Open letter to Mathew Gage.  He has already been generous enough to reply. 
My original letter was sent this past October 4.

Mathew Gage
School of Biological Science
University of East Anglia
Norwich Research Park
Norwich NR4 7TJ
Dear Mathew Gage:
I read with interest the article (Lukasz Michalczyk et al Inbreeding Promotes Female Promiscuity SCIENCE vol. 333 no. 6050 page 1739) with great interest.  I see you are the one to whom correspondence like this should be addressed. 

Your title is charmingly inflammatory.  “Don’t marry a cousin or your daughters will be tramps.”  That is hardly the spirit of your paper, of course.  What you found, among other things, is that female red flower beetles mate with more males and spend more time mating if they are inbred.  I do not know, but I suspect if the opposite had been true, the title would have been, “Inbreeding Discourages Reproductive Efforts of Females.”  There is a sort of inbred prejudice against kindred marriages in humans.  For instance years ago NATURE published an article on immune systems in primates.  Those species that were basically monogamous had weaker immune systems than those species of primates that were promiscuous.  The title was, “An Advantage of Promiscuity.”  No.  It isn’t an advantage.  Promiscuity costs a species because an otherwise necessarily robust immune system must be maintained, and a vigorous immune system – kind of like a police state I suppose – is expensive and may do things you don’t want it to do.  Incidentally, humans have the puny immune system of monogamous primates.  I should have thought that would have been headline news.

On the subject of kin marrying, I have come to be a bit like the Ancient Mariner, although older I guess and not possessed of Coleridge’s verbal magic.  The geezer in the poem is compelled to scurry about telling people, “Be kind to animals.”  I am compelled to say, “Be kind to babies,” particularly when it comes to mating choice.

I would say that compromising the fertility of your children could be called, “Unkind,” wouldn’t you?  Careful.  It’s a trap.  If you want your children to have normal fertility you need to marry kin and kin within a fairly narrow range.  A study done in Iceland found that when couples married their fertility could be predicted if their degree of kinship was known and – contrary to the expectation of just about everybody but me it seems – the more kin the more kids.  Again, given the dire depression of fertility in so many developed countries, I should think this would be headline stuff.  But I read more about troubles in the Middle East than I do about how we need to start marrying cousins again if we want to survive.

You are interested in inbreeding, and the Iceland study was able to demonstrate a degree of that.  Here is what happened with grandchildren. 

An Association Between Kinship And Fertility of Human Couples.  Agnar Helgason, Snaebjoern Palsson, Daniel F. Guobjartsson, Pordur Kristjansson and Karl Stefanson, SCIENCE vol 319 8 February 2008 page 813 figure 3 C. 

They have their own ways to calculating kinship, but they call the first bar “second cousin or closer,” the “third cousin or closer” and so forth.  The best fertility for your children, then, would be if you were to marry a third cousin – again by their way of counting kinship. 

So when you marry, you are choosing for your future children not only their genetic and social heritage but their fertility as well.  And yes, inbreeding is real; second cousin or closer matches have less than the best fertility.  Of course it is still not as low as that of eighth cousin or more distant pairs.  A study that completely supported the Iceland article was written for Denmark.  Alas the authors did not see that their agreement was massive and some quibbles about technique were irrelevant. 

For your experiment you prepared inbred beetles and you give the familiar explanation of inbreeding depression – the expression of deleterious recessive alleles – but there is more news on that front.  A quite recent article
(Elizabeth Pennisi Epigenetics Linked to Inbreeding Depression SCIENCE vol. 333 no. 6049 September 16, 2011 page 1563 announcing work by Philippine Vergeer
Hugens Building
Room HG 01.132
Radboud University Nijmegen
Molecular Ecology
Heyendaalseweg 135
6525 AJ Nijmegen
The Netherlands)
found that in a flower called the small scabious the deleterious effects of inbreeding could be completely reversed by treating the seedling with a demethylating agent.  That indicates that inbreeding depression, in that species of plant anyway, is not genetic at all.  It is an epigenetic control mechanism that is involved. 

