Tuesday, March 27, 2012

Synthetic life and vitalism

Illustration courtesy of Harry Campbell
In 1966, Francis Crick—the co-discoverer of the structure of DNA—gave a series of lectures at the University of Washington in which he discussed vitalism and the nature of life (Crick, 1966). Vitalism is this old idea according to which some sort of special force is present in living organisms, and that this force cannot be explained in terms of physics and chemistry. Crick notes that a way to refute vitalism would be to create a living organism synthetically—in other words, make a cell from scratch. Crick's remark finds a striking echo in today's research in synthetic biology, particularly in the efforts of Craig Venter.

In 2010, Venter and his team from the J. Craig Venter Institute achieved a scientific tour de force: the synthesis of a whole bacterial genome (one circular chromosome) and its transplantation into a recipient cell (a mycoplasma). The resulting bacterium was able to grow and multiply thanks to its artificial chromosome. The results were announced during a press conference in May 2010 and published in Science two months later. The long-term goal of the JCVI is not to disprove vitalism, but to design and implant synthetic genomes that can perform specific tasks, such as to produce biofuels. The mycoplasma synthetic genome, which is only slightly different from the original, serves as a proof of concept, paving the way to more important genome (re-)engineering. 

Venter's work aims at practical developments in bioengineering, but it is important to note that he also points at significance of a different order. Thus, in a New York Times article from 2010, he explains that his research is a philosophical as well as a technical advance. I suppose it is a philosophical advance in the sense that it may represent a further refutation of vitalism, and that it hints at the possibility to create life out of a chemical toolbox. But did Venter and his team create a new life form? In one of his TED lectures, in particular during the discussion that follows, Craig Venter clearly explains that they did not, in fact, create life, but rather took advantage of a preexisting life system. Even though, curiously, the 2010 paper insists on calling the transplanted mycoplasma a "synthetic cell", because after many cell divisions none of the original proteins present in the recipient cell are there anymore. Due to protein turnover, the new proteins are all encoded by the synthetic genome, and therefore the cell is synthetic. Well, this doesn't sound very convincing to me. [But the talk is highly enjoyable. Craig Venter is a great and witty speaker.]

In his TED talk, Venter also suggests that the work on synthetic genomes can help answer big questions, including "What is life?". Ha, that is one big question, no doubt about it. 

What is life? is also the title of a classic book by Erwin Schrödinger (1944), where the famous quantum physicist suggests that the key to life lies in the genes. At that time, however, the nature of genes was not known, and mistakenly thought to be proteins. Indeed, the question of the nature of life brought many physicists to biology, including Crick—according to Jim Watson in The Double Helix, it is the reading of Schrödinger's book which contributed to interest Crick in biology. (Francis Crick later wrote a book entitled Life itself, but since I haven't read it I cannot say anything about the content.)

Michel Morange, in his wonderful book Life explained [1] (2008), remarks that the interest in the question "What is life" decreased after the sixties. This coincided with the raise (and many successes) of molecular biology, and the thought that with the understanding of DNA and protein synthesis we had understood life. Nowadays, however, the question is more present than ever with the work of Venter and others. It seems that the question is far from being settled. Morange writes (p. 147): 
"An obvious way to demonstrate that we understand what life is would be to create life from elementary chemical components."
In that sense, it is true that Venter's project—synthesizing and implanting a genome—is a necessary element in the making of life. But as Morange further notes, for Venter's demonstration to be complete the proteins encoded by the artificial genome should be artificial as well, that is, be different from the known protein sequences in natural organisms.

So would the synthesis of life from scratch be the final blow to vitalism? Probably, but one may argue that the concept of vitalism has already virtually disappeared, at least from the scientific community. Nevertheless, I admit that I still find the idea of building a totally artificial cell thrilling! And the JCVI is by far not alone in his quest for a synthetic organism. Vincent Noireaux from the University of Minnesota, for instance, published a paper in PNAS last year that discussed the recipe for a self-replicating artificial cell.

But proving that we can imitate life, as exciting and mind-blowing as it is, does not necessarily mean that we comprehend the phenomenon. Let's give the final word to Francis Crick, in Of Molecules and Men (p.64):
"It seems to me far more important to be able to understand a living cell [in terms of structure, function and control mechanisms] rather than to worry about whether we could synthesize it completely, starting from the elements."
[1] Curiously, the original title of the book (La Vie expliquée ?) lost its question mark in the English translation.

Crick F. (1966). Of molecules and men (The John Danz Lectures). University of Washington Press.
Gibson D. G. et al. (2010). Creation of a bacterial cell controlled by a chemically synthesized genome. Science vol. 329, pp. 52-56.
Morange M. (2008). Life explained. Yale University Press and Editions Odile Jacob. 
Noireaux V., Maeda Y. T. and A. Libchaber (2011). Development of an artificial cell, from self-organization to computation and self-reproduction. PNAS vol.108, pp.3473-3480.


  1. j'adore ton blog Robin. Merci de partager tes lectures avec nous.