changing one species to another: one step closer to artificial life

Do you remember - if you have ever heard of it - of when Craig J. Venter, one of the pioneers of the human genome sequencing effort, decided he would now try to tackle the issue of synthetic biology, of making new life starting from synthetic (meaning man-made) chromosomes and the like? Well, it looks like he is one step closer to that, as a team of researchers at the Venter Institute successfully managed to switch one species...to another.

This amazing feat has been just published online by the journal Science, and will surely stir some significant amount of discussion among the public, as well as, I would expect, at Scienceblogs, once the current debate on atheism as a civil rights issue eventually dies down.

But let's go back to the 'feat' for a moment, and see what actually happened, and how Venter's team could manage to basically swap a species to another.

First of all, it is important to say that this study is more of a proof of principle than anything else. It is also the first step towards Venter's efforts to understand how to create a useful organism with the minimum number of genes required for life. The paper also steers away from the ethical implications of such proof of principles, which is really more of a tool than a revealing study in itself: "Genome transplantation is an enabling technique for the establishment of the new field of synthetic genomics. It may facilitate construction of useful microorganisms with the potential to solve pressing societal problems in energy production, environmental stewardship, and medicine. Chemically synthesized chromosomes must eventually be transplanted into a cellular milieu where the encoded instructions can be expressed. We have long been interested in defining a minimal genome that is just sufficient for cellular life (10, 11) and have advocated the approach of chemically synthesizing a genome as a means for testing hypotheses concerning the minimal set of genes. The societal and ethical implications of this work have been explored (12, 13)."

To facilitate such experiment, the research group picked two unicellular organisms which are closely related, and do not have cell walls (unlike some bacteria). They also chose a microorganism whose genome is composed of a single circular chromosome. The two species of choice were Mycoplasma mycoides and M. capricolum, already known innocuous goat pathogens. The idea was transfer the circular chromosome from one species to the other, and find a way to select for the organisms that successfully managed to uptake this chromosome, as well as get rid of the other one. The easiest way to check whether the chromosome was taken up was to engineer it so that it contained two additional genes, one for antibiotic resistance, and one for the production of a blue colour. Science's news section reports that "Carol Lartigue and colleagues removed the modified chromosome from M. mycoides, checked to make sure she had stripped off all proteins from the DNA, and then added the naked genome to a tube of M. capricolum. Within 4 days, blue colonies appeared, indicating that M.capricolum had taken up the foreign DNA. When they analyzed these blue bacteria for sequences specific to either mycoplasma, the researchers found no evidence of the host bacterium's DNA."

Basically, although the experiment was successful (which makes sense, as we know of many organisms, including bacteria, which are able to uptake naked DNA from the environment), it is not really understood how the organisms managed to 'get rid' of their older genome, which did not contain the gene for antibiotic resistance.

Glass, one of the authors of the paper, thinks that, initially, M. capricolum would be hosting both genomes, but that at the moment of cell division, one daughter cell would be inheriting only one of them. Then, exposing the organisms to antibiotics allowed for selection of those daughter cells that successfully managed to uptake the genome conferring antibiotic resistance (meaning, they were basically the only ones to survive. However, such organisms usually go through a DNA replication step - and this means that, by some system, the cells which took up the other chromosome must have been able to either detect its presence, and avoid DNA replication, or must have replicated both genomes, and given birth to four cells (which is highly unlikely).

It will be interesting to see how this experiment will be raising ethical, as well as patent issues very soon, and what the reaction of both the scientific community and the public opinion will be. I am personally worried more by the patent implications than by anything else, as it would be quite dangerous to have the means for the creation of new (potentially harmful) life into a few hands, and mostly out of the control of governments. But again, there was a huge 'stink' about cloning, and about recombinant organisms in the past, but nothing really disastrous has arisen from it. And as long as the wider scientific community will have free access to the tools of synthetic biology, chances are that this will not be the cause of a disaster either.

Reference: Genome Transplantation in Bacteria: Changing One Species to Another, Carole Lartigue, John I. Glass,* Nina Alperovich, Rembert Pieper, Prashanth P. Parmar, Clyde A. Hutchison III, Hamilton O. Smith, J. Craig Venter, Science, Published online 28 June 2007; 10.1126/science.1144622 Abstract