Duty or dream? Edwin G. Conklin's critique of eugenics and support for American individualism

This paper assesses ideas about moral andreproductive duty in American eugenics duringthe early twentieth century. While extremeeugenicists, including Charles Davenport andPaul Popenoe, argued that social leaders andbiologists must work to prevent individuals whowere ``unfit' from reproducing, moderates,especially Edwin G. Conklin, presented adifferent view. Although he was sympathetic toeugenic goals and participated in eugenicorganizations throughout his life, Conklinrealized that eugenic ideas rarely could meetstrict scientific standards of proof. Withthis in mind, he did not restrict his eugenicvision to hereditary measures. Relying onhis experience as an embryologist, Conklininstead attempted to balance more extremeeugenic claims – that emphasized the absolutelimits posed by heredity – with his own view of``the possibilities of development.' Throughhis critique he argued that most human beingsnever even begin to approach their hereditarypotential; he moderated his own eugenicrhetoric so that it preserved individualopportunity and responsibility, or what hasoften been labeled the American Dream.     

Ernst Mayr—Intellectual leader of ornithology

Ernst Mayr (1904–), naturalist and ornithologist since his early youth, is one of the architects of the synthetic theory of evolution of the 1940s. His main contribution was the analysis of the origin of species, i.e. the causes of biodiversity. The historical roots of these ideas reach far back to the early 1920s, when the 19-year-old student suggested to his mentor, Dr. Erwin Stresemann (Berlin), the development for birds of a theory of geographical variation and of the species. During the 1930s, Mayr himself assembled data for a comprehensive analysis of geographical variation and speciation in birds, when he studied the rich collections of the Whitney South Sea Expedition from the islands in the Pacific Ocean. He described from this and other regions 27 new species and 445 new subspecies of birds, more than any other living ornithologist. He established the basic principles of island biogeography, discussed critically the former existence of landbridges and emphasized that, in zoogeographical studies, instead of fixed regions, it is necessary to think of fluid faunas. His theoretical framework included active jump dispersal of birds and other animals as well as various types of vicariance processes which had an effect on faunal differentiation. Although Mayr was not the originator of the biological species concept, he demonstrated its validity more convincingly than anyone else before and proposed a superior and concise definition of the biospecies which everybody adopted. He also initiated with various studies a period of renewed interest in the macrosystematics of birds.Communicated by F. BairleinDedicated to Professor Ernst Mayr in admiration and friendship on the occasion of his 100th birthday on 5 July 2004     

The historical context of natural selection: The case of Patrick Matthew

Conclusions It should be evident from the foregoing discussion that one man's natural selection is not necessarily the same as another man's. Why should this be so? How can two theories, which both Matthew and Darwin believed to be nearly identical, be so dissimilar? Apparently, neither Matthew nor Darwin understood the other's theory. Each man's viewpoint was colored by his own intellectual background and philosophical assumptions, and each read these into the other's ideas. The words sounded the same, so they assumed the concepts must als be the same.¹²³ As Ghiselin has pointed out, historians attempting to evaluate Darwin's predecessors have been similarly blinded by a preoccupation with words, without regard to their proper context.¹²⁴ In the case of Matthew, the practice of quoting only brief passages from the appendix to Naval Timber and Arboriculture, without relating them to the rest of his work, has suggested a greater resemblance to Darwin's theory than actually exists.It is clear, both from the use which Matthew made of his ideas and from the philosophical roots of his natural world view, that he could not have arrived at the concept of natural selection by the same thought process which Darwin employed. His discussion of natural selection is presented not as an argument, but as an axiom. No theory is proposed, no evidence marshaled to support it. Natural selection is stated as a fact, a Law of Nature, unquestioned, and presumably, unquestionable.Despite his clamor for recognition as the discoverer of natural selection, Matthew recognized and acknowledged this very fundamental difference between Darwin and himself. In a letter to the Gardener's Chronicle of May 12, 1860, he wrote:To me the conception of this law of Nature came intuitively as a self-evident fact, almost without an effort of concentrated thought. Mr. Darwin here seems to have more merit in the discovery than I have had—to me it did not appear a discovery. He seems to have worked it out by inductive reason, slowly and with due caution to have made his way synthetically from fact to fact onwards; while with me it was by a general glance at the scheme of Nature that I estimated this select production of species as an a priori recognisable fact—an axiom, requiring only to be pointed out to be admitted by unprejudiced minds of sufficient grasp.¹²⁵ In the same letter, Matthew maintained that his ideas had not been accepted because the age was not ripe for such ideas.¹²⁶ Nor, he said, was the present age. He considered the inability of most of Darwin's critics to grasp his theory to be incurable. Yet he did not argue that natural selection should be accepted because of the evidence, but rather, that it should be accepted on faith:Belief here requires a certain grasp of mind. No direct proof of phenomena embracing so long a period of time is within the compass of short-lived man. To attempt to satisfy a school of ultra skeptics, who have a wonderfully limited power of perception of means to ends... would be labour in vain.... They could not be brought to conceive the purpose of a handsaw though they saw its action, if the whole individual building it assisted to construct were not presented complete before their eyes... Like a child looking upon the motion of a wheel in an engine they would only perceive and admire... without noticing its agency in... affecting the purposed end.¹²⁷ Here, then, is the final irony. In a passage urging acceptance of Darwin's theory, a theory which was to banish design and purpose from the natural world, we find echoes of Paley and of Providence.Loren Eiseley has lamented the fact that Matthew did not bring his views into the open, because the amount of ground he was able to cover in a few paragraphs suggests that he might have been able to sustain a longer treatise.¹²⁸ Now that the intellectual and historical context of Matthew's ideas are known, this statement is no longer tenable. Matthew was not a scientist, and his books were not written as biological treatises. His discussions of natural selection were not attempts to cover ground in advancing a particular scientific theory, but were simply reflections of his own assumptions about the natural world.Furthermore, despite Matthew's acceptance of evolution and natural selection, his biological thought was basically conservative on points where Darwin's was radical. Where Matthew saw a series of stable worlds interrupted by violent upheavals, Darwin saw a continuous process of change in an ever-fluctuating world. Where Matthew conceived of species in terms of Aristotelian classes and essences, Darwin revolutionized our concept of species by treating them as populations. Where Matthew saw a world of design and beauty functioning according to natural laws laid down by benevolent Providence, Darwin abolished design and Providence from nature and ushered in a world which cycles ever onward according to laws of chance and probability.It is not even particularly useful to point to Matthew as evidence that evolution was in the air prior to 1859.¹²⁹ His ideas did not represent the first wave of a coming revolution, but were the product of his own personal philosophical outlook, as expressed in the context of the biological thought of the 1830's. Matthew is important in the history of ideas, not simply because he accepted the concept of evolution or thought of something resembling natural selection, but because he did so without overthrowing, in his own mind, any of the basic philosophical assumptions which had underlain biological science since Aristotle. In recognizing Matthew's failure to do so, we are in a position to appreciate more fully the significance of the Darwinian Revolution.     

