January 30, 2013
to be posted on nobabies.net

Sean E. Harper
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320-1000
805 447 1000
fax 805 447 1010

Dear Sean Harper:
I am delighted to learn (Monya Baker Big Biotech Buys Iconic Genetics Firm NATURE vol. 497 no. 7429 20/17 December 2012 page 321) that Amgen has taken the Icelandic genetics and genealogy program decode GENETICS under its wing; I regard deCODE and the Iceland data to be the crown prince of the entire genome undertaking.  Well done.

The “Killer AP” for medical genomics is something everyone wants.  Maybe I can help.

Of course the best low hanging fruit in medical genetics was the resolution of the Rh incompatibility problem.  I find it very strange that fortunes have not been made nor names become world heroes over that.  But it does set the bar high.

Many years ago I was playing around with some numbers and compared the ages of southern Mesopotamian civilizations with the chance that they would collapse within a couple of generations.  Here is what I found:
(The Ottomans had a change in the way they recruited their Janissaries, so I treat them as two empires.)

Information taken from R. H. Carling THE WORLD HISTORY CHART International Timeline Inc. Vienna, VA 1985.  The experience of Southern Mesopotamia.  The vertical axis is The chance of an empire of any age continuing to rule locally for another 50 years.  The horizontal axis is the ages of the empires. 
A couple of things are obvious at once.  For one, since there is a simple rule to predict the fall of civilizations, they must all fall for the same reason. For another, that reason must be genetic.  For more of the logic and other evidence go to http://nobabies.net/A%20December%20summary.html

I thought it was clear that it took about ten generations for the effect to run its course.  And the only thing that made sense was that if you had a gene pool that got too big it would collapse.  My fantasy was to go to the Icelandic genealogy, select a cohort of couples, calculate their consanguinity by looking back 10 generations and then see how many children and grandchildren they had. 

In those halcyon days a gentleman could reach out to another gentleman and hope for a response.  Eventually I got in touch with somebody in Iceland by email and proposed the test.  He agreed that he understood and the study could be done without compromising anybody’s privacy.  Then he abruptly said he was going on vacation, never returned another email and in a few months had his email address canceled.  Needless to say I was disappointed. 
But to my delight, the study was done eventually. 

An Association between Kinship and Fertility of Human Couples Agnar Helgason et al. SCIENCE vol. 329 no. 5864 February 8, 2008 page 813 – 816

I thought that should end it.  The cat was out of the bag, so to speak.  We at last had a rational way of choosing how many children we wanted.  How not to have children has always, in principle, been pretty obvious.  A new much better world beckoned. 

The silence, as they say, was of thermonuclear proportion.  One thing that was very obvious was that the curve for grandchildren was almost identical with the curve for children.  It seemed eerie.  I wished they had gone on to look at great grandchildren but had nothing to offer except that it was obviously the next thing to do.

There is now more information: Low fertility increases descendant socioeconomic position but reduces long-term fitness in a modern post-industrial society Proc. R. Soc. B 2012 279, 4342-4351 first published online 29 August 2012 Anna Goodman, Ilona Koupil and David W. Lawson
What the study took an interest in was the relationship between wealth and fertility.  I take it as axiomatic that rich people rarely marry kin compared with poor people.  Well in the first two generations there was indeed depression of fertility dependent on wealth and the same eerie similarity of the curves is again visible.  But they went on and looked at great grandchildren.  The drop in that generation was greater than in the first two generations combined.

Bingo!  Case made.  The destructive effect of outbreeding accumulates for more than 2 generations.  Obviously that needs to be proved by carrying the study Helgason did out to great grandchildren and great great grandchildren.  It might take more work than I imagine, but at least it has been done already.  This is a matter of enormous importance.  I feel quite sure that fame and fortune await the capable hand that dares to reach out and take it.  I wish you courage and all the luck and success in the world.


M. Linton Herbert MD   

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