Friday, May 21, 2010

Synthetic Life, First Edition

Ham Smith and Craig Venter, together with their coworkers, have made what is certainly the first ever living organism put together by a chemically synthesized genome.

The ingredients of the genome came from four bottles of chemicals, containing the equivalents of adenine (A), thymine (T), guanine (G) and cytosine (C), and a computer-stored information of the entire "tape" of the entire DNA sequence of Mycoplasma mycoides, a microorganism. (You can hear a podcast of Venter describing their work by clicking this link)

They chemically synthesized fragments of the genome in test tube, then used the "awesome power of yeast genetics" to stitch the fragments into a "complete" genome (with certain "water marks" and mutations created for specific purposes of identification and/or engineering) in baker's yeast (a totally different organism). Then the synthetic genome was introduced into a second microbe, Mycoplasma capricolum (as related to Mycoplsma mycoides as mouse is to humans) in various stages, debugged until the newly introduced synthetic genome took over the host cell and simultaneously the host genome was jettisoned.

What they now have is a completely new synthetic cell because most of the chemical building blocks of the new cell is now replaced by new molecules whose synthesis is directed by the synthesized genome.

This is a landmark technology achievement. It will also be touted as a landmark philosophical, psychological, ethical and moral watershed moment.

There is no doubt that it is a high moment in biotechnology. The scientific cleverness and engineering sophistication that went into this is of the finest order (I am still reading the pre-print and already much impressed).

However, its philosophical and extra-scientific implications are less than what some will surely claim.

There is no paradigm shift here: the concept has been consistent with scientific potentials of the day at least since 1991.

In fact, the crucial idea--that a host cell can be made to house a completely different genome and somehow be changed to the properties of the guest genome--was thinkable since a 1990 publication by Ron Davis in which his lab introduced full yeast genome into mouse cells, and I wrote a proposal to NSF, and got funded to introduce whole Arabidopsis chromosomes into yeast cells in stages by cell fusion (but did not succeed beyond the early stages due to technical reasons).

The fact that you can take over a host cell's "shell" ultimately by a new genome IS a challenging proposition which is first demonstrated by the present publication, and this is its most surprising novelty (beyond the technical tour-de-force).

None of it would likely persuade a sophisticated"believer" that man now can create life from fully inanimate objects (man cannot yet do so, because they needed living yeast cells and Mycoplsma capricolum cells, and M. mycoides genome information).

However, I can imagine now a fully synthetic life form being created some time in the future, where no previously living organism's "body part" materials will be used--in this direction recent work in Jack Szostak's laboratory in Harvard Medical School will be crucial. That synthetic organism will still have to use the "information" encoded in an already living organism's genome.

Perhaps the synthetic genome could use a mosaic of information from multiple organisms' genomes, and thus create a completely synthetic species. This would have to solve the issues of compatibility of gene regulation--a very difficult technical and theoretical problem. It will be a great achievement is successful.

Nevertheless, I still cannot imagine a completely synthetic organism in which both the genome (the software) and the "shell" (the hardware) are synthetic and did not exist before. Possible on paper, but not in reality. When that happens, man will have created life.

(If you click on the title, you should be directed to an editorial on the paper. IF you cannot access it, write in the comment and I will see what I can do)

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