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Erasmus Darwin's Enlightened Views on Placental Function
Placenta 28 (2007) 775e778
Classics revisited
Erasmus Darwin’s Enlightened Views on Placental Function R. Pijnenborg*, L. Vercruysse Department of Gynaecology and Obstetrics, Katholieke Universiteit Leuven, Universitair Ziekenhuis Gasthuisberg, B3000 Leuven, Belgium Accepted 4 March 2007
Abstract In his major work ‘‘Zoonomia’’, Erasmus Darwin (1731e1802) devoted one chapter to the placenta, in which the new knowledge of the recently discovered element oxygen was applied to the functioning of this organ. He considered the ‘‘cavities’’ or ‘‘lacunae’’ in the placenta as the main areas for oxygenation of the fetal blood, as he thought them to be structurally comparable to the lungs and the gills of fish. He obviously was aware of species differences in the uterine arterial blood supply to the placenta between humans and cows, assuming a higher contractility of the vasculature in the latter species. The new evidence for a primarily respiratory role overshadowed ideas of a possible nutritive function of the placenta. Since Hunter’s definitive demonstration of separate maternal and fetal blood circulations, nutritive functions of the placenta needed to be explained by transmembrane transport processes, which were unknown at that time. Instead Erasmus Darwin erroneously considered the amniotic fluid as the main source of nutrients for the fetus. His understanding of placental respiration found expression in his long poem on the history of life on earth. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Placental vascularization; Placental structure; Erasmus Darwin; John Hunter; Respiration; Fetal nutrition; History
1. Introduction Erasmus Darwin (1731e1802), grandfather of Charles Darwin, was in his lifetime at least as famous as his grandson would become [1]. He built up a successful and busy medical practice, but also engaged himself in a broad range of scientific and technical investigations. He had a special knack for designing mechanical devices to solve diverse technical problems, and he delighted in discussing these with his friends of the Lunar Society [2]. His wide scientific interests together with his involvement in what later would be known as ‘‘the industrial revolution’’ show him to be a true representative of the British ‘‘Enlightenment’’. His interest in reproduction was awakened by studying Linnaeus’ new classification system for plants, which was based upon the structure and arrangement of the reproductive
* Corresponding author. Tel.: þ32 16 346190; fax: þ32 16 344205. E-mail address: [email protected] (R. Pijnenborg). 0143-4004/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.placenta.2007.03.003
organs (pistils, stamens, etc.) within the flower. He translated Linnaeus’ ‘‘Systema vegetabilium’’ into English, thereby facing criticisms because of the numerous explicit hints to sexual organs and their use. That did not prevent him to subsequently compose the long poem ‘‘The loves of the plants’’ (1789), in which the sexual organs of each group were ‘‘anthropomorphized’’ into sometimes eroticizing stories peppered with promiscuous misbehaviour [3]. It should be noted that the reproduction of plants was little understood at that time, and it was probably Erasmus Darwin’s main purpose to educate his readers on this topic while drawing their attention to similarities in human reproduction [4]. ‘‘Zoonomia; or the laws of organic life’’ (1794e1796) is usually considered to be his magnum opus, presenting a comprehensive view on the workings of the body. In this work he tried to base all bodily functions on the four properties ‘‘irritation, sensation, volition and association’’, and subsequently applied the same characteristics to a classification of all human diseases [5]. In later years, ‘‘Zoonomia’’ became mainly famous for his speculations on the descent of all living creatures
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from ‘‘one living filament’’, thus anticipating the evolutionary ideas of Lamarck and his grandson Charles Darwin. However, although Erasmus postulated the inheritance of acquired characters and hinted at a ‘‘struggle for life’’, he never hit upon his grandson’s concept of natural selection as a driving force in evolution. Apart from his considerations on evolution, this work also contains interesting sections on reproduction, including a chapter on ‘‘the oxygenation of the blood in the lungs, and in the placenta’’. This chapter highlights the respiratory function of the placenta, but also discusses its possible nutritive role e a controversial concept at that time. Darwin definitely was not a placentologist sensu strictu, but he managed very well to accomodate his understanding of the respiratory role of the recently discovered oxygen to the maternalefetal exchanges taking place in the placenta. He obviously drew a lot of his information from other investigators, and mentioned especially James Jeffray’s ‘‘Tentamen medicum’’ at the University of Edinburgh (1786) as well as the work of Forester French in Cambridge, thereby fleetingly expressing his hope ‘‘that Dr French will some time give his theses on this subject to the public’’. It is not always clear in Darwin’s text which of the reported observations were his own, but there can be no doubt that he had strong personal opinions in the matter. With regard to his interest in the placenta it may be revealing that in 1753, as a medical student, Erasmus spent one term in London to attend William Hunter’s (1718e1783) anatomical lectures. Although Hunter’s famous ‘‘Anatomy of the human gravid uterus’’ with its brilliant illustrations of dissected