Darwin,Cuvier and Geoffroy: comments and questions

In writing, in the Origin of Species, of 'two great laws' on which organic beings are formed, 'Unity of Type' and 'Conditions of Existence', Darwin was referring to the famous opposition between Cuvier and Geoffroy Saint-Hilaire, first stated publicly in the spring of 1830. After a brief statement of the chief points at issue in the debate, I raise the question of Darwin's attitude to the disagreement and the views of the two protagonists. There are numerous earlier, and some later, references to Cuvier and Geoffroy in the Darwin archives, notebooks, marginalia and correspondence. An examination of these materials suggests a shift in Darwin's sympathies, from Geoffroy to Cuvier. However, some of Geoffroy's principles are retained, and, in adopting Cuvier's phrase 'conditions of existence', Darwin partly alters its meaning. Finally, since originally, and in its adoption by such writers as Whewell and Owen, the expression 'conditions of existence' was interpreted as entailing design or final cause, I consider the vexed question of Darwin's attitude to teleology.     

Haeckel,un darwinien allemand ?

German biologist Ernst Haeckel (1834–1919) is often considered the most renowned Darwinian in his country since, as early as 1862, he declared that he accepted the conclusions Darwin had reached three years before in On the Origin of Species, and afterwards, he continuously proclaimed himself a supporter of the English naturalist and championed the evolutionary theory. Nevertheless, if we examine carefully his books, in particular his General Morphology (1866), we can see that he carries on a tradition very far from Darwin's thoughts. In spite of his acceptance of the idea of natural selection, that he establishes as an argument for materialism, he adopts, indeed, a conception of evolution that is, in some respects, rather close to Lamarck's views. He is, thus, a good example of the ambiguities of the reception of Darwinism in Germany in the second part of the 19th century. To cite this article: S. Schmitt, C. R. Biologies 332 (2009).     

The Causal Conditioned Reflex

E. A. Asratyan has long been the Director of the Institute of Higher Nervous Activity and Neurophysiology in Moscow. In this article he addresses himself to the difficult problem of accounting for complex forms of animal behavior from the base line of Pavlovian theory. This is the same task Boyko undertakes in his article in this issue, but Asratyan approaches it in a different manner. Going back to the stenographic notes of Pavlov's famous "Wednesdays" (sessions at which he discussed a wide variety of laboratory matters and topics of the day), Asratyan considers the little known concept of the "causal" reflex. From the remarks of the Russian editors of Problems of Philosophy (note 4), it is clear that Asratyan's ideas are by no means universally accepted.     

A Space of One’s Own: Barbosa du Bocage,the Foundation of the National Museum of Lisbon,and the Construction of a Career in Zoology (1851–1907)

This paper discusses the life and scientific work of José Vicente Barbosa du Bocage (1823–1907), a nineteenth-century Portuguese naturalist who carved a new place for zoological research in Portugal and built up a prestigious scientific career by securing appropriate physical and institutional spaces to the discipline. Although he was appointed professor of zoology at the Lisbon Polytechnic School, an institution mainly devoted to the preparatory training of military officers and engineers, he succeeded in creating the conditions that allowed him to develop consistent research in zoology at this institution. Taking advantage of the reconstruction and further improvement of the building of the Lisbon Polytechnic, following a violent fire in 1843, Bocage transferred a natural history museum formerly located at the Academy of Sciences of Lisbon to his institution, where he conquered a more prestigious place for zoology. Although successive governments were unwilling to meet Bocage’s ambitions for the Zoological Section of the newly created National Museum of Lisbon, the collaborators he found in different parts of the Portuguese continental territory and colonial empire supplied him the specimens he needed to make a career as a naturalist. Bocage ultimately became a renowned specialist in Southwestern African fauna thanks to José de Anchieta, his finest collaborator. Travels to foreign museums, and the establishment of links with the international community of zoologists, proved fundamental to build up Bocage’s national and international scientific reputation, as it will be exemplified by the discussion of his discovery of Hyalonema, a specimen with a controversial identity collected off the Portuguese coast.     

Margaret Mee's Amazon. Diaries of an artist explorer. * Margaret Mee. 2003. * Woodbridge Suffolk, UK: Antique Collectors' Club. * {pound}29{middle dot}50 (hardback). 320 pp, 400 colour illustrations

‘Delight’ said CharlesDarwin in his diaries in 1832, ‘is a weak term to expressthe feelings of a naturalist who, for the first time, has wanderedby himself in a Brazilian forest’. These feelings musthave been those which drove Margaret Mee to explore the Brazilianjungles on numerous expeditions between 1958 and 1964, creatingwonderful pictures despite all kinds of difficulties encounteredin this hostile world. And these feelings were also those Ihad when I read this book: delight about her precise drawingsand life-like paintings, which are extremely expressive from     

Alcide d’Orbigny entre Cuvier et Lamarck

In the History of Science, Alcide d’Orbigny has the distinctive characteristic to be placed, between Cuvier and Lamarck, who were the two masters of Natural Science for most of the 19th century. It is in this historical context that Alcide d’Orbigny lived. Of Cuvier, he remembered ideas on disasters and species fixedness without using the same evidence, for he was not a vertebrist. Of Lamarck, he rejected the ideas on life continuity and species transformation while using the research field opened by the Zoology and Invertebrate Palaeontology founder. Alcide d’Orbigny’s originality was to use Lamarck’s Invertebrate fossils as evidence of the ideas that Cuvier had based on Vertebrate fossils.     

Common to both academia and industry: the challenge of discovery. An interview with Perry Molinoff

Perry Molinoff recognizes the distinctions between basic and applied science, between academic and industrial research, and between the preclinical and clinical realities of drug development. But he generally discusses these categories in fluid, practical terms, having throughout his career crossed the lines of distinction that have sometimes been rather heavily drawn among pharmacologists. As a third-year medical student at Harvard, he decided "to take a year off" to conduct laboratory research. After receiving his MD and pursuing further clinical and postdoctoral work, he enjoyed an academic career that included fourteen years as the A.N. Richards Professor and Chair of Pharmacology at the University of Pennsylvania School of Medicine. He has just completed six years as Vice President of Neuroscience and Genitourinary Drug Discovery for Bristol-Myers Squibb and will soon return to teaching, in the Departments of Psychiatry and Pharmacology at Yale University. Referring to himself as either pharmacologist or neuroscientist, depending on context, he has made fundamental discoveries in receptor biology, has overseen the discovery and development of drugs and their subsequent clinical trials, and has mentored a host of pharmacologists and neuroscientists who themselves have established careers in industry and academia. The pursuit of discovery as its own reward emerges as a theme that has marked his professional life (and is perhaps reflected also in the images displayed in his office of the Himalayan mountains, photographed by Molinoff himself from the Everest base camp last year).     

Youth and personality formation--the world belongs to the strength of the young and to the wisdom of the elderly (a point of view of the communicologist)

It is known from the pedagogic, didactic and experience coordinates that a man doesn't become better by using words but by his actions. They are matchless examples for the self-apprehension process and the perception of the action itself as well as the only worthy and accurate offer for the assessment of the range and the significance of the achieved result. From the earliest stage of their life, from the childhood and then later on in different stages of their development and growth, the human being as a social being has a double need: to feel himself in the range of his "I" and to feel himself as a member of a group, a family and of the society in general. Satisfying the sense and the level of those needs doubtlessly depends on the examples given by the life itself and the circumstances of the living within the family, the school and finally the society, that is, the surroundings where the individual is affirming himself by his individual creative capability and skills with which he realizes himself as a subject on its own as well as within the social group he lives and works in. The conditions of the life and work of the elderly are necessary for this important and precious task in the development of a young man so that the applications of their experiences could ensure reliable guidelines for the harmony and success of the life and work of the young. On this bridge of generations the experience of the old is affirmed along with the need for its aimed, creative and fruitful offer to the young in the dynamic process of their development to the maturity and creativity.     

