The great process of revision of medicine in the light of genetics has sofar traced three main patterns in present medical thinking: normal human genetics, medical genetics, and eugenics.

The birth of genetics represents in nuce the birth of eugenics, or preventive genetics, which, on account of the study of the traits of a man and a woman, may judge of the probabilities of their children with respect to the same traits.

Eugenics makes objective and valid deductions, but one has always to rely on the responsibility of the propositi, and on auto-decision, engaging the conscience of intelligent and free beings.

The concepts and problems of Medical Genetics are considered in the light of modern advances in Biochemistry, the classic aspects of the gene, cistron, muton and recon, having been completed by the concepts of Operon and chronon, with respect to the traffic of structural genes and to the temporal dimension of the hereditary unit, respectively.

The impact of these various aspects of the gene is considered with respect to ontogenetic processes, heredity of diseases and heredity of disposition to-diseases. Ageing is also considered as a disease, due to the extinction of the genes, and therefore apt to be treated with a substitutive therapy.

The Authors report a case of translocation 21/21 in a woman who, after two miscarriages, gave birth to a mongoloid daughter — dead a few days after birth. The chromosomal aberration was present in 100% of the plates examined.

Occasional chromosomal alterations, found in the patient's karyotype, might be held responsible of small phenotypic alterations. No alteration was found in the husband's karyotype.

The Authors analyze the phenomenon whereby, in progressing from generation to generation, a hereditary disease may appear at an earlier, equal or later age (anticipation, repetition or posticipation, respectively). They believe that this represents the phenotypic effect of a temporal dimension of the gene, the “chronon”, which may reveal stability, plus-variance or minus-variance according to the standard genetic models. This interpretation provides an explanation of two family cases of diabetes mellitus, respectively exhibiting anticipation and posticipation, and repetition.

A familial mosaicism involving chromosomes of group A. The father shows two clones: 46/normal and 47/trisomy A; the mother, 46/normal and 45/monosomy A. The two children are three clone mosaics: 45/monosomy A, 46/normal, 47/trisomy A.

Only one of the children is phenotypically abnormal: the other three members of the family have a normal appearance.

Relationship between karyotype and malformations is discussed. A tentative explanation is suggested.

1. The proportions of red haired offspring within families in which one or both parents are red haired are too high to support the hypothesis that red hair is inherited as a simple recessive trait.

2. Family data and gene frequency analysis give strong support to the hypothesis that red pigment in human hair is dominant to its absence, and is hypostatic to brown and black.

Monozygotic twin (MZ), dizygotic twin (DZ), and sibling (SIB) pairs were taste-tested for hydrochloric acid, 1-quinine sulfate, and 6-n-propylthiouracil (PROP). The numbers of pairs involved were 75 MZ, 70 DZ, and 78 SIB, for the latter two compounds; 26, 45, and 45, respectively, for the acid.

There was a significant difference in intrapair variance, between the MZ and the same-sex DZ pairs, in thresholds for bitter-tasting 6-n-propylthiouracil (p < .001). The difference in intrapair threshold variance was not significant for bitter-tasting quinine (p > .05) or for sour-tasting hydrochloric acid (p > .10).

The male MZ pairs had a significantly lower intrapair threshold variance than the male DZ or male SIB pairs for hydrochloric acid (p < .01), but the female pairs manifested no such difference. The intrapair variance in hydrochloric acid threshold was significantly less for the nine male MZ pairs than for the 17 female MZ pairs (p < .02).

Repeated taste tests on the same subjects reproduced results similar within a single threshold range in a high proportion for each compound: for hydrochloric acid, 72.9% (N = 44); for quinine, 76.9% (N = 221); and for PROP, 76% (N = 225).

Correlations between thresholds for the different substances were positive and significant (N = 308): between PROP and quinine, r = + 0.44 ± .05 (p < .01); between quinine and hydrochloric acid, r = + 0.35 ± .05 (p < .01); between PROP and hydrochloric acid, r = + 0.17 ± .06 (p < .05).

Chromosomal evaluation was done in 62 patients affected with otosclerosis, clinically and surgically proven. Numerical and structural karyotype analysis of leucocyte and fibroblast cultures, showed normal results.

Cytogenetic findings published earlier by other authors in a small series of otosclerosis patients and where mosaicism in the D-group was detected, are contradicted.

The importance of the critical evaluation of the cytogenetic method used and of the necessity to investigate cytogenetically a large enough number of patients, before linking a clinical and phenotypical condition to cytogenetic finding, is stressed.

