The Author has examined the published statistics of multiple births in England and Wales 1938-45, in Italy 1948-49 and in New York 1936-37, to see to what extent the apparent increase in frequency of twin births as parity increases amongst mothers of a quinquennial age-group is exaggerated by the mere fact of grouping. He concludes that the effect of the 5 year grouping on the rates is small, and that the data from the three countries indicate that at certain ages the probability that a birth will be multiple tends to increase with the order of the birth.

The historiography of genetics is not very extensive. As a tribute to Gregor Mendel the Genesis of modern Genetics is briefly described in its full range, from the Paleolithic Age to Lysenko. Since the earliest times, the knowledge of heredity had been growing in proportion with the development of ideas on reproduction and continuity of the species. For various forms of life, the basic problems of interest remained essentially the same during all historical periods; only the emphasis shifted from the gross to the more detailed, and the answers oscillated between the theories of preformation and epigenesis. Against this historical background, Mendel and the Mendelian laws stand out as the basic foundation of genetics.

The vital growing ideas on generation and evolution of plants, animals, and man are briefly reviewed and exposed as they had occurred before and after Mendel. The historical sketch leads us to ancient Assyria, India, the biblical times, and the classical Antiquity, to the early Greek philosophers and physicians whose works are sampled to illustrate the ancient beliefs concerning the role of male and female semen in generation, and concerning the proportional share of parents in the formation of body and mind of the offspring. The medieval knowledge on heredity is at its highest in the writings of Albertus Magnus whose work represents the refinement of scholastic science.

In these earlier times people did not know the exact functions of the organs of generation, or the true nature of sex. After the invention of the microscope in the 16th, and with a more liberal spirit of research in the 17th centuries, the sexual life and the male and female germ cells of many bisexual beings, including man, were gradually discovered during the 200-year period from 1677 to 1877. This happened with all sorts of speculation about heredity and about the origin and evolution of life. Meanwhile, many practical and theoretical hybridizers saw the various peculiarities in the filial generations, and many observed normal and abnormal characters transmitted from parents to offspring. Yet, none could formulate these observations into a mathematical regularity of inheritance until the reports of Gregor Mendel in 1865 on the result of his plant-crossings.

His discovery was buried, however, until 1900 when other biologists came to the same results, and revived and accepted his rules as the laws of heredity. From then on, modern genetics advanced rapidly and branched into many activities, everywhere fully supporting the views of Mendel. Thus, Mendel is truly the father of genetics, except for communist Russians whose political theories demand the denial of Mendelian heredity and the adherence to older discarded theories.

Genetics has the destiny to solve many practical problems in the life of nations, and to investigate a number of important yet unknown factors, in order to utilize the gene theory of heredity, and the “nuclear energy”, for a wider and brighter service of humanity.

The concept and definition of constitutional pathology. Genetic erythropathies such as constitutional spherocytosis, leptocytosis, ovalocytosis and drepanocytosis and their relation to hemolytic clinical syndromes are discussed. Sickle cell trait, sickle cell anemia, and sickle cell disease have to be distinguished as clinical manifestations of drepanocytosis. They represent a special variety of a « status degenerativus » (Bauer). Four genetic types of human hemoglobin have so far been identified that differ from each other by their molecular architecture and chemical reactivity. Several constitutional abnormalities of erythropoiesis other than those just mentioned are discussed: a hereditary defect in hemoglobin synthesis; erythroid multinuclearity; acanthocytosis; Fanconi's syndrome of hypoplasia and abiotrophy of the bone marrow as another variety of a status degenerativus.

Other than a specific case of concordant Vitiligo in MZ twins, the development of which has been followed for more than 11 years up to now, MZ twins suffering from Vitiligo have been described only three times. In all the four cases, three were concordant, one discordant; this last was accompanied by a discordant disorder of basal metabolism, by hyperhydrosis and exophtalmus. The greater degree of concordance found up to the present day, notably contrasts with the relative extreme rarity of familiar Vitiligo.

