Ute Deichmann

Methods and equations for analysing the kinetics of enzyme-catalysed reactions were developed at the beginning of the 20th century in two centres in particular; in Paris, by Victor Henri, and, in Berlin, by Leonor Michaelis and Maud Menten. Henri made a detailed analysis of the work in this area that had preceded him, and arrived at a correct equation for the initial rate of reaction. However, his approach was open to the important objection that he took no account of the hydrogen-ion concentration (a subject largely undeveloped in his time). In addition, although he wrote down an expression for the initial rate of reaction and described the hyperbolic form of its dependence on the substrate concentration, he did not appreciate the great advantages that would come from analysis in terms of initial rates rather than time courses. Michaelis and Menten not only placed Henri's analysis on a firm experimental foundation, but also defined the experimental protocol that remains standard today. Here, we review this development, and discuss other scientific contributions of these individuals. The three parts have different authors, as indicated, and do not necessarily agree on all details, in particular about the relative importance of the contributions of Michaelis and Menten on the one hand and of Henri on the other. Rather than force the review into an unrealistic consensus, we consider it appropriate to leave the disagreements visible.

Inheritance and variation were a major focus of Charles Darwin’s studies. Small inherited variations were at the core of his theory of organic evolution by means of natural selection. He put forward a developmental theory of heredity (pangenesis) based on the assumption of the existence of material hereditary particles. However, unlike his proposition of natural selection as a new mechanism for evolutionary change, Darwin’s highly speculative and contradictory hypotheses on heredity were unfruitful for further research. They attempted to explain many complex biological phenomena at the same time, disregarded the then modern developments in cell theory, and were, moreover, faithful to the widespread conceptions of blending and so-called Lamarckian inheritance. In contrast, Mendel’s approaches, despite the fact that features of his ideas were later not found to be tenable, proved successful as the basis for the development of modern genetics. Mendel took the study of the transmission of traits and its causes (genetics) out of natural history; by reducing complexity to simple particulate models, he transformed it into a scientific field of research. His scientific approach and concept of discrete elements (which later gave rise to the notion of discrete genes) also contributed crucially to the explanation of the existence of stable variations as the basis for natural selection. © Springer Science+Business Media B.V. 2010

Until the 1930s Germany had been the international leader in biochemistry, chemistry, and areas of biology. After WWII, however, molecular biology as a new interdisciplinary scientific enterprise was scarcely represented in Germany for almost 20 years. Three major reasons for the low performance of molecular biology are discussed: first, the forced emigration of Jewish scientists after 1933, which not only led to the expulsion of future distinguished molecular biologists, but also to a strong decline of ''dynamic biochemistry'', a field which contributed greatly to molecular biology. Second, German university structures that strongly impeded interdisciplinary research. Third, the international isolation and self-isolation of German scientists that was a major obstacle to the implementation of new fields of research developed elsewhere. Despite the fact that there was no official boycott against Germany as there had been after WWI and despite the Cold War policy of integrating Germans into the West, as a consequence of National Socialism and WWI for many years only very few German scientists gained access to the international community of molecular biologists. Max Delbruck played an important role in helping the Germans establish modern, mostly molecular, biology because he retained strong connections to Germany. Most importantly, it required a new generation of young scientists who had received part of their training in the US to establish modern molecular biology at German universities and Max Planck Institutes.

: In contrast to anti-Jewish campaigns at German universities in the 19th century, which met with opposition from liberal scholars, among them prominent chemists, there was no public reaction to the dismissals in 1933. Germany had been an international leader in (bio-)chemistry until the 1930s. Due to a high proportion of Jewish physicists, (bio-)chemistry was strongly affected by the expulsion of scientists. Organic and inorganic chemistry were least affected, while biochemistry suffered most. Polymer chemistry and quantum chemistry, of minor importance among the majority of academic chemists (despite pioneering work by German physicists) was further weakened by the expulsion of renowned scientists. However, a look at the research carried out in Nazi Germany shows that no field of research "emigrated" as such, except research into molecular beams. The reception of emigré (bio-)chemists differed with respect to their field of research and the degree of competition in the host countries. Thus biochemists and physical chemists were accepted at American universities, whereas organic chemists were not. In contrast, they received high positions in Turkey, Palestine/Israel, and Egypt. After WWII, few emigrés were asked to come back. The delay of the resumption of international contacts by German (bio-)chemists contributed to the delay in rebuilding in particular German biochemistry, the physical chemistry of polymers, and physical organic chemistry.

