The concordance of physiological and pathological times in human identical twin pairs induced the authors to postulate the existence of a hereditary biological time.

Having formulated the hypothesis that the information of each gene has a given period of existence and that, therefore, every gene has its own inherited temporal dimension, the authors report on five different experimental studies intended to verify their hypothesis.

In the first study (cf II. 1) a twin research on bone age and dental age is performed. The chronological study of the appearance of ossification nuclei in carpal bones and of mineralization of the gems of permanent dentition, in 20 MZ and 20 DZ human twin pairs, indicates that these wellknown “biological timetables” exhibit about 70% of genotypical control.

In order to verify whether biological time is a function of the genotype as a whole, or a property of each individual gene, the authors carried out an experimental study on the mean lifespan in different strains of Drosophila melanogaster whose genotypes were fully known (cf II.2). Their results indicate that the specific information of certain genes controls the insect's lifespan; it may also be inferred that the differential persistence of its specific information is an attribute of each individual gene. This chronological dimension of the gene is called chronon, which the authors also define as “the period during which the original information of the gene remains unchanged” — whether it is used for transcription or duplication, or it remains at the potential stage.

The determination of alkaline phosphatase activity in the same strains of D. melanogaster (cf II.3) affords an estimate of the amount of genie information (intensity of the individual trait) and the variation thereof during the gene's chronon. The authors observe that the amount of information decreases gradually during the gene's chronon, suggesting that this be due to the gradual exhaustion of a given specific energy. The decrease in the amount of information in the longitudinal study of chronon leads the authors to identify a further fundamental parametric unit of the gene which they call ergon.

Ergon is defined as “the degree of stability of a gene”.

In the fourth study (cf II.4) the twin test is applied to the chromosome association index in subcultures of lymphocytes from MZ and DZ twins at age 6 and age 60. This study affords a parallel estimate of chronon (i.e., duration of information) and ergon (i.e., stability of information).

Chronon and ergon are found to be interrelated; they may be considered as variables in a dimensional equation of the gene. Thus, the existence of the Ergon/Chronon (E/C) system is postulated.

Nine parameters of development and of senescence (first smile, first word, first steps, first pubic hair, menarche, first white hair, first loss of a permanent tooth, first use of reading glasses, onset of menopause) are studied in an experimental population of 666 twin pairs of either zygosity, leading the authors to formulate several conclusions concerning the characteristics of the E/C system (cf II.5).

The interpretation of their experimental findings leads the authors to consider the ergon (energy of stability) of a gene as the total result of the stabilities of all the nucleotides making up the DNA sequence of that gene. Since it is well known that the stability of adenine-thymine (AT) bonds exceeds the stability of guanine-cytosine (GC) bonds, and that different combinations of codons (differing in at least one nucleotide) may provide the same information, it is clear that identical polypeptide chains may be produced under the control of genetically different ergons resulting in genetically different chronons.

The authors summarize these concepts in the following two aphorisms: “one gene, one stability” (ergon) and “one gene, one time” (chronon).

Biological time, development, senescence, homeostasis and disease are interpreted by the authors in the light of the E/C system.

Pharmacogenetics represents a field of connection and cooperation between pharmacology and genetics, which will promote knowledge in both fields. It concerns the plusvariant action of drugs in those families in which they produce toxic reactions, as well as the minusvariant action in particularly resistant families, so that drugs become useless at normal doses. These phenomena stress both the mechanism of action of such drugs and the existence of hereditary metabolic defects. Some typical cases are reported, with special concern to twin observations. It is finally suggested that pharmacogenetics may concern three specific branches: (a) regulation, (b) substitution and (c) repair.

A case of apparent pseudo-hermaphroditism is described, which seems to represent a new kind of genital pathology. The phenotypic (genital ambiguity) and genotypic (mosaicism of both autosomes and gonosomes) alterations are interpreted as the result of a series of clonal errors of mitosis in the ontogenetic development of a Xy zygote, due to mutant genes for the control of mitosis.

The authors trace an outline of the problems involved in the relationship between immunogenetics an reproductive pathology, indicating the need for further specific research.

The authors formulate a “central interpretation” of several aspects of immunology, based on the role assigned by nature to primary sensitization in the protection of germinal and fetal antigens against immunological rejection. The implications of such an interpretation may be far-reaching in such fields as reproductive pathology, autoimmune diseases, anthropology and population genetics.

After a historical review of the problem of progressive myoclonic epilepsy, the author makes a detailed clinical and genetic description of 5 families from the Valais canton, affected with the disease. The metabolic disturbances observed in these cases (urinary elimination of mucopolysaccharides) are given particular attention. The author further discusses the various classifications of myoclonic epilepsy which were established on the basis of clinical symptomatology, electroencephalographic tracings, pathological anatomy and biochemical findings.

A 5 year old female child is described with mental and growth retardation, prominent occiput, low-set ears, moderate mid-face hypoplasia, congenital heart defect, mal-set toes, and a relatively high frequency of whorls on the fingers. The abnormal E18 chromosome found is thought to represent a partial deletion of the long arm with trisomy for a small terminal segment of the short arm as the result of a pericentric shift followed by crossing-over within the inverted shifted segment. Thus this case may represent a further example of “aneusomy by recombination”.

