Weismann Rules! OK? Epigenetics and the Lamarckian temptation

August Weismann rejected the inheritance of acquired characters on the grounds that changes to the soma cannot produce the kind of changes to the germ-plasm that would result in the altered character being transmitted to subsequent generations. His intended distinction, between germ-plasm and soma, was closer to the modern distinction between genotype and phenotype than to the modern distinction between germ cells and somatic cells. Recently, systems of epigenetic inheritance have been claimed to make possible the inheritance of acquired characters. I argue that the sense in which these claims are true does not challenge fundamental tenets of neo-Darwinism. Epigenetic inheritance expands the range of options available to genes but evolutionary adaptation remains the product of natural selection of ‘random’ variation.     

August Weismann's theory of the germ-plasm and the problem of unconceived alternatives

I have argued elsewhere that scientific realism is most significantly challenged neither by traditional arguments from underdetermination of theories by the evidence, nor by the traditional pessimistic induction, but by a rather different historical pattern: our repeated failure to conceive of alternatives to extant scientific theories, even when those alternatives were both (1) well-confirmed by the evidence available at the time and (2) sufficiently scientifically serious as to be later embraced by actual scientific communities. Here I use August Weismann's defense of his influential germ-plasm theory of inheritance to support my claim that this pattern characterizes the history of theoretical scientific investigation generally. Weismann believed that the germ-plasm must become disintegrated into its constituent elements over the course of development, I argue, only because he failed to conceive of any possible alternative mechanism of ontogenetic differentiation. This and other features of the germ-plasm theory, I suggest, reflect a still more fundamental failure to imagine that the germ-plasm might be a productive rather than expendable resource for the cell. Weismann's case provides impressive support for the problem of unconceived alternatives while rendering its challenge to scientific realism deeper and sharper in a number of important ways.     

Hugo De Vries: from the theory of intracellular pangenesis to the rediscovery of Mendel

On the basis of the article by the Dutch botanist Hugo De Vries 'On the law of separation of hybrids' published in the Reports of the Académie des Sciences in 1900, and the beginning of the controversy about priority with Carl Correns and Erich von Tschermak, I consider the question of the posthumous influence of the Mendel paper. I examine the construction of the new theoretical framework which enabled its reading in 1900 as a clear and acceptable presentation of the rules of the transmission of hereditary characters. In particular, I analyse the introduction of the idea of determinants of organic characters, understood as separable material elements which can be distributed randomly in descendants. Starting from the question of heredity, such as it was defined by Darwin in 1868, and after its critical developments by August Weismann, Hugo De Vries was able to suggest such an idea in his Intracellular Pangenesis. He then laid out a programme of research which helps us to understand the 'rediscovery' published in 1900.     

The Development of Francis Galton's Ideas on the Mechanism of Heredity

Galton greeted Darwin's theory of pangenesis with enthusiasm, and tried to test the assumption that the hereditary particles circulate in the blood by transfusion experiments on rabbits. The failure of these experiments led him to reject this assumption, and in the 1870s he developed an alternative theory of heredity, which incorporated those parts of Darwin's theory that did not involve the transportation of hereditary particles throughout the system. He supposed that the fertilized ovum contains a large number of hereditary elements, which he collectively called the “stirp,” a few of which are patent, developing into particular cell types, while the rest remain latent; the latent elements can be transmitted to the next generation, while the patent elements, with rare exceptions, cannot since they have developed into cells. The problem with this theory is that it does not explain the similarity between parent and child unless there is a high correlation between latent and patent elements. Galton probably came to realize this problem during his subsequent statistical work on heredity, and he quietly dropped the idea that patent elements are not transmitted in Natural Inheritance (1889). Galton thought that brothers and sisters had identical stirps, and he attributed differences between them to variability in the choice of patent elements from the stirp, that is to say to developmental variability. He attributed the likeness of monozygotic twins to the similarity of their developmental environment. Galton's twin method was to track the life history changes of twins to see whether twins who were similar at birth diverged in dissimilar environments or whether twins who were dissimilar at birth converged in similar environments. It is quite different from the modern twin method of comparing the similarities between monozygotic and dizygotic twins, on the assumption that monozygotic twins are genetically identical whereas dizygotic twins are not. It has been argued that Galton foreshadowed Weismann's theory of the continuity of the germ-plasm, but this is only true in a weak sense. They both believed that the inheritance of acquired characters was either rare or impossible, but Galton did not forestall the essential part of Weismann's theory, that the germ-plasm of the zygote is doubled, with one part being reserved for the formation of the germ-cells. This revised version was published online in July 2006 with corrections to the Cover Date.     