A recent cover of the German news magazine Der Spiegel announced: “Victory over Genes. Smarter, healthier, happier: How we can outwit our genome” (2010). The magazine’s article, instead, emphasizes the importance of epigenetics. According to Florian Maderspacher (2010), who reprinted the cover in his editorial in Current Biology, the relief or “schadenfreude” about the apparent victory over genes—which the cover, the article, and commentaries to it reveal—is, in part, a German phenomenon. It echoes “a latent anti-scientific attitude in parts of the German public,” which for historic reasons is particularly strong with regard to genetics: “After all, the idea that people’s properties—good or bad—are determined by ..

In Goethe's Faust, the poet refers to alchemists' widespread ideas on artificial creation of life in the laboratory. In Faust, such an attempt was not successful: the little man,Homunculus, created by the scholar Wagner through crystallization, was a pure spirit; his form and light disappeared in an attempt to become real life. According to Goethe, life was obviously not a crystal, and he pointed to decisive differences between crystals and organic beings, the latter for example elaborating their food into clear-cut organs and unable to be reconstituted from their ingredients, once destroyed. Thus Goethe's "sensitivity to the 'Gestalt' of the entire complicated organism and his general philosophical attitude ..

Between November 30th and December 2nd, 2015, the Jacques Loeb Centre for the History and Philosophy of the Life Sciences at Ben-Gurion University of the Negev in Beer Sheva held its Eighth International Workshop under the title “From Genome to Gene: Causality, Synthesis and Evolution”. Eric Davidson, the founder of the concept of developmental Gene Regulatory Networks, had regularly attended the previous meetings, and his participation in this one was expected, but he suddenly passed away 3 months before. In this paper, we provide an introduction and overview on five papers that were presented at the workshop and examine the importance of genomes and gene regulatory networks in extant biology, developmental biology, evolutionary biology and medicine, as well as a collection of remembrances of Eric Davidson, of his personality as well as of his scientific contributions. Historical perspectives are provided, and the ethical issues raised by the new tools developed to modify the genome are also discussed.

Eukaryotic genomes are packaged into a nucleoprotein complex known as chromatin. The term was introduced in 1879 by German cytologist Walther Flemming. While observing the processes of mitosis in a light microscope, Flemming coined the term to describe the easily stainable threads in the nucleus. He predicted that it would not have a long life: “The word chromatin may serve until its chemical nature is known, and meanwhile stands for that substance in the cell nucleus which is readily stained”. However, Flemming’s prediction did not come true. Although the chemical nature of chromatin—a complex of nucleic acid and proteins—was already elucidated at the end of the 19th century, the..

Eric Davidson, a passionate molecular developmental biologist and intellectual, believed that conceptual advances in the sciences should be based on knowledge of conceptual history. Convinced of the superiority of a causal-analytical approach over other methods, he succeeded in successfully applying this approach to the complex feature of organismal development by introducing the far-reaching concept of developmental Gene Regulatory Networks. This essay reviews Davidson’s philosophy, his support for the history of science, and some aspects of his scientific personality.

In this second decade of the 21st century, we find the pervasive influence of synthetic biology everywhere, not only in research laboratories, but also in the discourses of politicians and ethicists. Despite its ubiquity, the precise meaning of the notions of "synthetic biology" and "synthetic life," as well as their history, potential, and risks, remain obscure not only to the layperson, but also to most biologists.The aim of this special issue is twofold. First, it is intended to help the reader better appreciate what synthetic biology is all about and what are its roots. Second, once the overall picture has been expounded and made clearer, the questions of whether research in synthetic biology raises new and ..

The concepts of hierarchical organization, genetic determinism and biological specificity have played a crucial role in biology as a modern experimental science since its beginnings in the nineteenth century. The idea of genetic information and genetic determination was at the basis of molecular biology that developed in the 1940s with macromolecules, viruses and prokaryotes as major objects of research often labelled “reductionist”. However, the concepts have been marginalized or rejected in some of the research that in the late 1960s began to focus additionally on the molecularization of complex biological structures and functions using systems approaches. This paper challenges the view that ‘molecular reductionism’ has been successfully replaced by holism and a focus on the collective behaviour of cellular entities. It argues instead that there are more fertile replacements for molecular ‘reductionism’, in which genomics, embryology, biochemistry, and computer science intertwine and result in research that is as exact and causally predictive as earlier molecular biology.