pregnant uteri was not yet published at that time [6], William’s brother John (1728e1793) had already obtained and dissected a first gravid uterus in 1751. It is thus highly probable that questions concerning the problem of fetale maternal vascular relationship were already included in William Hunter’s lectures at the time of Erasmus Darwin’s sojourn in London [7,8]. Using coloured wax injections, John Hunter was able to prove that fetal and maternal circulations in the placenta are separate, thus refuting previously held ideas of one continuous maternal to fetal circulation. The complete story was told by John several years later (1786), emphasizing his own priority in the discovery. He also pointed out that his first observations on an injected specimen were made in 1754, that is one year after Erasmus Darwin’s visit to London [9]. There can be no doubt, however, that in later years Erasmus became familiar with William [6] and John Hunter’s [9] books, which were published, respectively, 20 and 10 years before ‘‘Zoonomia’’. 2. ‘‘Zoonomia’’ and the respiratory function of the placenta The oxygen question and the nature of respiration were hot topics in Erasmus Darwin’s time. Until the discoveries by Lavoisier and Priestly, combustion had been considered as a process by which a (hypothetical) substance ‘‘phlogiston’’ is set free. The discovery of oxygen had brought a radical conceptual change, leading also to an understanding of its vital
role in respiratory processes, including its uptake and transport by the blood. As Erasmus Darwin stated ‘‘. it appears that the basis of atmospheric air, called oxygene, is received by the blood through the membranes of the lungs; and that by this addition the colour of the blood is changed from a dark to a light red’’. He then described how a similar process takes place in fish, since water contains air and oxygen ‘‘in its pores’’ which is taken up in the blood through the gills. By this process, the blood ‘‘. changes its colour at the same time from a dark to a light red in the vessels of their gills, which constitute a pulmonary organ adapted to the medium in which they live’’. Finally, he noted that exactly the same happens in the placenta, since this organ ‘‘consists of arteries carrying the blood to its extremities, and a vein bringing it back, resembling exactly in structure the lungs and gills above mentioned; and that the blood changes its colour from a dark to a light red in passing through these vessels’’. To extend the analogy he added that, just as ‘‘air-breathing creatures’’ and fish can only survive for a few minutes without air or water, the fetus, after separation of its placenta from the uterus, cannot survive unless its lungs are expanded for starting the breathing of air. Darwin must have known from Hunter’s work that maternal and fetal circulations are not connected into one continuous circulatory system, which necessarily leads to the question as to how both circulations are interrelated. In this context Darwin made the astute remark that after separation of the placenta, uterine blood vessels start bleeding, while the placental vessels do not, indicating that the ‘‘terminations’’ of the placental vessels must be inserted in some way into the uterine vasculature while remaining closed off from the mother’s circulation. He then referred to ‘‘the curious structure of the cavities or lacunae of the placentae, demonstrated by Mr J. Hunter’’, which are present on the placental side in contact with the uterus. ‘‘Those cavities or ‘‘cells’’ [sic] are filled with blood from the maternal arteries, which open into them; which blood is again taken up by the maternal veins, and is thus perpetually changed’’. These lacunae or ‘‘cells’’ obviously refer to parts of the intervillous space which may be partially compartmentalized by interlobular septa. He also noted that these lacunae can only be appreciated on cross sections of placentae still attached to the uterus, but would not be visible on the maternal surface (the basal plate) of a delivered placenta. Darwin obviously considered Hunter’s cavities or ‘‘cells’’ to be of vital importance, since ‘‘thus, as the growing fetus requires greater oxygenation, an apparatus is produced resembling exactly the air-cells (alveoli) of the lungs’’. Such daring and sometimes provocative comparisons and generalizations are not uncommon in the ‘‘Zoonomia’’. It is also interesting that Darwin commented upon the cotyledonary placentas of cows, where he noticed that separation of the numerous ‘‘placentas’’ (cotyledons) at birth did not result in bleeding at the uterine side. Of course at that time they had no idea about haemochorial and epitheliochorial types of placentation. Darwin thought that the multiple ‘‘placentas’’ of cows and other ruminants allowed a bigger surface for oxygenation, which was important for such animals ‘‘. as the
R. Pijnenborg, L. Vercruysse / Placenta 28 (2007) 775e778
