Handling the extracted DNA takes considerable care: even a small genome is a gigantic, fragile molecule. “It’s going to break into 100 pieces if you just look at it wrong,” Gibson says. If it were suspended in a liquid solution, the DNA could be destroyed merely by the movement of the liquid. So Gibson immobilizes the genomes in agarose, an algae-derived gel commonly used as a medium for microbes. Enclosed in this protective pellet, they can safely be stored until the researchers are ready to transplant them into recipient cells.
In a lab down the hall, Ma has prepared the cells that will receive the new sequence: a species of bacteria called Mycoplasma capricolum that’s closely related to the species from which the synthetic genome is derived. While an enzyme that degrades agarose liquefies DNA-containing pellets in one test tube, Ma gets another test tube and mixes the bacteria with calcium chloride and polyethylene glycol, a cocktail that the researchers believe makes the cells’ surfaces malleable and sticky. Now it’s a matter of chance and a steady hand. Ma pipettes some of the cell mixture into the vial containing the synthetic genome loops. The sticky cells begin fusing with one another. To maintain their spherical shape after fusion, they must take in volume from the solution around them. As this happens, some cells–about one in 100,000–also take in the synthetic genome. The result is a sort of supercell with three genomes–the synthetic genome and one from each of the two cells. The supercell then divides into three smaller cells, one of which contains the synthetic genome.
Ma smears the cell solution on culture plates containing an antibiotic to which only cells with the synthetic genome are resistant (during the genome editing process, the researchers added a gene that makes them impervious to it). Those cells will live, growing and dividing under the control of the new genome. The rest die off, leaving behind a pure colony of synthetic cells.
The next step for the Venter Institute researchers is to use their genomic editing, synthesizing, and transplanting techniques to design and test genomes with fewer and fewer genes. The goal is to create a “minimal” cell–one with only the genes it needs to survive. Such a cell could be easier than a natural one to alter through genetic engineering.
The researchers’ methods are currently very expensive: it costs $300,000 to $500,000 to make and transplant a synthetic genome if the researchers synthesize the DNA in house, or about three times that much if they purchase it from an outside supplier. Yet the price of DNA synthesis is falling and may continue to decline even further as demand increases and technology improves. If that happens and the genome-building techniques prove as useful as the Venter researchers hope they will, more people will begin to adopt their methods, says James Collins, a professor of biomedical engineering at Boston University.
“This is a significant advance for synthetic biology,” Collins says. “Now we’ve got to see, what are the changes that can be introduced to the genome?”