Scientists Poised to Create Life
Researchers say they are one step away from first man-made organism.
Like cooks whipping up a recipe from scratch, a team of genetics researchers has artificially assembled all of the genes needed to make a simple bacterium, in hopes of creating a synthetic organism by the end of the year.
The team led by maverick scientist J. Craig Venter chose the smallest target possible by building the genome of Mycoplasma genitalium, one of the tiniest known species of bacteria. But they have much larger ambitions, such as understanding the most basic requirements for life and designing new bacterial life-forms capable of producing biofuels.
“If the experiments are successful, we could enter into a new design phase of biology,” Venter said Thursday during a press teleconference from Davos, Switzerland.
Despite such lofty goals, the new study published online in the journal Science does not demonstrate godlike control over life.
The team has tried but failed to insert the genes into a bacterial cell and”reboot” the cell into a new, living organism. Venter’s colleagues said theyare hard at work on the problem, which is complicated by cellular compoundsthat can break down DNA before it takes hold.
So far, the researchers have been able to string together a copy of the 582,970 chemical components in the existing bacterium’s DNA. The copy is perfect, except it disrupts a gene necessary for the bacteria to infect people and contains genetic “watermarks” the group added to identify their synthetic genome.
Although the prospect of man-made organisms evokes images of scientistsdrunk with absolute power, the short-term uses of the new research are not much different from the methods of genetic manipulation that scientists haveused for decades. Other scientists already have synthesized working viruses such as polio, though viruses are considered less complex forms of life than bacteria.
Whether an organism based on a synthesized genome would be truly”synthetic” is open to question. According to one definition, humans have beenbreeding synthetic forms of life since prehistoric times.
“When you see tangerines, corn, grapefruit or a Chihuahua – trust me, noneof those were around when our first ancestors showed up on the savanna,” said Art Caplan, chair of the department of medical ethics at the University of Pennsylvania.
Rev. Thomas Nairn, a professor of Catholic ethics at the CatholicTheological Union in Chicago, agreed that the technique need not raisefundamentally new ethical questions.
“From a religious point of view the creation of new viruses or bacteriawould not necessarily create a huge problem, depending on how they’re used,” Nairn said. “The two major principles are to do no harm, and do the work respectfully.”
For scientists, synthetic genomes hold the promise of making more precisechanges to an organism’s DNA than current methods allow, though mostapplications would depend on gaining more knowledge about how various geneswork together. One of Venter’s major interests is experimenting with syntheticorganisms to discover the smallest set of genes needed to sustain life – whatVenter calls an organism’s “minimal operating system.."
A ‘seminal achievement’
The potential for a new era in genetics makes the work of Venter’s team a ”seminal achievement,” said Daphne Preuss, a University of Chicago professorof molecular genetics and cell biology. Preuss is CEO of Chromatin Inc., abiotech firm that is studying ways of synthesizing small chromosomes to changeplants’ genetic makeup.
“I look at this as part of a continuum that started in the ’70s” withgenetic modification, Preuss said. “What this gives you is greater control ofthe design and composition of genes that you’re using.”
Venter has long been a notorious yet brilliant figure in genetics; he ismost famous for starting a private gene-sequencing venture to compete with thefederally run Human Genome Project. That effort ended in a tie in 2000 whenVenter and the federal researchers published their results simultaneously.
Assembling a genome
To make the new synthetic genome, Venter and his colleagues at the J. CraigVenter Institute assembled a team of prominent researchers, including Nobelprize-winning geneticist Hamilton Smith.
Venter’s group already had sequenced the relatively small set of genes inMycoplasma genitalium, a bacterium originally discovered in the male urinarytract.
The organism’s genome, which carries all the instructions it needs to liveand reproduce, resides on a single, circular chromosome. The DNA on thechromosome is made of four chemical building blocks set in a specific order.
Working from that genetic blueprint, Venter and his colleagues beganpiecing together the building blocks – all readily available, off-the-shelfchemicals. They contracted with an outside company that used automatedchemical processes to assemble the first, small pieces of DNA, calledcassettes.
But such lab techniques do not work well with the kinds of long DNA chainsthe group needed to make the bacterium’s full genome. As DNA strands getlonger they become brittle and can break.
The researchers discovered they could use the bacteria E. coli and a formof yeast as natural “factories” to make longer, stronger sections of the DNAand eventually assemble them into a full chromosome.
The next logical step will be to implant the synthetic genome in abacterial cell and get the new genes to take over its functions. That would inessence create a new organism, but so far technical barriers have stymied theeffort.
“If we knew the answers, it wouldn’t be called research,” Venter said,though he added he would be “surprised and disappointed” if they do notsucceed sometime this year.
The U.S. government has been aware of Venter’s work on synthetic life andsupported its early stages with at least $12 million in grants from theDepartment of Energy, though the current study was funded by a Venter-ledbiotech company, Synthetic Genomics.
Some worries
The most troubling aspect of such work to many ethicists is the potentialfor bioterrorism, in particular the assembly of deadly viruses based onpublicly available genetic sequences. Caplan said the federal government needsa new, transparent regulatory body to review research on synthetic life.
“Right now nobody’s really responsible for this,” he said.
In his recent autobiography, “A Life Decoded,” Venter described a 2003dinner in Washington, D.C., during which he described the possible risks ofhis research to a group of President Bush’s senior science advisers. Venterexplained he could synthesize a small virus in less than a week, and moredeadly microbes such as Marburg and Ebola in about a month.
Venter wrote that one Homeland Security official “just sat there, silentlymouthing ‘wow’ over and over.”
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WHAT SCIENTISTS DID
Researchers synthesized from scratch the complete set of genes necessary tomake a simple bacterium. A photo micrograph shows the Mycoplasma genitaliumgenome.
WHAT’S LEFT TO BE DONE
To create a live organism, the team must insert the synthetic genome in acell and make it “boot up” with the new instructions. So far, they have notsucceeded.