progeny of this class of animals are more completely formed before their nativity’’. The fact that in these species placental separation does not result in bleeding of uterine arteries is, according to Darwin, due to ‘‘the greater power of contractions of their uterine lacunae or alveoli’’, and he adds that ‘‘for the same cause they are not liable to a sanguiferous menstruation’’. These rather inapt remarks indicate that Darwin correctly assumed that menstruation has something to do with expulsion of endometrial tissue, but did not understand the differences in tissue architecture between the human (haemochorial) and cow (epitheliochorial) placenta, the latter lacking a decidualized endometrium which is therefore not expelled at parturition. Nevertheless he clearly felt that, because of their ‘‘greater power of contractions’’, the uterine arteries of cows, or at least their outlets in the ‘‘lacunae’’, must be different from those in the human. Is this a foreshadowing of the later concept that uterine vessels in the human are ‘‘physiologically changed’’ during pregnancy [10]? With these considerations on the respiratory function of the placenta Darwin thought to have provided an acceptable answer to an old question posed by William Harvey (1578e 1657) in ‘‘De generatione animalium’’ (1651), quoted in ‘‘Zoonomia’’: ‘‘Why is not the fetus in the womb suffocated for want of air, when it remains there even to the tenth month without respiration: yet if it be born in the seventh or eighth month, and has once respired, it becomes immediately suffocated for want of air, if its respiration be obstructed?’’ 3. Confusion about fetal nutrition It is clear from the above mentioned that for Erasmus Darwin the placenta was mainly a respiratory organ. But what about fetal nutrition? At that time the mechanisms of digestion and nutrient uptake were poorly understood, because investigators had to rely on direct visualization, just as Darwin perceived oxygen uptake by the changing colour of the blood. The only intestinal absorption process that could be directly observed was the uptake of fats into the intestinal lymphatics, referred to as lacteal vessels because they acquire a milky colour during the process. The transfer of glucose and amino acids into mesenteric vessels was of course unknown. By injecting milk directly into ligated intestinal segments John Hunter had observed uptake by lacteals but not by mesenteric blood vessels, and he thought therefore that the latter did not play any role in nutrient uptake [11]. Following a similar line of thought, anatomists were eager to detect the presence of seemingly nutritive fluids or coagulates in the contact zone between placenta and uterus, which they thought were absorbed by the placenta in a similar way as observed in the gut. While dissecting pregnant uteri, the then undisputed authority in anatomy Alexander Monro (1697e1767) reported the presence of ‘‘a thick, fungous, succulent, cellular substance’’ between the muscular coat of the uterus and the placenta, which he thought would be absorbed by ‘‘lacteal vessels’’ of the placenta (Monro, 1734; quoted by Boyd & Hamilton) [12]. His ‘‘thick, . cellular (i.e. frothy) substance’’ probably represented decidual tissue. Monro thought that this
777
material would be taken up by placental open-tipped ‘‘lacteals’’ which crossed the placentaleuterine border and imbibed it e using Corner’s words e ‘‘as a straw does in a bottle of soda’’ [13]. These ‘‘lacteals’’ were entirely hypothetical, since they were assumed to be too small to be observed. Unfortunately for Monro, John Hunter’s observations in coloured wax-injected placental specimens completely refuted the presence of such fetal vessels ending up in the uterine wall [11]. Ascribing a mainly respiratory function to the placenta may have facilitated the acceptance of the concept of separate maternal and fetal circulations. A total ignorance of processes of transmembrane transport must indeed have provided a major obstacle at that time for accepting nutrient transfer taking place between two separate vascular systems. For this reason also Erasmus Darwin may have gladly minimalized the idea of a nutritive function of the placenta. Since an alternative supply-line of fetal nourishment had to be identified, he adopted the earlier opinions of William Harvey of the amniotic fluid being the main source of fetal nutrition [14]. An important argument was the supposed analogy between amniotic fluid and the white of a chicken’s egg, but Darwin offered several more. He reasoned that amniotic fluid cannot be ‘‘excrementitious’’, ‘‘because it is found in greater quantity, when the fetus is young, decreasing after a certain period till birth’’. Similarly, when a young chick hatches from its egg, ‘‘scarceley any [albumen] remains’’, indicating that it presumably has been taken up and digested. It was thought that amniotic fluid must have nutritious quality, because it is ‘‘coagulable by heat, by nitrous acid, and by spirit of wine. like milk’’. Darwin did not mention whether he ever tasted this coagulated amniotic fluid, but he quoted Baron Haller, who reported ‘‘a saltish taste. not unlike the whey of milk, which it even resembles in smell’’. Besides, similar fluids are found within the stomach of the fetus at the time of birth. An extra argument was that the presence of meconium in the bowels of newborn infants clearly indicated that something must have been digested. Therefore, Erasmus Darwin concluded that ‘‘the fetus in the womb is nourished by the fluid which surrounds it’’ via his own gastrointestinal system. In the subsequent section ‘‘Of generation’’ in the ‘‘Zoonomia’’, he speculated that this liquor amnii is probably produced ‘‘by the irritation of the fetus as an extraneous body’’. He also thought to see analogies with the fluid surrounding gadfly maggots in a cow’s skin, and even in ‘‘vegetable secretion and concretion. thus produced on oak leaves by the gall-insect’’. These analogies offer again striking examples of Darwin’s generalizing attitude towards a wide variety of biological processes in nature. From these considerations on fetal nourishment by amniotic fluid, Darwin concluded that the placenta must have been ‘‘produced for some other important purpose. giving due oxygenation to the blood of the fetus; which is more necessary, or at least more frequently necessary, than even the supply of food’’. Needless to say, these ideas on fetal nutrition were largely overtaken by later findings.
