Venter’s synthetic cell

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.

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5 thoughts on “Venter’s synthetic cell

  1. Thanks for the very nice summary, Carson! I was wondering what the fuss was all about.

    I obviously don’t know much about this, but it sounds like in the context of biology, being able to ‘build a new house’ from scratch is actually a major breakthrough. Isn’t it true that what you can do with plasmid (e.g. your insulin example) and viral vector insertion is rather limited? I mean, there are only so many kbp’s available in a plasmid or virus. And what if you need multiple genes in different locations of the genome to accomplish your task?

    Whether or not you agree that a life-form with 100% artificial genome pleases the intellect, it sounds like being able to bypass such limitations can have tremendous practical consequences.

    No?

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  2. Oh sure it is a technological advance and it will have impact but I don’t think looking back in history, this will be considered a defining moment. Everyone expected it would happen at some point. I think we’ll remember Watson and Crick, discovering the code, recombinant DNA methods, and sequencing the human genome as the major moments. This will be considered to be a minor step along the way, like say the discovery of exons and introns or siRNA. My guess is that eventually, people will not be using this particular method per se to build synthetic cells. The main significance will mostly be overcoming a psychological barrier.

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  3. I guess only the verdict of history will tell.

    But if you think about it, just because that was a natural progression in its lineage doesn’t mean it’s not going to make history. History is all about figuring out *how* to do it and *actually* doing it:

    – Aviation: breaking the barrier of sound. (Trivializing it: if you can fly at 500mph, why not at 768?)
    – Space exploration: man on the moon. (Trivializing it: if you can get into orbit, why not land right there?)
    – Astronomy: Galileo’s telescope (Trivializing it: if you can magnify 4x or so for terrestrial objects, why not 20x to see the moon’s details and other bodies?)

    etc.

    Although these feats can all be trivialized given their context at the time, they are undoubtedly historical landmarks.

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  4. Sound barrier was nontrivial because it required new technology and there were people predicting it was impossible. Wright Brothers is a better example because I think someone would have done it within five years.

    Given that we haven’t been back to the moon shows that it was nontrivial. I would say getting into orbit around the moon is as important as landing.

    Galileo’s advance was small technologically but immense philosophically and scientifically. That was the beginning of modernity.

    The main reason I think the synthetic cell is not a major landmark is because I don’t believe it will lead to anything for a long time. I think we will find that it will be very difficult to be able to construct and control ab initio life forms. My prediction is that any impact synthetic biology will have in the near term will involve small modifications to known organisms using standard techniques. By the time we will learn enough to construct an ab initio organism, the technology will have leap frogged Venter’s cell.

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