Thursday, May 20, 2010

Synthetic Life

Here is a research article published today in the AAAS Science Magazine:

Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome

Daniel G. Gibson,1 John I. Glass,1 Carole Lartigue,1 Vladimir N. Noskov,1 Ray-Yuan Chuang,1 Mikkel A. Algire,1 Gwynedd A. Benders,2 Michael G. Montague,1 Li Ma,1 Monzia M. Moodie,1 Chuck Merryman,1 Sanjay Vashee,1 Radha Krishnakumar,1 Nacyra Assad-Garcia,1 Cynthia Andrews-Pfannkoch,1 Evgeniya A. Denisova,1 Lei Young,1 Zhi-Qing Qi,1 Thomas H. Segall-Shapiro,1 Christopher H. Calvey,1 Prashanth P. Parmar,1 Clyde A. Hutchison, III,2 Hamilton O. Smith,2 J. Craig Venter1,2,*

We report the design, synthesis, and assembly of the 1.08-Mbp Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome sequence information and its transplantation into a Mycoplasma capricolum recipient cell to create new Mycoplasma mycoides cells that are controlled only by the synthetic chromosome. The only DNA in the cells is the designed synthetic DNA sequence, including "watermark" sequences and other designed gene deletions and polymorphisms, and mutations acquired during the building process. The new cells have expected phenotypic properties and are capable of continuous self-replication.

1 The J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA.
2 The J. Craig Venter Institute, 10355 Science Center Drive, San Diego, CA 92121, USA.
This scientific achievement isn't completely "synthetic" life in the sense of "design your own organism". Its more limited Here is what it did accomplish:

The DNA was synthesized on a machine. It is all human "hand made" but is the equivalent of natural DNA belonging to the bacteria Mycoplasma mycoides, but with "watermarks" and some other minor DNA changes that are detectable by scientists to verify that the synthetic bacteria is truly viable and reproducing. This artificially created (but natural) DNA was then inserted into a bacterial cell that is related but distinct, the Mycoplasma capricolum which belongs to the Mycoplasma mycoides cluster. The success of synthetic life is demonstrated when the machinery of the receiving host bacteria was comandeered by the inserted synthetic DNA to create a normal, active bacterium whose descendants can be checked to verify that they have the synthetic DNA running them.
Here is a schematic of the synthetic bacterium from an article in Wired Science:

Like all new science, the actual "breakthrough" is fairly limited. But it is the first step on a big journey. Humans can now "tailor" life. This experiment demonstrates that it can be done. The race is now on to create more daring and experimental life forms.

Humans have broken free of traditional evolution. They first broke free when they developed techniques to allow cultural evolution to compete with traditional genetic evolution. Now the culture has created a whole new level of change: direct manipulation of genes to create artificial life.

This transition point is as significant as the transition from intelligent ape but without the language or cultural tools that enabled it to bypass slow genetic change. That explosion took place over the last 120,000 years. We are on the threshold of a change just as significant. The future is going to be a world inhabited by not just traditional life increasingly cluttered by humans and their cultural artifacts. It will be a world increasingly cluttered by variations of synthetic life.

For those of you terrified of "change" here is a bit of reassurance. This is from a blog posting entitled The Laser Turns 50! From 'Death Ray' To The Supermarkets by Marcelo Gleiser at the NPR' 13.7 blog:
The “death ray” of sci-fi movies was finally at hand. Even H. G. Wells, in his War of the Worlds (1898), had dreamed up such a weapon. And yet, although high-powered lasers can cut through metal, that’s not what they are mostly known for. They record CDs and DVDs at hundreds of millions of households across the world, they travel along fiber optics cables as the blood stuff of telecommunications, they are used in supermarkets checkout stations to read off prices in bar codes, they’re used in surgery, and, yes, in fundamental research. For example, lunar ranging lasers are used to test Einstein’s very own theory of relativity. I’m sure he would be pleased with this turn of events. And would get a kick out of playing with my son’s blue laser pointer.
So the terrifying "death ray" ends up being a very convenient device for music and communication and sale transactions. Those terrifying visions of awful "synthetic" life will morph over time into wonderfully useful life forms cozily occupying our world with us.

In the meantime, you can brush up on what synthetic life is by reading the Wikipedia article.

And you can read other scientist's reactions on the Nature News web site.

Update 2010may22: Here is a bit from an article by Carl Zimmer on the Discover blog about the new sythetic life:
This old English major’s heart is warmed by the news that the new synthetic cell carries a line from James Joyce, inscribed in its DNA: “To live, to err, to fall, to triumph, to recreate life out of life.”

What would Joyce have thought if someone had told him that one day that the synthesized genome of a goat pathogen would carry his words? I would hope that whoever told him would make sure that he did not think this moment marked his literary immortality. In fact, his deathless prose is probably being desecrated by the relentless erosion of evolution right now.


It turns out that the genome of the synthetic cell is not identical to its original, even if you ignore the watermarks. Mutations slipped into its sequence during its synthesis. Yet those mutations caused no harm to the microbe, presumably because they didn’t disrupt an essential function encoded in its DNA. Once the synthetic cell came to life and began to grow and divide, it copies its entire DNA, including Joyce’s words. But as lovely as those words may be, and as important as they may have been to the scientists during their experiment, they mean nothing to the microbe. Every time an organism replicates, each spot in its DNA has a tiny chance of mutating.

In the growing colony of synthetic cells, now numbering in the billions, it’s almost certain that Joyce’s watermark has already been defaced by a mutation. The bacteria that carry these degraded versions of Joyce presumably do not suffer from these mutations, since the watermarks don’t matter to them anyway. So they can keep replicating. By contrast, the DNA in the really useful parts of their genome is changing very little over the generations, thanks to selection. Inserting Joyce into the first synthetic cell was certainly a kind gesture, but not a timeless memorial. It would be fascinating to go back to the synthetic cell colony in a few years and sequence Joyce’s line again. I’d bet that it won’t even be recognizable anymore.

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