Library of Excerpts

The Engines of Neoteny: Evidence of Heterochronic Processes in the Neuropsychological Literature on Hormonal Change

"Even if it is true that a male-related factor modulates intrauterine growth of certain cortical regions, it is obvious that cortical development will be susceptible to many other influences, some closely related to the hormonal effects, some more remote. Ward and Weisz (1980) showed that if a female rat is stressed during the course of pregnancy, the male offspring show demasculinization. After the stress there is a rapid rise of testosterone in male fetuses, followed by a fall to subnormal levels. It is not clear exactly how stress on the mother leads to this sequence of changes. It is interesting to note that the female offspring of such a stressed mother will also tend to have demasculinized male offspring, even though these famales are not themselves stressed in pregnancy. Phenobarbital administered during pregnancy has similar effects, and the male offspring have permanently low testosterone levels.This is an example of a phenomenon already mentioned, whereby chemical effects on the fetus may produce permanent alterations in metabolism. When present in the female they can lead to a mechanism of nongenetic transmission to the following generation. Sherman et al. (1980) have also demonstrated an environmental effect on lateralization. In studies carried out some years earlier it had been shown that brief periods of handling of newborn rats exerted permanent effects on emotionality and on other traits such as resistance to infection. In the more recent experiments it was shown that male rats who had been handled showed a greater right hemisphere lateralization in tests of emotionality and spatial performance than animals who had not been." (Geschwind & Galaburda 1987: 115, Cerebral Lateralization)

"The flounder had both eyes on one side of its head. In some individuals the eyes are on the right; in others they are on the left. The distribution on the two sides varies in the different species that occupy particular geographic niches. Cross-breeding experiments between species have been carried out, with findings that do not fit readily into any standard nuclear genetic model (Policansky 1982). It is possible that variations in the distribution to asymmetry may be deterined to a great extent by differing environmental conditions, such as water temperature or food supply. This possibility gains credence form the fact that sex ratio of the offspring of certain species shifts sharply from female predominant to male predominant depending on temperature or food supply. (Clutton-Brock 1982); Harvey and Slatkin 1982). In several species the sex ratio can vary considerably depending on the hormonal conditions of pregnancy. James (1980a,b) has suggested that this may be true even in humans. It is thus also conceivable that there is a genetic bias toward one form of laterality, which is modified by environmental conditions that alter hormonal milieu or the time of fertilization." (Geschwind & Galaburda 1987: 128-9, Cerebral Lateralization)

"Environmental factors can be an important source of nongenetic influences on laterality. Since the effect of a gene is to play a role in some form of chemical reaction, it is not surprising that genetic determination is not absolute. Every chemical reaction can be modified by alterations in pressure, temperature, pH, light, the presence of other substances, the availability of chemical precursors, and the rate at which products are removed. With growing sophistication of molecular genetics, it has become increasingly clear that nongenetic effects can play a powerful role; methylation, for example, has been shown to suppress expression of many genes. We will now consider some of the random effects that might modify lateralization. One implication of our hypothesis is that even if the genetic endowment of any particular fetus were known precisely, it would not be possible to make predictions concerning the distribution in a population basis. One of the reasons for this relative freedom from genetic determination is that if hormones do play a role in determining laterality, then the effects of testosterone or related substances on the developing brain will be modified by factors not under the control of the fetal genes. Androgens are produced not only by fetal testes and the placenta but also by the maternal ovaries, adrenals, and nonglandular tissues. The fetus can be influenced by the actions of many of the unshared maternal genes. It is reasonable to expect that if a fertilized ovum were transplanted into the uterus of an unrelated female, the final pattern of the brain would be quite different, because the brain would develop in an environment of hormones and other substances that would certainly differ in many respects. It might therefore be reasonable to take a different approach than usual to the genetics of many condiditons. One should perhaps consider, not the genes carried by the offspring alone, but rather the genes of that organism existing or active only for the nine months of pregnancy; in other words, one should consider the mother and the fetus as a unit. This unit contains three groups of different genes: one paternal set present in the fetus, one maternal set present in the mother, and another maternal set present both in the mother and in the fetus. The situation is even more complex when dizygotic twins are involved, since the maternal-fetal unit will contain another group of paternal genes. The effects of substances produced by the mother will, however, be diminished by the capacity of the placenta to act as a barrier to some maternal hormones. The fetus is protected to a great extent form maternal testosterone, which is converted to estradiol by placental aromatase. Dihydrotestosterone, which is not aromatized and therefore crosses the placenta, is, however, usually present in the mother at much lower levels than testosterone. The protection from maternal testosterone is not complete, since offspring do show signs of masculinization when mothers are exposed to this hormone. In addition, progesterone administered to the mother may masculinize female fetuses. It is clear that the placental barrier is far from complete. Furthermore, it is likely that there are individual variations in the aromatizing capacity of the pla
centa. It is conceivable that some maternal genes not shared by the offspring have greater effects on females fetuses. Thus, the testosterone to which female fetuses are exposed comes predominantly from maternal tissues, whereas males produce it themselves in high quantities. In the study of Nichols and Chen (1981) sex hormones given to mothers were associated with a higher rate of hyperactivity in female offspring than in males." (Geschwind & Galaburda 1987: 133-134, Cerebral Lateralization)