The Authors report EEG alterations found in two brothers affected by pigmentary retinopathy, syndactilia and hypoacusia, and in their relatives. The EEG resulted to be altered aspecifically in the propositi, in their mother and their two clinically healthy sisters. The father was normal. Reports on EEG alterations in patients with pigmentary retinopathy are rather frequent, while such report is rare in healthy relatives.

The concepts of Chronon and Chronaxy of Gedda are discussed in the light of recent biochemical-genetic knowledge. It is proposed that the term «positive chronaxy» and «negative chronaxy» be employed to designate the period during which a gene is in active and inactive state, respectively. Other terms proposed are «recurrent positive chronaxy», «recurrent negative chronaxy» and « uncoordinated chronaxy». It is pointed out that the different chronaxy states of genes may be subject to modification by certain agents. If a given agent is able to change a gene from a negative chronaxy state into positive chronaxy state, the gene toward this agent behaves as being in a «conditionally negative chronaxy state». In the same sense, we can speak also of a «conditionally positive chronaxy state» of a gene. It is proposed that mutations facilitating malignant transformation of cells can, theoretically, occur in both the active and inactive segments of the DNA. If active segments of the DNA are affected, i.e. those in positive chronaxy state, the effects of such mutations would be expressed immediately. If, however, genes in negative chronaxy state have similar mutations, their effect would be expressed only if these genes become activated by some agents, either physiological or unphysiological. Malignancies facilitated by hormonal inbalance may represent instances or mutated gene activation by physiological agents while tumors caused by carginogenic substances with a structure resembling steroid hormones could be examples of gene activation by unphysiological agents.

A family is reported in which 5 individuals out of 2 generations were found to suffer from dysostosis cleidocranialis. In that kindred twins occurred twice, one twin pair being DZ and suffering from the disease, the other pair MZ and healthy. The number of affected family members is in agreement with the autosomal dominance of the trait as indicated by numerous earlier observations. The characteristics found were: reduced growth, macrocephalus with late fontanel occlusion, protrusive frontal bone, hypertelorism, dysplasia of the clavicles and the pelvis, retarded development of hand skeleton. There was a certain variability in the expression of the traits in both DZ twin sisters, particularly concerning the malformation of clavicles and pelvis. Their children showed rather uniform alterations concerning head and hand skeleton, clavicles and pelvis.

Blood group tests performed did not reveal linked inheritance of the pathological trait and any of the used serological markers.

In 3 out of 161 cases of thalidomide embryopathy seen in Hamburg, typical malformations of thalidomide causation were associated with cleft lip and/or palate. The same association was present in 6 out of 918 cases of thalidomide embryopathy reported by correspondence. Clefts of the face are more common in thalidomide children than in other children. Usually, they are associated with ear deformities. In cases of aplasia of the radius observed before the introduction of thalidomide but not in those connected with thalidomide intake, clefts are more common than in the general population. The association of clefts and ear deformities has been known before the introduction of thalidomide. Thalidomide is probably the cause of only some cases of association.

The authors have studied the frequency and nature of associated malformations in a series of 1000 patients with congenital heart disease. Etiological factors have been statistically analyzed, too.

The Author reports the case of two MZ twins concordantly affected by a neoplasm of the testicle. The various etiopathogenetic theories of this form, the data reported in the literature and the genetic interpretation are discussed.

The first cellular differentiation in the process of segmentation leads to the embryonic period, the major organogenetic period for the nervous system. In man, it appears between the second and the eighth week after conception.

During the foetal and perinatal periods, the nervous organization mainly develops at the cerebellum and cerebral cortex levels. The cerebrum functional maturation continues well beyond birth.

Neuroblasts are the most widespread mother-cells in the developing nervous system during the embryonic period, but some are still to be found after birth.

Animal experiment has demonstrated that ionizing radiations were able to disorganize neurogenesis in any of its maturation stages, even at very low doses. It is possible to establish a chronological table showing the anatomical or functional deformities in relation with the embryonic age at which rays have been given.

It appears that in man the most dangerous period is between the beginning of the second and the end of the eighth week after conception. At that moment, pregnancy is often ignored and a dose of 20 to 40 r is sufficient to entail serious damages, such as microcephaly, protrusions of the brain or mental retardation. On drawing near to birth the foetal or neonatal nervous system of rodents or primates is still radiosensitive, especially at the cerebral cortex level and the consequences will be of a neurophysiologic or psychosensorial nature. Certain embryopathies or neurologic alterations would only be apparent in subsequent generations, following mutations induced into the mother-cells of the nervous system. Genetic deformities of the nervous system can also result from moderate irradiations of the gonads.

