Heredity and Development: Second Edition (1972)

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HEREDITY AND DEVELOPMENT: SECOND EDITION 7 1 Darwin’s Theory of Pangenesis BACKGROUND FOR THE THEORY OF PANGENESIS Charles Darwin’s (1809–82) interest in genetics was a consequence of his studies of evolution. It will be necessary, therefore, to give a brief statement of his theory of evolution in order to show its relation to genetics. Darwin imagined that evolution occurred in this manner: Among the indi- viduals of any species there would be many differences. For example, some might be slightly larger than the average, or have longer legs, or have a thicker coat of fur. If any of these variations made their possessors better adapted to survive, those with the better characteristics would have a greater chance of leaving offspring (‘survival of the fittest,’ as Spencer later described it). With the passage of time the original population would change, its individuals gradually becoming larger, or developing longer legs or a thicker coat of fur, or whatever characteristic was of value for survival. In this way one species could evolve into another or give rise to two or more different species. We cannot discuss in detail Darwin’s theory of evolution. For the present, we should merely note the importance of variations. Evolution cannot occur unless there are differences among the individuals of the same species. If all individuals are identical and remain so generation after generation, obviously there is no evolution. So variation is essential and, furthermore, to be of importance in evolution it must be inherited. A thick coat of fur might be advantageous for a mammal living in the Arctic, but unless this variation is inherited it is unimportant for evolution. 

HEREDITY AND DEVELOPMENT: SECOND EDITION 8 Darwin fully realized that his theory of evolution must be based on a sound understanding of the mechanism of inheritance. There was no such under- standing in his day. He attempted, therefore, to assemble data and ideas from individuals who had speculated about inheritance and those who had been concerned with the practical aspects of animal and plant breeding. He added some observations of his own, thought deeply about the problems, and devel- oped the first comprehensive theory of heredity, or as we now call it, genet- ics. This appeared in 1868 as a two-volume work entitled The Variation of Animals and Plants under Domestication. Darwin’s work in this field was of major interest in the last half of the nine- teenth century. He was, of course, the outstanding biologist of his time, so anything he did attracted attention. We shall examine his theory briefly, not only for its historical interest but to see how the problems were stated, what data were available, and finally, to what extent the theory contributed to an understanding of natural events. Let us constantly keep in mind that our purpose is twofold: first, learning genetics, and second, learning how scientific theories develop and change. For this second purpose, it will be important for us to keep an open mind and, if possible, not to be prejudiced by what we may have read or learned before. It is difficult not to be influenced by what we may know of genetics, but if possible this knowledge should be ignored. If we are discussing the state of genetics in 1868 our approach should be this: Given the data available in 1868, how would we view the problems of inheritance? First, something of the background. Knowledge of cell structure, which in later years was to form a foundation for genetic concepts, was in a rudimen- tary state. It was known that animals and plants were composed of cells, but little was known about the internal structure of cells. The nucleus was thought to be a universal cell constituent, although its role in the life of the cell was unknown. It was generally believed, as we believe today, that cells arise solely from pre-existing cells and not de novo. Opinions on heredity were vague and varied. The crossing of varieties in both animals and plants had been practiced for centuries, but no general laws or rules to explain the results had been discovered. In fact, the data were so confusing that some doubted that they could be scientifically explained. One type of observation that convinced Darwin of the ‘force of inheri- tance’ was that ‘with man and the domestic animals, certain peculiarities have appeared in an individual, at rare intervals, or only once or twice in the history of the world, but have reappeared in several of the children or grand- children.’ One of the most spectacular instances of this 

HEREDITY AND DEVELOPMENT: SECOND EDITION 9 was the porcupine man, whose skin was covered by warty projections (Fig. 1–1). Six of his children and two of his grandchildren showed this same defect. Another instance was found in some domestic pigs, entirely lacking hind legs, whose abnormality was carried through three generations. To some biologists of the mid-nineteenth century, such instances seemed to be the result of mere chance, or of environmental influence, 1–1 The hand of the porcupine man. 

