Genetically modified organisms typically have one or two genes added or replaced. So, for example, a gene that promotes the production of insulin might be added to a microbe that scientists want to turn into a cellular factory of the diabetes medication. But now microbiologists and geneticists at the J. Craig Venter Institute in Rockville, Md., have successfully transferred the entire genome—roughly 500 genes, in this instance encased in more than one million base pairs of DNA—from one microbe to another, transforming the latter into the donor and raising prospects of designing organisms from scratch to solve specific problems, such as the world's dependence on fossil fuels or global warming.
The researchers worked with Mycoplasma mycoides (a microbe that infects goats) because it has one of the smallest genetic blueprints of any known self-replicating organism and lacks cell walls, making it easier to insert new DNA. They isolated its entire genetic code—one chromosome that forms a circle—stripping it of all its proteins, and then added genes to make a host organism blue (to make it easy to pick out in a Petri dish) as well as resistant to the antibiotic tetracycline.
The scientists added close relative Mycoplasma capricolum (another goat pathogen) to a solution containing M. mycoides's genetic material and gently mixed it for a minute. After three hours of incubation, the resulting microbes were exposed to the antibiotic tetracycline. Only those cells that absorbed the M. mycoides genome survived.
After three days, large colonies of blue, antibiotic-resistant microbes had formed. Roughly one in 150,000 of the M. capricolum microbes had absorbed the new DNA and transferred it to daughter cells. The daughter cells displayed no trace of their original DNA while taking on the entire form and function of the original bacterium, says microbiologist Carole Lartigue of the Venter Institute, who led the research. "The result is a clean change of one bacterial species into another," the researchers wrote in Science.
"We don't know for certain how the donor genome takes over," says microbiologist (and Nobel laureate) Hamilton Smith, also of Venter. "We've been doing experiments which suggest that the donor genome has a restriction system that could cleave up the recipient chromosome and thus destroy it." Or the tetracycline may simply be wiping out all those bacteria that carry the original genome, Lartigue says.
As radical as this transformation is—transmuting one species into another by transferring just the genetic code—it represents only the first step toward man-made organisms. "Synthetic biology itself and the synthetic genome still remain to be proven but we are much closer to knowing that it is theoretically possible," biologist J. Craig Venter says. "Just the naked DNA, just the chromosome itself without any accessory proteins, is all that is necessary to boot up this cell system. It really simplifies the task."
The goal is ultimately to design new organisms that fulfill specified functions, such as manufacturing new fuels to replace oil and gas or capturing carbon dioxide, without evolving so that these capabilities are locked in over time. Venter hopes to create fuels from such an engineered organism within a decade or less. The next step is attempting to synthesize the chromosome of another Mycoplasma in the laboratory and transferring that, Venter says.
But this technique is unlikely to work in other types of cells and no synthetic genomes have yet been created, Venter notes. Scientists remain unable to create synthetic life in the lab. "If we're trying to understand the origins of life and cellular life, it would be ideal to have all the chemical components in a soup to spontaneously go together and form a cell," Venter says. "We're a long way from that."