Signor Presidente della Repubblica Italiana,

Signor Sindaco,

Signor Ministro,

Eccellenza Rev.ma,

Signori Ambasciatori,

Signor Preside della Facoltà Medica dell'Università di Roma,

Onorevoli Autorità, Congressisti di 30 Nazioni, Gemelli e Amici dei Gemelli,

Nel settembre del 1953 veniva inaugurato in Roma l'Istituto di Genetica Medica e di Gemellologia Gregorio Mendel.

Per i vent'anni dell'Istituto Mendel abbiamo aperto la celebrazione con il Congresso Internazionale di Neurogenetica ed ora la chiudiamo con il Primo Congresso Internazionale di Studi Gemellari. La Neurogenetica come specializzazione della Genetica Medica e gli Studi Gemellari come espressione scientifica della Gemellologia inquadrano bene il significato del lavoro che l'Istituto Mendel va sviluppando, e la vostra presenza, cosí autorevole, significativa e cordiale, dona il più ambito coronamento civico, scientifico e umano al ricordo della nostra fondazione.

Noi vi ringraziamo con semplicità ma con schiettezza e rispettosamente ringrazio il Capo dello Stato per il prestigio della sua carica e della sua persona, ed anche perché proviene da una regione italiana, la Campania, che batte il record per la frequenza dei gemelli nella popolazione (25‰). Come ringrazio sentitamente il Sindaco che ci permette di aprire il Congresso in Campidoglio, luogo che ha il potere, come nessun altro al mondo, di evocare e sublimare quella singolare condizione umana che consiste nella gemellità: l'essere gemelli. Qui vi è la lupa che dà il suo latte ai gemelli dimostrando che la fiera è pietosa più della donna che espone i suoi figli alla morte. Qui sono Romolo e Remo che il mito esalta come fondatori di città, Romolo di Roma e Remo di Siena.

Twins have an important place in mythology and a sacred character appears to be attached to them since the most ancient times. In ancient Egypt, the royal placenta was worshipped, being considered as the Pharao's twin (a conception that is still alive among certain African populations), and actually everyone was considered to possess a spiritual twin, the Ka or astral body, through whom it was supposed to be possible to operate with magic rituals and hit enemies. Twin gods were worshipped by Babylonians and Assyrians (who even introduced them among astronomic constellations), and may be also found in the Persian and Veda religions. In the classic, Greco-Roman world, the examples of twin gods and heroes are innumerable: from the twin sons of Zeus, the Dioscuri, to the opposite-sexed twin gods Apollo and Diana, to Rome's founders, Romulus and Remus, etc. Since the most ancient times, a magic conception is connected to the twins, either in a positive or a negative sense, but often with some kind of a “fatidic” aspect. Such a two-faced approach to the phenomenon of twinning, that variously characterizes neareast, protomediterranean, classic, and other ancient civilizations, may still be found in contemporary primitive societies.

In primitive societies twinning raises emotions varying from extreme terror to hope and joy. The first impulse prevailing among the less civilized people seems to be to regard twins as unnatural and monstrous and therefore as portending evil. Accordingly, they must be put to death and the offence repudiated. This negative attitude stems from a series of explanations which can generally be connected with the widespread belief in superfetation and double paternity. In a few cases only, would the custom of sacrificing twins arise from economic necessities. However, in many agricultural primitive tribes, twinning is regarded as a happy event. In this case, the worship of twins entrusts them namely with power over water allowing to confer fertility to the soil and also to women and animals. In the past, the mother of twins was often executed with her offspring or simply banished. In many tribes, she is still compelled to go through elaborate purification in order to forestall the evil omen. If twins are welcomed, their parents are similarly respected as they symbolize the fertility power of the clan. Superstitions and myths pertaining to twinning are universal and often present converging features among cultures without mutual contact. This would point to the twin cult as one of the earliest religious beliefs of mankind.

Suppose that L like-sexed and U unlike-sexed twins have been observed. Weinberg's method estimates the numbers of DZ andMZ twins as DZ = 2U and MZ = L—U. This method is based on the assumptions that (1) the sex ratio in DZ twins is 1/2 and (2) the sexes of DZ twins are determined independently and with the same probability in all parents; in consequence there should, on average, be equal numbers of like-sexed and unlike-sexed DZ twins. The first assumption is not exactly true, but the necessary correction is negligible. Departures from the second assumption would probably lead to an excess of like-sexed over unlike-sexed DZ twins; in consequence, Weinberg's method would underestimate the numbers of DZ twins and overestimate the numbers of MZ twins. The literature on the frequencies of like-sexed and unlike-sexed pairs among twins known to be DZ through other genetic markers is reviewed. It is concluded that there is no evidence of an excess of like-sexed twins among them, and that there is therefore no reason to doubt the validity of Weinberg's method. The extension of Weinberg's method to estimate the zygosity types of triplets and quadruplets is described; it is shown that the resulting estimates agree well with the results of direct zygosity determination by blood grouping.