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4. A poetical epilogue Erasmus Darwin’s last work, a long poem entitled ‘‘The temple of nature’’, was published posthumously in 1803 [3]. It is an extensive poetical account of evolutionary history, in which the placenta appears on the scene again. An important step in the history of life on earth was the all-important invasion of the dry land out of the sea: as a metaphorical evocation of this event, Erasmus describes the birth of a child from the watery environment of the uterus, subsequently taking his first breath: ‘‘Thus in the womb the nascent infant laves Its natant form in the circumfluent waves; With perforated heart unbreathing swims, Awakes and stretches all its recent limbs; With gills placental seeks the arterial flood, And drinks pure ether from its Mother’s blood. Erewhile the landed stranger bursts its way, From the warm wave emerging into day; Feels the chill blast, and piercing hight, and tries His tender lungs, and rolls his dazzled eyes; Gives to the passing gals his curling hair, And steps a dry inhabitant of air’’ (Canto I)
Interwoven in these lines may well be the first and possibly only poetical evocation of placental function, at least as far as its respiratory role is concerned. The ‘‘ether’’ drunk by the fetus refers of course to oxygen, in these days also referred to as ‘‘pure air’’ [3]. Did Erasmus’ grandson Charles Darwin deal with the placenta in any of his works, possibly following up his grandfather’s writings? To our disappointment, a search through his books brought up virtually nothing. In ‘‘On the origin of species’’ he surely refers to Placental Mammals, but only in the last (sixth) edition was the term explained in a glossary (compiled by a Mr. W.S. Dallas), stating that, ‘‘when the embryo has attained a certain stage, a vascular connection [sic], called the placenta, is formed between the embryo and the mother’’ [15]. Although he put forward a few considerations on human embryonic development in his ‘‘Descent of man’’ (1871) [16], the placenta is never mentioned in this or any other of his works. Although at the end of his life Charles Darwin reported in a biographical note to have been greatly impressed by his grandfather’s ‘‘great originality of thought, his prophetic spirit both in science and in the mechanical arts, and to his overpowering tendency to theorise and generalise’’ [17], his reading of the Zoonomia had obviously not inspired him to elaborate discussions on this fascinating organ, the placenta. On the other hand, the relationship between placental structure and mammalian classification had been of major interest to his lifelong defender and champion, Thomas Huxley [18], and there is no doubt that Charles Darwin was well acquainted with this work. In conclusion, we may state that, following the pioneering work of Lavoisier and Priestley, new insights in the nature of oxygen became integrated in the understanding of the functioning of respiratory organs, including the placenta. While the evidence for a respiratory function was quite convincing,
the role of the placenta in the transfer of nutrients from mother to fetus was underestimated in Erasmus Darwin’s time, which was partly due to a limited knowledge of nutrient uptake in the body. Lastly, Erasmus Darwin’s considerations of different vascular interrelationships in human and cow placentae may reflect an awareness of functional differences that must exist between the supplying uterine arteries in both species, foreshadowing later insights into differences in placental types and maternal vascular adaptations. While reading the ‘‘Zoonomia’’, Erasmus Darwin repeatedly baffles us with daring generalizations of diverse natural phenomena. He clearly had a remarkable intuitive grasp on the workings of nature, which he tried to put into a proper scientific framework. Nevertheless, he never made the same impact on biology as Charles Darwin did, but he certainly deserves to step out of the shadow of his illustrious grandson where he remained hidden for such a long time. References [1] King-Hele D. Erasmus Darwin: a life of unequalled achievement. London: Giles de la Mare; 1999. [2] Uglow J. The lunar men: the friends who made the future. London: Farber & Farber; 2002. [3] Darwin E. The essential writings of Erasmus Darwin. In: King-Hele D, editor. London: MacGibbon & Kee; 1968. [4] Browne J. Botany for gentlemen: Erasmus Darwin and the loves of the plants. Isis 1989;80:593e621. [5] Darwin E. Chapter 38: Of the oxygenation of the blood in the lungs, and in the placenta. Chapter 39: Of generation. In: Zoonomia; or the laws of organic life. 3rd ed. London: J. Johnson; 1801. [6] Hunter W. Anatomia uterina humani gravidi tabulis illustrata. [The anatomy of the human gravid uterus exhibited in figures]. Birmingham, Alabama: Gryphon Editions; 1980 [Facsimile edition of the original edition (Birmingham: John Baskerville 1774)]. [7] Dunn PM. Dr William Hunter (1718e83) and the gravid uterus. Archives of Disease in Childhood. Fetal and Neonatal Edition 1999;80:F76e7. [8] Moore W. The knife man: the extraordinary life and times of John Hunter, father of modern surgery. London: Bantam Press; 2005. [9] Hunter J. On the structure of the placenta [Reprint of the original 1786 edition, with notes by Richard Owen]. In: Observations on certain parts of the animal oeconomy. Philadelphia: Haswell, Barrington & Haswell; 1840. p. 93e103. [10] Brosens I, Robertson WB, Dixon HG. The physiological response of the vessels of the placental bed to normal pregnancy. Journal of Pathology and Bacteriology 1967;93:569e79. [11] Hunter J. Of absorption by veins [Reprint of the original 1786 edition, with notes by Richard Owen]. In: Observations on certain parts of the animal oeconomy. Philadelphia: Haswell, Barrington & Haswell; 1840. p. 304e11. [12] Boyd JD, Hamilton WJ. Historical survey. In: The human placenta. Cambridge: W. Heffer & Sons; 1970. p. 1e19. [13] Corner GW. Exploring the placental maze: the development of our knowledge of the relation between the bloodstreams of mother and infant in utero. American Journal of Obstetrics and Gynecology 1963;86:408e18. [14] Meyer AW. An analysis of the ‘‘De generatione animalium’’ of William Harvey. Stanford University Press; 1936. p. 103e32. [15] Darwin C. The origin of species by means of natural selection [1872, with additions and corrections]. 6th ed. London: John Murray; 1882. [16] Darwin C. The descent of man. London: John Murray; 1871. [17] Darwin C. The life of Erasmus Darwin. Cambridge University Press; 2003. [18] Pijnenborg R, Vercruysse L. Thomas Huxley and the rat placenta in the early debates on evolution. Placenta 2004;25:233e7.