Die Verfasser berichten ausführlich über einen seltenen Familienbefund einer osteogenesis imperfecta tarda bei einer fünfzigjährigen Frau und ihren beiden Zwillingstöchtern, MZ, im Alter von zwanzig Jahren. Dieser neue veröffentlichte Fall bestätigt die Erblichkeit der Krankheit und ihren dominanten Charakter; ausserdem zeugt er von einem hohen Durchdringungsvermögen und der Möglichkeit eines Familienmerkmals, welches — vie im vorliegenden Falle — in einem Vorwiegen der Plastizität über die Zerbrechlichkeit der Knochen und in fehlender Otosklerose besteht.

Beim Skelett der Zwillinge bemerkt man ausserdem — im Gegensatz zur Mutter — Zonen von Knochenverdìchtung (lokalisierte, sekundäre Osteosklerose); und zwar an ähnlichen Stellen, was darauf schliessen lässt, dass sie genotypisch bedingt sind, obwohl dieses ein ungewöhnliches Symptom ist.

Provided the assumptions underlying Weinberg's method of differentiation of types of twin pairs are correct, this analysis of the statistics of twin births in Italy in the two years 1949 and 1950 shows that there are variations in the frequency of monovular twin births greater than can be attributed to chance deviations from a constant frequency of monovular twinning. There is a tendency for the frequency to increase with maternal age, and for young mothers, a tendency for it to increase also with parity. In general, the occurrence of monovular twinning is probably more closely related to maternal age than to parity.

The frequency of binovular twinning appears to be independently related to both maternal age and parity. Amongst births of each rank the frequency of twin births increases to a maximum at maternal ages 35-39 years; and, at each age level, the frequency does not change between birth ranks 1 and 2 but subsequently increases fairly continuously. There is a suggestion that there may be a modal birth rank as well as a modal maternal age, and that binovular twinning may be no more closely related to maternal age than to parity.

Thalassemia, that I propose to call Microkarterocytosis, can be divided into three forms to be distinguished under the names of minima (healthy carriers), minor (Rietti and Greppi's disease), major (Cooley disease).

It can be inferred that Thalassemia is a mutation developped in a mediterranean superior paleolitic race that showed also the character high cheek bones.

In my researches of 1941-42 I for first showed that thalassemia is a dominant hereditary character with homozigotic letal effect (heterozigotes the healthy carriers, homozigotes Cooley' patients).

Heterozigotes throug an increased expression of the morbid gene develop Rietti and Greppi disease, as I inferred in 1949.

The researches on genetics that I carried later on Drepanocytosis have shown a behaviour equal yo that observed in Thalassemia.

In Drepanocytosis the heterozigote condition determines the healty carriers and the less serious cases of sickle cell anemia, the condition of homozigote the most serious form of this anemia.

A morbid form clinically similiar to the slight cases of Cooley disease is detectable in subjects whose parents show separately one the Thalassemia-stigmata and the other the Drepanocytosis-stigmata. For this latter form the name of Thalassodrepanocytosis is suggested.

The presence of drepanocytosis inindividuals of european races can be explained with very ancient crosses with individuals of negro races.

I. The results are reported of Rh—Antigens examinations on 61 families with together 154 children and on 423 mother—child relations. No deviations from the theory of inheritance concerning the Rh-Caracteristics could be noticed.

II. The results obtained by examination of 2472 persons concerning the distribution of the Rh-types C, c, D and E in the German population makes it possible to obtain safe conclusions concerning the Rh-type representative for us and its use to the forensic paternity exclusion by calculating the application of the type (acc. to Hirszfeld). There is a far-reaching correspondence between our observations and Anglo-American (Wiener and Race), and Norvegian reports (Hartmann and his staff), about the distribution of the types.

III. A survey of paternity exclusions as observed from our material substantiates the theoretic conclusions and shows also in practice the importance of the RH-Antigens of certain characters (C, c, D and E) for the forensic medicine.