Phenoptosis as genetically determined aging influenced by signals from the environment

Aging is a complex and not well understood process. Two opposite concepts try to explain its causes and mechanisms — programmed aging and aging of “wear and tear” (stochastic aging). To date, much evidence has been obtained that contradicts the theories of aging as being due to accumulation of various damages. For example, creation of adequate conditions for the functioning of the organism’s components (appropriate microenvironment, humoral background, etc.) has been shown to cause partial or complete reversibility of signs of its aging. Programmed aging and death of an organism can be termed phenoptosis by analogy to the term apoptosis for programmed cell death (this term was first suggested by V. P. Skulachev). The necessity of this phenomenon, since A. Weismann, has been justified by the need for population renewal according to ecological and evolutionary requirements. Species-specific lifespan, age-dependent changes in expression pattern of genes, etc. are compatible with the concept of phenoptosis. However, the intraspecific rate of aging was shown to vary over of a wide range depending on living conditions. This means that the “aging program” is not set rigidly; it sensitively adjusts an individual to the specific realities of its habitat. Moreover, there are indications that in rather severe conditions of natural habitat the aging program can be completely cancelled, as the need for it disappears because of the raised mortality from external causes (high extrinsic mortality), providing fast turnover of the population.     

Weismann Versus Morgan Revisited: Clashing Interpretations on Animal Regeneration

This paper has three principal aims: first, through a detailed analysis of the hypotheses and assumptions underlying Weismann’s and Morgan’s disagreement on the nature of animal regeneration, it seeks to readdress the imbalance in coverage of their discussion, providing, at the same time, a fascinating case-study for those interested in general issues related to controversies in science. Second, contrary to Morgan’s beliefs according to which Weismann employed a speculative and unempirical method of scientific investigation, the article shows that Weismann performed experiments, made observations and proposed ‘undogmatic’ theories open to refutation. Third, through the reconstruction of Weismann’s and Morgan’s disagreement, this study illustrates how biology, during the very late nineteenth and early twentieth centuries, was undergoing important changes. I argue that this controversy clearly and convincingly demonstrates how some important epistemic assumptions became increasingly problematic for some members of the younger generations of biologists. At the end of my discussion I will also argue that Weismann and Morgan both had strong well-grounded arguments supporting their conclusions; for this reason I suggest a few factors (“taken-for-granted” beliefs or assumptions) that could explain why their disagreement was doomed to remain unresolved. In particular, I will analyze their diverse explicative interests, their different theoretical concerns and their distinct use of the available evidence.     

The Case of Paul Kammerer: Evolution and Experimentation in the Early 20th Century

To some, a misguided Lamarckian and a fraud, to others a martyr in the fight against Darwinism, the Viennese zoologist Paul Kammerer (1880–1926) remains one of the most controversial scientists of the early 20th century. Here his work is reconsidered in light of turn-of-the-century problems in evolutionary theory and experimental methodology, as seen from Kammerer’s perspective in Vienna. Kammerer emerges not as an opponent of Darwinism, but as one would-be modernizer of the 19th-century theory, which had included a role for the inheritance of acquired characteristics. Kammerer attempted a synthesis of Darwinism with genetics and the chromosome theory, while retaining the modifying effects of the environment as the main source of favorable variation, and he developed his program of experimentation to support it. Kammerer never had a regular university position, but worked at a private experimental laboratory, with sidelines as a teacher and a popular writer and lecturer. On the lecture circuit he held forth on the significance of his science for understanding and furthering cultural evolution and he satisfied his passion for the arts and performance. In his dual career as researcher and popularizer, he did not always follow academic convention. In the contentious and rapidly changing fields of heredity and evolution, some of his stances and practices, as well as his outsider status and part-Jewish background, aroused suspicion and set the stage for the scandal that ended his career and prompted his suicide.     