Classics revisited
Erasmus Darwin’s Enlightened Views on Placental Function R. Pijnenborg*, L. Vercruysse Department of Gynaecology and Obstetrics, Katholieke Universiteit Leuven, Universitair Ziekenhuis Gasthuisberg, B3000 Leuven, Belgium Accepted 4 March 2007
Abstract In his major work ‘‘Zoonomia’’, Erasmus Darwin (1731e1802) devoted one chapter to the placenta, in which the new knowledge of the recently discovered element oxygen was applied to the functioning of this organ. He considered the ‘‘cavities’’ or ‘‘lacunae’’ in the placenta as the main areas for oxygenation of the fetal blood, as he thought them to be structurally comparable to the lungs and the gills of fish. He obviously was aware of species differences in the uterine arterial blood supply to the placenta between humans and cows, assuming a higher contractility of the vasculature in the latter species. The new evidence for a primarily respiratory role overshadowed ideas of a possible nutritive function of the placenta. Since Hunter’s definitive demonstration of separate maternal and fetal blood circulations, nutritive functions of the placenta needed to be explained by transmembrane transport processes, which were unknown at that time. Instead Erasmus Darwin erroneously considered the amniotic fluid as the main source of nutrients for the fetus. His understanding of placental respiration found expression in his long poem on the history of life on earth. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Placental vascularization; Placental structure; Erasmus Darwin; John Hunter; Respiration; Fetal nutrition; History
1. Introduction Erasmus Darwin (1731e1802), grandfather of Charles Darwin, was in his lifetime at least as famous as his grandson would become [1]. He built up a successful and busy medical practice, but also engaged himself in a broad range of scientific and technical investigations. He had a special knack for designing mechanical devices to solve diverse technical problems, and he delighted in discussing these with his friends of the Lunar Society [2]. His wide scientific interests together with his involvement in what later would be known as ‘‘the industrial revolution’’ show him to be a true representative of the British ‘‘Enlightenment’’. His interest in reproduction was awakened by studying Linnaeus’ new classification system for plants, which was based upon the structure and arrangement of the reproductive
* Corresponding author. Tel.: þ32 16 346190; fax: þ32 16 344205. E-mail address: [email protected] (R. Pijnenborg). 0143-4004/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.placenta.2007.03.003
organs (pistils, stamens, etc.) within the flower. He translated Linnaeus’ ‘‘Systema vegetabilium’’ into English, thereby facing criticisms because of the numerous explicit hints to sexual organs and their use. That did not prevent him to subsequently compose the long poem ‘‘The loves of the plants’’ (1789), in which the sexual organs of each group were ‘‘anthropomorphized’’ into sometimes eroticizing stories peppered with promiscuous misbehaviour [3]. It should be noted that the reproduction of plants was little understood at that time, and it was probably Erasmus Darwin’s main purpose to educate his readers on this topic while drawing their attention to similarities in human reproduction [4]. ‘‘Zoonomia; or the laws of organic life’’ (1794e1796) is usually considered to be his magnum opus, presenting a comprehensive view on the workings of the body. In this work he tried to base all bodily functions on the four properties ‘‘irritation, sensation, volition and association’’, and subsequently applied the same characteristics to a classification of all human diseases [5]. In later years, ‘‘Zoonomia’’ became mainly famous for his speculations on the descent of all living creatures
776
R. Pijnenborg, L. Vercruysse / Placenta 28 (2007) 775e778
from ‘‘one living filament’’, thus anticipating the evolutionary ideas of Lamarck and his grandson Charles Darwin. However, although Erasmus postulated the inheritance of acquired characters and hinted at a ‘‘struggle for life’’, he never hit upon his grandson’s concept of natural selection as a driving force in evolution. Apart from his considerations on evolution, this work also contains interesting sections on reproduction, including a chapter on ‘‘the oxygenation of the blood in the lungs, and in the placenta’’. This chapter highlights the respiratory function of the placenta, but also discusses its possible nutritive role e a controversial concept at that time. Darwin definitely was not a placentologist sensu strictu, but he managed very well to accomodate his understanding of the respiratory role of the recently discovered oxygen to the maternalefetal exchanges taking place in the placenta. He obviously drew a lot of his information from other investigators, and mentioned especially James Jeffray’s ‘‘Tentamen medicum’’ at the University of Edinburgh (1786) as well as the work of Forester French in Cambridge, thereby fleetingly expressing his hope ‘‘that Dr French will some time give his theses on this subject to the public’’. It is not always clear in Darwin’s text which of the reported observations were his own, but there can be no doubt that he had strong personal opinions in the matter. With regard to his interest in the placenta it may be revealing that in 1753, as a medical student, Erasmus spent one term in London to attend William Hunter’s (1718e1783) anatomical lectures. Although Hunter’s famous ‘‘Anatomy of the human gravid uterus’’ with its brilliant illustrations of dissected pregnant uteri was not yet published at that time [6], William’s brother John (1728e1793) had already