Further to the precise experimental research work on the radiovulnerability of the embryonic or foetal nervous system of the animal, certain clinical observations are presented, which lead to similar conclusions.

The atomic bombardments have caused numerous neurological trouble among the children who had been irradiated in utero. And the genetic effects are not yet perfectly known to-date.

This set of experimental and clinical data must prompt us to be very careful when using ionizing radiations, even at low doses, in pregnant women and newborn.

Analysis of the chromosomes of the proposita, who died at 10 weeks of age, revealed a D/E translocation. The child showed the following abnormalities: hypertelorism; high palate; low set, malformed ears; left paresis of facial nerve; micrognathia; hemimelia with radius aplasia on the left side; open foramen ovale; open ductus botalli; ventricel septum defect; pelvic kidney left; hypotonia of the musculature; shortened thigh-adductors; and a dorsal flexion of the first toe on both sides.

The chromosome complement of the father included both reciprocals of a translocation between a D- and E-chromosome. The chromosome number of both father and child was 2n=46.

The Authors report the results of a cytogenetical investigation on a group of 140 Down's syndrome patients: nine of them had a translocation (D/G or G/G) and four a mosaic (trisomy 21-22/apparently normal); a mongol girl had 48 chromosomes due to the presence of a small centric chromosome and 21-22 trisomy. All other patients had a regular 21-22 trisomy. Some additional morphological anomalies are described, but interpreted as being expression of the normal human karyotype's variability.

It has been recently shown that the human requirement for exogenous ascorbic acid and the disease, scurvy, are the result of a typical genetic disease syndrome caused by a defect on the gene controlling the synthesis of the enzyme protein, L-gulonolactone oxidase. The lack of this active enzyme in the human liver prevents Man from producing his own ascorbic acid; a synthesis which is regularly carried out by nearly all other mammals. This genetic disease has been named, Hypoascorbemia. This new concept of the genetic etiology of scurvy gives a much broader outlook and opens perspectives which were lacking in the previous fifty year old nutritional or trace “vitamin C” hypothesis. “Correction” of this genetic defect in Man is now possible since the availability of ascorbic acid in large quantities. By “correction” is meant the long-term administration of ascorbic acid in the large amounts the human liver would be synthesizing had this genetic defect not occurred. The mammals have long used the increased liver biosynthesis of ascorbic acid, under stress, to maintain homeostasis. The genetic defect prevents Humans from utilizing this important mammalian biochemical protective mechanism. Supplying exogenous ascorbic acid at the proper high dosage for full “correction” is merely duplicating a normal mammalian reaction. The medical implications of the full “correction” of this genetic disease are discussed and speculations on the effects of “correction” in the rheumatoid diseases, cardiovascular conditions, strokes, cancer and the aging process are extrapolated from the meager data already in the medical literature. This paper is mainly a plea for more thought along the medical possibilities opened by this new concept and for more clinical tests based on the rationales derived from the genetic disease viewpoint.

The present author found significant differences in physical characters among some populations, namely the Garo, the Kachari, the Rabha and the Rajbansi of South Goalpara, Assam. They were accompanied by an increase and decrease of the various characters. Shapiro in his study of Japanese immigrants into Hawaii also found similar phenomenon of increase and decrease in respect of anthropometric characters. In this study the data of the present author have been compared with those of Shapiro.

It is seen that the results obtained by the present author agree with those of Shapiro in respect of some characters, while in respect of some they vary. But it appears that the changes in physical characters due to migration into two widely different geographical regions — from a temperate country like Japan to a tropical country like Hawaii — are nearly of similar nature in a small area like South Goalpara.

Male and female rats of three different strains were subjected to physical restraint, when it was demonstrated that there is a relationship between the strain of the rat and its susceptibility to gastric ulcer formation. Severity of ulceration was greatest in Wistar rats. Hooded Wistar rats were also ulcer-susceptible, but not to such a great extent as Wistar animals. Sprague-Dawley rats were resistant to ulcer formation. Sex differences in ulcer severity were found only with restrained Hooded Wistar rats.

The results of this investigation compare favourably with results published for individual strains of rats by other workers. It is possible that genetic influences may be responsible for the differences observed, but the way in which they operate is not understood.