Two monozygous twin girls, now 7 years old, with complete concordance of an almost total universal albinism were found in an « isolate » near Aosta in the Western Italian Alps. Their parents show normal pigmentation, and are first cousins, their common grandmothers having a brother who was the grandfather of another albinotic girl, aged 22. The parents of the latter were examined by the Dutch ophthalmogeneticist P. J. Waardenburg: while her father did not show definitely diaphane irides, her mother did. As a similar discrepancy in otherwise normal parents of albinos was stated in 2 more families (Hanhart 1952), the presence of diaphane or not diaphane irides cannot be regarded as sufficient symptom to distinguish two different biotypes of simple-recessive universal albinism. Heterogeny, though rather probable, of this character has not yet been proved in white man.

In Switzerland, and Italy as well, there are considerable local accumulations of universal albinism, so that calculations on the basis of a medium frequency do not hold. The percentage of 7.9 for first cousin marriages of normal parents of albinotic children and 8% for second cousins can hardly be taken as a proof for heterogeny of the gene concerned.

The observation of monozygous twins with concordant universal albinism is the first made in Europe, and the third published all over the world. It is unique on account of the near consanguinity of the normal parents of these twins. Its incidence in Northern Italy speaks in favour of a relatively frequent occurrence of this character in this country, suggested already by the author's population studies.

The A. explains the case of a pair of male twins five month aged, contemporaneously and suddenly died of a cardiac insufficiency from hyperthymism.

The examination of both their parents permitted to assure a syphilitic inherited lemish in their children.

Considering the question from the medico-legal standpoint, he does not justify any suspicion of a criminal action when the event may be justificable under the acquaintance of gemellology.

He confirms, besides, reflecting upon the genealogic factors of the parent's families, the theory of Gedda on the hereditary mechanism of gemellogenesis which in the above mentioned case declares itself as an heredity jointed to the sex.

New data on the heredity of the M-N types in 420 families with 645 children conform precisely with the requirements of the genetic theory of Landsteiner and Levine. To date as many as 1580 families with 3379 children have been tested in our laboratory. According to our experiences, the three M-N types are entirely reliable for use in medicolegal cases of disputed paternity, provided that the individual who performs the tests is qualified.

New data on the distribution of the M-N types in 954 individuals are presented, as well as data on the distribution of the M-N S types in 394 individuals. The findings regarding the M-N-S types agree with previous reports concerning their distribution in Caucasoids. The medicolegal application of the M-N-S types is discussed and it is pointed out that more work must be done before the S and s factors can be safely used. What is needed most is methods for preparing anti-S and anti-s sera of satisfactory specificity and avidity.

The genetic roots of speech development in children are being investigated. On the basis of observations in the development of speech in 12 monozygotic twin pairs it could be shown that not only the retarded but also the normal development of speech is an idiotypic characteristic. It must be considered however, that we are not dealing with a simple characteristic, but with the result of a whole complex (intelligence, type of immagination, fine-motor and vitality) of the mentioned root. Further examinations regard the disposition for stammering. On the basis of research with monozygotic twins, of which one partner during the examination presented only signs of cluttering, the other one, however, clonic-tonic stammering, while both twins had a pathologic electroencephalogram, the hereditary basis of speech defects and stammering is shown. However, only in half of the cases of monozygotic twins one can find a disposition for dyslalia, which can be of a very different (periphercentral) nature.

A certain amount of material is provided for studying the heredity of fissures of the iris, and it seems that such a heredity is probably not of monohybrid nature. The relationship between fissures and pigmentation of the iris has been confirmed and noted also by earlier researches. This connection may be explained by the fact that fissures of the iris-appearing even earlier, during embriological development—leave fewer chromatophores in the stratum limitans anterior for the formation of pigment. It thus follows that the colour of the iris, which is determined by comparing it with table of colours of the eye, would not be of monohybrid heredity. It is doubtful even when both colour and structure of the iris are contemporaneously studied in order to realise a polysymptomatic resemblance—as for the diagnosis of monovular twins of the diagnostic of paternity—since the logical basis for establishing a polysymptomatic comparison of resemblance is, in fact, given by the independance of partial signs connected one with another. This goes for all cases, whether or no statistical methods are used for the critical examination of such researches, such as, for example, Essen-Möller's formula (3,4) (Wichmann 22, 23).

A sample of 583 twins, delivered in two English hospitals, and divided into groups of like sex and unlike sex, has been analysed as regards distributions, means and standard deviations of mother's age, order of birth, birth weight and length of gestation time.

