Smith said, "it's a dead duck."

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