HEREDITY AND DEVELOPMENT: SECOND EDITION 10 but to Darwin they were evidence that ‘something’ was transmitted from par- ent to offspring. The following quotation illustrates the way he reasoned. When we reflect that certain extraordinary peculiarities have thus appeared in a single individual out of many millions, all exposed in the same country to the same general conditions of life, and again, that the same extraordinary peculiar- ity has sometimes appeared in individuals living under widely different condi- tions of life, we are driven to conclude that such peculiarities are not directly due to the action of the surrounding conditions, but to unknown laws acting on the organisation or constitution of the individual;—that their production stands in hardly closer relation to the conditions than does life itself. If this be so, and the occurrence of the same unusual character in the child and parent cannot be attributed to both having been exposed to the same unusual conditions, then the following problem is worth consideration, as showing that the result cannot be due, as some authors have supposed, to mere coincidence, but must be conse- quent on the members of the same family inheriting something in common in their constitution. Let it be assumed that, in a large population, a particular affection occurs on an average in one out of a million, so that the a priori chance that an individual taken at random will be so affected is only one in a million. Let the population consist of sixty millions, composed, we will assume, of ten million families, each containing six members. On these data, Professor Stokes has calculated for me that the odds will be no less than 8333 millions to 1 that in the ten million families there will not be even a single fam- ily in which one parent and two children will be affected by the peculiarity in question. But numerous cases could be given, in which several children have been affected by the same rare peculiarity with one of their parents; and in this case, more especially if the grandchildren be included in the calculation, the odds against mere coincidence become something prodigious, almost beyond enumeration. Even today, it would be hard to supply better reasons for the belief that ‘some- thing’ was transmitted from the first porcupine man to his son. Darwin ruled out the possibility of the external environment having any causal relation to the appearance of the defect: If something in the environment was the stimu- lus, why did just these few persons and no others have the defect? If there had been some unusual feature of the environment, such as rare climatic condi- tions or a peculiar substance in the diet, many individuals might be expected to have a ‘porcupine skin.’ Neither could it be due to chance. It was incon- ceivable that a defect, so rare as never to be recorded before, should affect a father, son, and grandson merely by chance. Darwin concluded that the best explanation was that the son had inherited his father’s defect. This, in turn, means that something is 

HEREDITY AND DEVELOPMENT: SECOND EDITION 11 transmitted from father to son. If this is the case, it should be possible to obtain information on the laws governing this transmission. If these laws could be formulated, not only would this represent a tremendous advance for genetics, but a firm foundation would be provided for the theory of evolution. The Data To Be Explained. Darwin’s procedure, that is, his ‘scientific method,’ was as follows: First, he assembled all the information he could find that seemed to have a bearing on heredity. Second, he proposed a theory to account for all of the information he had assembled. The mass of data con- tained in his two-volume work is considerable, but it can be combined into a small number of categories. These were the types of data that Darwin felt must be explained by any comprehensive theory of inheritance. 1. Transmission of Characters from Parent to Offspring. Darwin summa- rized a tremendous mass of observations on this topic. Most of the char- acters known to him were morphological, such as differences in body, size, type of feathers, or hair and color patterns. Others were physiologi- cal; examples are the inheritance of profuse bleeding in man, and pecu- liar tics or nervous defects. The inherited characters might be large or small, important or unimportant. He concluded, ‘When a new character arises, whatever its nature may be, it generally tends to be inherited, at least in a temporary and sometimes in a most persistent manner.’ Dar- win had no conception of an orderly or predictable transmission of char- acters from parent to offspring. Inheritance to him was a capricious phe- nomenon, sometimes temporary and sometimes persistent. 2. Mutilations. Some races of man habitually knock out their teeth, cut off parts of their fingers, or perforate their ears or nostrils, yet their children do not show corresponding defects. There were other cases where muti- lations appeared to be inherited and they were given on such good authority that Darwin found it ‘difficult not to believe them.’ One of these was ‘a cow that had lost a horn from an accident with consequent suppuration, produced three calves which were hornless on the same side of the head.’ Once again the situation was complex. Mutilations appeared to be inherited in some instances but not in others. 3. Atavism (or Reversion). This is the presence in an individual of some peculiar characteristic not expressed in its immediate parents, but resembling a remote ancestral condition. Children occasionally resem- ble their grandparents or more distant ancestors more closely than they do their parents. Domestic animals may have peculiar features not char- acteristic of their breed, but resembling the wild species from which the domestic forms were derived. For example, it was believed that the wild 