Darwin's artificial selection as an experiment

Darwin used artificial selection (ASN) extensively and variedly in his theorizing. Darwin used ASN as an analogy to natural selection; he compared artificial to natural varieties, hereditary variation in nature to that in the breeding farm; and he also compared the overall effectiveness of the two processes. Most historians and philosophers of biology have argued that ASN worked as an analogical field in Darwin's theorizing. I will argue rather that this provides a limited and somewhat muddled view of Darwinian science. I say "limited" because I will show that Darwin also used ASN as a complex experimental field. And I say "muddled" because, if we concentrate on the analogical role exclusively, we conceive Darwinian science as rather disconnected from contemporary conceptions of "good science". I will argue that ASN should be conceived as a multifaceted experiment. As a traditional experiment, ASN established the efficacy of Darwin's preferred cause: natural selection. As a non-traditional experiment, ASN disclosed the nature of a crucial element in Darwin's evolutionary mechanics: the nature of hereditary variation. Finally, I will argue that the experiment conception should help us make sense of Darwin's comments regarding the "monstrous" nature of domestic breeds traditionally considered to be problematic.     

The reactions on Hugo de Vries's Intracellular pangenesis: the discussion with August Weismann

In 1889 Hugo de Vries published Intracellular Pangenesis in which heformulated his ideas on heredity. The highexpectations of the impression these ideaswould make did not come true and publicationwas negated or reviewed critically. From thereactions of his Dutch colleagues and thediscussion with the famous German zoologistAugust Weismann we conclude that the assertionthat each cell contains all hereditary materialwas controversial and even more the claim thatcharacters are inherited independently of eachother. De Vries felt that he had to convincehis colleagues of the validity of his theory byproviding experimental evidence. He establishedan important research program which resulted inthe rediscovery of Mendel's laws and thepublication of The Mutation Theory.This article also illustrates somephenomena that go beyond an interesting episodein the development of theories of heredity. Itshows that criticism from colleagues can move aresearcher so deeply that he feels compelled toset up an extensive research program. Moreoverit illustrates that it is not unusual that acreative scientist is only partially willing totake criticism on his theories into account.Last but not least it demonstrates that commonopinion on the validity of specific argumentsmay change in the course of time.     

Meiosis in perspective.

Our understanding of meiosis springs from two suggestions made by Weismann in 1887. One was that meiosis would be found to compensate for fertilization in the life cycles of both sexes and all organisms. The other was that the development of sexual reproduction in evolution depended on the value of meiosis in exposing the results of genetic recombination to natural selection. In confirming these propositions we were bound to discover that the properties of meiosis appear both as the causes and the consequences of evolution: it is the hinge on which turns the evolution of breeding method, reproductive habit, life cycle and hereditary structure, that is the genetic system, in all sexually reproducing species of organism. We have had three main fields of attack on our problem. First, there was the natural variation of meiosis including that of two-track hereditary within the species: here, animals took the lead. Secondly, there was the experimental field - both with genetic controls such as polyploidy and the sterilizing mutations of mitosis as well as meiosis, and with physical and chemical controls: here, the higher plants and micro-organisms have given us our great opportunities. Thirdly, we have the widening field where physicochemical knowledge and genetic control converge and collaborate. In all this work we have to be aware that meiosis works with chromosomes which always have the two functions of accomplishing evolution and of implementing its results in heredity. In consequence, the adaptation of meiosis is perpetually imperfect.     

