MEDIA: Venter/Celera/Minimal Gene Project

k_aegis@mindspring.com
Fri, 10 Dec 1999 11:24:59 -0500

Genetic Find Could Lead to Creating Life in Lab

By Rick Weiss
Washington Post Staff Writer
Friday , December 10, 1999 ; A8

A team of geneticists has come close to determining the minimum number of genes required for life to arise, an advance that could ultimately allow scientists to design and create living organisms from scratch.

Tired of waiting for philosophers to answer the question "What is life?" the researchers took a scientific approach and concluded that about 300 genes are needed for a candidate life form to pass for "alive" a state generally defined by an ability to reproduce and to respond to the environment.

The discovery of what appears to be the simplest recipe for making a living thing, described in today's issue of the journal Science, could shed new light on the origins of life and the myriad ways that biology has cooked itself up since evolution first stirred the primordial soup.

But of greater interest to ethicists, who have been tracking the Minimal Genome Project since its inception two years ago, the new research may enable scientists to engineer life in the laboratory for the first time from essential chemical ingredients not by altering existing organisms, as genetic engineers do today.

That ability could be liberating or could sow seeds of destruction, said J. Craig Venter of Celera Genomics in Rockville, the senior scientist on the new report. Novel cells could be designed to clean up toxic wastes with unprecedented efficiency, he said. Or they could be programmed to serve as horrendous biological weapons.

For people who already fear that gene researchers are playing God, the prospect of scientists actually becoming creators may seem downright blasphemous, Venter acknowledged. That's why he and his Minimal Genome colleagues most of whom are at the Institute for Genomic Research (TIGR), a nonprofit center he founded in Rockville have agreed not to attempt a replay of Genesis until more public discussion takes place.

But an accompanying Science report by a 25-member ethics panel, commissioned by TIGR through an unrestricted grant, finds no compelling reason to stop researchers from making new life forms if the scientific and ethical implications are carefully weighed.

The creation of new, free-living life forms "does not violate any fundamental moral precepts or boundaries, but does raise questions that are essential to consider before the technology advances further," according to the panel, led by Mildred K. Cho of the Stanford University Center for Biomedical Ethics.

Among the metaphysical questions Cho and her colleagues want considered: Is it appropriate to define life in narrow, scientific terms, or is there a spiritual component to being alive? There is a "serious danger," the team warns, that the creation of new life forms will be "perceived by the public as proving that life is reducible to, or nothing more than, DNA."

On a more practical level, the team expresses concern about the ecological harm that may result from releasing novel life forms into the environment.

The genetic research that has prompted all this soul-searching was relatively prosaic. It involved the use of molecular tools to "knock out" hundreds of genes, one at a time, in two of the world's simplest one-celled organisms Mycoplasma genitalium and M. pneumoniae, both of which have had their entire genetic codes spelled out.

By seeing which knockouts were lethal to the organisms and which were not, the scientists came up with a provisional tally of the genes that are essential to life.

The researchers had to take into account that many genes are redundant. A microbe may do fine when either of two redundant genes is knocked out, so long as the other is there to take over, but that does not mean that both are dispensable.

By combining their knockout data with a correction factor for redundancy, the group concluded that 265 to 350 of M. genitalium's 480 genes are essential for life under laboratory conditions. By contrast, human cells have about 80,000 genes each a large number of which help the body's trillions of cells communicate with one another.

Many of the 300 essential genes identified in the new study were already familiar to scientists because of their established roles in energy generation, reproduction or other basic functions. Surprisingly, however, about 100 of the genes are complete unknowns, and their contributions to life could prove fascinating, Venter said.

Biologists hope someday to make new organisms by loading essential genes onto artificial chromosomes (already under development in many laboratories) and placing those chromosomes inside real or synthetic cells. By adding extra genes, the cells might be made to secrete human medicines or break down radioactive wastes more efficiently than those now being used for such purposes, which are made by modifying existing cells.

One point that became apparent to the Minimal Genome team is that the definition of life is relative. An organism can get by with just a few genes in an environment that provides everything it needs, such as a warm, well-stocked laboratory dish. Try to raise that piece of life in the back yard, however, and it's not going to rank as a life form anymore.

That relativistic view could introduce a new twist to debates about abortion, embryo research and the question of when life begins, said Arthur Caplan, a University of Pennsylvania ethicist who served on the TIGR ethics panel. If a frozen embryo, created in a laboratory dish, has never been placed in a womb where it can live, is it alive? Such questions cry out for more than a scientific answer, Caplan said. "Ultimately," he said, "the definitive debate over what life is and when life begins is up to us as a society."