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Last week several friends and colleagues pointed me to the excellent New York Times story about the latest self-replicating RNA system from Gerald Joyce’s lab. The article is delightful reading and it outlines one of the cutting edges in creating physicochemical life: the development of minimal information replication and evolution. It is also delightful to see how this story was the second most emailed NYT article on July 28, 2011.

The emergence of artificial life certainly captivates our imagination.

Since the late 1980’s Jerry’s lab has been one of the world leaders in developing life-like RNA systems.  I met Jerry at the first Artificial Life workshop at Los Alamos, September 1987, where he, in my opinion, showed some of the most exciting results and had one of the most promising research agendas. In the following years I’ve visited his lab a couple of times.  I remember him explaining how he started out doing simple computer simulations of the origins of life systems, but was provoked by Lesley Orgel to work with real molecules. A couple of years later, at the 2nd Alife meeting, Jerry was the first in the community to show the now well know picture of “Campbell’s Primordial Soup”, as the appropriate starting material for the origins of life work in the laboratory. That brought smiles and applause from the audience.

The scientific discussion of the technical issues in the NYT article can be found in: Tracy Lincoln & Gerald Joyce, Self-sustained replication of an RNA enzyme, Science 323 (2009) 1229. A cartoon of their RNA replicator system from this paper is shown below:

Annotation, August 2, 2011: After I posted this blog yesterday, one of Jerry’s students found it and pointed Jerry to it. Jerry then sent me a much cooler 3D graphics of their RNA replicator system, and he said: “We don’t have a crystal structure of the replicator, but we used the known structure of the related L1 ligase to do homology modeling and provide a 3-D representation of the process. This figure has not been published, so for now it would be a steennewmexico exclusive.” So enjoy our blog-exclusive 3D figure of, as far as I know, the best working artificial RNA replicator system: 

In the upper cycle we see replication of the RNA enzyme E’ by ligation (binding together) of two smaller complementary RNA pieces A and B. The lower cycle shows the replication of the complementary RNA enzyme E, by the ligation of the two smaller complementary TNA pieces A’ and B’.  The result of these two cycles is that the RNA molecule E’ (and E) is amplified through replication. However, a “mutation” can occur on the original RNA molecule E’ such that the original sequence is modified a little. This can result in a slightly faster overall replication process such that the new RNA will outgrow the original one. This is an example of Darwinian evolution at the molecular level.

Do these simple, but very cleverly designed, self-replicating and evolving RNA systems constitute life?

Not quite. The coupling between information and energetics is missing.

In my opinion, one cannot have life without an internal metabolism, an energy transduction mechanism. Living systems need to be able to transform resources into building blocks to enable growth and self-propagation in the environment, which usually requires an ability to break and make covalent bonds. Nothing happens in nature without free energy; no new molecules can be formed without free energy and noting moves without free energy. So in physical terms, a living system needs to be pumped with free energy, so that it can generate local order by pumping entropy (disorder) away from the system into the environment. The system has to operate away from thermodynamic equilibrium to be alive.

Jerry’s system has an external metabolism. The laboratory environment provides the free energy necessary for the RNA replication together with the chemical building blocks. Two small RNA resource molecules come with energized (triphosphate) bonds and this free energy is used when they self-assemble in the appropriate manner directed by a larger template RNA molecule. The RNA replication system is thus operating strictly thermodynamically downhill.

The role of energy in the definition of life is an interesting issue.  It’s an issue that physicists and chemists tend to emphasize, while many molecular biologists and more biologically oriented groups tend to pay less attention to the energetics.  However, all camps agree that information replication and evolution is critical for life, and this is where Jerry’s lab has made an array of breakthroughs over the years.

Another thorny issue associated with an agreeable definition of minimal life, has to do with how “innovative” the associated evolutionary processes are, which I’ll get back to at some later point.

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