Blind, stupid luck may suffice:
There is a paper (R. A. Waterland and R. L. Jertle Transposable elements: targets for early nutritional effects on epignentic Gene regulation MOLECULAR CELL BIOLOGY August 23, 2003 pages 5293-300) that recounts a study in which yellow agouti mice were treated with a cocktail of folic acid, vitamin B12, choline and betaine as a dietary supplement resulting in changes in the methylation of DNA, with the sites located.
Folic acid comes from “foliage.” Somebody threw some leaves into sodium hydroxide, extracted some salts, purified them, neutralized them and separated an acid by that name. Medically folic acid is necessary for DNA production among other things. Lacking it produces an anemia because the red blood cells cannot be made easily. Vitamin B12 is also needed for cell reproduction and lacking it, or lacking the ability to absorb it also produces an anemia, “pernicious anemia.” The lack also causes a kind of paralysis.
Years ago, it was standard practice if a patient had a folic acid deficiency anemia to give both drugs. Otherwise the replacement of the folic acid could cause a burst of cell division depleting vitamin B12 and causing the neurologic damage.
More recently it has been found that lack of folic acid also causes developmental problems. At one point the embryo, schematically, consists of three layers called the endoderm, which matures into the lining of the GI tract, the mesoderm, which matures into muscle and bone, and the ectoderm, which matures into skin and the nervous system. Endoderm and ectoderm roll up into tubes during early development. If the neural tube of the ectoderm does not roll up completely, there may be a baby that has a defect leaving parts of the nervous system, classically the lower spinal cord and its roots, exposed to the outside world with resulting loss of function. Of course this is tragic, so it is important for pregnant women to have adequate folic acid even before they know they are pregnant. The result was a law requiring that bread and certain other foods be given added folic acid and vitamin B12. This law went into effect in 1996.
I don’t know about you, but bread just does not taste as good as it used to. Even French bread in France is of indifferent quality. I used to think that the governments of the world were buying the fresh grain, keeping it as strategic reserves, and then selling it off when it was getting stale. But now I am thinking that it is the vitamin B12 that has taken good bread away from us.
At all events, the women are getting their folic acid in ample supply and I suppose there are fewer neural tube problems.
The problem is, as the paper points out, that these vitamins also increase methylation. The authors caution that the end result of this is unknown and possibly dangerous.
So I thought about it. The infertility that comes from marrying someone who is not moderately close kin appears to be mediated by an epigenetic process, probably methlyation. If the patterns of methylation of the DNA do not match sufficiently, there will be – in mammals – both pre zygotic and post zygotic infertility. If you are increasing methylation then you are likely increasing methlylation in the places where the infertility is being caused. There are a number of possible outcomes.
One outcome might be that the relevant sites get saturated. Every site that can be methylated gets methylated. That would mean that everybody’s pattern would match everybody else’s pattern. The hole issue of needed consanguinity would evaporate and all we would have to do is deal with the resulting population explosion. Or maybe the methylation would be just a tad less than complete and the result would be fertility just at the replacement rate, like the UN statisticians predict. We all live happily ever after, at least as long as we are able to make the chemical.
The more fool I. Here I am trying to awaken people to a terrible danger that they do not want to hear about, and it all may be cured with a simple vitamin supplementation that we do for a completely different reason. I wonder why I think at all. We are at the mercy of powers we ken not. I doubt this fertility matter is even the worst of them, although it is very bad indeed.
Oh well. One life wasted. Maybe next incarnation I can do something useful.
At the other extreme the methylation we are producing may be so slight as to be trivial. Then we are back to square one. Nothing changes.
In between there is a serious problem. Maybe methylation as we are causing it is neither low enough to be trivial nor high enough to help. Maybe it is just throwing a significant number of randomly distriubuted methyl groups onto the DNA. In that case, no two people are likely to have a remotely similar pattern. Every man and every woman would then be totally infertile no matter whom they chose to mate with.
Since the program is only sixteen years old, those affected would be essentially everybody in the developed world under the age of sixteen. And the effects would not become visible in the statistics for another four years or so. At that point, even were we to realize what was going on, the birth rate would fall to zero.
Coincidentally, that is the same time when women of about twenty will start postponing child bearing until about age 40. (The evidence for this is on Gapminder.com. The print has become very small and the stats have not been updated for seven years, but it is still impressive. If you can’t read the instructions do this: go to the site and load Gapminder. When you get the graph, click on the bottom, the horizontal axis. You will get a menu. Number of children born per woman is the top of the list. Then click on the left side, the vertical axis. The third choice from the bottom is “Population.” Click that. Now you get another menu. At the bottom is “age at first marriage for women.” Click that. Now drag the time slider at the bottom all the way to the left, to 1800. Then click “play” close to the slider. Watch and weep. Things bounce around for a while, and then in recent years country after country shows a drop in fertility which goes below 2 and then stabilizes. Then the age at first marriage starts up inexorably. You have watched the pre zygotic infertility max out and post zygotic infertility set in. The girls’ biological clocks are stopping. A little measuring with the thumbnail and you should find that at least for Sweden the age at first marriage will reach 40 just about when the girls now 16 reach 40.)
So you spends yo’ money and you takes yo’ choice. Actually the government spends your money and you live with the consequences.
What happens five years from now. Will the 20 to 21 year olds present us with a population explosion? With absolute barrenness? With the perfect balance? I have no idea, no idea at all. And so far as I know nobody else is wondering about it at all. If you have the occasion, please scream for help. I have been yelling for help for many years with very little to show for it. Maybe you can do better.
So what is more likely to work, my efforts or sheer luck? My track record is pretty clear. The smart money is on luck.
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