HEREDITY AND DEVELOPMENT: SECOND EDITION 12 ancestors of the domesticated sheep had been black. Thus, when a black sheep suddenly appeared in a flock of carefully bred white sheep, it was explained as a consequence of the persistence of a long-dormant heredi- tary feature. Instances are reported of reversion during the life of a sin- gle individual. Darwin crossed white hens with black cocks. Some of the individual chicks were white the first year but black the second. 4. Sex. Most characters appeared to be inherited with equal facility from either the mother or the father, but Darwin knew of a few instances in which the sex of the parent was important. Cases are quoted on traits being transmitted from father to son but never to daughters, or from mother to daughter but never to sons. In color blindness, males are much more commonly affected than females, yet the defect can be transmitted through normal females. In fact, it seemed probable to Darwin that fathers can never transmit color blindness to their sons. Daughters of color-blind fathers, on the other hand, though normal themselves, trans- mit color blindness to their sons. Thus, the father, grandson, and great- great-grandson will exhibit a peculiarity—the grandmother, daughters, and great-granddaughter having transmitted it in a latent state.’ From observation of this sort Darwin states, ‘We thus learn, and the fact is an important one, that transmission and development are distinct powers.’ 5. Inbreeding and Inheritance. If two organisms are crossed and their off- spring bred with each other generation after generation, we speak of this as inbreeding. The data available to Darwin suggested that inbreeding would result in a relatively homogeneous population in which there is a blending of characteristics. Darwin regarded this as the general rule, but he adds (in small print!) that in other cases ‘some characters refuse to blend, and are transmitted in an unmodified state either from both par- ents or from one. When gray and white mice are paired, the young are not piebald nor of an intermediate tint, but are pure white or the ordinary gray color.’ 6. Selection and Inheritance. Selection is a breeding method that has been employed since the early days of agriculture. If a farmer is interested in increasing the size of his chickens, he selects the largest individuals and breeds them. From their offspring he selects the largest and breeds from them. With this procedure, it is usually possible to increase the average size of the descendants in a few generations. One of the most puzzling aspects of selection was the fact that frequently it was possible to pro- duce an organism with characteristics not even remotely suggested in the original stock. For example, continued selection produced the most bizarre varieties of pigeons with characteristics not occurring in the ancestors. In short, selection could create something new. This will be considered next. 

HEREDITY AND DEVELOPMENT: SECOND EDITION 13 7. Origin of Variability. All domestic and wild species familiar to Darwin were variable. Many varieties bred true, indicating the hereditary nature of the special features. In some cases a variety was known to have origi- nated from a single exceptional individual. In many cases it appeared that the new variety was ‘new’ in the sense of never having occurred before. To Darwin the cause of variability was ‘an obscure one; but it may be useful to probe our ignorance.’ He favored the view that ‘varia- tions of all kinds and degrees are directly or indirectly caused by the conditions of life to which each being, and more especially its ancestors, have been exposed.’ The great importance of the ‘conditions of life’ can be brought out by the following quotation: ‘…if it were possible to expose all the individuals of a species during many generations to abso- lutely uniform conditions of life, there would be no variability,’ The actual conditions of life that were thought to cause variability included excess food (probably the most important), climate, hybridization, graft- ing in plants, and in fact ‘a change of almost any kind in the conditions of life.’ 8. Regeneration. When the tail or the legs of a salamander are cut off, the lost structures are replaced perfectly by regeneration. The ability to regenerate lost parts is of widespread occurrence and appears to be simi- lar to events occurring in embryonic development. Darwin felt that both the formation of a structure during the course of normal development and its replacement following injury to the adult were due to the work- ings of inheritance. 9. Inheritance and Mode of Reproduction. There are two main types of reproduction, sexual and asexual. An animal like Hydra is capable of both. Sexual reproduction consists of the fertilization of an ovum by a spermatozoon. Asexual reproduction in Hydra is by budding. In this process a small protuberance forms on the side of the Hydra. This grows and eventually detaches as a small individual. A Hydra that originates from a fertilized ovum is identical with a Hydra developing from a bud. Thus, to Darwin inheritance is the same whether by sexual or asexual means. 10. Delayed-Action Inheritance. Darwin listed several cases, which he believed to be well substantiated, of the male gametes having an effect on the female organs. One of these was published by Lord Morton. An Arabian chestnut mare was crossed to a quagga (a wild African species belonging to the horse genus and closely resembling the zebra). The first offspring was intermediate in form and color. The mare was subse- quently crossed to a black Arabian horse. One filly and one colt were produced. In coloration and type of mane these two offspring showed a striking resemblance to the quagga. For example, dark bars were present on the hind part of the body and the mane was stiff and erect. Darwin 

