The Imprinted Brain

How genes set the balance between autism and psychosis

Epigenesis: What People Don't Understand about Epigenetics

Epigenetics is about how DNA determines development, not the contrary.

The Homunculus, Sir, in however low and ludicrous light he may appear, in this age of levity, to the eye of folly or prejudice;—to the eye of reason and scientifick research, ... consists  as we do, of skin, hair, fat, flesh, veins, arteries, ligaments, nerves, cartilages, bones, marrow, brains, glands, genitals, humours and articulations;—is a Being of as much activity,—and, in all senses of the word, as much and as truly our fellow-creature as my Lord Chancellor of England.—He may be benefited,—he may be injured,—he may obtain redress:—in a word, he has all the claims and rights of humanity... 

Thus wrote Laurence Sterne in his comic novel of 1759, Tristram Shandy, satirizing the notion of  the homunculus (left). According to this, pre-scientific doctrine of development, the organism grows from a completely formed, perfect, miniature prototype—what is known as preformationism.

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Today such crude pre-determinism might seem absurd, but those who wish to challenge the fact that there are innate sex differences in skills such as maths or throwing missiles take an essentially preformationist view when they argue that “since newborn babies can neither do math nor hit a target accurately, we may not infer that these behaviours are influenced by biological factors.” (p. 1) 

Another example is the widely credited claim that single genes cannot be important in development. The one-to-one preformationist assumption here is that many genes must be involved in every characteristic simply because the organism is much larger and more complex than its DNA.

The alterntive to preformation is epigenesis. We owe the term to Aristotle, who used the example of making a net as an analogy of how epigenesis generates organisms rather than preforming them. Indeed, with the benefit of hindsight we can now see that this was a wonderfully apt analogy, given the fact that DNA spells out instructions for stringing together amino acids, whose patterns of folding determine many of the characteristics of the proteins they form. Looked at this way, you could indeed see the organism as a tightly woven net of proteins. Certainly, this view is much more accurate than that of seeing it as material which has been printed from a ready-made template as preformationism did. Think of the difference between a woven tartan and a printed one: the former corresponds to epigenesis, the latter to preformation.

The blank slate dogma of development, so popular in the twentieth century as a denial of genetics, was also preformationist in the sense that it saw the child’s mind as imprinted material—certainly not as woven in any sense. Furthermore, preformationist caricatures of development like that quoted just now in relation to innate sex differences also served DNA denial because they made the counter claims of genetics seem absurd.

But single genes can and do determine complex features of entire organisms. A single gene, SRY, determines sex in mammals, not by listing and specifying every aspect in which one sex differs from the other in the adult organism, but by switching development away from the female route it would otherwise follow and into the male one.

Indeed, a single gene can even determine the pattern of coloring of an entire animal. A good example is seen in Siamese cats, whose ears, faces, paws and tails are normally dark, while the remainder is lighter colored. The preformationist view would suggest that if this were the result of the cat’s DNA, it would have to contain some kind of map or diagram of where the melanin that makes for darker colour should be expressed during development—the genetic equivalent of painting-by-numbers. But the truth is that only a single gene is required: one that determines that the expression of melanin should be subject to ambient temperature. Where the skin of the animal is normally colder—the extremities—more melanin is expressed than in the warmer, central areas, resulting in the observed pattern of coloration.

There are even cases where sex is determined by temperature. Much the same gene as SRY is involved, but in the case of crocodiles and turtles its expression has been linked to ambient temperature, just like the expression of melanin in Siamese cats. Such findings might suggest that the often-heard cliché about environment or nurture being equally as important as nature or DNA in determining outcomes is true, but the fact that the mechanism works in opposite ways in crocodiles and turtles proves the contrary.

Clearly, if the environment were truly an independent factor, it could cut both ways. Temperature variation could produce more of one sex or the other, and indeed it does: warmer nests produce more males in crocodiles, but more females in turtles. But only evolution can explain why it is this way round, rather than the contrary. The reason is that warmer incubation produces larger hatchlings, and in crocodiles this favors males who will go on to compete for females, but in turtles favors females, who can carry more eggs when they are adults. In both cases the ultimate reproductive success of the larger individuals explains which way the temperature-triggered epigenetic switch that determines sex is set by evolution. This means that evolution and DNA are the dominant determinants, and that the nurturing environment is enlisted by them in epigenesis: nurture via nature if you like.

Finally, what has all this got to do with the imprinted brain theory? Everything because it is the only theory extant that can explain mental illness in genuinely epigenetic terms. Indeed, it is worth pointing out that the nervous system and brain develop from the same layer of blastocyst cells that form the skin in mammals. In other words, what you can clearly see in Siamese cats you can also see as a pattern for the epigenesis of the human brain. And the way that evolution has exploited incubation temperature to determine sex in crocodiles and turtles sets a strking precedent for growth-modulating imprinted genes affecting sex-specific cognitive configuration as proposed by the imprinted brain theory. 

Christopher Robert Badcock, Ph.D., is author of The Imprinted Brain: how genes set the balance between autism and psychosis. 

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