This is most thrilling.  I wrote Philippine Vergeer and encouraged her to do the same thing with fruit flies.  I strongly suspect that she will find the same mechanism at work there.  Since I have not heard from her I suspect that she is not interested, but you already have the inbred insects well characterized.  Raising them in a demethylating environment might not be difficult.  If you find the same mechanism at work in animals, we shall have a new law of biology.  Perhaps the two of you can make common cause.

Plants are quite different from animals, of course.  But none other than Charles Darwin was bold enough to say that the inbreeding depression he found with plants also applied to people, so people should not marry cousins.  His own son took him up in the matter and did a study to see whether the marriage of cousins caused more insanity than the average.  What he found was just the opposite.  There was less insanity from cousin marriages.  Yet the intense prejudice against them remains. 

I suspect that what he was finding was that the enormous health burden of Rh incompatibility there and then was slightly alleviated, since cousins would be slightly more likely to share blood type and thus not have the condition strike.  When I go over the numbers, that seems plausible.

But with regard to Rh incompatibility and cousin marriages there is another issue.  Of course it can kill or do brain damage to an infant, generally not the first infant since the mother’s immune system must be activated first.  But according to the Iceland study cousin marriages produce large families.  And if there are many children, it is not only the lives of the infants that are endangered.  I can go into the pathophysiology if you like, but it is very disagreeable.  The way the mother dies (Or did die, it is very rare here and now; in more troubled countries I do not know but only guess and fear.) is terrible in the extreme.  I wonder if our pathological aversion to cousin marriages might be in part due to the memory of such events; cousin brides died horribly.  I know it is true.  I have a friend it almost happened to. 

At all events if you are willing to screen for Rh factor and to avoid marriages between mismatched Rh types, as was once the law, the whole problem goes away.  Now there is a treatment, which is imperfect, and there is a prevention, which may be pretty good but cannot be better than judicious mating choice.

Of course other deleterious alleles can be screened for nowadays.  But according to the work of Philippine Vergeer and her team, if applicable to humans, genes aren’t the problem anyway.

At cost of rattling on a bit more, one must wonder why in the world evolution should do this?  Build in a mechanism that takes a small stressed population and weakens it further.  I suspect that this is a side effect of a more important issue, which is speciation effect.  Let us assume that it takes an average of two thousand generations of population separation for speciation to supervene.  It may be a bit longer.  Sixty thousand years is in the range that human populations are thought to have been separated, but whoever said humans were average?  Going with two thousand, consider a chromosome of one parent being inherited by two offspring, which are then separated by a geological event for two thousand generations.  When those two chromosomes – or bits of chromosomes – get back together, they cannot do business.  Then suppose the same setup except that mating is random and the population is a thousand or greater.  Now on average it will take two thousand generations or more for the chromosomes to get together again.  They can’t do business.  Neither can any other chromosomes, and the whole population dies.  Since two thousand is a big number, keeping the population air tight is unlikely so the whole species would die.

Since there are living species, nature must have a mechanism for snuffing out populations that get to large.  We can see it at work in the graph above.  My own efforts at a computer model of the process seem to indicate that any such mechanism will also result in inbreeding depression.  Therefore it seems to me highly likely that in the graph, it is not only the left descent of the curve but also the right descent that is mediated by an epigenetic mechanism.

Now suddenly your new law of nature becomes far more important.  It does not apply just to very inbred communities but applies to absolutely everybody who is interested in having children. 

That is a bit much to hang on an experiment that has not been done, but I think it strongly suggests such an experiment ought to be done.

Actually I have a lot more evidence, which I have posted on my web site.  New relevant information turns up regularly, such as yours and Philippine Vergeer.  But I fear I overtax your patience. 

Let me know what you think.


M. Linton Herbert MD

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