obtained and dissected a first gravid uterus in 1751. It is thus highly probable that questions concerning the problem of fetale maternal vascular relationship were already included in William Hunter’s lectures at the time of Erasmus Darwin’s sojourn in London [7,8]. Using coloured wax injections, John Hunter was able to prove that fetal and maternal circulations in the placenta are separate, thus refuting previously held ideas of one continuous maternal to fetal circulation. The complete story was told by John several years later (1786), emphasizing his own priority in the discovery. He also pointed out that his first observations on an injected specimen were made in 1754, that is one year after Erasmus Darwin’s visit to London [9]. There can be no doubt, however, that in later years Erasmus became familiar with William [6] and John Hunter’s [9] books, which were published, respectively, 20 and 10 years before ‘‘Zoonomia’’. 2. ‘‘Zoonomia’’ and the respiratory function of the placenta The oxygen question and the nature of respiration were hot topics in Erasmus Darwin’s time. Until the discoveries by Lavoisier and Priestly, combustion had been considered as a process by which a (hypothetical) substance ‘‘phlogiston’’ is set free. The discovery of oxygen had brought a radical conceptual change, leading also to an understanding of its vital
role in respiratory processes, including its uptake and transport by the blood. As Erasmus Darwin stated ‘‘. it appears that the basis of atmospheric air, called oxygene, is received by the blood through the membranes of the lungs; and that by this addition the colour of the blood is changed from a dark to a light red’’. He then described how a similar process takes place in fish, since water contains air and oxygen ‘‘in its pores’’ which is taken up in the blood through the gills. By this process, the blood ‘‘. changes its colour at the same time from a dark to a light red in the vessels of their gills, which constitute a pulmonary organ adapted to the medium in which they live’’. Finally, he noted that exactly the same happens in the placenta, since this organ ‘‘consists of arteries carrying the blood to its extremities, and a vein bringing it back, resembling exactly in structure the lungs and gills above mentioned; and that the blood changes its colour from a dark to a light red in passing through these vessels’’. To extend the analogy he added that, just as ‘‘air-breathing creatures’’ and fish can only survive for a few minutes without air or water, the fetus, after separation of its placenta from the uterus, cannot survive unless its lungs are expanded for starting the breathing of air. Darwin must have known from Hunter’s work that maternal and fetal circulations are not connected into one continuous circulatory system, which necessarily leads to the question as to how both circulations are interrelated. In this context Darwin made the astute remark that after separation of the placenta, uterine blood vessels start bleeding, while the placental vessels do not, indicating that the ‘‘terminations’’ of the placental vessels must be inserted in some way into the uterine vasculature while remaining closed off from the mother’s circulation. He then referred to ‘‘the curious structure of the cavities or lacunae of the placentae, demonstrated by Mr J. Hunter’’, which are present on the placental side in contact with the uterus. ‘‘Those cavities or ‘‘cells’’ [sic] are filled with blood from the maternal arteries, which open into them; which blood is again taken up by the maternal veins, and is thus perpetually changed’’. These lacunae or ‘‘cells’’ obviously refer to parts of the intervillous space which may be partially compartmentalized by interlobular septa. He also noted that these lacunae can only be appreciated on cross sections of placentae still attached to the uterus, but would not be visible on the maternal surface (the basal plate) of a delivered placenta. Darwin obviously considered Hunter’s cavities or ‘‘cells’’ to be of vital importance, since ‘‘thus, as the growing fetus requires greater oxygenation, an apparatus is produced resembling exactly the air-cells (alveoli) of the lungs’’. Such daring and sometimes provocative comparisons and generalizations are not uncommon in the ‘‘Zoonomia’’. It is also interesting that Darwin commented upon the cotyledonary placentas of cows, where he noticed that separation of the numerous ‘‘placentas’’ (cotyledons) at birth did not result in bleeding at the uterine side. Of course at that time they had no idea about haemochorial and epitheliochorial types of placentation. Darwin thought that the multiple ‘‘placentas’’ of cows and other ruminants allowed a bigger surface for oxygenation, which was important for such animals ‘‘. as the
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progeny of this class of animals are more completely formed before their nativity’’. The fact that in these species placental separation does not result in bleeding of uterine arteries is, according to Darwin, due to ‘‘the greater power of contractions of their uterine lacunae or alveoli’’, and he adds that ‘‘for the same cause they are not liable to a sanguiferous menstruation’’. These rather inapt remarks indicate that Darwin correctly assumed that menstruation has something to do with expulsion of endometrial tissue, but did not understand the differences in tissue architecture between the human (haemochorial) and cow (epitheliochorial) placenta, the latter lacking a decidualized endometrium which is therefore not expelled at parturition. Nevertheless he clearly felt that, because of their ‘‘greater power of contractions’’, the uterine arteries of cows, or at least their outlets in the ‘‘lacunae’’, must be different from those in the human. Is this a foreshadowing of the later concept that uterine vessels in the human are ‘‘physiologically changed’’ during pregnancy [10]? With these considerations on the respiratory function of the placenta Darwin thought to have provided an acceptable answer to an old question posed by William Harvey (1578e 1657) in ‘‘De generatione animalium’’ (1651), quoted in ‘‘Zoonomia’’: ‘‘Why is not the fetus in the womb suffocated for want of air, when it remains there even to the tenth month without respiration: yet if it be born in the seventh or eighth month, and has once respired, it becomes immediately suffocated for want of air, if its respiration be obstructed?’’ 