Last Thursday, the creation of a `synthetic cell’ by Craig Venter’s institute was announced in the journal Science to much media fanfare. What they actually did was to synthesize an entire genome of a known bacterium and transplant it into another bacterium. This achievement was not unexpected although Venter’s team had to overcome two significant technological hurdles to make this happen now rather than later. The first was the ability to transplant an entirely new genome into a bacterial cell and have the new cell actually function. This was achieved last year by Venter’s team and published in Science. The second was to synthesize a continuous ring of DNA consisting of a million base pairs, which was over a factor of 20 more than what had been done before.
It is still mysterious as to how the feat of transplantation actually works. They first incubate the recipient cells in a soup that essentially consists of beef broth and sugar at 37 degrees Celsius, which makes the soup more acidic. This causes the bacterial cells to change shape and become more elongated and branched. They then carefully add the synthesized DNA, which are cushioned in specially prepared gel plugs. They gentle rock the tube, incubate it some more and in a few day cultures of the new cells, which they have been manipulated to be blue, appear. It is not clear how generalizable this procedure will be for other types of cells but amazingly it works at all.
The task of synthesizing the DNA was less about inspiration and more about perspiration. They divided the sequence of the donor genome into a little over a thousand 1080 base pair long segments or cassettes and had the company Blue Heron synthesize these cassettes from scratch. Venter’s group then combined these cassettes into a hundred nine 10,000 base pair long assemblies, combined these into eleven 100,000 base pair assemblies, which were then joined into the circular genome that was transplanted. The whole procedure was only possible because of half a century of molecular biology know how.
I don’t think that this achievement represents a major transitional moment for society or even science. The hype is that this now allows us to design synthetic bacteria that secretes gasoline or can clean up oil spills. However, in reality this just provides another means to achieve those ends. Prior to this work, people would insert and delete genes in existing organisms to attain some end. For instance, human insulin has been produced by bacterial cells for three decades by genetically manipulating genes. Now, instead of swapping genes in and out, they can synthesize the entire genome. The difference is the same as that between building a new house versus renovating an old house. If you only want a bigger kitchen or bathroom, then its best to renovate. If you want an entirely new floor plan then it might be better to build from scratch. However, just as new houses don’t look that much different from existing houses, I think this will be true of synthetic cells as well. We simply do not understand enough (and perhaps never can from a computational complexity point of view) to be able to design ab initio life forms that are completely independent of what already exists. Hence, our forays into synthetic biology will likely always involve some form of modification to existing life forms. It then becomes a question of expediency and cost whether you build from scratch or renovate.