Soviet Psychology in English: Translations of Books

The English-speaking reader was given an opportunity — apparently not utilized too effectively — to familiarize himself early with the germinal ideas of research on what Pavlov first called the "so-called psychical processes" (Pavlov, I.P., Scientific study of so-called psychical processes of higher animals. Science, 1906, 24, 613-619, published in the U.S.A.; Lancet, 1906, 84,2,911-915, published in Great Britain), and what he later (1923, in Russian) referred to as "higher nervous activity (behavior)." The term "behavior" was used, in parenthesis, by Pavlov himself, and does not represent our interpretation or addition.     

Darwin on Aristotle

Charles Darwin's famous 1882 letter, in response to a gift by his friend, William Ogle of Ogle's recent translation of Aristotle's Parts of Animals, in which Darwin remarks that his “two gods,” Linnaeus and Cuvier, were “mere school-boys to old Aristotle,” has been thought to be only an extravagantly worded gesture of politeness. However, a close examination of this and other Darwin letters, and of references to Aristotle in Darwin's earlier work, shows that the famous letter was written several weeks after a first, polite letter of thanks, and was carefully formulated and literally meant. Indeed, it reflected an authentic, and substantial, increase in Darwin's already high respect for Aristotle, as a result of a careful reading both of Ogle's Introduction and of more or less the portion of Ogle's translation which Darwin says he has read. Aristotle's promotion to the pantheon, as an examination of the basis for Darwin's admiration of Linnaeus and Cuvier suggests, was most likely the result specifically of Darwin's late discovery that the man he already knew as “one of the greatest ... observers that ever lived” (1879) was also the ancient equivalent both of the great modern systematist and of the great modern advocate of comparative functional explanation. It may also have reflected some real insight on Darwin's part into the teleological aspect of Aristotle's thought, indeed more insight than Ogle himself had achieved, as a portion of their correspondence reveals. This revised version was published online in July 2006 with corrections to the Cover Date.     

Thomas huxley: Fossils,persistence, and the argument from design

Conclusion In struggling to free science from theological implications, Huxley let his own philosophical beliefs influence his interpretation of the data. However, he was certainly not unique in this respect. Like the creationists he despised, he made many important contributions to the issue of progression in the fossil record and its relationship to evolutionary theory. Certainly other factors were involved as well. Undoubtedly, just the sheer inertia of ideas played a role. He was committed to a theory of type and was heavily influenced by von Baer, who argued that one could not rate the different types as being higher or lower than the others. By the mid-1850s his animosity toward Owen had become extreme and he tried to discredit the man whenever possible; yet, as I have pointed out, he also was more than willing to cite Owen's early work when it suited his needs.But I believe the crucial factor in Huxley's eventually accepting progression was that he finally disassociated it from the idea of divine plan. This happened gradually through the 1860s and 1870s, as more and more fossil finds provided support for Darwin's theory. In evaluating this new evidence that supported gradualism, Huxley also realized that progression was an intrinsic part of Darwin's theory:The hypothesis of evolution supposes that at any given period in the past we should meet with a state of things more or less similar to the present, but less similar in proportion as we go back in time... if we traced back the animal world and the vegetable world we should find preceding what now exist animals and plants not identical with them, but like them, only increasing their differences as we go back in time, and at the same time becoming simpler and simpler until finally we should arrive at that gelatinous mass which, so far as our present knowledge goes, is the common foundation of all life.In concluding his first lecture to the Americans, he told them: The hypothesis of evolution supposes that in all this vast progression there would be no breach of continuity, no point at which we could say This is a natural process, and This is not a natural process.⁸⁵ Finally for Huxley, progression was no longer linked to Divine Plan.     

Charles Darwin's debt to malthus and Edward Blyth

Conclusion It is not justifiable to accuse Darwin of conscious or unconscious plagiarism. This charge is contrary to the historical evidence and to the extensive information that we have about his character. When Darwin listed the writers on the origin of species by natural selection before himself, he did not mention Blyth, and this omission did not disturb the cordial relations between Darwin and Blyth. Blyth continued to supply Darwin with information which Darwin used in his later publications with due acknowledgment to Blyth. For example, in The Descent of Man, Darwin cited Blyth: Mr. Blyth, as he informs me, saw Indian crows feeding two or three of their companions which were blind.⁶³ Blyth felt no resentment. If he did, he would have so informed Darwin. Blyth did not regard himself as in any sense a predecessor of Darwin and he certainly did not resent Darwin as a plagiarizer of himself. Moreover, Darwin went to a great deal of trouble to find his own predecessors and to give them proper credit.⁶⁴ After Darwin had completed his work on natural selection, he wrote a letter to the Reverend Baden Powell in which he clearly showed recognition of the contribution of others to his own work:No educated person, not even the most ignorant, could suppose I mean to arrogate to myself the origination of the doctrine that species had not been independently created. The only novelty in my work is the attempt to explain how species became modified, and to a certain extent how the theory of descent explains certain large classes of facts; and in these respects I received no assistance from my predecessors.⁶⁵ *** DIRECT SUPPORT *** A8402011 00002     