In birth weight the unlike sex have greater means than the like sex, from which it may be deduced that dizygotic twins are heavier at birth than monozygotic.

The correlation of birth weight in twins is 0.727 for like and 0.676 for unlike sex.

Length of gestation time has a correlation with birth weight of 0.345 for like and 0.403 for unlike sex.

Neonatal mortality (including stillbirths) is high for twins, being 16.6% as compared with 4.5 % in single births. When these rates are sub-divided into groups of birthweight, it is found that the rates for the very low weight groups are a little better for twins than for single births, but those round the mean and above it are about 3 times those for single births of average or above average weight.

The mortality rates are a little lower for twins of unlike sex.

Twins deriving from a single zygote were produced in Triton alpestris and Triton taeniatus by two different series of experiments. The first type of experiments proceeded, by means of a glass thread put on and cutting through the median plane of early gastrulae, to a division of these into two lateral (right and left) halves. These halves may give rise to normally formed identical twins (fig. 2), or to twins with more or less accentuated deficiencies on their inner sides (figg. 3 and 4). In extreme cases they may even produce left or right half-embryos, or much reduced malformations with very imperfect organ formation. Generally considered, the regolation in the head region is better than that in the tail one, and much better than in the trunk. Most of the heads show two eyes of equal size and normal position; in rare cases we encounter two eyes of different size, or synophthalmus or cyclopia. The «real» half-embryos have only one laterally situated eye (tab. 2). The normally formed identical twins deriving from half an egg each, develop into properly proportionned embryos of half the normal size; the resulting larvae reach the normal size of the equally-aged control larvae deriving from entire eggs, often before the stage of nourishment, (fig. 5, tab. 3).

In the second series of experiments, an early gastrula was cut through in correspondence to the median plane, and then the complete presumptive epidermis of another gastrula and, respectively, of a third one, was stuck on to the wound surfaces of the halves in normal orientation (fig. 6). The right and the left combinations resulting therefrom give rise, in the original median line, to long, narrow and apparently somewhat too great neural plates, the external half-portion of which was fournished by the host half-gastrula and is somewhat more strongly developped than the inner half-portion deriving from the presumptive epidermis (fig. 7 a, b). This epidermis that was stuck on to the gastrula-halves' surfaces, takes part in the formation of the embryos either totally or at least for its greatest part. No perfect larvae will be formed (tab. 4). The head is always bilaterally developped, but it is often asymmetric and shows synophthalmous or cyclopic character (figg. 8, 9, 10, tab. 5). The trunk is sometimes normal (fig. 8 a), but it may also show an axial system of too great length (fig. 8 b), or dorsal deficiencies—often in the form of either symmetrical or asymmetrical Spina bifida—with dorsal incurvation (fig. 9 a, b). The tail can be either normal, or crooked, or defective, or doubled. In the best cases we see, in the first series of experiments, the regolation of the half-organiser of the gastrula-half into an entire organiser of half the normal size, while, in the second series of experiments, the regolation can produce an approximately normally sized entire organiser, which however, in the anterior head region is lacking of its full indutcive capacity.

In both series of experiments the right hand member of the twins was observed to show inversion of the situs viscerum.

The conclusions they arrive at, is that from the standpoint of the Rotest, the twins (mono-or-dizygotic) present themselves as distinct and original personalities. The predominant rôle played by the peristasis over the constitution is thus emphasized.

Thirty couples of twins (23 mono-and 7 dizygotic) were studied with the Rorschach-test.

Detailed analysis is given especially for the larger groupe of monozygotic twins; the identical responses and the quantitatively identical Ro-factors, being particularly discussed with the help of synoptic tables. In spite of their findings, the authors underline the scarcity and little significance of the identical factors.

The present work deals with the question of the heredity of intracranial tumours, the twin method constituting hereby the basis for investigation.

1. In an unselected series of twins collected from the Psychiatric and Neurological Clinic of the university of Münster (Psychiatrische und Nervenklinik der Universität Münster) in the case of seven examined pairs of twins (3 monozygotic, 4 dizygotic: like sex and unlike sex) manifestation of cerebral tumours is dissimilar (table II).