The rates of human multiple maternities in the Nordic countries were studied from continuous series of data. In the Åland and Åboland archipelagos the parish records for births and baptisms since the 1650's were used. Various sources, some unpublished, in the archives of statistics were used for Sweden (since 1749) and Finland (since 1859) as a whole. Until recently, the rates of multizygotic multiple maternities in isolated island populations in the Åland and Åboland archipelagos have been some of the highest known among Whites (15-20‰). Highly significant temporal fluctuations in the twinning rates were noted. In Sweden, the twinning rate during the last part of 18th century was about twice as high as it was in 1966-70. The triplet and quadruplet rates were about three to four times as high as they are nowadays. There has been a secular decline in DZ twinning. This downward trend set in first in the isolated populations. In Sweden, it started in the 1930's, but in Finland, not until the 1960's. The steep downward trend in the twinning rates is shown to set in about one generation after the break-up of isolation. This can be interpreted as evidence that the changes in matrimonial migration patterns have affected the rates of DZ twinning.

The decline of the twinning rate in Germany since 1900 is exclusively due to a fall of the DZ rate. The analysis of the birth data in Baden-Württemberg from 1955 to 1972 shows that the decline of the DZ twinning rate can be explained only to a small extent by the shift of the maternal age-parity distribution towards younger mothers and lower parities. It appears reasonable that the greater part of this decline is caused by the lessening prevalence of the more fecundable, DZ twin-prone women due to the growing influence of family planning. Furthermore, it is imaginable that the probability for multiple ovulation is decreased after cessation of hormonal contraception.

The twinning phenomenon has always interested the great public, the artists, and naturally the scientists. Isidore Geoffroy St. Hilaire has established a classification still now valid. This classification considers the different types of double monsters which are found in nature in all classes of vertebrates, including man. To explain the twinning phenomenon, the experimental realizations have progressed by successive bounds after the preliminary attempts of different authors. Now, when it is question of experimental duplication, anybody thinks of Speman for the amphibians, of Lutz for the birds, of Seidel for the rabbit, and of Tarkowsky for the mouse. Now, it is possible to conceive a twinning resulting from the separation of the first blastomeres (amphibian, rabbit, mouse) and a twinning originating from the fissuration of the blastoderm (bird, mammal). All these experiments confirm the unicist-theory. If a total or partial regulation of the excedents may be experimentally realized, no argument can however support this theory in the realization of the double monstrosity.

Since the first publication in 1961, cases of monozygotic heterocaryotic twinning have been repeatedly found and a total of 14 observations can now be analysed. The mechanism involved in this type of twinning is yet uncertain and eventually is not identical in each case, the main uncertainty being to decide whether the chromosomal error affecting one of the twins is related, directly or indirectly, to the process of MZ twinning per se. Regarding the time of occurrence, the error seems to occur at few days of development at the most and, in one case at least, was contemporary to the first division cleavage. Considering the possibility of twins of different sex (e.g., one XY and one XO) the MZ heterocaryotic twinning could be considered as a potential equivalent of autofecundation in species in which the XO is a fertile female. Evolutive implications shall be discussed.

Twenty-two cases of conjoined twins have been collected in Thailand. The numbers occurring in the various parts of Thailand are listed. No known cases have occurred between the years 1968-1973. The extent of union between the conjoined twins is described and illustrated. Some theories are offered as to etiological factors which might account for the occurrence of conjoined twins.

Two cases of monoamniotic conjoined male twins, born at term after normal pregnancies, are reported. The first case, a bicephalus, shows hypoplastic and malformed left-side organs, absence of the left umbilical artery, and two communicating hearts, the left one with three cameras. The second case, a pygotho-racopagus, consists in a twin “parasite”, with no head but with two upper and two lower limbs, slightly less developed than those of the formed twin. The left eye of the formed twin is double than the right one and contains two eye apples — one well-formed and the other rudimentary. There is a rudiment of a second mouth on the left cheek. The umbilical cord contains five blood vessels — one umbilical vein and four umbilical arteries. The cytogenetic study of the pygothoracopagus reveals aneuploidy, more pronounced in the “parasite” than in the formed twin.

Among 56,249 maternities in the Collaborative Perinatal Project, 615 were twin maternities. One of these resulted in stillborn thoracoomphalopagus MZ female twins with multiple cardiovascular, alimentary and other malformations. The case is of further interst in that the mother had a surgically removed brain tumor in childhood and exhibited neurological symptoms and bizarre behavior before and during pregnancy. Drugs and treatments which she received during pregnancy are not known to be teratogenic.

Six new cases of monoamniotic twins are reported. All had true knots of the cord, the result being double survival in 5 cases and 11 normal children. The mechanism of twin development is described and monoamniotic twins are placed in accordance with the two theories from the literature. A short review of both the Scandinavian and the world cases is presented.