HEREDITY AND DEVELOPMENT: SECOND EDITION 14 concluded, ‘Hence, there can be no doubt that the quagga affected the character of the offspring subsequently begot by the black Arabian horse.’ He felt that the quagga sperm had acted directly on the reproduc- tive organs of the female in such a way as to affect the characteristics of future offspring sired by other males. THE THEORY OF PANGENESIS These ten categories represent the types of data that Darwin felt must be explained by any comprehensive theory of inheritance and he set about to formulate a theory to explain them. The result was ‘…the hypothesis of Pan- genesis, which implies that the whole organization, in the sense of every sepa- rate atom or unit, reproduces itself.’ He began by postulating the existence of gemmules, which determine all characteristics of the organism. The proper- ties that gemmules were assumed to possess were these: Each and every cell of an organism, and even parts of cells, produce gemmules of a specific type corresponding to the cell or part. These are able to circulate throughout the body and enter the sex cells. Every sperm and every egg will contain gem- mules of all sorts and so they are transmitted to the next generation. During development they unite with partially formed cells or with other gemmules, and in this way produce new cells of the type from which they were formed. We should think of a liver cell as producing gemmules for every part of that cell, enough kinds to produce the identical cell type in the next generation. All other parts of the body would also be producing their own specific gem- mules. These must be present in tremendous numbers, since every sperm and ovum will have some of all types produced in the body. In some instances the gemmules could remain dormant for generations. Today we might wonder about the space problem. If every part of the body produced a specific gemmule, would it not be difficult for all of them to fit into an ovum of microscopic dimensions, or into the even smaller sperm? Thus, if gemmules exist, obviously they must be very small. Darwin did not think this difficulty was fatal to his hypothesis. Biologists, especially those working on disease or with cells, realized that very small things could be extremely important. The basic postulate of his theory was the existence of the gemmules and their production by cells. Was there any evidence? At the time Darwin wrote we must remember that the ‘cell theory’ was in the process of being accepted. Darwin reasoned this way: If cells can divide and produce other cells, per- haps they can produce other bodies with the assumed characteristics of gem- mules by a similar process. In his own words, ‘The existence of free gem- mules is a gratuitous assumption, yet can hardly be considered as very improbable, seeing that cells have the 

