whati is life

Issues in Biology


Complex Structures

'Nothing creates more misunderstanding of the results of scientific research than scientists' use of metaphors. It is not only the general public that they confuse, but their own understanding of nature that is led astray' Richard Lewontin, The New York Review of Books, May 27, 2010

There are valid scientific and philosophical reasons to reject the claim by Craig Venter that a cell with a synthetic genome should be considered a synthetic cell. The scientific reasons are briefly outlined in the previous page. They can be summarized by the notation that it takes a cell to 'bring a genome to life', and not a DNA synthesizer, as is claimed by the inventors of the synthetic Mycoplasma genome. Ironically, the synthetic genome contains an encoded quotation by James Joyce: 'To live, to fall, to triumph, to recreate life out of life.' It would be my understanding that synthetic life is created not out of life, but out of a synthesizer/computer (you name the machine). Here is how Venter explains his choice to call a genomically engineered cell 'synthetic'.

'We refer to such a cell controlled by a genome assembled from chemically synthesized pieces of DNA as a "synthetic cell", even though the cytoplasm of the recipient cell is not synthetic. Phenotypic effects of the recipient cytoplasm are diluted with protein turnover as cells carrying only the transplanted genome replicate. Following transplantation and replication on a [nutrient] plate to form a colony (millions of genetically identical cells, all the offspring of a single parent cell, the one with the synthetic genome, my addition), progeny will not contain any protein molecules that were present in the original recipient cell. [...] The properties of the cells controlled by the assembled genome are expected to be the same as if the whole cell had been produced synthetically (the DNA software builds its own hardware).'

Now that is a big IF.

Exactly the opposite argument should be made. As the original cell, using its original proteins (transcription factors, enzymes), ribosomes, RNAs, cell membrane and metabolites, copies the transplanted synthetic DNA, the copy of this DNA is no longer synthetic, but made by the original bacterial cell (and I suspect this copying happens before said original proteins are diluted). All further cells with all their molecular content are no longer made in a synthesizer. They no longer use materials from little flasks labeled 'A', 'C', 'G' and 'T'.

Let us not call this cell 'synthetic'. Call it anything you want. A reprogrammed cell. A cell booted from a synthetic genome. Or call it Mycoplasma venterii. Anything but 'synthetic'.

Let me add a challenge. If it were true that this synthetic genome is software that builds its own hardware, then this genome could be injected into any (bacterial) cell, like an E.coli, and remake it into a mycoplasma. This would indeed show that the genome controls the cell, rather than the cell controlling the genome. I bet that the latter is the true nature of life as we know it.

The reader should not take my objections to mean that I am not impressed by this synthetic genome approach. I do share Venter's original motivation of understanding the minimal genome (see the New York Times article on Venter, May 30, 2012). I believe that synthetic genomes will allow many interesting experiments. Here is a short list of what I would like to do with it besides probing the minimal gene set theory or create biofuel from algae:

Does a bacteria need a circular chromosome or can it be linear?
Could the genome be packaged into two or more individual fragments, linear or circular?
Can the cassettes be arranged out of order, or does gene order matter?
Can cassettes be duplicate and inverted?
Does the 'conversion' of M.capricolum into M.mycoides demonstrate that these two bacteria are not truly different species? i.e., use synthetic genomes to test species boundaries.

No matter what, the genome centric view, or more radically, the information centric view taken by Venter will prove technologically very useful. This project, after all, looks like the culmination of a half-century of reductionist genetics, a.k.a. molecular biology. Philosophically, however, I am mindful that we may claim more than there is. The entire aspect of what is synthetic and what is natural is not easily solved, in my view, and my mind even finds a bigger concern behind the engineering of this synthetic cell. Does such a successful approach not also suggest that what we call natural life could have been made by a creator? I would not be surprised that creationists jump at this gift of a synthetic cell given to them. Claiming this to be the 'first self-replicating species that we have on the planet whose parent is a computer', the whole narrative comes dangerously close to intelligent design.

Rejecting any validity to creationism, irreducible complexity or intelligent design to explain life on Earth, I am only suggesting that for now it be wise to not call this cell 'synthetic'.


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