The study of Italian Vital Statistics, from 1957 to 1966, reveals various classes of fertility (sterility, infertility, mean fertility, hyperfertility) and the curve of fertility in the woman's biological time. The study of lying-in women in Obstetrics Departments also yields data revealing an interaction between class and moment of fertility. The study of the Mendel Institute's twin file finally yields data stressing the existence of a relation between hyperfertility and multiple births. Endocrine fertility may thus be considered as genetically conditioned, and multiple births as an epiphenomenon of the hyperfertile class.

The genetic study of sterility, although rather complex, may be carried out, as far as the parents are concerned, on the basis of existing detection methods. A number of forms of individual sterility may be detected on the basis of the caryotype (ovarian and testicular dysgenesis, hermaphroditism), while a chromosomal pathologic phenotype is missing for others, and the corresponding genotypes must be detected through clinico-genealogical methods (pseudohermaphroditism, adrenogenital syndrome, Laurence-Moon-Bardet-Biedl syndrome, hereditary malformations). It is noted that the problem of immunitary incompatibility is not sufficiently clear. Examples are presented of others forms of sterility depending on a lethal load of the conceptus, for which consanguineous marriages may be held largely responsible. Cases of sterility may also be found in relation to mental diseases. The importance of eugenic counseling is stressed.

A description is given of the Danish Twin Register which is based on the total twin population born in Denmark in the years 1870-1910 with a more recent addition of all same-sexed pairs from the period 1911-1920. Twins belonging to pairs where one or both partners are found to have died before attaining the age of six years are disregarded in the more intensive studies whereas the remaining part of the twin population is being followed by periodical inquiries.

The methods used in the collection of the material, in the establishment of the zygosity diagnosis and in specific investigations of selected diseases and abnormalities are described and discussed.

A survey is given of the more important results of the research based on the Register. In the group of somatic diseases, greatest attention has so far been paid to malignant growths, diabetes mellitus and peptic ulcer. A number of psychiatric disorders and deviations are at present being studied with schizophrenia and criminality as the first subjects for intensive research. Some of the main results obtained are given as illustrations of the potentialities and scope of this approach to the application of twin studies in a broad variety of research areas.

Shortened fifth middle phalanges, defined as being less than half the length of the fourth middle phalanx, were found in 12 of 96 Philadelphia Chinese and none of 200 Philadelphia Negro children. At least nine of these can be characterized as having stunted cratered diaphyses, with precocious cone epiphyses, which underwent very early epiphyseal union.

The possible extension of a current vascular hypothesis for cone epiphyses, to include inherited osseous variation in this region of the little finger, is discussed.

A classification of metacarpal brachydactyly is presented, with the intention of investigating the syndrome of pseudopseudohypoparathyroidism. Reports of cases which have been held to negate the theory that Albright's hereditary osteodystrophy is sex linked were found to have the pattern of phalangeal shortening exhibited by one of the forms of metacarpal brachydactyly. This finding lends support to the contention of others that these reported cases are not pseudo-pseudohypoparathyroidism.

Essential hypertension was first recognized as morbid entity in 1911 and the word “essential” was substituted by “constitutional” in 1933. Diastolic hypertension may be constitutional or “symptomatic” if it belongs to the symptoms of a disease of specific organs (kidneys, endocrine, metabolic disease, cerebral or vascular disease). It is futile to search for such a diseased specific organ in constitutional hypertension (1933). Constitutional hypertension is a constitutional variant due to insufficient perfection of the homeostatic (feed-back) system maintaining the habitual blood pressure at a constant normal level. It is of multifactorial (polygenic) etiology (1960). It is a definite predisposition to actual diseases. It is a matter of semantics whether or not it should be called a disease of its own. The syntropy of constitutional hypertension and diabetes, obesity and arteriosclerosis is best explained by sharing various parts of polygenomes that are the common genetic basis of each of these morbid states.

A twin study was undertaken with the twofold aim (a) of studying the hereditary behaviour of digital dermatoglyphic traits both at the qualitative and quantitative level, and (b) of working out a method for discriminating MZ and DZ twins by means of fingerprints.

Fingerprints of 50 MZ (25 ♂ and 25 ♀) and 50 DZ (25 ♂ and 25 ♀) twin pairs were thus examined and analyzed by means of a special methodology and of a 7044/K32 IBM computer.