3. Confusion about fetal nutrition It is clear from the above mentioned that for Erasmus Darwin the placenta was mainly a respiratory organ. But what about fetal nutrition? At that time the mechanisms of digestion and nutrient uptake were poorly understood, because investigators had to rely on direct visualization, just as Darwin perceived oxygen uptake by the changing colour of the blood. The only intestinal absorption process that could be directly observed was the uptake of fats into the intestinal lymphatics, referred to as lacteal vessels because they acquire a milky colour during the process. The transfer of glucose and amino acids into mesenteric vessels was of course unknown. By injecting milk directly into ligated intestinal segments John Hunter had observed uptake by lacteals but not by mesenteric blood vessels, and he thought therefore that the latter did not play any role in nutrient uptake [11]. Following a similar line of thought, anatomists were eager to detect the presence of seemingly nutritive fluids or coagulates in the contact zone between placenta and uterus, which they thought were absorbed by the placenta in a similar way as observed in the gut. While dissecting pregnant uteri, the then undisputed authority in anatomy Alexander Monro (1697e1767) reported the presence of ‘‘a thick, fungous, succulent, cellular substance’’ between the muscular coat of the uterus and the placenta, which he thought would be absorbed by ‘‘lacteal vessels’’ of the placenta (Monro, 1734; quoted by Boyd & Hamilton) [12]. His ‘‘thick, . cellular (i.e. frothy) substance’’ probably represented decidual tissue. Monro thought that this
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material would be taken up by placental open-tipped ‘‘lacteals’’ which crossed the placentaleuterine border and imbibed it e using Corner’s words e ‘‘as a straw does in a bottle of soda’’ [13]. These ‘‘lacteals’’ were entirely hypothetical, since they were assumed to be too small to be observed. Unfortunately for Monro, John Hunter’s observations in coloured wax-injected placental specimens completely refuted the presence of such fetal vessels ending up in the uterine wall [11]. Ascribing a mainly respiratory function to the placenta may have facilitated the acceptance of the concept of separate maternal and fetal circulations. A total ignorance of processes of transmembrane transport must indeed have provided a major obstacle at that time for accepting nutrient transfer taking place between two separate vascular systems. For this reason also Erasmus Darwin may have gladly minimalized the idea of a nutritive function of the placenta. Since an alternative supply-line of fetal nourishment had to be identified, he adopted the earlier opinions of William Harvey of the amniotic fluid being the main source of fetal nutrition [14]. An important argument was the supposed analogy between amniotic fluid and the white of a chicken’s egg, but Darwin offered several more. He reasoned that amniotic fluid cannot be ‘‘excrementitious’’, ‘‘because it is found in greater quantity, when the fetus is young, decreasing after a certain period till birth’’. Similarly, when a young chick hatches from its egg, ‘‘scarceley any [albumen] remains’’, indicating that it presumably has been taken up and digested. It was thought that amniotic fluid must have nutritious quality, because it is ‘‘coagulable by heat, by nitrous acid, and by spirit of wine. like milk’’. Darwin did not mention whether he ever tasted this coagulated amniotic fluid, but he quoted Baron Haller, who reported ‘‘a saltish taste. not unlike the whey of milk, which it even resembles in smell’’. Besides, similar fluids are found within the stomach of the fetus at the time of birth. An extra argument was that the presence of meconium in the bowels of newborn infants clearly indicated that something must have been digested. Therefore, Erasmus Darwin concluded that ‘‘the fetus in the womb is nourished by the fluid which surrounds it’’ via his own gastrointestinal system. In the subsequent section ‘‘Of generation’’ in the ‘‘Zoonomia’’, he speculated that this liquor amnii is probably produced ‘‘by the irritation of the fetus as an extraneous body’’. He also thought to see analogies with the fluid surrounding gadfly maggots in a cow’s skin, and even in ‘‘vegetable secretion and concretion. thus produced on oak leaves by the gall-insect’’. These analogies offer again striking examples of Darwin’s generalizing attitude towards a wide variety of biological processes in nature. From these considerations on fetal nourishment by amniotic fluid, Darwin concluded that the placenta must have been ‘‘produced for some other important purpose. giving due oxygenation to the blood of the fetus; which is more necessary, or at least more frequently necessary, than even the supply of food’’. Needless to say, these ideas on fetal nutrition were largely overtaken by later findings.