From discovering to understanding

Friedrich Miescher''s attempts to uncover the function of DNAIt might seem as though the role of DNA as the carrier of genetic information was not realized until the mid-1940s, when Oswald Avery (1877–1955) and colleagues demonstrated that DNA could transform bacteria (Avery et al, 1944). Although these experiments provided direct evidence for the function of DNA, the first ideas that it might have an important role in processes such as cell proliferation, fertilization and the transmission of heritable traits had already been put forward more than half a century earlier. Friedrich Miescher (1844–1895; Fig 1), the Swiss scientist who discovered DNA in 1869 (Miescher, 1869a), developed surprisingly insightful theories to explain its function and how biological molecules could encode information. Although his ideas were incorrect from today''s point of view, his work contains concepts that come tantalizingly close to our current understanding. But Miescher''s career also holds lessons beyond his scientific insights. It is the story of a brilliant scientist well on his way to making one of the most fundamental discoveries in the history of science, who ultimately fell short of his potential because he clung to established theories and failed to follow through with the interpretation of his findings in a new light.…a brilliant scientist well on his way to making one of the most fundamental discoveries in the history of science […] fell short of his potential because he clung to established theories…Open in a separate windowFigure 1Friedrich Miescher (1844–1895) and his wife, Maria Anna Rüsch. © Library of the University of Basel, Switzerland.It is a curious coincidence in the history of genetics that three of the most decisive discoveries in this field occurred within a decade: in 1859, Charles Darwin (1809–1882) published On the Origin of Species by Means of Natural Selection, in which he expounded the mechanism driving the evolution of species; seven years later, Gregor Mendel''s (1822–1884) paper describing the basic laws of inheritance appeared; and in early 1869, Miescher discovered DNA. Yet, although the magnitude of Darwin''s theory was realized almost immediately, and at least Mendel himself seems to have grasped the importance of his work, Miescher is often viewed as oblivious to the significance of his discovery. It would be another 75 years before Oswald Avery, Colin MacLeod (1909–1972) and Maclyn McCarthy (1911–2005) could convincingly show that DNA was the carrier of genetic information, and another decade before James Watson and Francis Crick (1916–2004) unravelled its structure (Watson & Crick, 1953), paving the way to our understanding of how DNA encodes information and how this is translated into proteins. But Miescher already had astonishing insights into the function of DNA.Between 1868 and 1869, Miescher worked at the University of Tübingen in Germany (Figs 2,​,3),3), where he tried to understand the chemical basis of life. A crucial difference in his approach compared with earlier attempts was that he worked with isolated cells—leukocytes that he obtained from pus—and later purified nuclei, rather than whole organs or tissues. The innovative protocols he developed allowed him to investigate the chemical composition of an isolated organelle (Dahm, 2005), which significantly reduced the complexity of his starting material and enabled him to analyse its constituents.Open in a separate windowFigure 2Contemporary view of the town of Tübingen at about the time when Miescher worked there. The medieval castle housing Hoppe-Seyler''s laboratory can be seen atop the hill at the right. © Stadtarchiv Tübingen, Germany.Open in a separate windowFigure 3The former kitchen of Tübingen castle, which formed part of Hoppe-Seyler''s laboratory. It was in this room that Miescher worked during his stay in Tübingen and where he discovered DNA. After his return to Basel, Miescher reminisced how this room with its shadowy, vaulted ceiling and its small, deep-set windows appeared to him like the laboratory of a medieval alchemist. Photograph taken by Paul Sinner, Tübingen, in 1879. © University Library Tübingen.In carefully designed experiments, Miescher discovered DNA—or “Nuclein” as he called it—and showed that it differed from the other classes of biological molecule known at that time (Miescher, 1871a). Most notably, nuclein''s elementary composition with its high phosphorous content convinced him that he had discovered a substance sui generis, that is, of its own kind; a conclusion subsequently confirmed by Miescher''s mentor in Tübingen, the eminent biochemist Felix Hoppe-Seyler (1825–1895; Hoppe-Seyler, 1871; Miescher, 1871a). After his initial analyses, Miescher was convinced that nuclein was an important molecule and suggested in his first publication that it would “merit to be considered equal to the proteins” (Miescher, 1871a).Moreover, Miescher recognized immediately that nuclein could be used to define the nucleus (Miescher, 1870). This was an important realization, as at the time the unequivocal identification of nuclei, and hence their study, was often difficult or even impossible to achieve because their morphology, subcellular localization and staining properties differed between tissues, cell types and states of the cells. Instead, Miescher proposed to base the characterization of nuclei on the presence of this molecule (Miescher, 1870, 1874). Moreover, he held that the nucleus should be defined by properties that are related to its physiological activity, which he believed to be closely linked to nuclein. Miescher had thus made a significant first step towards defining an organelle in terms of its function rather than its appearance.Importantly, his findings also showed that the nucleus is chemically distinct from the cytoplasm at a time when many scientists still assumed that there was nothing unique about this organelle. Miescher thus paved the way for the subsequent realization that cells are subdivided into compartments with distinct molecular composition and functions. On the basis of his observations that nuclein appeared able to separate itself from the “protoplasm” (cytoplasm), Miescher even went so far as to suggest the “possibility that [nuclein can be] distributed in the protoplasm, which could be the precursor for some of the de novo formations of nuclei” (Miescher, 1874). He seemed to anticipate that the nucleus re-forms around the chromosomes after cell division, but unfortunately did not elaborate on under which conditions this might occur. It is therefore impossible to know with certainty to which circumstances he was referring.Miescher thus paved the way for the subsequent realization that cells are subdivided into compartments with distinct molecular composition and functionsIn this context, it is interesting to note that in 1872, Edmund Russow (1841–1897) observed that chromosomes appeared to dissolve in basic solutions. Intriguingly, Miescher had also found that he could precipitate nuclein by using acids and then return it to solution by increasing the pH (Miescher, 1871a). At the time, however, he did not make the link between nuclein and chromatin. This happened around a decade later, in 1881, when Eduard Zacharias (1852–1911) studied the nature of chromosomes by using some of the same methods Miescher had used when characterizing nuclein. Zacharias found that chromosomes, such as nuclein, were resistant to digestion by pepsin solutions and that the chromatin disappeared when he extracted the pepsin-treated cells with dilute alkaline solutions. This led Walther Flemming (1843–1905) to speculate in 1882 that nuclein and chromatin are identical (Mayr, 1982).Alas, Miescher was not convinced. His reluctance to accept these developments was at least partly based on a profound scepticism towards the methods—and hence results—of cytologists and histologists, which, according to Miescher, lacked the precision of chemical approaches as he applied them. The fact that DNA was crucially linked to the function of the nucleus was, however, firmly established in Miescher''s mind and in the following years he tried to obtain additional evidence. He later wrote: “Above all, using a range of suitable plant and animal specimens, I want to prove that Nuclein really specifically belongs to the life of the nucleus” (Miescher, 1876).Although the acidic nature of DNA, its large molecular weight, elementary composition and presence in the nucleus are some of its central properties—all first determined by Miescher—they reveal nothing about its function. Having convinced himself that he had discovered a new type of molecule, Miescher rapidly set out to understand its role in different biological contexts. As a first step, he determined that nuclein occurs in a variety of cell types. Unfortunately, he did not elaborate on the types of tissue or the species his samples were derived from. The only hints as to the specimens he worked with come from letters he wrote to his uncle, the Swiss anatomist Wilhelm His (1831–1904), and his parents; his father, Friedrich Miescher-His (1811–1887), was professor of anatomy in Miescher''s native Basel. In his correspondence, Miescher mentioned other cell types that he had studied for the presence of nuclein, including liver, kidney, yeast cells, erythrocytes and chicken eggs, and hinted at having found nuclein in these as well (Miescher, 1869b; His, 1897). Moreover, Miescher had also planned to look for nuclein in plants, especially in their spores (Miescher, 1869c). This is an intriguing choice given his later fascination with vertebrate germ cells and his speculation on the processes of fertilization and heredity (Miescher, 1871b, 1874).Another clue to the tissues and cell types that Miescher might have examined comes from two papers published by Hoppe-Seyler, who wanted to confirm his student''s results, which he initially viewed with scepticism, before their publication. In the first, another of Hoppe-Seyler''s students, Pal Plósz, reported that nuclein is present in the nucleated erythrocytes of snakes and birds but not in the anuclear erythrocytes of cows (Plósz, 1871). In the second paper, Hoppe-Seyler himself