HEREDITY AND DEVELOPMENT: SECOND EDITION 15 power of multiplication through the self-division of their contents.’ Darwin’s Theory of Pangenesis was based on gemmules but he had no real evidence for their existence. They were invented to account for the observed events in inheritance. This is legitimate scientific procedure. Atoms were invented to account for the data of chemistry. The planet that was later named Pluto was invented to account for irregularities in the orbits of known plan- ets. Atoms and Pluto were useful hypotheses long before one could be certain of their reality. The Theory Explains the Data. The Theory of Pangenesis can be applied to the ten categories of data requiring explanation. 1. Transmission of Characters from Parent to Offspring. The appearance of the same characters in parent and offspring was made possible by the production of gemmules by all parts of the parent’s body. These entered the ova and sperm and were transmitted to the offspring where they caused their specific effects. This was true, as well, for those special characters such as those of the porcupine man. The skin cells of the por- cupine man produced ‘porcupine’ gemmules. These reached his chil- dren by way of the sperm. 2. Mutilations. Mutilations are usually not inherited because normal gem- mules would have been produced by the structure before the mutilation occurred. These gemmules would enter the gametes and be passed to the next generation. The few cases in which mutilations appeared to be inherited usually involved diseased parts. Darwin explained this as fol- lows: ‘In this case it may be conjectured that the gemmules of the lost part were gradually all attracted by the partially diseased surface, and thus perished.’ 3. Atavism. Atavism, according to the Theory of Pangenesis, was due to the ancestral gemmules remaining in a dormant condition for many gen- erations and then suddenly developing. 4. Sex. Both sexes transmit inherited characters with equal facility, since both transmit gemmules representing every cell of the body. In the case of color blindness in man, and similar instances of inheritance modified by sex, it was assumed that gemmules were dormant in one sex. A color- blind man transmits gemmules of color blindness to his daughter (in whose body they are dormant) and she may in turn transmit them to her sons. In the sons they develop and the sons are color-blind. 5. Inbreeding and Inheritance. The blending in the offspring of characteris- tics of the parents is due to the mixing of the parental gemmules. Those cases in which the characteristics of one parent predominate indicate that the predominating ones ‘have some advantage in number, affinity, or vigour over those derived from the other parent.’ 6. Selection and Inheritance. It is possible to influence the inherited 

HEREDITY AND DEVELOPMENT: SECOND EDITION 16 characteristics of organisms through selection in this manner: The farmer choosing the largest chickens from his flock is choosing the ones that will produce gemmules for large size. If this is repeated every gen- eration, the gemmules for large size will be retained, those for small size will be eliminated, and the chickens will reach their maximum possible size. 7. Origin of Variability. According to Darwin, new structures appear as a result of some environmental influence. The new or changed structure will produce new types of gemmules. These will be transmitted to the next generation, and thus the new character will reappear. 8. Regeneration. Regeneration of lost parts is possible because the gem- mules for the lost parts were produced prior to the loss and are present in the rest of the body. If, for example, the leg of a salamander has been removed, the leg gemmules, which are present in the body, can migrate to the cut surface and develop into a new limb, identical to the old one. 9. Inheritance and Mode of Reproduction. Inheritance is the same, whether via sexual or asexual means, since the basis is identical—the transmission of gemmules. In the case of our specific example, Hydra, every cell of the body would produce gemmules. These would move to all parts, including the gametes and the cells that form the buds. Thus, the new individual would receive the same gemmules irrespective of whether they came from a fertilized ovum or from a bud. 10. Delayed-Action Inheritance. In those peculiar cases where the male gametes were thought to have a lasting effect on the reproductive organs of the females (as in Lord Morton’s mare) a ready explanation was pos- sible. Some of the gemmules from the male gametes entered the repro- ductive organs of the female and were included in ova produced long afterwards. Darwin’s Theory of Pangenesis, like all great theories, involved a great sim- plification in man’s view of his universe. By assuming the existence of gem- mules with definite properties he was able to ‘make sense’ out of a previously bewildering mass of data. Inheritance is the transmission of the physical enti- ties that are the basis of development in succeeding generations. But to postu- late is not to prove. The facts available to Darwin were not sufficient to decide whether his theory was ‘right’ or ‘wrong.’ His main contribution was the collection of a tremendous amount of genetic data, and an attempt to pro- vide a theoretical framework for its interpretation. He was most modest about his efforts: ‘I am aware that my view is merely a provisional hypothesis or speculation; but until a better one be advanced, it may be serviceable by bringing 