The ability to secrete ABH antigen in the saliva has been determined in 160 men and 87 mothers with 45 boys and 42 girls. Mother-child studies on the secretor-nonsecretor distribution and Gc serum types showed a good agreement between observed and expected numbers in the different classes.

The malformative syndrome with cryptophthalmos is characterized by cryptophthalmos or congenital symblepharon of the upper lid, dyscephalia with malformations of the ears, nose and mouth, syndactylia, malformations of the urogenital organs and other less constant anomalies.

After an intense cytostatic treatment of the patient F.N., whose bone marrow was completely infiltrated with lympho-sarcocytes, a bone marrow transplantation was made. The donor was the patient's sister. The difference in sex chromosomes made it possible to observe the fate of the transferred cells. Immediately after the treatment, till 6½ months later, cells with feminine caryotype were traceable in the patient's peripheral blood (up to 2%). This proves the proliferation of donor cells in the acceptor.

The distribution of G6PD-D in the Ferrara country has been studied by means of the Brilliant Cresyl Blue discoloration test: 2437 males have been tested in 11 localities.

The highest gene frequency of G6PD-D observed is consistent with the one expected after 25-30 generations of malaria selection, assuming an increased fitness of the heterozygotes, as it has been shown in computer simulated evolutionary trends for sex-linked genes. The thalassemia trait has also been shown to be very frequent in the same localities; its frequency is correlated with G6PD-D gene frequency and with the incidence of malaria in the past (1900).

G6PD-D frequency is not significantly correlated with malaria. Such a result is due to the significantly lower gene frequency of G6PD-D observed in the localities where the percentage of population affected by malaria was higher (40-60%). On the other hand, G6PD-D is frequently significantly correlated with malaria in the remaining localities where the incidence of the latter ranged from 0 to 35% of the affected population.

The mechanisms possibly involved in the determination of this distribution of G6PD-D are discussed.

General formulae for the chances of excluding paternity by blood grouping tests have been derived for the case where the falsely accused man is dead, but both his parents are available for testing. With the aid of the formulae, the chances of excluding paternity are shown to be about 31.1%, when tests are carried out for the A-B-O blood groups and subgroups, the M-N types, the Rh-Hr types and the Kell factor. These combined chances are about half the chances of exclusion when the putative father is alive and can be tested, so that it is very much worth while to carry out blood grouping tests in cases of this nature.

Three siblings were born of consanguineous parents (first cousins), two of which, our probands, affected by van Bogaert-Bertrand disease. Clinical diagnosis was made by cerebral biopsy of one of the two sisters.

The genetic research ascertained a schizophrenic paternal cousin and a girl cousin showing neurotic character and epilepsy. One maternal sister died with a picture of progressive encephalopathy that could be similar to the one showed by our probands. In this family syphilis was present for three subsequent generations.

The authors describe the essential symptoms of the disease and point out the present trend of biological research for the discovery of the supposed metabolic trouble.

A research has been carried out on a sample of 29.309 Milan school children. Among them, 321 carriers of congenital aural fistula (FAC) have been found. Pedigrees could be drawn in 93 cases, covering three generations and including as collateral branches families of uncles and aunts. According to Smith's test (modified) the trait appears to be inherited as an autosomal dominant, with a penetrance of 85%. The phenotypical frequency (genetically controlled, i.e. excluding phenocopies) is of 1%, while the gene frequency may be estimated around 0.5%.

The present paper deals with an analysis of the statistics concerning twin births in a sample of the Belgian population in 1960 and 1961. The frequency of twin births is of 0.01198 (± 0.00043), the frequency of a DZ birth among twins is 0.65081. Mothers of twins generally are older than mothers with children resulting from single gestation, the age difference concerning, as could be demonstrated, the distribution of DZ twins with the exclusion of MZ twins: whereas the frequencies of the total amount of twin births and of the total amount of DZ births increase with the mother's age, being highest in the 35-39 age class, the frequency of MZ births seems to be independent of the mother's age. The frequency of twin births also increases with the order of birth or gestation. Given that the mother's age and the order of birth are correlated, the influence of one of the two factors involved upon the frequency of twin births could be determined by keeping the other factor constant; the data from Mac Arthur (1953) were used to that effect.

Finally, a bibliographic survey revealed that whereas the frequency of DZ births is very variable, that of MZ births is more constant.

Taste sensitivity to PTC has been studied on a number of families from the same population, half of which showed in their members evident biological, pathological or degenerative variants. The percentage of non-tasters is of 22% in the healthy sample and of 26% in the loaded one, but this difference does not appear to be statistically significant. The biological loads considered should therefore not influence PTC sensitivity thresholds and taste perception.

Chromosomal aneuploidy in individuals is very frequent, and is generally a sporadic occurrence. Some aneuploidies seem to be familial, however; that is, parents may have more than one aneuploid child, or they may come from families in which an agglomeration of aneuploidies is distributed over several generations. Since, in such instances, parents often seek eugenic counsel to learn their chances of having aneuploid children, four types of familial aneuploidy and their recurrence risks are described. Special emphasis is given to the more important types of familial interchange, for which the recurrence risks can be calculated with fair accuracy. Familial mosaicism, a rare and puzzling genetic entity with which aneuploidy seems definitely correlated, is discussed.