The qualitative analysis has shown a significantly higher concordance in MZ than in DZ twin pairs, with a certain variability of single finger concordance values. The quantitative analysis has shown significantly higher correlation values in MZ than in DZ twin pairs, with very limited confidence intervals in the former. Single ridge counts apparently behave as cumulative counts on the five or ten fingers, although with an obviously higher random variability.

Digital dermatoglyphics thus appear to show practically complete genetic conditioning, which, rather than at a cumulative level for the ten fingers, as is largely believed, appears to act on single finger quali-quantitative traits. The total finger ridge count, rather than a trait, only appears to be a useful, but artificial cumulative value. Actually, applied to the diagnosis of zygosity, it provides, by itself, a fairly high, general probability (0.86) of a correct diagnosis.

Je souhaite la bienvenue, et j'adresse mes remerciements, à tous les chercheurs et savants, venus de diverses régions d'Europe et d'Amérique et qui, aujourd'hui, se trouvent réunis dans notre Institut pour discuter des problèmes qui ne peuvent pas être plus actuels, concernant les recherches sur les antimitotiques.

Je remercie les Autorités qui ont bien voulu donner leur adhésion à ce Symposium et ont voulu l'honorer de leur présence.

Notre réunion prend une signification particulière du fait que les études sur les antimitotiques à régard de la chimiothérapie expérimentale des tumeurs ne remontent pratiquement, de façon officielle, qu'à une vingtaine d'années. C'est en effet en 1946 que parurent les travaux de Haddow et Sexton sur « Influence of carbamic esters (uretanes) on experimental animal tumors » (Nature, 157, 1946) et ceux de Gilman et Philips sur « The biological actions and the therapeutic applications of the o-chlo-roethyl-amines and sulphides » (Science, 103, 1946). Ce n'est que deux années plus tard que paraîtront les observations de Sidney Farber et de ses collaborateurs sur l'emploi des antifoliques dans la leucémie aiguë des enfants. Au cours des années successives, noue assistons à une floraison de recherches sur les antimitotiques, spécialement à Londres, au Chester Beatty, à New York, au Sloan-Kettering, et à Boston, au Children's Cancer Research Foundation. Je ne rappellerai que les étapes les plus importantes de ces recherches qui ont conduit à une sélection de substances antimitotiques d'une efficace action antitumorale: en 1953, apparaissent la 6-mercaptopurine, le Colcemid, le dyméthansulphoniloxibutane; en 1956, le Chlorambucil; en 1960, le Trenimon, l'Endoxan, la Vinblastine, le 5-Fluorouracil; en 1962, la Vincristine et l'hydroxyurée; en 1963, les méthylidrazines. Et ce ne sont là que quelques uns des nombreux cytostatiques étudiés jusqu'à présent.

The mechanism and the familial pattern of the late lepromin reaction (Mitsuda reaction) have been discussed. The interpretation of the familial correlation as mainly depending on a pair of allelic genes has been analysed thoroughly. A new technique has been described for identifying constitutional resistance or susceptibility to leprosy at an in vitro tissular level. The possibilities of this technique have been stressed.

A kindred is described with a probably new “cervico-dermo-reno-genital syndrome”, comprising a congenital muscular torticollis, multiple spontaneous keloids, cryptorchidism, pyelonephritis and other anomalies.

We believe that in this observation a single gene is responsible for the multiple mesodermal and ectodermal defects. Pleiotrophic effects of a single X-linked gene is the most likely possibility for this inborn error of connective tissue.

From an extensive review of the literature we may conclude that the nosological association of congenital muscular torticollis, multiple spontaneous keloids and cryptorchidism has thus far never been published.

Sex linked or sex limited inheritance for congenital muscular torticollis or multiple keloidosis has not yet been published with certainty.

Our observation and the frequent keloidosis in gonadal dysgenesis, may suggest the presence of gene material on the X-chromosome responsible for connective tissue hyperplasia.

Data obtained in a study of mentally defective twins permitted the examination of interdependence and efficiency of blood groups and fingerprints in zygosity diagnosis. After exclusion of Down's syndrome, the series consisted of 49 MZ pairs, 52 DZ pairs and 18 pairs of uncertain type.

Same-sex pairs discordant for Down's syndrome seemed to include some pairs of uniovular or irregular origin, but this could not be investigated cytologically. Concordance appeared to occur independently in different blood group systems. However, DZ twins concordant in the ABO blood groups were significantly more similar in their fingerprints than were other pairs, and the within-pair differences were more uniform.