HEREDITY AND DEVELOPMENT: SECOND EDITION 17 together a multitude of facts which are at present left disconnected by any efficient cause. As Whewell, the historian of the inductive sciences, remarks: “Hypotheses may often be of service to science, when they involve a certain portion of incompleteness, and even of error.” Under this point of view I ven- ture to advance the hypothesis of Pangenesis, which implies that the whole organization, in the sense of every separate atom or unit, reproduces itself.’ We should now pause to ask a few questions: Did Darwin’s Theory of Pan- genesis explain the data of heredity? If you are aware of later developments in this field you will probably answer ‘no,’ but if you can repress the bias of the knowledge of what was to come, you will probably conclude that the answer is ‘yes.’ If the answer is ‘yes,’ does this mean that the theory is correct? Darwin’s approach to the study of inheritance was one of two possible methods of attack. He was concerned nearly entirely with the results of inher- itance, i.e. the kind of offspring obtained when parents of different types were crossed. From the results he attempted to reconstruct the basis of inheri- tance. As we have already seen, he concluded that every cell produces gem- mules and that these are the basis of inheritance. In the thirty years following the presentation of the Theory of Pangenesis little or no advance, based on breeding experiments, was made in our understanding of the mechanism of inheritance. The second possible method of investigation involves the study of ova and sperm. These gametes are the sole physical link between the parents and off- spring, so presumably they would be responsible for the transmission of any inherited characteristics. A careful study of the gametes might be expected to throw some light on inheritance. The branch of biology that is concerned with the study of cells, including the ova and sperm of course, is cytology. These two approaches to inheritance, studying offspring or studying cells, together were eventually to give us a sound theory of inheritance. The major advances during the last half of the nineteenth century were made almost entirely in cytology: they will be considered in Chapter 2. In Chapter 3 we return to the other approach, the study of the characteristics of the offspring. This sister discipline came to be called genetics. Suggested Readings Charles Darwin was only one of many early workers interested in inheri- tance. Excerpts from the writings of others, such as Hippocrates, Aristotle, and Galton are given in Chapter 1 of the companion volume 

HEREDITY AND DEVELOPMENT: SECOND EDITION 18 Readings in Heredity and Development. You will also find there a longer list of references. DARLINGTON, C.D. 1969. Genetics and Man. New York: Schocken Books. The breadth of approach makes this book especially appealing to non-science students. DARWIN, CHARLES. 1868. The Variation of Animals and Plants under Domestication. 2 volumes. London: John Murray. Chapter 27 is “Provisional Hypothesis of Pangenesis.” DUNN, L.C. 1965. A Short History of Genetics. The Development of Some of the Main Lines of Thought: 1864–1939. New York: McGraw-Hill. A fine book with which to begin. OLBY, ROBERT C. 1966. Origins of Mendelism. New York: Schocken Books. STURTEVANT, A.H. 1965. A History of Genetics. New York: Harper and Row. Questions 1. On the basis of your knowledge of biology, how would you account for the ten types of data that Darwin felt must be explained by any compre- hensive theory of inheritance? 2. What sorts of experiments or observations could you suggest to test Darwin’s theory of pangenesis? Were Galton’s experiments (Readings, Chapter 1) an adequate test? 3. Compare Darwin’s theory of pangenesis with that of Hippocrates (Read- ings, Chapter 1). 4. To what extent can the arguments that Aristotle used to refute pangene- sis (Readings, Chapter 1) be used against Darwin’s theory? 5. Why did Aristotle believe that the male and female make qualitatively different contributions to inheritance (Readings, Chapter 1)? 6. Evaluate this quotation from Aristotle (Readings, Chapter 1) in terms of what you may know of current theories of inheritance: “…why not admit straight away that the semen at the onset is such that out of it blood and flesh can be formed, instead of maintaining that the semen is itself both blood and flesh?”. 7. What precautions did Galton (Readings, Chapter 1) take in selecting the rabbits that were to be transfused with blood? Why were these precau- tions necessary? Why did Galton think it important to estimate the amount of blood transfused? Evaluate his experiments in relation to what you know about immunology and infection. 8. Do you find Darwin’s criticism of Galton’s experiments convincing (Readings, Chapter 1)?