by Jeremy Manier
Chicago Tribune
CHICAGO - 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 their ambitions are much larger, 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 they are hard at work on the problem, which is complicated by cellular compounds that 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 that it disrupts a gene necessary for the bacteria to infect people, and contains genetic watermarks’’ that the group added to identify their synthetic genome.
Although the prospect of man-made organisms evokes images of scientists drunk with absolute power, the short-term uses of the new research are not much different from the methods of genetic manipulation that scientists have used 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 been breeding synthetic forms of life since prehistoric times. When you see tangerines, corn, grapefruit or a Chihuahua-trust me, none of 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 Catholic Theological Union in Chicago, agreed that the technique need not raise fundamentally new ethical questions.
From a religious point of view the creation of new viruses or bacteria would 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 precise changes to an organism’s DNA than current methods allow, though most applications would depend on gaining more knowledge about how various genes work together. One of Venter’s major interests is experimenting with synthetic organisms to discover the smallest set of genes needed to sustain life-what Venter calls an organism’s minimal operating system.'' 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 professor of molecular genetics and cell biology. Preuss is CEO of Chromatin Inc., a biotech firm that is studying ways of synthesizing small chromosomes to change plants’ genetic makeup.
I look at this as part of a continuum that started in the '70s'' with genetic modification, Preuss said. What this gives you is greater control of the design and composition of genes that you’re using.’’
Venter has long been a notorious yet brilliant figure in genetics; he is most famous for starting a private gene-sequencing venture to compete with the federally run Human Genome Project. That effort ended in a tie in 2000 when Venter and the federal researchers published their results simultaneously.
To make the new synthetic genome, Venter and his colleagues at the J. Craig Venter Institute assembled a team of prominent researchers including Nobel prize-winning geneticist Hamilton Smith.
Venter’s group already had sequenced the relatively small set of genes in Mycoplasma genitalium, a bacterium originally discovered in the male urinary tract.
The organism’s genome, which carries all the instructions it needs to live and reproduce, resides on a single, circular chromosome. The DNA on the chromosome is made of four chemical building blocks set in a specific order.
Working from that genetic blueprint, Venter and his colleagues began piecing together the building blocks-all readily available, off-the-shelf chemicals. They contracted with an outside company that used automated chemical processes to assemble the first, small pieces of DNA, called cassettes.
But such lab techniques do not work well with the kinds of long DNA chains the group needed to make the bacterium’s full genome. As DNA strands get longer they become brittle and can break.
The researchers discovered they could use the bacteria E. coli and a form of yeast as natural factories'' to make longer, stronger sections of the DNA and eventually assemble them into a full chromosome. The next logical step will be to implant the synthetic genome in a bacterial cell and get the new genes to take over its functions. That would in essence create a new organism, but so far technical barriers have stymied the effort. If we knew the answers it wouldn’t be called research,’’ Venter said, though he added that he would be surprised and disappointed'' if they do not succeed sometime in 2008. The U.S. government has been aware of Venter's work on synthetic life and supported its early stages with at least $12 million in grants from the Department of Energy, though the current study was funded by a Venter-led biotech company, Synthetic Genomics. The most troubling aspect of such work to many ethicists is the potential for bioterrorism, in particular the assembly of deadly viruses based on publicly available genetic sequences. Caplan said the federal government needs a 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 2003 dinner in Washington, D.C., during which he described the possible risks of his research to a group of President Bush's senior science advisers. Venter explained he could synthesize a small virus in less than a week, and more deadly microbes such as Marburg and Ebola in about a month. Venter wrote that one Homeland Security official just sat there, silently mouthing ‘wow’ over and over.’’