"The time of conception is another nongenetic random variable that may well significantly influence laterality. Seasonal effects have often been considered narrowly. The fact that schizophrenics are more likely to be born in January than July, a finding documented repeatedly has often been interpreted as a result of increased susceptibility of newborn infants to virus infection in the winter. There are many other possibilities, however. Consider, for example, changes in sex hormones with day length. The pineal gland, activated in the dark months, tends to suppress gonadal hormonal production. When it is suppressed, during periods of long days, sex hormones rise. We have already alluded to Badian's (1983) report of a higher rate of nonrighthandedness in males conceived from December through May (days being shortest on December 21 and increasing in length for the following six months). A pineal role in laterality has no direct experimental support, but it certainly deserves study."
(Geschwind & Galaburda 1987: 135-6, Cerebral Lateralization)

"There is another possible but surprising souce of random variation. When rats are subjected to stress during pregnancy, the offspring show altered emotional behavior. In turn, the offspring of affected female offspring show similar changes in emotional behavior despite the fact that their mothers were not exposed to any additional stress. This can readily be explained. The offspring of a mother subjected to stress in pregnancy show permanent alterations in their own behavior and are more susceptible to stress effects than normal animals. Therefore, when the females among them become pregnant, even minor stresses will affect them, and their offspring will in turn be affected---an example of what might loosely be termed a "Lamarckian" effect. There are two mechanisms by which such persistent effects of stress could be mediated. Stress produces structural alterations in the brain of the offspring and/or permanent metabolic alterations. Thus, newborn female rats exposed to testosterone manifest a series of permanent metabolic changes. They are more sensitive in later life to androgens than normal females. They carry sex-linked protein, which is normally found only in males (Michaelson 1981), and certain liver enzymes normally found in females disappear. (Gustaffson et al. 1978). There is thus an increased possibility that the female who was subjected to excessive testosterone effects in utero will herself show an increased tendency to hormonal masculinization. which will in turn affect her offspring. In the rat diethylstilbestrol (DES) has masculinizing effects on brain regions involved in reproduction behavior (MasLusky and Naftolin 1981). In the human DES also appears to have certain masculinizing effects (Bongiovanni, Di George, and Grumback 1959); moreover, as mentioned earlier, DES daughters have been reported in some series to have a higher rate of infertility and difficulties in pregnancy, although this result is controversial (Beral and Colwell 1981). We hypothesize that these women will have a higher proportion of children with anomalous dominance, that is, a higher rate of lefthandedness and of the other associations of atypical laterality. Preliminary studies now under way appear to confirm this. There will be certain limitations on such transgenerational masculinizing effects. Even if the mother is masculinized by endogenous of exogenous hormones, the fetus may be shielded from them to a varying degree by the placenta and by the effects of paternal genes." (Geschwind & Galaburda 1987: 136-7, Cerebral Lateralization)