confirmed Miescher''s findings and reported that he had detected nuclein in yeast cells (Hoppe-Seyler, 1871).In an addendum to his 1871 paper, published posthumously, Miescher stated that the apparently ubiquitous presence of nuclein meant that “a new factor has been found for the life of the most basic as well as for the most advanced organisms,” thus opening up a wide range of questions for physiology in general (Miescher, 1870). To argue that Miescher understood that DNA was an essential component of all forms of life is probably an over-interpretation of his words. His statement does, however, clearly show that he believed DNA to be an important factor in the life of a wide range of species.In addition, Miescher looked at tissues under different physiological conditions. He quickly noticed that both nuclein and nuclei were significantly more abundant in proliferating tissues; for instance, he noted that in plants, large amounts of phosphorous are found predominantly in regions of growth and that these parts show the highest densities of nuclei and actively proliferating cells (Miescher, 1871a). Miescher had thus taken the first step towards linking the presence of phosphorous—that is, DNA in this context—to cell proliferation. Some years later, while examining changes in the bodies of salmon as they migrate upstream to their spawning grounds, he noticed that he could, with minimal effort, purify large amounts of pure nuclein from the testes, as they were at the height of cell proliferation in preparation for mating (Miescher, 1874). This provided additional evidence for a link between proliferation and the presence of a high concentration of nuclein.Miescher''s most insightful comments on this issue, however, date from his time in Hoppe-Seyler''s laboratory in Tübingen. He was convinced that histochemical analyses would lead to a much better understanding of certain pathological states than would microscopic studies. He also believed that physiological processes, which at the time were seen as similar, might turn out to be very different if the chemistry were better understood. As early as 1869, the year in which he discovered nuclein, he wrote in a letter to His: “Based on the relative amounts of nuclear substances [DNA], proteins and secondary degradation products, it would be possible to assess the physiological significance of changes with greater accuracy than is feasible now” (Miescher, 1869c).Importantly, Miescher proposed three exemplary processes that might benefit from such analyses: “nutritive progression”, characterized by an increase in the cytoplasmic proteins and the enlargement of the cell; “generative progression”, defined as an increase in “nuclear substances” (nuclein) and as a preliminary phase of cell division in proliferating cells and possibly in tumours; and “regression”, an accumulation of lipids and degenerative products (Miescher, 1869c).When we consider the first two categories, Miescher seems to have understood that an increase in DNA was not only associated with, but also a prerequisite for cell proliferation. Subsequently, cells that are no longer proliferating would increase in size through the synthesis of proteins and hence cytoplasm. Crucially, he believed that chemical analyses of such different states would enable him to obtain a more fundamental insight into the causes underlying these processes. These are astonishingly prescient insights. Sadly, Miescher never followed up on these ideas and, apart from the thoughts expressed in his letter, never published on the topic.…Miescher seems to have understood that an increase in DNA was not only associated with, but also a prerequisite for cell proliferationIt is likely, however, that he had preliminary data supporting these views. Miescher was generally careful to base statements on facts rather than speculation. But, being a perfectionist who published only after extensive verification of his results, he presumably never pursued these studies to such a satisfactory point. It is possible his plans were cut short by leaving Hoppe-Seyler''s laboratory to receive additional training under the supervision of Carl Ludwig (1816–1895) in Leipzig. While there, Miescher turned his attention to matters entirely unrelated to DNA and only resumed his work on nuclein after returning to his native Basel in 1871.Crucially for these subsequent studies of nuclein, Miescher made an important choice: he turned to sperm as his main source of DNA. When analysing the sperm from different species, he noted that the spermatozoa, especially of salmon, have comparatively small tails and thus consist mainly of a nucleus (Miescher, 1874). He immediately grasped that this would greatly facilitate his efforts to isolate DNA at much higher purity (Fig 4). Yet, Miescher also saw beyond the possibility of obtaining pure nuclein from salmon sperm. He realized it also indicated that the nucleus and the nuclein therein might play a crucial role in fertilization and the transmission of heritable traits. In a letter to his colleague Rudolf Boehm (1844–1926) in Würzburg, Miescher wrote: “Ultimately, I expect insights of a more fundamental importance than just for the physiology of sperm” (Miescher, 1871c). It was the beginning of a fascination with the phenomena of fertilization and heredity that would occupy Miescher to the end of his days.Open in a separate windowFigure 4A glass vial containing DNA purified by Friedrich Miescher from salmon sperm. © Alfons Renz, University of Tübingen, Germany.Miescher had entered this field at a critical time. By the middle of the nineteenth century, the old view that cells arise through spontaneous generation had been challenged. Instead, it was widely recognized that cells always arise from other cells (Mayr, 1982). In particular, the development and function of spermatozoa and oocytes, which in the mid-1800s had been shown to be cells, were seen in a new light. Moreover, in 1866, three years before Miescher discovered DNA, Ernst Haeckel (1834–1919) had postulated that the nucleus contained the factors that transmit heritable traits. This proposition from one of the most influential scientists of the time brought the nucleus to the centre of attention for many biologists. Having discovered nuclein as a distinctive molecule present exclusively in this organelle, Miescher realized that he was in an excellent position to make a contribution to this field. Thus, he set about trying to better characterize nuclein with the aim of correlating its chemical properties with the morphology and function of cells, especially of sperm cells.His analyses of the chemical composition of the heads of salmon spermatozoa led Miescher to identify two principal components: in addition to the acidic nuclein, he found an alkaline protein for which he coined the term ‘protamin''; the name is still in use today; protamines are small proteins that replace histones during spermatogenesis. He further determined that these two molecules occur in a “salt-like, not an ether-like [that is, covalent] association” (Miescher, 1874). Following his meticulous analyses of the chemical composition of sperm, he concluded that, “aside from the mentioned substances [protamin and nuclein] nothing is present in significant quantity. As this is crucial for the theory of fertilization, I carry this business out as quantitatively as possible right from the beginning” (Miescher, 1872a). His analyses showed him that the DNA and protamines in sperm occur at constant ratios; a fact that Miescher considered “is certainly of special importance,” without, however, elaborating on what might be this importance. Today, of course, we know that proteins, such as histones and protamines, bind to DNA in defined stoichiometric ratios.Miescher went on to analyse the spermatozoa of carp, frogs (Rana esculenta) and bulls, in which he confirmed the presence of large amounts of nuclein (Miescher, 1874). Importantly, he could show that nuclein is present in only the heads of sperm—the tails being composed largely of lipids and proteins—and that within the head, the nuclein is located in the nucleus (Miescher, 1874; Schmiedeberg & Miescher, 1896). With this discovery, Miescher had not only demonstrated that DNA is a constant component of spermatozoa, but also directed his attention to the sperm heads. On the basis of the observations of other investigators, such as those of Albert von Kölliker (1817–1905) concerning the morphology of spermatozoa in some myriapods and arachnids, Miescher knew that the spermatozoa of some species are aflagellate, that is, lack a tail. This confirmed that the sperm head, and thus the nucleus, was the crucial component. But, the question remained: what in the sperm cells mediated fertilization and the transmission of hereditary traits from one generation to the next?On the basis of his chemical analyses of sperm, Miescher speculated on the existence of molecules that have a crucial part in these processes. In a letter to Boehm, Miescher wrote: “If chemicals do play a role in procreation at all, then the decisive factor is now a known substance” (Miescher, 1872b). But Miescher was unsure as to what might be this substance. He did, however, strongly suspect the combination of nuclein and protamin was the key and that the oocyte might lack a crucial component to be able to develop: “If now the decisive difference between the oocyte and an ordinary cell would be that from the roster of factors, which account for an active arrangement, an element has been removed? For otherwise all proper cellular substances are present in the egg,” he later wrote (Miescher, 1872b).Owing to his inability to detect protamin in the oocyte, Miescher initially favoured this molecule as responsible for fertilization. Later, however, when he failed to detect protamin in the sperm of other species, such as bulls, he changed his mind: “The Nuclein by contrast has proved to be constant [that is, present in the sperm cells of all species Miescher analysed] so far; to it and its associations I will direct my interest from now on” (Miescher, 1872b). Unfortunately, however, although he came tantalizingly close, he never made a clear link between nuclein and heredity.The final section