December 13, 2009

Nick Lane
The Macmillan Building
4 Crinan Street
London N1 9XW

Dear Nick Lane: (Anyone else skip down and look at the section in bold.  Then come back here.)
I was very excited by your article on the “bar code.”  What I have done, as the enclosed DVD will show, is to produce a computer program that models the genetics and fertility of a population over generations on the assumption of recessive lethal mutations and mutations with a judicious amount of detuning per mutation.  The good news is that the model splendidly predicts the relationship between kinship (or population size) and fecundity as observed in the real world both among humans and other animals.  No other such model exists. Basically a mating pair must be fairly closely related or fertility will be below replacement. 

The less good news is that the detuning concerns the matching of homologous loci.  That is not intuitively appealing.  Tuning should be between different loci, one would think.  Then there is the fact that in a large number of cases in humans an egg and sperm that would not ordinarily produce an embryo can be induced to do so by injecting the sperm into the ovum.  “Damn the mismatch” if you’ll pardon my expression.

But the two problems may cancel each other out.  I suspect that there is a safety mechanism; if it isn’t going to be a good embryo, the egg won’t let the sperm in.  That makes sense from an evolutionary standpoint.  It means the risk and cost of a doomed pregnancy can be averted.  Indeed my fertility colleagues will inject a number of ova, let the embryos develop and then implant the best looking one. 

So my trusty computer program may not really model homologous alleles, it may model the safety lock.  It is a linear array of elements that are subject to mutation and must match up for a pregnancy to be established by normal means.  I would have used the term “bar code” had I been clever enough to think of it. 

This bar code has been proposed as the cause of speciation.  I would have said that the cause of speciation is genetic mismatch, just like the cause of infertility in couples insufficiently kin.  But if the evidence turns out to be right, I should be only too happy to change and say that the infertility on non kin couples is due to the “bar code” DNA on the mitochondria.

(I am going to post this as an open letter on the web site and pause here to explain to my long suffering readers.  The “bar code” refers to a segment of DNA that resides in the mitochondria, little organelles in the cell separate from the nucleus.  This segment is so uniform within species and so reliably different between species that it can be used to define species and classify.  Hence the term “bar code.”  The article Dr. Lane has written (On the Origin of Bar Codes NATURE vol. 462 no. 7271 Nov. 19, 2009 page 272) examines a current theory that speciation is in fact caused by a mismatch between the mitochondria and the DNA of the nucleus if the parents are too distantly related.)

This all leads to one serious question and one blazing hope.  The question is whether the bar code (on the whole mitochondrial genome) mutates fast enough to account for observations in the real world.  It appears clear that relatively infertile mating between relatively non kin accumulates loss of fertility fast enough to destroy civilizations in several generations, typically within three centuries.  Fifth cousins are significantly less fertile than third of fourth, so the mutation rate should be able to make a difference within six generations.  Is that too fast?

The second issue is the hope.  When I look at the numbers I get the melancholy impression that our last hope of saving the civilized world probably came to an end in about 1950.  Since then we have been committed to a course that has not produced enough cousins for our populations to survive.  However, if it is just a matter of mating with the right mitochondria, or a male mating with a cousin (less close than second) with his mother’s mitochondria, then the cure might be quick and easy.  We can have babies back.  I do have my doubts, but there seems to be a chance. 

It is clear from your article that you are able to talk to people and get answers.  That is a skill I seem to lack.  So if you are interested or know of anybody who might be, let me know.  There is a lot at stake here.


M. Linton Herbert MD 

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