There will also be nongenetic effects. Thus, when the mother is anomalously dominant, she will often be hormonally anomalus in such a way as to favor the production of children with similar dominance patterns. the anomalous hormonal pattern of the mother may reflect her own genetic pattern, but when the responsible genes are not shared with the fetus, then the effects on the fetus will be independent to a great extent of its own genetic endowment. There will be other cases in which the mother was herself exposed to an anomalous hormonal environment, as a result of her own genetic endowment or as a result of nongenetic effects, for example, hormones controlled by maternal genes that she did not share or exogenous stimuli that altered the hormonal atmosphere, such as sex steroids, other drugs, and even the season of birth." (Geschwind & Galaburda 1987: 177, Cerebral Lateralization)

"Huntington's disease is transmitted as a Mendelian dominant; that is, on the average half of both male and female children are affected, and the disease is passed on equally often by affected fathers and affected mothers. Unexpectedly, however, early onset cases of this disorder are overwhelminly often transmitted by the father (Myers et al. 1983). (Geschwind & Galaburda 1987: 177, Cerebral Lateralization)

"E. J. Quart (personal communication) found an elevated rate of a past history of dyslexia in a group with Reye syndrome. This intriguing possibility deserves further study, especially in view of the evidence that this disorder involves disturbance of mitochondrial (dytoplasmic) enzymes. We have discussed already, and will discuss again, the possible rode of cytoplasmic inheritance as a determinant of laterality, as suggested by Corballis and Morgan (1978). (Geschwind & Galaburda 1987: 198, Cerebral Lateralization)

"The hormonal atmosphere in utero may well permanently alter expression of genes or alter genes themselves (for instance, by methylation). (Geschwind & Galaburda 1987: 218, Cerebral Lateralization)

"When the day is artificially lengthened in the winter, Holstein cows increase their milk production and steers gain weight faster (though not when castrated, which strongly suggests that the testes play a role). It is likely that the pineal gland exerts a major control in this regard. During the dark months it is active and suppresses the gonads, but during the longer days it becomes inactive and the production of gonadal hormones therefore rises. This mechanism clearly makes it more likely that animals will be born in the spring, a useful adaptation since conditions of food and climate are far more favorable for survival. Sensitivity to long days appears to diminish over time, so that it is less marked by the end of the summer (Reiter 1980). Male rats raised in constant darkness show diminished sexual activity, but this is reversed by pinealectomy (Baum 1968), presumably because of the removal of pineal inhibition. The yearly cycle is not merely attended by changes in the other metabolic alterations. The hyperglycemic response to epinephrine in humans is higher in the winter than in the summer (Altschule and Siegel 1951). The goldenhamster shows greater thermogenesis in response to a cold stimulus in midwinter than in midsummer (Pohl 1965). Though the yearly metabolic cycle can probably not be attributed entirely to activity of the pineal, it must play a major role. We have already noted that cyclic alteration in the production of sex hormones is likely to be important in many ways; for example, it might affect the percentage of children with anomalous dominance born at different seasons. Children conceived in March or April will spend most of their first months in utero at a time when hormones are high. Children conceived six months later, in September or October, will tend to spend their early period in utero under much lower hormonal influences. Obviously, different quarters of the year will give rise to different patterns, but adequate information regarding the outcomes is still lacking. Badian (1983) found that nonrighthandedness was twice as common among boys born in the six months beginning in September (and thus conceived from December through May) than among those born in the following six months. Furthermore the number of nonrighthanders born in each of these months was higher than the number born in every month in the other half year. Similar effects were not found in females. It is intriguing that compared to controls, rabbits raised postnatally in darkness for seven months were fond to show an increase if synaptic contact zones in the medial visual cortex and the motor cortex on the left, but not on the right (Vrensen and deGroot 1974); however, the authors are cautious in their interpretation of this. There are other possible relevant data. It has been confirmed repeatedly that schizophrenics are born predominantly in the first half of the year particularly in the first quarter. They are thus conceived between approimately April 1 and October 1, that it, predominantly during the period in which the days are longer than 12 hours. It is possible that schizophrenia is more common in individuals who have spent the first six months of pregnancy under maximal hormonal influences. Mental defectives are also more likely to be born at the beginning of the year. On the other hand, many extensive studies of the birth months of eminent people have shown that they too tend to be born predominantly early in the year; even more consistently, the rate of such births is low in the midsummer months of July and August (Peterson 1979). (In all of these studies the data have been corrected for the normal yearly pattern of births.)" (Geschwind & Galaburda 1987: 219-20, Cerebral Lateralization)