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4. A poetical epilogue Erasmus Darwin’s last work, a long poem entitled ‘‘The temple of nature’’, was published posthumously in 1803 [3]. It is an extensive poetical account of evolutionary history, in which the placenta appears on the scene again. An important step in the history of life on earth was the all-important invasion of the dry land out of the sea: as a metaphorical evocation of this event, Erasmus describes the birth of a child from the watery environment of the uterus, subsequently taking his first breath: ‘‘Thus in the womb the nascent infant laves Its natant form in the circumfluent waves; With perforated heart unbreathing swims, Awakes and stretches all its recent limbs; With gills placental seeks the arterial flood, And drinks pure ether from its Mother’s blood. Erewhile the landed stranger bursts its way, From the warm wave emerging into day; Feels the chill blast, and piercing hight, and tries His tender lungs, and rolls his dazzled eyes; Gives to the passing gals his curling hair, And steps a dry inhabitant of air’’ (Canto I)
Interwoven in these lines may well be the first and possibly only poetical evocation of placental function, at least as far as its respiratory role is concerned. The ‘‘ether’’ drunk by the fetus refers of course to oxygen, in these days also referred to as ‘‘pure air’’ [3]. Did Erasmus’ grandson Charles Darwin deal with the placenta in any of his works, possibly following up his grandfather’s writings? To our disappointment, a search through his books brought up virtually nothing. In ‘‘On the origin of species’’ he surely refers to Placental Mammals, but only in the last (sixth) edition was the term explained in a glossary (compiled by a Mr. W.S. Dallas), stating that, ‘‘when the embryo has attained a certain stage, a vascular connection [sic], called the placenta, is formed between the embryo and the mother’’ [15]. Although he put forward a few considerations on human embryonic development in his ‘‘Descent of man’’ (1871) [16], the placenta is never mentioned in this or any other of his works. Although at the end of his life Charles Darwin reported in a biographical note to have been greatly impressed by his grandfather’s ‘‘great originality of thought, his prophetic spirit both in science and in the mechanical arts, and to his overpowering tendency to theorise and generalise’’ [17], his reading of the Zoonomia had obviously not inspired him to elaborate discussions on this fascinating organ, the placenta. On the other hand, the relationship between placental structure and mammalian classification had been of major interest to his lifelong defender and champion, Thomas Huxley [18], and there is no doubt that Charles Darwin was well acquainted with this work. In conclusion, we may state that, following the pioneering work of Lavoisier and Priestley, new insights in the nature of oxygen became integrated in the understanding of the functioning of respiratory organs, including the placenta. While the evidence for a respiratory function was quite convincing,
the role of the placenta in the transfer of nutrients from mother to fetus was underestimated in Erasmus Darwin’s time, which was partly due to a limited knowledge of nutrient uptake in the body. Lastly, Erasmus Darwin’s considerations of different vascular interrelationships in human and cow placentae may reflect an awareness of functional differences that must exist between the supplying uterine arteries in both species, foreshadowing later insights into differences in placental types and maternal vascular adaptations. While reading the ‘‘Zoonomia’’, Erasmus Darwin repeatedly baffles us with daring generalizations of diverse natural phenomena. He clearly had a remarkable intuitive grasp on the workings of nature, which he tried to put into a proper scientific framework. Nevertheless, he never made the same impact on biology as Charles Darwin did, but he certainly deserves to step out of the shadow of his illustrious grandson where he remained hidden for such a long time. References [1] King-Hele D. Erasmus Darwin: a life of unequalled achievement. London: Giles de la Mare; 1999. [2] Uglow J. The lunar men: the friends who made the future. London: Farber & Farber; 2002. [3] Darwin E. The essential writings of Erasmus Darwin. In: King-Hele D, editor. London: MacGibbon & Kee; 1968. [4] Browne J. Botany for gentlemen: Erasmus Darwin and the loves of the plants. Isis 1989;80:593e621. [5] Darwin E. Chapter 38: Of the oxygenation of the blood in the lungs, and in the placenta. Chapter 39: Of generation. In: Zoonomia; or the laws of organic life. 3rd ed. London: J. Johnson; 1801. [6] Hunter W. Anatomia uterina humani gravidi tabulis illustrata. [The anatomy of the human gravid uterus exhibited in figures]. Birmingham, Alabama: Gryphon Editions; 1980 [Facsimile edition of the original edition (Birmingham: John Baskerville 1774)]. [7] Dunn PM. Dr William Hunter (1718e83) and the gravid uterus. Archives of Disease in Childhood. Fetal and Neonatal Edition 1999;80:F76e7. [8] Moore W. The knife man: the extraordinary life and times of John Hunter, father of modern surgery. London: Bantam Press; 2005. [9] Hunter J. On the structure of the placenta [Reprint of the original 1786 edition, with notes by Richard Owen]. In: Observations on certain parts of the animal oeconomy. Philadelphia: Haswell, Barrington & Haswell; 1840. p. 93e103. [10] Brosens I, Robertson WB, Dixon HG. The physiological response of the vessels of the placental bed to normal pregnancy. Journal of Pathology and Bacteriology 1967;93:569e79. [11] Hunter J. Of absorption by veins [Reprint of the original 1786 edition, with notes by Richard Owen]. In: Observations on certain parts of the animal oeconomy. Philadelphia: Haswell, Barrington & Haswell; 1840. p. 304e11. [12] Boyd JD, Hamilton WJ. Historical survey. In: The human placenta. Cambridge: W. Heffer & Sons; 1970. p. 1e19. [13] Corner GW. Exploring the placental maze: the development of our knowledge of the relation between the bloodstreams of mother and infant in utero. American Journal of Obstetrics and Gynecology 1963;86:408e18. [14] Meyer AW. An analysis of the ‘‘De generatione animalium’’ of William Harvey. Stanford University Press; 1936. p. 103e32. [15] Darwin C. The origin of species by means of natural selection [1872, with additions and corrections]. 6th ed. London: John Murray; 1882. [16] Darwin C. The descent of man. London: John Murray; 1871. [17] Darwin C. The life of Erasmus Darwin. Cambridge University Press; 2003. [18] Pijnenborg R, Vercruysse L. Thomas Huxley and the rat placenta in the early debates on evolution. Placenta 2004;25:233e7.