In late May of 2010–as most of you probably know–J. Craig Venter announced that he and his colleague at the J. Craig Venter Institute (JCVI) (Rockville, MD) had created a “synthetic cell”. This was a bacterial cell containing an entire genome that had been synthesized based on a nucleotide sequence stored on a computer, which had then been inserted into the cytoplasm of another bacterial cell. The JCVI paper was first published online in Science on May 20. It has now appeared in print in the July 2, 2010 issue of Science, where it made the cover of the journal.
Commentaries on the JCVI paper were published in Nature (here and here) and in the New York Times, among other places.
To summarize the JCVI report: the researchers assembled sets of chemically synthesized oligonucleotides, in stages, into a 1.08 million base pair DNA molecule with the slightly modified sequence of the genome of the bacterium Mycoplasma mycoides. Among the slight modifications were “watermarks”, i.e., four added sequences in nonessential genome regions that identify the researchers, and enable researchers to differentiate synthetic genomes from natural ones. The researchers then transferred the synthetic M. mycoides genome into the closely related bacterium M. capricolum, where then new genome took over the cells, resulting in bacteria that expressed the proteome of M. mycoides. The resulting cells were dubbed “synthetic cells”.
The work of the JCVI researchers was a technical tour de force. It required the accurate sequencing of the M. mycoides genome, as well as advanced technologies for accurate chemical synthesis of oligonucleotides, oligonucleotide extraction and assembly, and transplantation into recipient bacterial cells. There were many stumbling blocks in this process. The final stumbling block was a single base pair deletion in an essential gene for chromosomal replication. Once they discovered and corrected this error, the researchers were able to successfully transplant the synthetic genome and get it to commandeer the recipient M. capricolum cells, resulting in expression only of M. mycoides proteins as directed by the synthetic genome.
In evaluating the importance of the “synthetic cell” beyond this technical virtuosity, there are two perspectives–philosophical and scientific/technological. From the philosophical point of view, some commentators hailed this work as the final refutation of vitalism, i.e., the contention that there is something special about processes in living organisms that cannot be artificially created from nonliving systems. Interestingly, the commentators who expressed this conclusion are philosophers and bioethicists. (See, for example, the statements of philosopher Mark Bedau and bioethicist Arthur Caplan in the 27 May Nature discussion article.)
However, as one can see from the same discussion article, scientists–including leading working synthetic biologists–know better. The old biologists’ dictum, “all life comes from life”, espoused by Louis Pasteur among others, still holds. Not only were living M. capricolum cells required for the creation of “synthetic” M. mycoides cells, but the researchers utilized the yeast homologous recombination system in vivo to assemble their “synthetic” genome.
From the scientific and technological perspective, what has the “synthetic cell” project done to advance synthetic biology, beyond the demonstration of technical virtuosity? The answer of most leading scientific commentators, including working synthetic biologists, is “not very much”.
We agree. We’ll discuss why in Part 2 of this article.