Re: Doogie Mice

Robert J. Bradbury (
Thu, 2 Sep 1999 14:00:52 -0700 (PDT)

On Thu, 2 Sep 1999, Philip Witham wrote:

> This is amazing. How could it be that nature didn't select for this?
> So simple, so apparently effective,

>From the paper:
> the total number of NR2B-containing NMDA receptors per single synapse
> is also increased in transgenic neurons at this stage.

Sorry, but it isn't "simple" to for nature to increase the expression of a receptor in some part of the brain.

That requires very accurate gene duplication of the gene in question (without duplicating any negative genes), or a very specific mutation in the NMDA expression or transcription regulatory region(s).

> there must be a down side, like - the brilliant mouse decides that
> having children would pinch her lifestyle.

Doesn't have to be a down side. Could simply be that nature is working blindfolded with its hands tied behind its back.

Mice only have to have a learning rate and sufficient memory to be able to survive and reproduce. Since their longevity is short (due to a high hazard function), the selective advantages of improving these mental traits may be diminished compared with a species with a longer lifespan. The selection pressure on mice is to find food and reproduce fast. Whether learning & memory (from a "human" perspective) enhances this is an open question. I would agree that you could make a case that enhanced memory could facilitate finding food and mates. But I'd argue that there are other traits (such as an enhanced sense of smell or being able to spot birds in the sky or run quickly) that would enhance its survival more and therefore have more selection pressure on them. It would be interesting to look at this gene in squirrels or other animals whose survival may depend to a greater degree on their memory.

It is also possible that the mouse genome is at a local optima. Nature might not be able to do the mutations in the regulatory regions because this might cause interference with other regulatory factors. The flexibility of gene regulation isn't well understood yet and until we know all of the preferred binding sites (8-12 DNA bases) for the hundreds to thousands of regulatory factors it is difficult to work this out. It could be that the specificity of the control elements is tuned just like a piano and if you have one note thats off the whole song sounds bad.

However, this article is important because (a) It shows that learning & memory seem to be "throughput"

      related, increase the throughput of the synapses and you
      increase your ability to memorize things.
  (b) learning/memory can be increased through genetic methods
      [that ought to stick in the craw of the Anti-Ag-Bio people,
      at least the ones that hate genetic engineering in princple].
  (c) it will start the ball rolling on finding more of these genes
      which will then lead to germline engineering of children which
      will really start the ethics debates rolling -- "The Catholic
      Church stands for the right of people to have stupid children.
      If God had intended everyone to be smart he would have made us
      that way."  :-)

Overall, though, IMO, its more likely that nanotech will make this only marginally relevant. A good part may be that it forces us to confront the issues before we have the technology to implement them.