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TITLE:  Scientists Planning to Make New Form of Life
SOURCE: Washington Post, USA, by Justin Gillis
        http://www.washingtonpost.com/wp-dyn/articles/A17496-2002Nov20.html
DATE:   Nov 21, 2002

------------------ archive: http://www.gene.ch/genet.html ------------------


Scientists Planning to Make New Form of Life

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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