Genetics

“ In the disentanglement of the properties and interactions of these elementary factors, the science we must call to our aid is Physiological Chemistry. The relations of Genetics with the other branches of biology are close. Such work can only be conducted by those who have the good fortune to be able to count upon continual help and advice from specialists in the various branches of Zoology, Physiology, and Botany. ”

“ All the processes of which I have spoken are accomplished by means of cell-divisions, and in the one cell-union which occurs in fertilisation. If we could watch [Pg 19] the factors segregating from each other in cell-division, or even if by microscopic examination we could recognize this multitudinous diversity of composition that must certainly exist among the germ-cells of all ordinary individuals, the work of genetics would be much simpler than it is. ”

“ Genetics, the study of heredity, can not successfully proceed by direct observation in the human species as it does with plants and rapidly-breeding animals, because the generations are too long. Less than three generations are of little value for genetic researches, and even three can rarely be observed to advantage by any one person. ”

“ The aim of eugenics is therefore not primarily the collection of facts, but the construction and advocacy of practical proposals. The character of these proposals will of course depend on our conception of the laws of heredity, but the study of these laws forms the subject matter of the science of genetics. Genetics is a department of biology; and the last word in all controversies connected with heredity must rest with the biologist. ”

“ To the student of genetics, man, like any other animal, is material for working out the manner in which characters, whether physical or mental, are transmitted from one generation to the next. Viewed in this way he must be regarded as unpromising, not only from the small size of his families, the time consumed in their production, and the long period of immaturity, but also because full experimental control is here out of the question. ”

“ It is however becoming probable that if more knowledge of the chemical and physical structure of organisms is to be attained, the clue will be found through Genetics, and thus that even in the uncoordinated accumulation of facts of Variation we are providing the means of analysis applicable not only to them, but to the problems of normality also.
The only classification that we can yet institute with any confidence among the phenomena of Variation is that which distinguishes on the one hand variations in the processes of division from variations in the nature of the substances divided. ”

“ Inheritance is of definite traits, such as eye color, height, musical genius, high or low resistance to a germ disease, for example, tuberculosis. Research work in genetics is at the present time especially concerned with discovering what are the unit characters and how each is transmitted.
Special cells, called germ cells, are the carriers of heredity; these contain the determining factors for physical and mental characteristics. These, like all the other cells of the body, are microscopic in size. The body of the individual is the temple in which the sacred cells of the race are protected. ”

“ If we want to raise mangels that will not run to seed, or to breed a cow that will give more milk in less time, or milk with more butter and less water, we can turn to Genetics with every hope that something can be done in these laudable directions. ”

“ Experimental embryology, histology, regeneration, comparative physiology, neurology, cytology, and heredity have in recent years successfully adopted an experimental aspect and have made significant progress thereby. Biology has now taken its place beside chemistry and physics as an experimental science.
The latest great advance in biology has been in the field of heredity. The rediscovery of the Mendelian principles of heredity in 1900 brought to light the most important generalization in biology in recent times. The new science of genetics is essentially the experimental study of heredity. ”

“ And since full comprehension of it requires some understanding of the nature of the physical mechanism by which hereditary traits are handed on from generation to generation, a small amount of space is given to this phase. Then, that the reader may appreciate to their fullest extent the facts gathered concerning man, a review of the more significant principles of genetics as revealed through experiments in breeding plants and animals has been undertaken. ”

“ In man and in domesticated animals we find that individuals appear occasionally that are defective in one or another respect. Some of the defects are inherited. Rarely a new one appears that has not been seen before. But the majority of them are reappearances of characters that have been carried under the surface as recessive genes in the germ-plasm. Today we recognize that each of these modifications, if recessive, has first arisen as a mutational change in a single gene before it appeared on the surface as a character by the coming together of two such genes. ”

“ We do not know how widespread recessive genes are in the human germ-plasm. The fact that defective individuals appear in certain communities may be safely interpreted to mean that individuals bearing the same gene have at last come together. On the other hand, the absence of such individuals from the community, at large, may only mean that the chance of suitable combinations is small, and does not mean necessarily that the gene in question is confined to the community within which the defects have been recorded. ”

“ Hence whatever we learn about those hereditary elements that stand for defects, we learn just as much about the behavior of the normal partners of those elements. In a word, heredity is not confined to a study of the shuffling of those genes that produce abnormal forms, but is equally concerned with what is going on when normal genes are redistributed. This method of pitting one gene against the other furnishes the only kind of information relating to heredity about which we have precise knowledge. ”

“ But when we proceed to ask how the germ-cells will be constituted in the case of an individual who is cross-bred in some respect, containing that is to say, an ingredient from the one side of his parentage and not from the other, the answer is entirely contrary to all the preconceptions which either science or common sense had formed about heredity. ”

“ Strong constraint versus gene expression across development.Within each developmental time point, genes were ranked by their level of expression and then grouped into high, moderate, and low expression levels - each group comprising of one-third of all genes. Within each gene set within each time point, the fraction of 4D synonymous sites under strong constraint was calculated using the bootstrap. ”