A family is described in which the tendency to bear twins is expressed in the offspring of males as well as females. All of the twins born in this family show marked discordance in birth weight and gestational age. In 5 of the 6 pairs, one twin was normal while the other was either a macerated fetal mass, stillborn, or died of prematurity in the neonatal period. The one pair in which both twins did survive is known to be DZ and showed a difference in maturity and a 21% discrepancy in birth weight. Thus, twinning in this family appears to be transmitted as an autosomal dominant trait which is expressed in the offspring of both female and male carriers. Of all possible genetic mechanisms which could explain this familial aggregation of markedly discordant twins, supcrfetation seems most consistent with the genetic transmission and expression of the trait in the offspring of both males and females. The most plausible explanation of the pedigree is that a dominant gene is segregating in the family which is expressed in the fetal placenta where it acts to reverse the normal hormonal inhibition of ovulation. Since both the father and the mother contribute to the genotype of the placenta, superfeiation could occur among offspring of both males and females who carry the gene.

Whereas the existence of some genetic factor underlying the phenomenon of twinning is almost generally accepted with respect to DZ twins, no such agreement exists with respect to MZ twins. The possible existence of genetic factors underlying MZ twinning has been verified through an analysis of segregation in the sibships of MZ twins and in those of their parents, carried out on a sample of 57 MZ twin pairs (30 M and 27 F). Haldane's a priori method has been applied, considering the sample as obtained through a complete and through an incomplete ascertainment. The results may lead to cautiously confirm the hypothesis of some genetic conditioning of MZ twinning.

Aiming to show that delayed ovulation may induce MZ twinning, follicular maturation was induced in the rabbit by a small quantity of Pregnant Mare Serum Gonadotropin (16 UI four times): coitus, which induces ovulation in the rabbit, was delayed 60 hours after the last injection. From the 387 blastocysts obtained after this treatment, 6 (7.5%) were pairs of MZ twins, twinning being otherwise exceptional in the rabbit. Other anomalies were shown by the embryos, apparently related to a deficient quality of the eggs: high embryonic mortality (62% vs. 27% in controls) and chromosomal anomalies (20%) such as trisomies, triploidies, and chimaeras. The relation between MZ twinning, chromosomal anomalies, and embryonic mortality induced by delayed ovulation, could be connected and related to the poor perinatal conditions frequently observed in human MZ twins.

A 26-year-old subfertile woman with a history of abortions at the 7-9th week was treated with Clomid, 50 mg for 5 days. A pregnancy resulted, which ended in the premature birth of a set of alive triplets that sex and blood-group determinations showed to be trizygotic. It is suggested that this production of a multiple ovulation in a woman with luteal deficiency be the result of excessive dosage of Clomid.

The use of twins as a research tool is still proving its worth both by the number of scientists engaged in twin research and by the significance of their results. Old, familiar research designs are finding new applications, and new research designs are appearing. Of greatest current interest are the epidemiological studies made possible by the assembly and the aging of large numbers of twins in twin registries. As an outgrowth partly of the twin registries, partly of conceptual and mathematical progress, new methods have emerged for diagnosis of twin types and for analysis of twin data. One line of development started with the questionnaire method of zygosity diagnosis and has given rise most recently to zygosity diagnosis by principal component analysis. Another line started with probability calculations and has led to the use of generalized distance and noncentral chi-square. The appropriateness of these methods in different contexts needs to be critically considered. Also of importance are the psychologists' new methods of extracting genetic “factors”. The greatest weakness of twin studies, long recognized, is their dependence on the assumption that DZ pairs provide an adequate control on the environmental differences within MZ pairs. This may be valid with respect to environmental influences that are highly self-selected. It is debatable for self-selected influences that differ among families, and clearly untenable for most influences imposed by the social environment peculiar to twins.

It is commonly, but incorrectly, assumed that the presence of genotype × environment covariance must necessarily reduce the heritability (h2) as estimated from twin data, when the formula used to obtain h2 makes no assumption about G × E covariance or assumes that it is zero. But, in fact, G × E covariance does not always reduce the genetic variance, and it can be shown under some conditions, an increase in the G × E covariance implies a greater genetic variance. The effect of G × E covariance on h2 as estimated from data on MZ and DZ twins, depends jointly upon the degree of assortative mating and the degree of environmental correlation between MZ twins and between DZ twins. A method, based on the solution of a pair of simultaneous quadratic equations, is proposed for estimating the range of h2 from twin data under varying assumed values for assortative mating, the environmental correlations between MZ and DZ twins, and the G × E covariance. The solution of three simultaneous equations permits direct estimation of the genetic variance, environmental variance, and G × E covariance, under varying reasonable assumed values for assortative mating and the MZ and DZ environmental correlations. Examples of the method are based on intelligence tests scores of MZ and DZ twins.

In a statistical sense, the objective of twin research is to partition the variance on some criterion measure among genetic and environmental factors. Although certain elaborate models have been developed, these models do not supply a convenient test statistic to show which factors make a significant contribution. Consequently several procedures drawn from analysis of variance have been adapted for use with twin data.