of his 1874 paper on the occurrence and properties of nuclein in the spermatozoa of different vertebrate species is of particular interest because Miescher tried to correlate his chemical findings about nuclein with the physiological role of spermatozoa. He had realized that spermatozoa represented an ideal model system to study the role of DNA because, as he would later put it, “[f]or the actual chemical–biological problems, the great advantage of sperm [cells] is that everything is reduced to the really active substances and that they are caught just at the moment when they exert their greatest physiological function” (Miescher, 1893a). He appreciated that his data were still incomplete, yet wanted to make a first attempt to pull his results together and integrate them into a broader picture to explain fertilization.At the time, Wilhelm Kühne (1837–1900), among others, was putting forward the idea that spermatozoa are the carriers of specific substances that, through their chemical properties, achieve fertilization (Kühne, 1868). Miescher considered his results of the chemical composition of spermatozoa in this context. While critically considering the possibility of a chemical substance explaining fertilization, he stated that: “if we were to assume at all that a single substance, as an enzyme or in any other way, for instance as a chemical impulse, could be the specific cause of fertilization, we would without a doubt first and foremost have to consider Nuclein. Nuclein-bodies were consistently found to be the main components [of spermatozoa]” (Miescher, 1874).With hindsight, these statements seem to suggest that Miescher had identified nuclein as the molecule that mediates fertilization—a crucial assumption to follow up on its role in heredity. Unfortunately, however, Miescher himself was far from convinced that a molecule (or molecules) was responsible for this. There are several reasons for his reluctance, although the influence of his uncle was presumably a crucial factor as it was he who had been instrumental in fostering the young Miescher''s interest in biochemistry and remained a strong influence throughout his life. Indeed, when Miescher came tantalizingly close to uncovering the function of DNA, His''s views proved counterproductive, probably preventing him from interpreting his findings in the context of new results from other scientists at the time. Miescher thus failed to take his studies of nuclein and its function in fertilization and heredity to the next level, which might well have resulted in recognizing DNA as the central molecule in both processes.One specific aspect that diverted Miescher from contemplating the role of nuclein in fertilization was a previous study in which he had erroneously identified the yolk platelets in chicken oocytes as a large number of nuclein-containing granules (Miescher, 1871b). This led him to conclude that the comparatively minimal quantitative contribution of DNA from a spermatozoon to an oocyte, which already contained so much more of the substance, could not have a significant impact on the latter''s physiology. He therefore concluded that, “not in a specific substance can the mystery of fertilization be concealed. […] Not a part, but the whole must act through the cooperation of all its parts” (Miescher, 1874).It is all the more unfortunate that Miescher had identified the yolk platelets in oocytes as nuclein-containing cells because he had realized that the presumed nuclein in these granules differed from the nuclein (that is, DNA) he had isolated previously from other sources, notably by its much higher phosphorous content. But influenced by His''s strong view that these structures were genuine cells, Miescher saw his results in this light. Only several years later, based on results from his contemporaries Flemming and Eduard A. Strasburger (1844–1912) on the morphological properties of nuclei and their behaviour during cell divisions, and Albrecht Kossel''s (1853–1927) discoveries about the composition of DNA (Portugal & Cohen, 1977), did Miescher revise his initial assumption that chicken oocytes contain a large number of nuclein-containing granules. Instead, he finally conceded that the molecules comprising these granules were different from nuclein (Miescher, 1890).Another factor that prevented Miescher from concluding that nuclein was the basis for the transmission of hereditary traits was that he could not conceive of how a single substance might explain the multitude of heritable traits. How, he wondered, could a specific molecule be responsible for the differences between species, races and individuals? Although he granted that “differences in the chemical constitution of these molecules [different types of nuclein] will occur, but only to a limited extent” (Miescher, 1874).And thus, instead of looking to molecules, he—like his uncle His––favoured the idea that the physical movement of the sperm cells or an activation of the oocyte, which he likened to the stimulation of a muscle by neuronal impulses, was responsible for the process of fertilization: “Like the muscle during the activation of its nerve, the oocyte will, when it receives appropriate impulses, become a chemically and physically very different entity” (Miescher, 1874). For nuclein itself, Miescher considered that it might be a source material for other molecules, such as lecithin––one of the few other molecules with a high phosphorous content known at the time (Miescher, 1870, 1871a, 1874). Miescher clearly preferred the idea of nuclein as a repository for material for the cell—mainly phosphorous—rather than as a molecule with a role in encoding information to synthesize such materials. This idea of large molecules being source material for smaller ones was common at the time and was also contemplated for proteins (Miescher, 1870).The entire section of Miescher''s 1874 paper in which he discusses the physiological role of nuclein reads as though he was deliberately trying to assemble evidence against nuclein being the key molecule in fertilization and heredity. This disparaging approach towards the molecule that he himself had discovered might also be explained, at least to some extent, by his pronounced tendency to view his results so critically; tellingly, he published only about 15 papers and lectures in a career spanning nearly three decades.The modern understanding that fertilization is achieved by the fusion of two germ cells only became established in the final quarter of the nineteenth century. Before that time, the almost ubiquitous view was that the sperm cell, through mere contact with the egg, in some way stimulated the oocyte to develop—the physicalist viewpoint. His was a key advocate of this view and firmly rejected the idea that a specific substance might mediate heredity. We can only speculate as to how Miescher would have interpreted his results had he worked in a different intellectual environment at the time, or had he been more independent in the interpretation of his results.We can only speculate as to how Miescher would have interpreted his results had he worked in a different intellectual environment at the time…Miescher''s refusal to accept nuclein as the key to fertilization and heredity is particularly tragic in view of several studies that appeared in the mid-1870s, focusing the attention of scientists on the nuclei. Leopold Auerbach (1828–1897) demonstrated that fertilized eggs contain two nuclei that move towards each other and fuse before the subsequent development of the embryo (Auerbach, 1874). This observation strongly suggested an important role for the nuclei in fertilization. In a subsequent study, Oskar Hertwig (1849–1922) confirmed that the two nuclei—one from the sperm cell and one from the oocyte—fuse before embryogenesis begins. Furthermore, he observed that all nuclei in the embryo derive from this initial nucleus in the zygote (Hertwig, 1876). With this he had established that a single sperm fertilizes the oocyte and that there is a continuous lineage of nuclei from the zygote throughout development. In doing so, he delivered the death blow to the physicalist view of fertilization.By the mid-1880s, Hertwig and Kölliker had already postulated that the crucial component of the nucleus that mediated inheritance was nuclein—an idea that was subsequently accepted by several scientists. Sadly, Miescher remained doubtful until his death in 1895 and thus failed to appreciate the true importance of his discovery. This might have been an overreaction to the claims by others that sperm heads are formed from a homogeneous substance; Miescher had clearly shown that they also contain other molecules, such as proteins. Moreover, Miescher''s erroneous assumption that nuclein occurred only in the outer shell of the sperm head resulted in his failure to realize that stains for chromatin, which stain the centres of the heads, actually label the region where there is nuclein; although he later realized that virtually the entire sperm head is composed of nuclein and associated protein (Miescher, 1892a; Schmiedeberg & Miescher, 1896).Unfortunately, not only Miescher, but the entire scientific community would soon lose faith in DNA as the molecule mediating heredity. Miescher''s work had established DNA as a crucial component of all cells and inspired others to begin exploring its role in heredity, but with the emergence of the tetranucleotide hypothesis at the beginning of the twentieth century, DNA fell from favour and was replaced by proteins as the prime candidates for this function. The tetranucleotide hypothesis—which assumed that DNA was composed of identical subunits, each containing all four bases—prevailed until the late 1940s when Edwin Chargaff (1905–2002) discovered that the different bases in DNA were not present in equimolar amounts (Chargaff et al, 1949, 1951).Unfortunately, not only Miescher, but the entire scientific community would soon lose faith in DNA as the molecule mediating heredityJust a few years before, in 1944, experiments by Avery and colleagues had demonstrated that DNA was sufficient to transform bacteria (Avery et al, 1944). Then in 1952, Al Hershey (1908–1997) and Martha Chase (1927–2003) confirmed these