December 13, 2014

Dr. Gary Churchill
207 288 6189

re: I’d like to cite your work. 

Dear Professor:
I have been invited to write a review article about intrinsic population regulation and your work excites me very much.  (Vivien Marx, Models: Stretching the Skills of Cell Lines and Mice NATURE REPRENT COLLECTION, Technology Features, November 2014 page 514)  So far as I can tell, you are engaged in outbreeding mice and have reached the seventeenth generation although I am not clear on how long ago that was.  Your purpose is noble and your approach wise, but those alone do not account for my enthusiasm.

The white whale, so to speak, breaches with the article On the Regulation of Populations of Mammals, Birds, Fish and Insects, Richard M. Sibly, Daniel Barker, Michael C. Denham, Jim Hope and Mark Pagel SCIENCE vol. 309 July 22, 2005 page 607. If you glance it over you will see that for some seventeen hundred studies of wild populations the team found that fertility rises very quickly at low population sizes and falls very slowly at large sizes with the equilibrium point at about the knee of the curve.  In other words there is a self regulating mechanism for population sizes. 

This of course is intensely good news.  Any growth rate other than zero cannot be maintained indefinitely, be it humans or any other animal.  And of course where kinship gets closest inbreeding depression cuts in and eliminates the population remnant.  But what happens when kinship is too low and population effectively too big?  I have found that with insects there is a damped oscillation.  This was also found many years ago by a man named Nicholson, the difference being that he attributed it to starvation; my bugs don’t starve.

There is evidence that disaster also strikes in mammals when the population gets too diverse, big, outbred, whatever you might call it.  Massively important though this must be if true – and we are speaking of an existential threat to civilization – it is odd that it does not get much attention.  In fact there was a man named Calhoun (Calhoun, J. Death Squared: The Explosive Growth and Demise of a Mouse Population Proceedings of the Royal Society of Medicine 1973, 66, 80-88.) who simply put some mice in a nice big cage and counted them for a few years.  On day 600 the last live mouse was born.  Then they all died out over a long time.  It sounds like a failure of fertility to me. 
If you say (This is most embarrassing.  Here I am addressing a world expert on mouse generations and I am quoting a helpful lad at a pet store.) a mouse generation takes a month, that would be 20 months from the beginning to the last live birth, but the last birth of a fertile male should have been a few months before that … 17? 
Calhoun tested a few males from the cage after live births stopped and found they had no interest in females of proven reproductive capability.  So it looks like outbreeding per se can be as destructive as inbreeding.  And it looks like you may be on the ragged edge of how far outbreeding can be pushed in mice.  In humans it is pretty clear that it is nine generations; Newton (ambiguously) pointed that out, it is consistent with historical experience and a study of (evidently) thousands of couples in Iceland (An Association between Kinship and Fertility of Human Couples Agnar Helgason et al. SCIENCE vol. 329 no. 5864 February 8, 2008 page 813 – 816) found no couple less kin than eighth cousin (their way or reckoning.)  Calhoun blamed it all on crowding, but obviously that doesn’t hold for Iceland nor for you.

So I am absolutely salivating to know what your current data look like.  Are your outbred mice showing the depressed fertility I would expect?  Either way I very much want to include your work in my review.

I have more data if you’d like to see it.  Would you like to see a draft of the review?


M. Linton Herbert MD

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