Craig Venter is making history

…or at least trying to.

Venter’s J. Craig Venter Institute, the successor of TIGR and TCAG, has been working on what they characterize as the first man-made organism: Mycoplasma laboratorium. The ongoing project centers on “Synthia”, a slimmed-down synthetic chromosome that they are calling (and patenting as) a “minimal bacterial genome”. It consists of 381 of the ca. 470 genes of the tiny parasitic bacterium Mycoplasma genitalium. (The name “Synthia” comes not from Venter, et. al., but from the critical ETC Group; it seems to have stuck.) Add Synthia to an empty cell, and viola! Life!

The project builds on earlier work in which Venter’s team (led by restriction enzyme pioneer and Nobel laureate Hamilton O. Smith, Clyde A. Hutchinson, III and Cynthia Pfannkoch) recreated the genome of the bacteriophage phi X-174 from scratch and stuck it into an empty coat to create a viable phage; they generated the 5,386 base pair sequence in 14 days. In the 2003 PNAS report, they described a plan to use similarly-sized chunks of synthetic DNA to assemble whole genomes. Since the phi X-174 project, they have been developing and improving DNA cloning methods that can deal with ever larger target sequences without high levels of error–a boon for DNA sequencing as well as chromosome synthesis. (Synthetic phi X-174 could be selected for infectivity to week out high-error sequences, but that’s not an option with arbitrary 5,000 bp “gene cassettes”.)

Since 2003, they’ve gotten to the point of putting together a whole genome (if a very small one). They quietly started filing patents for “Synthia” in 2006, and in June 2007 announced that man-made life in the form of M. laboratorium was right around the corner. Proving that the synthetic genome is viable by sticking it into a genome-less cell and making it live will be a powerful proof-of-concept for new and more drastic kinds of genetic engineering.

“Man-made life” makes a great headline, but it’s worth picking apart. At the fundamental level, even Venter’s team is quick to note that M. laboratorium won’t be a wholesale synthetic organism, as it will rely on the molecular machinery and cellular environment taken from natural cells. (At least, as natural as a laboratory organism with its genome carefully removed can be.) The conflation of genes with life has been the constant complaint of all the biologists except the molecular ones since the rise of molecular biology. It was one of the chief complaints of those who thought the Human Genome Project was (all funding levels being equal) a bad idea. In a recent article in I forget which history of science journal, (atheist) Emile Zuckerkandl accuses HGP leader (Christian-turned-atheist-turned-Christian) Francis Collins of exploiting the genes=life fallacy in his best-selling quasi-intelligent design book The Language of God. (The language of God, of course, is the genome.) The all-powerful gene is a potent political and rhetorical force (and has been a great basis for securing grants, at least since the 1940s), even if biological reality is considerably more complex.

But even looking past the conflation of a genome with life itself, M. laboratorium has a dubious claim as synthetic life. As the ETC Group points out, “Synthia” only distinguishes itself from a natural chromosome by what is missing (i.e., a fifth of its genes). This organism would have a shakier claim at being man-made life even than the 1972 oil-eating bacterium of Diamond v. Chakrabarty (the landmark patent case that established the legitimacy of patenting genetically-engineering lifeforms); at least Chakrabarty’s bug had a combination of characteristics that no natural organism had. Does putting together most of the DNA of an organism (which happens to be synthesized artificially) together with everything but the DNA of that organism mean scientists have created artificial life? It’s hard not to invoke Frankenstein.

Venter has been very successful at framing his science in ways that grab headlines, generate public interest, and seem self-evidently of central historical importance (whatever the later historical verdict). I haven’t decided whether that’s a good thing or a bad thing. He’s certainly earning his place in history, one headline and Discovery channel documentary at a time.

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