findings by observing that viral DNA—but no protein—enters the bacteria during infection with the T2 bacteriophage and, that this DNA is also present in new viruses produced by infected bacteria (Hershey & Chase, 1952). Finally, in 1953, X-ray images of DNA allowed Watson and Crick to deduce its structure (Watson & Crick, 1953) and thus enable us to understand how DNA works. Importantly, these experiments were made possible by advances in bacteriology and virology, as well as the development of new techniques, such as the radioactive labelling of proteins and nucleic acids, and X-ray crystallography—resources that were beyond the reach of Miescher and his contemporaries.In later years (Fig 5), Miescher''s attention shifted progressively from the role of nuclein in fertilization and heredity to physiological questions, such as those concerning the metabolic changes in the bodies of salmon as they produce massive amounts of germ cells at the expense of muscle tissue. Although he made important and seminal contributions to different areas of physiology, he increasingly neglected to explore his most promising line of research, the function of DNA. Only towards the end of his life did he return to this question and begin to reconsider the issue in a new light, but he achieved no further breakthroughs.Open in a separate windowFigure 5Friedrich Miescher in his later years when he was Professor of Physiology at the University of Basel. In this capacity he also founded the Vesalianum, the University''s Institute for Anatomy and Physiology, which was inaugurated in 1885. This photograph is the frontispiece on the inside cover of a collection of Miescher''s publications and some of his letters, edited and published by his uncle Wilhelm His and colleagues after Miescher''s death. Underneath the picture is Miescher''s signature. © Ralf Dahm.One area, however, where he did propose intriguing hypotheses—although without experimental data to support them—was the molecular underpinnings of heredity. Inspired by Darwin''s work on fertilization in plants, Miescher postulated, for instance, how information might be encoded in biological molecules. He stated that, “the key to sexuality for me lies in stereochemistry,” and expounded his belief that the gemmules of Darwin''s theory of pangenesis were likely to be “numerous asymmetric carbon atoms [present in] organic substances” (Miescher, 1892b), and that sexual reproduction might function to correct mistakes in their “stereometric architecture”. As such, Miescher proposed that hereditary information might be encoded in macromolecules and how mistakes could be corrected, which sounds uncannily as though he had predicted what is now known as the complementation of haploid deficiencies by wild-type alleles. It is particularly tempting to assume that Miescher might have thought this was the case, as Mendel had published his laws of inheritance of recessive characteristics more than 25 years earlier. However, there is no reference to Mendel''s work in the papers, talks or letters that Miescher has left to us.Miescher proposed that hereditary information might be encoded in macromolecules and how mistakes could be corrected…What we do know is that Miescher set out his view of how hereditary information might be stored in macromolecules: “In the enormous protein molecules […] the many asymmetric carbon atoms allow such a colossal number of stereoisomers that all the abundance and diversity of the transmission of hereditary [traits] may find its expression in them, as the words and terms of all languages do in the 24–30 letters of the alphabet. It is therefore completely superfluous to see the sperm cell or oocyte as a repository of countless chemical substances, each of which should be the carrier of a special hereditary trait (de Vries Pangenesis). The protoplasm and the nucleus, that my studies have shown, do not consist of countless chemical substances, but of very few chemical individuals, which, however, perhaps have a very complex chemical structure” (Miescher, 1892b).This is a remarkable passage in Miescher''s writings. The second half of the nineteenth century saw intense speculation about how heritable characteristics are transmitted between the generations. The consensus view assumed the involvement of tiny particles, which were thought to both shape embryonic development and mediate inheritance (Mayr, 1982). Miescher contradicted this view. Instead of a multitude of individual particles, each of which might be responsible for a specific trait (or traits), his results had shown that, for instance, the heads of sperm cells are composed of only very few compounds, chiefly DNA and associated proteins.He elaborated further on his theory of how hereditary information might be stored in large molecules: “Continuity does not only lie in the form, it also lies deeper than the chemical molecule. It lies in the constituent groups of atoms. In this sense I am an adherent of a chemical model of inheritance à outrance [to the utmost]” (Miescher, 1893b). With this statement Miescher firmly rejects any idea of preformation or some morphological continuity transmitted through the germ cells. Instead, he clearly seems to foresee what would only become known much later: the basis of heredity was to be found in the chemical composition of molecules.To explain how this could be achieved, he proposed a model of how information could be encoded in a macromolecule: “If, as is easily possible, a protein molecule comprises 40 asymmetric carbon atoms, there will be 2⁴⁰, that is, approximately a trillion isomerisms [sic]. And this is only one of the possible types of isomerism [not considering other atoms, such as nitrogen]. To achieve the incalculable diversity demanded by the theory of heredity, my theory is better suited than any other. All manner of transitions are conceivable, from the imperceptible to the largest differences” (Miescher, 1893b).Miescher''s ideas about how heritable characteristics might be transmitted and encoded encapsulate several important concepts that have since been proven to be correct. First, he believed that sexual reproduction served to correct mistakes, or mutations as we call them today. Second, he postulated that the transmission of heritable traits occurs through one or a few macromolecules with complex chemical compositions that encode the information, rather than by numerous individual molecules each encoding single traits, as was thought at the time. Third, he foresaw that information is encoded in these molecules through a simple code that results in a staggeringly large number of possible heritable traits and thus explain the diversity of species and individuals observed.Miescher''s ideas about how heritable characteristics might be transmitted and encoded encapsulate several important concepts that have since been proven to be correctIt is a step too far to suggest that Miescher understood what DNA or other macromolecules do, or how hereditary information is stored. He simply could not have done, given the context of his time. His findings and hypotheses that today fit nicely together and often seem to anticipate our modern understanding probably appeared rather disjointed to Miescher and his contemporaries. In his day, too many facts were still in doubt and too many links tenuous. There is always a danger of over-interpreting speculations and hypotheses made a long time ago in today''s light. However, although Miescher himself misinterpreted some of his findings, large parts of his conclusions came astonishingly close to what we now know to be true. Moreover, his work influenced others to pursue their own investigations into DNA and its function (Dahm, 2008). Although DNA research fell out of fashion for several decades after the end of the nineteenth century, the information gleaned by Miescher and his contemporaries formed the foundation for the decisive experiments carried out in the middle of the twentieth century, which unambiguously established the function of DNA.As such, perhaps the most tragic aspect of Miescher''s career was that for most of his life he firmly believed in the physicalist theories of fertilization, as propounded by His and Ludwig among others, and his reluctance to combine the results from his rigorous chemical analyses with the ‘softer'' data generated by cytologists and histologists. Had he made the link between nuclein and chromosomes and accepted its key role in fertilization and heredity, he might have realized that the molecule he had discovered was the key to some of the greatest mysteries of life. As it was, he died with a feeling of a promising career unfulfilled (His, 1897), when, in actual fact, his contributions were to outshine those of most of his contemporaries.…he died with a feeling of a promising career unfulfilled […] when, in actual fact, his contributions were to outshine those of most of his contemporariesIt is tantalizing to speculate the path that Miescher''s investigations—and biology as a whole—might have taken under slightly different circumstances. What would have happened had he followed up on his preliminary results about the role of DNA in different physiological conditions, such as cell proliferation? How would his theories about fertilization and heredity have changed had he not been misled by the mistaken identification of what appeared to him to be a multitude of small nuclei in the oocyte? Or how would he have interpreted his findings concerning nuclein had he not been influenced by the views of his uncle, but also those of the wider scientific establishment?There is a more general lesson in the life and work of Friedrich Miescher that goes beyond his immediate successes and failures. His story is that of a brilliant researcher who developed innovative experimental approaches, chose the right biological systems to address his questions and made ground-breaking discoveries, and who was nonetheless constrained by his intellectual environment and thus prevented from interpreting his findings objectively. It therefore fell to others, who saw his work from a new point of view, to make the crucial inferences and thus establish the function of DNA.? Open in a separate windowRalf Dahm     