2. This unselected series combined with previous casuistic reports published until now in world literature (table I) of twins with cerebral tumours has not yet brought a sufficient basis for definite genetic conclusion. The question of inheritance in cerebral tumours will only be elucidated by procuring and reviewing material from a larger unselected series of twin patients afflicted with cerebral tumours.

1. Data are presented relative to twin pregnancies within the total, the “white” and the “colored” populations of the United States for the 15 year interval from 1922 to 1936, inclusive.

2. Attention is called to the fact that twin pregnancy frequencies in all human populations fall within rather narrow limits, and it is suggested that this fact supports the conclusion based on other lines of evidence that human twinning has some genetic basis.

3. It is shown that the twin pregnancy frequency for the “colored” population is significantly higher than is the corresponding percentage for the “white”. It is concluded that this difference is due, in part at least, to a difference in heredity.

4. It ise stimated that 33.43 percent of all twin pregnancies within the total population are of the monozygotic type and that within the “white” and the “colored” populations considered separately the corresponding percentages are 34.16 and 28.91, respectively.

5. Calculations show that the higher percentage of twin pregnancy frequency within the “colored” population than within the “white” is exclusively the result of a higher percentage of the dizygotic type of pregnancy.

6. It is shown that livebirths among twins have a significantly lower percentage of males than do livebirths among members of single pregnancies. This is attributed primarily to a higher percentage of male deaths in twin than in single pregnancies during early uterine stages.

7. It is shown that the percentage of stillbirth for twin pregnancies is twice as high as is the percentage for members of single pregnancies. Even so it is suggested that there may be at present or in the future a trend started in the direction of an increase in the percentage of plural births within the human species.

8. It is shown that the percentage of sets of twins in which both members are stillborn is higher than the one expected on the assumption that the deaths of the two members are independent events.

9. The percentage of sets of twins in which both members are stillborn is found to be significantly higher for same sex sets than for opposite sex sets. This is attributed primarily to the inclusion of monozygotic sets among the former.

10. It is also shown that the percentage of sets of twins in which only one member is stillborn is significantly higher for same sex sets than for opposite sex sets. This is attributed primarily to the inclusion among the former of monozygotic sets in which one member is handicapped as a result of an unequal twinning process or of some related phenomenon.

11. Many additional differences relative to twin pregnacies are shown in the accompanying tables, but are not discussed either because they are relatively insignificant or because they require supporting data.

In a family 5 females belonging to 3 generations were found with following malformations: Syndactyly (webbed up to the nails), oligodactyly, tendency towards duplication of digits, and brachydactyly. The intrafamiliar variability was not considerable with exception of an probandus having with 5 digits (with duplication on one digit). On the base of ontogeny the question is discussed if the disturbing factor concerning the palm of hand or concerning the squeleton is prevalent. In this family the two dispositions are probably combined. In bibliography a pedrigree with this combination of multiple malformations was not found.

In a pair of 14 year old DZ twins of different sexes, a particularly profound emotional separation becomes manifest during childhood.

The twins come from a family whose members are considerably introvert, and where very few exchanges of emotional manifestations take place. The male twin offers a more fundamental alteration of personality, and his emotional control is often overwhelmed by antisocial tendencies of relative frequency. In accordance with her family surroundings his twin, instead, possesses a particularly rigid and severe moral conscience.

The twins are spiritually separated when at the age of eight and nine years, the boy attempts certain sexual approaches on the little girl. At first the child consents, but gradually a most intense feeling of guilt rises up in her, which is accompanied by an aversion, rapidly changing into invincibile hatred towards her brother, whom she fears will subject her to further sexual practises.

Notwithstanding the preponderance of the sexual factor, the antisocial behaviour of the boy, also contributed to a certain extent to this separation.

From a psychoanalytic point of view, the girl's behaviour, characterised by a typical inversion of feelings could be in- terpreted as a reaction formation.

As the boy has been classified from a psychiatric diagnosis as bearing a psychopathic personality which occupies a position between neurosis and psychosis, the eventual possibility of a certain degree of familiar and social adjustement is not to be excluded.