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04/29/2016

A Bit More about the Minimal Genome

Earlier this week, Mark McQuain posted a nice summary of the recently-published work by J. Craig Venter’s group to identify a “minimal genome” for a type of bacterium, the mycoplasmas, which are, as the group points out, “the simplest cells capable of autonomous growth.”  Mark wondered aloud what the implications would be for our understanding of what it is to be human—how many genes do you need to be human?

A few preliminary thoughts about that:

  • ·       I would say—perhaps contra Dr. Venter—that we are not our genes.  The great technical achievement of Dr. Venter’s group is to use modern genetic methods to synthesize mycoplasma genomes on the lab bench, and implant them into the rest of an existing mycoplasma, and show that the result can thrive with characteristics driven by the synthesized genome.  But I don’t think even he, who has said that “DNA is the software that writes its own hardware,” would say that the DNA alone is the organism, even for the mycoplasmas.
  • ·       It took a lot of attempts to piece together a set of “minimally required” genes.
  • ·       The effort was not from the ground up, but was done by breaking the genome into pieces and iteratively testing the pieces to find out how essential they are.  Indeed, taking what had been thought to be known about how essential individual genes are, and “just” deleting the other ones, did not leave them with viable organisms.
  • ·       In the process, there were a lot of failures.
  • ·       One advantage of working with mycoplasmas is that their genetic simplicity is in large part because they are “fastidious” organisms, with narrow strictures on what they need to survive, and so not very adaptable to changes in environments.  Lots of genes in lots of organisms are presumably there to make the organisms adaptable and robust.
  • ·       Indeed, their work found that there were certain “quasi-essential” genes, that might leave the resulting organism “alive,” but not capable of much growth—that is, not so alive after all.  Or should we say the organism has a poor “quality of life?”

So this work is intriguing in the first case for what it might eventually tell about the life of single-celled organisms.  I want to imagine novel antibiotics someday, as a result—maybe we should hope someday soon, given the rise of antibiotic-resistant bacteria.

But I extrapolate from the same complexities and challenges of this work to argue that a search for a “minimal human genome” is a quest that ought never be attempted, because to try would be to create, on purpose, a series of critically deficient human or humanoid embryos that would have to be raised to substantial viability to determine just how “well-endowed” they were.  It seems to me this would have to be, if not the final goal of the enterprise, an intermediate goal.  Before embarking on it, humanity would require that it be the absolute scientific/technological last resort to solving a critical human need.  That might be a good sci-fi story, but not a path that I would expect ever to become illuminated.  The more likely approach of “try it and see where it leads” is, I think, morally unacceptable.  I would say the same thing about the other big goal of synthetic biology (the fusion of biology and engineering); viz., creation of a “protocell”—a cell made of only the minimum set of biomolecules necessary to function.  I could see doing that to a yeast or bacterium for production of drugs in a lab or factory, but not to human somatic cells, much less to human germ cells. 

And I have a hard time embracing the notion of ever extending minimal genome or protocell work to animals or even higher organisms, because—why?  What’s the goal of the research? 

The current minimal genome work is far from the point at which we ought to limit our tinkering, but I believe that point exists, a point at which knowledge is not a sufficient justification, at which sufficiently good ends cannot be articulated, and at which we ought to observe a “presumption to forbear.”

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