The life and work of Hiroya Kawanabe: the priest ecologist

Hiroya Kawanabe was born the son of a Buddhist priest and teacher of Japanese literature, who died when Kawanabe was very young. Kawanabe also studied Buddhism by himself, and passed the examination to be a priest of his sect while still in high school. He studied zoology and ecology at Kyoto University and earned his doctorate under the guidance of Denzaburo Miyadi, a well-known Japanese ecologist, in 1960. During his academic career at Kyoto University, Kawanabe advanced to hold the chair of Animal Ecology as Professor in the Department of Zoology. Kawanabe's doctoral research concerned the social behavior and population ecology of the ayu, Plecoglossus altivelis, an amphidromous fish that lives in streams as adults and grazes algae. His research lead to the discovery that social structure changed from territoriality to schooling as population density increased, and also varied with changes in food and habitat. During this work, he pioneered the use of underwater observation to study ecolo gy of freshwater fishes in streams. Kawanabe also observed ayu social structure from the northern to southern limits of their range, and advanced the theory that the more stable territoriality in the Lake Biwa population was a relic social structure to guarantee food supply during earlier glacial periods when productivity was lower. Additional work on stream fishes in central Japan and Okinawa Island led Kawanabe to propose that interactions among individuals affect interspecific relationships, and thereby, community structure. Discussions with Charles Elton, the famous British ecologist of Oxford University, strengthened Kawanabe's view that communities could be best understood as the whole of interrelationships among organisms. Kawanabe advanced these ideas during a joint study he led with a host of Japanese and Zairean scientists on the fishes of Lake Tanganyika, beginning in 1979. This work, as well as additional research on Lake Biwa in Japan, led to a deeper understanding of the complexity of biotic interactions (including competition, predation, mutualism, commensalism, and indirect effects) that promote the high species diversity in these ecosystems. In addition to basic research, Kawanabe was part of research teams organized during the 1960s by D. Miyadi to study the effects of public works projects on natural environments and biota in Lake Naka-umi and Lake Biwa. During the late 1980s he expanded his network to an international venue, both by organizing and hosting important international ecological meetings in Japan, such as the Fifth International Ecological Congress, and by increasing his international activities to promote global biodiversity. In 1991, Kawanabe founded the Center for Ecological Research at Kyoto University to study the interrelationships among organisms and their environments. Recently retired from the University, he became Director General of the new Lake Biwa Museum in 1996, and continues to promote conservation of biodiversity worldwide through an international network of scientists and organizations.     

God and natural selection: The Darwinian idea of design

Conclusion If we arrange in chronological order the various statements Darwin made about God, creation, design, plan, law, and so forth, that I have discussed, there emerges a picture of a consistent development in Darwin's religious views from the orthodoxy of his youth to the agnosticism of his later years. Numerous sources attest that at the beginning of the Beagle voyage Darwin was more or less orthodox in religion and science alike.⁷⁸ After he became a transmutationist early in 1837, he concluded that the doctrine of secondary causes must be extented even to the history of life and that after the first forms of life were created, there was no further need for divine intervention, except where man was concerned. Man's body, he thought, was produced by the process of transmutation, but he believed for a time that man's soul was superadded. By mid-1838 he had become convinced that nothing, after the creation of life, was due to miracles. God works only through laws, which are capable of producing every effect of evey kind which surrounds us. The existence of man, the idea of God in man's mind, and the harmony of the whole system were in his eyes prearranged goals of deterministic laws imposed by God. Such a conception excludes the miracles on which Christianity depends; but it is not possible to say whether Darwin's loss of Christian faith, which occurred at about this same time, preceded and made possible his materialism or was rather caused or hastened by it.⁷⁹ In the weeks after his reading of Malthus, Darwin's belief in a plan of creation gave way to the belief that God created matter and life and designed their laws, leaving the details, however, to the workings of chance. This remained his view until the 1860s.There is no exact parallel between this development of Darwin's religious views and the development of his ideas on evolution, but there is a general correspondence. When he believed in a plan of creation, Darwin's theory of transmutation did not depend on struggle or the selection of chance variations. Adaptation was, for him, an automatic response to environmental chance. From late 1838 to 1859 he believed in designed laws and chance, and this belief, too, has its parallel in his theory. The element of chance in natural selection meant that there could be no detailed plan,in which even man's idea of God would be a necessary outcome of nature's laws (man himself is not a necessary outcome of the working of natural selection).⁸⁰ But Darwin still believed nature was programmed to achieve certain general ends. We might say that he believed in a general, though not a special, teleology. Natural selection was for him a law to maximize utility, creating useful organs, retaining vestiges for future use. For many years it was a law designed to produce organisms perfectly adapted to their environments. Only later did Darwin come to doubt even this sort of design in nature.⁸¹ One way of describing the development of Darwin's evolutionary thought is to say that it shows a gradual abandoning of his theistic assumptions, so that by the late 1860s his theory was informed to a slighter extent by notions of purpose and design than it was in 1838 or 1844 or 1859.     

The “biological ego”. From Garrod's “chemical individuality” to Burnet's “self”

Starting from the conceptual premises of Garrod, who as long ago as 1902 spoke of chemical individuality, and of Burnet (1949), who recognized as self one's own molecular antigenic structures (as opposed to the antigenic alien: the non- self), the discovery and understanding of HLA antigens and of their extraordinarily individual and differentiated polymorphisms have gained universal recognition. Transplant medicine has now dramatically stressed, within man's knowledge of himself, the characteristic of his biological uniqueness. Today man, having become aware of being a biological antigenic-molecular individuality which is unique and different from that of all of his fellow men (except for monozygotic twins), can therefore easily consider himself a true biological Ego.Abbreviations BMT bone marrow transplantation - GVHD graft versus host disease - HLA human leukocyte antigens - MHC major histocompatibility complex - MLC mixed lymphocyte culture - MLR mixed lymphocyte reaction