COLD SPRING, N.Y.— J. Craig Venter and his colleagues recently announced that they had created the first cell to run on a fully artificial genome. So what's next for this synthetic strain of microscopic Mycoplasma mycoides and the new technology?
The "synthetic cell" achievement has been lauded, condemned and undercut, but it has yet to fully demystify life's underlying code, the genome. "It's amazing how little we know about genomics," Venter said June 1 at the Cold Spring Harbor Symposia on Quantitative Biology in Cold Spring, N.Y.
Researchers built much of the bacterium's genome without fully understanding the function of many of the million-plus base pairs involved. About half of the genes, in fact, are still "a complete black box," said Richard Roberts of New England Biolabs, Inc., in a commentary after Venter's talk.
But a bit like complex erector sets can help illuminate some of the basic rules of physics and engineering, scientists are hoping that constructing—and deconstructing and reconstructing—whole genomes will help them better understand genomic principles. "We have to find what the rules are," Roberts said. Scientists, for instance, don't yet know what role or importance the order of genes in the genome plays. They have seen that in some cases, genes can have their order swapped with little visible outcome on life, whereas, specific sequence might be more important elsewhere on the genome.
Although the researchers based their synthetic genome on the natural one, their cell did not behave exactly the same, Venter noted. Usually when you mess around with the inner workings of a cell, especially its genetic code, growth rate tends to slow. With this one, however, there was a substantial increase in the growth rate. "That was a surprise," Venter said. "We have no idea why the cells grew faster."
Future studies will examine the behavior of the microbe and its progeny to see how these behavioral changes match up to genetic changes. The initial paper was only intended as a proof of concept, Venter pointed out. Nevertheless, he said, "people are disappointed that it doesn't sing and dance."
So how long will it be until scientists can synthesize genomes for other, more complex forms of life? Even expanding the capability to various kinds of bacteria will likely take a long time, Roberts noted. "Maybe we'll even be able to take the Jurassic Park scenario," but he said, happily, that there wasn't much chance of crossing paths with a recreated dinosaur—in his lifetime anyway.
One of the group's long-term goals, said Venter (who has "never been known for his extreme modesty," Roberts, a long-time acquaintance, said at the symposium), is to develop a universal recipient cell, into which researchers can plug a variety of synthetic genomes and see how they run. And in the future, he proposed, it might be cheaper for scientists to synthesize simple organisms than to grow them.
Roberts is happy to see the synthetic genome advance as a way to refocus research interest and attention on bacteria, which he calls "cute…lovely little organisms." In particular, being able to better understand the genomes of bacteria can have broad health implications for people, who host some 100 trillion microbial cells in and on their bodies.
The field of genomics, however, can be slow-going and riddled with many costly mistakes. Just one error small in earlier attempts to assemble a synthetic code set the researchers on Venter's team back months. But James Watson, former head of Cold Spring Harbor Laboratory whose co-discovery of DNA more than 50 years ago helped to lay the foundation for this work, was pleased by the speed of progress. "We've been so much more successful that you might have predicted," he said at the symposium.
And for those keeping score, the synthetic genome, which contains coded Web and email addresses, has been cracked by 26—and counting—scientists so far, Venter said on Tuesday.
Image of Venter courtesy of Wikimedia Commons