Linear discriminant functions designed for zygosity diagnosis make much better use of dermatoglyphic information than do simpler measures, and the latter could not be much improved by comparing left and right hands separately.

Studies on the glucose-6-phosphate dehydrogenase activity of erythrocytes from 416 males and 820 females are reported. The total number of deficient males (intermediate + complete) varied from 3.9% among the whites (102 persons) to 15.1% among Dark Mulattoes (99 individuals); the incidence in the Negroid sample in general (316 persons) was 12.4%. The data obtained among the women were utilized to study problems of penetrance of the G-6-PDD genes. Results obtained in both sexes were employed to verify, unsuccessfully, possible selection differentials through age analysis and the comparison of the gene incidences of people affected with minor ailments and controls. Problems of gene flow analysis in populations like this one in which the “Negro” and “White” forms of the deficiency are present were stressed.

1. The Author has investigated on a twin material of 34 twin pairs the papillary line patterns on the fingers, the interdigital areas of the palms, and the hallucal area of the soles according to a systematics accounted for by the Author in earlier works.

2. The diagnosis of zygosity has been based on a comparison for the morphological particularities and on blood group analyses, in the cases in which the relative chance for dizygosity for the concordant pairs has been calculated.

3. The frequency distribution for the papillary line patterns of the twin pairs showed no significant divergence with respect to the large Swedish population, earlier investigated.

4. The 19 MZ twin pairs showed a concordance of 84.2-89.5% for the total qualitative value, total ridge-count and for the hallucal patterns.

The authors report three cases of enlargement in length of the short arm of a G chromosome: in a mother and her trisomy 21 son, and in a child with congenital glaucoma and systemic malformations. They discuss the nature of this odd chromosome. The latter can represent altered chromosomal behavior of anomalous coiling, but it is quite possible that it represents a translocation. The authors observed another case of congenital glaucoma with short arm enlargement in a G chromosome.

The cytotoxic effects of hydroxyurea and of related hydroxamic acid derivatives in vivo are briefly described. They occur selectively in tissues with high rates of cell renewal and they are of brief duration. Tissue concentration of hydroxyurea diminish rapidly as the result of renal excretion and metabolism; there is a close temporal relation between the physiological disposition of the agents and the cytotoxic changes. Hydroxyurea induces an immediate inhibition of DNA synthesis in proliferating tisdsues such as thymus, small intestine, and regenerating liver. Autoradiographic studies of mouse duodenum using tritiated thymidine have shown that the lethal susceptibility to hydroxyurea is restricted to cells in the S-phase of the mitotic cycles. Cells in G1, G2, and M are not damaged by the agent.

In peripheral blood cultures of a phenotypically abnormal Caucasian girl, a ring-shaped chromosome was observed in place of an E group member. The rest of the chromosomes of the complement did not show any obvious structural anomaly. The ring chromosome was noted in 100% of the recorded cells, and its size in individual metaphases remained fairly constant. It is suggested that this ring chromosome has become a permanent part of the complement of the patient.

Data are reported about the occurrence of glucose-6-phosphate dehydrogenase deficiency (G-6-PDD) and abnormal hemoglobins in a sample (316 males and 679 females) of the Negroid population of Porto Alegre, Brazil. The prevalence of double carriers (AS/G-6-PDD) was that expected from the isolated incidence of both anomalies. A review of the literature shows similar results for 3491 males and 289 females from African and American Negroid groups both from areas with and without malaria. Therefore there seem to exist no grounds for postulating an adaptive interaction between these two polymorphisms.

Dosage of the hematic level of ATP has been afforded in 20 (7 MZ and 13 DZ) twin pairs aged 4-6 years. The intrapair correlation coefficient has been calculated and resulted to be significantly higher in MZ than DZ twin pairs. The hereditary “quantum” in the determination of the hematic level of ATP was also estimated and resulted to be of about two thirds.

Chemotherapy of murine Rauscher virus-induced leukemia using Trenimon, 6-Mercaptopurine, 5-Fluorouracil and Melphalan is described. Therapy is based on nucleated cell counts in peripheral blood and body weight of the animals. Remarkable remissions of the number of nucleated cells — not occurring in untreated animals — are induced by Trenimon and 6-Mercaptopurine. Prolongation of survival times exceeds 100% in the groups treated with Trenimon, 6-Mercaptopurine, and 5-Fluorouracil.