“ Human Social Genomics
Initial indications that social environments might significantly affect the functional activity of the human genome came from studies dissecting leukocyte gene expression profiles into genetic and environmental components [8] , [9] . Gibson and colleagues found that ∼5% of genes expressed in leukocytes showed appreciable genetic regulation (e.g., via expression quantitative trait loci) , whereas >50% showed significant differences in expression across pastoral, rural, and urban social environments [9] . ”

“ Of course if a dominant character is advantageous in itself, it will have a better chance of spreading through the race, than will an advantageous recessive character, because every hybrid that carries one dominant gene shows also the character, which increases the chance that it will propagate and spread the genes. ”

“ If one can control the matings, so that out-breeding takes place each time, the result would undoubtedly be like that in our diagram; but what chance is there for a recessive character, that is neither beneficial nor injurious, if left to itself, to contaminate widely the race with its gene? The answer is that for any one defect there is hardly any chance at all. On the other hand, there is always a possibility that a defect may become widespread despite the chances against each in turn. ”

“ For it is obvious that the contributions of the male and female gametes may in respect of any of the ingredients be either the same, or different. In any case in which the contribution made by the two cells is the same, the resulting organism—in our example the man—is, as we call it, pure-bred for that ingredient, and in all respects in which the contribution from the two sides of the parentage is dissimilar the resulting organism is cross-bred. ”

“ In such an observation two things are strikingly exemplified, (1) the fact of the permanence of the unit, and (2) the fact that a mixture of types in the family means that one or other parent is cross-bred in some respect, and is giving off gametes of more than one type.
The problem of heredity is thus a problem primarily analytical. We have to detect and enumerate the factors out of which the bodies of animals and plants are built up, and the laws of their distribution among the germ-cells. ”

“ In default we are obliged to examine the constitution of the germ-cells by experimental breeding, so contrived that each mating shall test the composition of an individual in one or more chosen respects, and, so to speak, sample its germ-cells by counting the number of each kind of offspring which it can produce. ”

“ These go over into the first generation hybrids, and are sorted out in the germ cells of the hybrid. Consequently, when the F1’s are inbred, there are all sorts of recombinations of the minor factors. This explains the greater variability of the second generation.
It is probable that in most of our domesticated animals, including man, much of the variability is due to multiple factors, which makes a study of inheritance in these groups extremely difficult, especially when, as in the case of man, the number of offspring from a pair is small, and critical combinations for study can not be made. ”

“ If we could conceive of an organism like one of those to which disease may be due becoming actually incorporated with the system of its host, so as to form a constituent of its germ-cells and to take part in the symmetry of their divisions, we should have something analogous to the case of a species which acquires a new factor and emits a dominant variety. ”

“ But while noting parenthetically that this question of opportunity has an importance, which some day it may be convenient to estimate, the one certain fact is that all the powers, physical and mental that a living creature possesses were contributed by one or by both of the two germ-cells which united in fertilisation to give it existence. The fact that two cells are concerned in the production of all the ordinary forms of life was discovered a long while ago, and has been part of the common stock of elementary knowledge of all educated persons for about half a century. ”

“ The recognition of the unit-factors may lead—indeed must lead—to great advances in chemical physiology which without that clue would have been impossible, but in causation the chemical phenomena of heredity must be regarded as secondary to the physical or [Pg 34] mechanical phenomena by which the cells and their constituents are divided and separated. When therefore we speak of the essential phenomena of heredity we mean the mechanics of division, especially, though not, as we shall see, exclusively, of cell-division ”

“ In connection with the question of spreading of mutant genes in the race there is another consideration, seldom referred to, that may occasionally have some weight in accounting for the dispersal of genes. ”

“ In the F2 generation the frequency for the extracted double dominant will be that of the original strain, that of the F2 heterozygotes will be the same as that of the F1, and the extracted double recessive class will not develop cancer at all. ”

“ This first divides to form a new group of germ cells, which are within the embryo or new body when it begins to develop, and so on through indefinite generations. Thus the germ cells in an individual living to-day are the lineal descendants, by simple division, of the germ cells in his ancestors as many generations, or thousands of generations, ago as we care to imagine. All the complicated body specializations and sex phenomena may be regarded as super-imposed upon or grouped around this succession of germ cells, continuous by simple division. ”

“ It is true that we are dealing here with complex phenomena and limited exact experimentation, and a distinct mutant in the direction of high efficiency might occur at any time and be chosen for breeding which would maintain itself without continuous selection. ”

“ The behaviour of homologous twinning in heredity has been little studied. It does not exist as a normal feature in any animal which is amenable to experiment, and we cannot positively assert that a comparable phenomenon exists in plants; for in them—the Orange, for example—polyembryony may evidently be produced by a parthenogenetic development of nucellar tissue. ”

“ In such an imaginary situation, the ratio of cancer-developing mice may not appear to correspond to any of the known Mendelian ratios, because superimposed on the genetic situation there would be added results depending on the frequency of mutation when a specific gene is present. ”

“ In the case of plant breeders working to produce new races, the mutation theory introduces a new element and leads the breeder to search for a mutant possessing desirable characters which he can isolate and which he may expect will reproduce its characters as soon as he has purified the type from mixtures derived through hybridization with other types. ”