DNA repair in neural cells: basic science and clinical implications

As one part of a distinguished scientific career, Dr. Bryn Bridges focused his attention on the issue of DNA damage and repair in stationary phase bacteria. His work in this area led to his interest in DNA repair and mutagenesis in another non-dividing cell population, the neurons in the mammalian nervous system. He has specifically taken an interest in the magnocellular neurons of the central nervous system, and the possibility that somatic mutations may be occurring in these neurons. As part of this special issue dedicated to Bryn Bridges upon his retirement, I will discuss the various DNA repair pathways known to be active in the nervous system. The importance of DNA repair to the nervous system is most graphically illustrated by the neurological abnormalities observed in patients with hereditary diseases associated with defects in DNA repair. I will consider the mechanisms underlying the neurological abnormalities observed in patients with four of these diseases: xeroderma pigmentosum (XP), Cockayne's syndrome (CS), ataxia telangectasia (AT) and AT-like disorder (ATLD). I will also propose a mechanism for one of the observations indicating that somatic mutation can occur in the magnocellular neurons of the aging rat brain. Finally, as a parallel to Bridges inquiry into how much DNA synthesis is going on in stationary phase bacteria, I will address the question of how much DNA synthesis in going on in neurons, and the implications of the answer to this question for recent studies of neurogenesis in adult mammals.     

John Lawrance Nicholls, MNZM BSc (NZ), 2 December 1920 – 19 August 2010

The passing of John Nicholls in Rotorua on 19 August 2010 marks the end of an era in New Zealand forest ecology. John was intimately involved in the National Forest Survey of 1946–55 and oversaw the subsequent Ecological Survey (1960–67) that filled gaps in the original survey. Though undertaken initially to assess remaining timber volumes, these initiatives also acquired a vast amount of ecological data. Through them and his own thirst for knowledge, John gained unparalleled insights into the compositional variation of New Zealand forests that were later to prove invaluable in his career in forest mapping, reserve designation, and biogeographic classification.     

Nuclear responses to MPF activation and inactivation in Xenopus oocytes and early embryos

The cell cycle of most organisms is highlighted by characteristic changes in the appearance and activity of the nucleus. Structural changes in the nucleus are particularly evident when a cell begins to divide. At this time, the nuclear envelope is disassembled, the chromatin condenses into metaphase chromosomes, and the chromosomes associate with a newly formed spindle. Upon completion of cell division the nuclear envelope reassembles around the chromosomes as they form telophase nuclei, and subsequently interphase nuclei, in the daughter cells. The cytoplasmic control of nuclear behavior has been the theme of Yoshio Masui's research for much of his career. His pioneering demonstration that the cytoplasm of maturing amphibian oocytes causes the resumption of the meiotic cell cycle when it is injected into an immature oocyte provided unequivocal evidence that a cytoplasmic factor could initiate the transition from interphase to metaphase (M-phase) in intact cells. As described in several reviews in this and the previous issue of Biology of the Cell (see Beckhelling and Ford; Duesbery and Vande Woude; Maller), Masui initially called this activity maturation promoting factor (MPF), but when it was realized that it was a ubiquitous regulator of both mitotic and meiotic cell cycles, MPF came to stand for M-phase promoting factor. Biochemical evidence indicates that MPF activity is composed of a mitotic B-type cyclins and cyclin-dependent kinase 1. The increase in the protein kinase activity of cdk1 initiates the changes in the nucleus associated with oocyte maturation and with the entry into mitosis. This article will attempt to provide a brief summary of the responses of the nucleus to the activation of MPF. In addition, the effect of MPF inactivation on nuclear envelope assembly at the end of mitosis will be discussed. This article is written as a tribute to Yoshio Masui on his retirement from the University of Toronto, and as an expression of gratitude for his guidance while I was a student in his laboratory. I have felt very privileged to have known him as a mentor and a friend.     

The Origins of Species: The Debate between August Weismann and Moritz Wagner

Weismann’s ideas on species transmutation were first expressed in his famous debate with Moritz Wagner on the mechanism of speciation. Wagner suggested that the isolation of a colony from its original source is a preliminary and necessary factor for speciation. Weismann accepted a secondary, facilitating role for isolation, but argued that natural and sexual selection are the primary driving forces of species transmutation, and are always necessary and often sufficient causes for its occurrence. The debate with Wagner, which occurred between 1868 and 1872 within the framework of Darwin’s discussions of geographical distribution, was Weismann’s first public battle over the mechanism of evolution. This paper, which offers the first comprehensive analysis of this debate, extends previous analyses and throws light on the underlying beliefs and motivations of these early evolutionists, focusing mainly on Weismann’s views and showing his commitment to what he later called “the all sufficiency of Natural Selection.” It led to the crystallization of his ideas on the central and essential role of selection, both natural and sexual, in all processes of evolution, and, already at this early stage in his theoretical thinking, was coupled with sophisticated and nuanced approach to biological organization. The paper also discusses Ernst Mayr’s analysis of the debate and highlights aspects of Weismann’s views that were overlooked by Mayr and were peripheral to the discussions of other historians of biology.     

