Making life from the bottom up

I wrote below about Craig Venter’s vision of synthetic biology – taking an existing, very simple, organism, reducing its complexity even further by knocking out unneccessary genes, and then inserting new genetic material to accomplish the functions you want. One could think of this as a kind of top-down synthetic biology; one is still using the standard mechanisms and functions of natural biology, but one reprogrammes them as desired. Could there be a bottom-up synthetic biology, in which one designs entirely new structures and systems for metabolism and reproduction?

One approach to this goal has been pioneered by Steven Benner at the University of Florida. He’s been concentrating on creating synthetic genetic systems by analogy with DNA, but he’s not shy about where he wants his research to go: “The ultimate goal of a program in synthetic biology is to develop chemical systems capable of self-reproduction and Darwinian-like evolution.” He’s recently written a review of this kind of approach in Nature Genetics Reviews (subscription only): Synthetic biology.

David Deamer, from UC Santa Cruz, has a slightly different take on the same problem in another recent review, this time in Trends in Biotechnology (again, subscription only, I’m afraid). “A giant step towards artificial life?” concentrates on the idea of creating artificial cells by using self-assembling lipids to make liposomes (the very same creatures that L’Oreal uses in its expensive face creams). Encapsulated within these liposomes are some of the basic elements of metabolism, such as the mechanisms for protein synthesis. How close can this approach get to creating something like a living, reproducing organism? In Deamer’s words: “Everything in the system grows and reproduces except the catalytic macromolecules themselves, the polymerase enzymes or ribosomes. Every other part of the system can grow and reproduce, but the catalysts get left behind. This is the final challenge: to encapsulate a system of macromolecules that can make more of themselves, a molecular version of von Neumann’s replicating machine.” He sees a glimmer of hope in the work of David Bartel at MIT, who has made a RNA enzyme that synthesizes short RNA sequences, pointing the way to RNA-based self-replication.

But all these approaches still follow the pattern set by the life we know about on earth; they depend on the self-assembling properties of a familiar repertoire of lipids and macromolecules, like DNA, RNA and proteins, in watery environments. Could you do without water entirely? Benner is quoted in an article by Philip Ball in this week’s Nature (Water and life: Seeking the solution, subscription required) arguing that you can: “Water is a terrible solvent for life…. We are working to create alternative darwinian systems based on fundamentally different chemistries. We are using different solvent systems as a way to get a precursor for life on Earth.”