"Further work showed that for most genes, corrections would be made---splicing out the nonsense---after an RNA copy is made of a DNA gene. Even with "interrupted" DNA, an edited and corrected message in RNA could be used by the cell's machinery to make the correct protein. Even more surprisingly, for antibody genes the DNA itself can also be spliced. In other words, DNA that is inherited can be altered. Amazing!" (Behe 1996: 127, Darwin's Black Box.)

"Fed on identical diets, two genetically different men will not grow to the same height. Fed on different diets, two identical twins will grow to different heights. Nature is the length of the rectangle, nurture the width. There can be no rectangle without both. The genes for height are really only genes for responding to diet by growing." (Ridley 1993: 265, The Red Queen)

"My own expectation is that when the almost totally unknown realm of processes whereby DNA determines embryology is studied, it will be found that DNA mentions nothing but relations." (Bateson 1979: 174, Mind and Nature)

"That genetic change can at least partly avoid the price of imposing rigidity on the system by being delayed until it is probable that the circumstance which was coped with by the soma at a reversible level is indeed permanent and by acting only indirectly on the phenotypic variable. The genetic change presumably shifts only the bias or setting (see Glossary, "Logical Type") of the homeostatic control of the phenotypic variable." (Bateson 1979: 175, Mind and Nature)

"It is of primary importance to note that insofar as embryos are protected in eggs or in the mother's body, the external environment will not have a strong selective effect on genetic novelties until epigenesis has proceeded through many steps. In the past and still continuing into the present, extenal natural selection has favored those changes that protect the embryo and juvenile from external dangers. The result has been an increasing separation between the two stochastic systems." (Bateson 1979: 196, Mind and Nature)

"Another example is much more common, but less acknowledged. It is the case of cell differentiation in embryonic development. Once a cell differentiates by responding to an environmental factor (i.e. an inductor substance), it usually passes its characteristics to descendants. (Alberts et. al. 1989, Blau, 1989). Again, after the acquisition of the differentiated character, there is hereditary transmission of it." (Aboitiz, F. (1992) Mechanisms of adaptive evolution. Darwinism and Lamarkism restated. Medical Hypothesis 38(3): pp. 196)

"In the light of modern genetics, it is presently considered that IAC is practically an impossibility. In metazoans, the germline and the genetic material are supposed to be isolated form perturbations coming from the environment. Thus, ontogentic changes may not effect heredity. This assumption seems correct for metazoans, in whom the majority of phenotypic traits is indirectly inherited. However, as already mentioned, interitance of acquired characteristics becomes more plausible in cases in which direct inheritance makes a significant portion of the phenotype, as in cell division. If, for example, a cytoskeletal feature is modified during a cell's ontogeny, this is likely to be inherited by descendants. This point was referred to as the transgenerational dimension of modifications to directly inherited characters." (Aboitiz, F. (1992) Mechanisms of adaptive evolution. Darwinism and Lamarkism restated. Medical Hypothesis 38(3): pp. 196)