The bacteriophage, its role in immunology: how Macfarlane Burnet's phage research shaped his scientific style

The Australian scientist Frank Macfarlane Burnet-winner of the Nobel Prize in 1960 for his contributions to the understanding of immunological tolerance-is perhaps best recognized as one of the formulators of the clonal selection theory of antibody production, widely regarded as the 'central dogma' of modern immunology. His work in studies in animal virology, particularly the influenza virus, and rickettsial diseases is also well known. Somewhat less known and publicized is Burnet's research on bacteriophages, which he conducted in the first decade of his research career, immediately after completing medical school. For his part, Burnet made valuable contributions to the understanding of the nature of bacteriophages, a matter of considerable debate at the time he began his work. Reciprocally, it was while working on the phages that Burnet developed the scientific styles, the habits of mind and laboratory techniques and practices that characterized him for the rest of his career. Using evidence from Burnet's published work, as well as personal papers from the period he worked on the phages, this paper demonstrates the direct impact that his experiments with phages had on the development of his characteristic scientific style and approaches, which manifested themselves in his later career and theories, and especially in his thinking regarding various immunological problems.     

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Summary Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro.In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research.     

Prokaryotic species are sui generis evolutionary units

Many gene flow barriers associated with genetic isolation during eukaryotic species divergence, are lacking in prokaryotes. In these organisms the processes associated with horizontal gene transfer (HGT) may provide both the homogenizing force needed for genetic cohesion and the genetic variation essential to speciation. This is because HGT events can broadly be grouped into genetic conversions (where endogenous genetic material are replaced with homologs acquired from external sources) and genetic introductions (where novel genetic material is acquired from external sources). HGT-based genetic conversions therefore causes homogenization, while genetic introductions drive divergence of populations upon fixation of genetic variants. The impact of HGT in different prokaryotic species may vary substantially and can range from very low levels to rampant HGT, producing chimeric groups of isolates. Combined with other evolutionary processes, these varying levels of HGT causes diversity space to be occupied by unique groups that are mostly incomparable in terms of genetic similarity, genomic cohesion and evolutionary age. As a result, the conventional, cut-off based metrics for species delineation are not adequate. Rather, a pluralistic approach to prokaryotic species recognition is required to accommodate the unique evolutionary ages and tendencies, population dynamics, and evolutionary fates of individual prokaryotic species. Following this approach, all prokaryotic species may be regarded as unique and each of their own kind (sui generis). Taxonomic decisions thus require evolutionary information that integrates vertical inheritances with all possible sources of genetic heterogeneity to ultimately produce robust and biologically meaningful classifications.     

William Bateson from <Emphasis Type="Italic">Balanoglossus</Emphasis> to <Emphasis Type="Italic">Materials for the Study of Variation</Emphasis>: The Transatlantic Roots of Discontinuity and the (un)naturalness of Selection

William Bateson (1861–1926) has long occupied a controversial role in the history of biology at the turn of the twentieth century. For the most part, Bateson has been situated as the British translator of Mendel or as the outspoken antagonist of W.␣F. R. Weldon and Karl Pearson’s biometrics program. Less has been made of Bateson’s transition from embryologist to advocate for discontinuous variation, and the precise role of British and American influences in that transition, in the years leading up to the publication of his massive Materials for the Study of Variation (1894). In this paper, I first attempt to trace Bateson’s development in his early career before turning to search for the development of the moniker “anti-Darwinist” that has been attached to Bateson in well-known histories of the neo-Darwinian Synthesis.