Avery’s et al. ’s 1944 paper provides the first direct evidence of DNA having gene-like properties and marks the beginning of a new phase in early molecular genetics (with a strong focus on chemistry and DNA). The study of its reception shows that on the whole, Avery’s results were immediately appreciated and motivated new research on transformation, the chemical nature of DNA’s biological specificity and bacteria genetics. It shows, too, that initial problems of transferring transformation to other systems and prominent criticism of its results nurtured skepticism. Avery’s experiment was downplayed and neglected particularly by many of those scientists who worked in the new fields of biochemical and biophysical genetics, genetic phage, and TMV research. This was not due to the fact that the implications of the paper could not be connected to generally accepted knowledge. Contrary to a widespread belief, the assumed uniformity of DNA as opposed to proteins was not used as an argument against the validity of Avery’s et al.’s finding. The indifference rather reflected, among other things, the disciplinary gap between the chemically oriented microbiologists and the old and new geneticists who remained committed to genetic and physical methods (in particular x-ray studies) and clung to the assumption that proteins were the sole carriers of biological specificity. The responses to Avery’s et al.’s paper show how different research interests in the areas between microbiology, genetics, and biochemistry interacted with the prejudices, dogmas, individual farsightedness or short-sightedness, and scientific authority during a pivotal period of early molecular biology.

Dissatisfied with the descriptive and speculative methods of evolutionary biology of his time, the physiologist Jacques Loeb , best known for his “engineering” approach to biology, reflected on the possibilities of artificially creating life in the laboratory. With the objective of experimentally tackling one of the crucial questions of organic evolution, i.e., the origin of life from inanimate matter, he rejected claims made by contemporary scientists of having produced artificial life through osmotic growth processes in inorganic salt solutions. According to Loeb, the answer to the question of whether or not life could be created artificially had to come from macro-molecular chemistry, in particular from the research on the recently discovered DNA. He was convinced that a prerequisite for making living matter from inanimate substances was the chemical synthesis of nuclear material capable of self-replication. Moreover, Loeb, experimentally refuting some vitalistic explanations as well as colloidal chemists’ far-reaching claims that biologically relevant macromolecules follow colloidal rather than chemical laws, pioneered research on the physical and chemical explanations of biological phenomena

The encounter between two fundamentally different approaches in seminal research in molecular biology-the problems, aims, methods and metaphysics - is delineated and analyzed. They are exemplified by the microbiologist Oswald T. Avery who, in line with the reductionist mechanistic metaphysics of Jacques Loeb, attempted to explain basic life phenomena through chemistry; and the theoretical physicist Max Delbrück who, influenced by Bohr’s antimechanistic views, preferred to explain these phenomena without chemistry. Avery’s and Delbrück’s most important studies took place concurrently. Thus analysis of their contrasting approaches lends itself to examination of the Weltanschauungen view concerning the role of fundamental (metaphysical) assumptions in scientific change, that is, the view that empirical research cannot be neutral in regard to the worldviews of the researchers. This study shows that the initial ostensible disparity (non-integratibility) of the two approaches lasted for just a short time. Ironically it was a student of Delbrück’s school, James Watson, who (with Crick) proposed a chemical model, the DNA double helix, as a solution to Delbrück’s problem. The structure of DNA has not been seriously challenged over the past half century. Moreover, Watson’s and Crick’s work did not call into question the validity of Delbrück’s research, but opened it up to entirely new approaches. The case of Avery and Delbrück demonstrates that after initial obstacles were overcome the different fundamental attitudes and the resulting research practices were capable of integration. © 2008 Stazione Zoologica Anton Dohrn.

Reliabilist philosophy of science considers scientific misconduct a transgression against the principles of good cognitive practice. Good practice in research is characterised by the reliability, efficiency and fertility of the cognitive processes involved. The reliabilist approach is closely connected to the idea of mutual cognitive dependency of the research community. Trust in the testimony of others is not an inevitable but a favouring factor of scientific progress — and misconduct damages the testimonial chain, respectively the principle of trustworthiness. Within the reliabilist framework, the main focus on questionable research is not on whether or not there are fraudulent intentions , but on recognisable consequences for the research community. Criticising the constructivist modeling of questionable research, we reconstruct certain contributions by Emil Abderhalden, Richard Goldschmidt, Franz Moewus, and Ernst Waldschmitz-Leitz as serious misconducts respectively frauds. We also show that specific social factors — often regarded as “apologising” conditions — decisively interfere with the principle of trustworthiness in the scientific community

Inheritance and variation were a major focus of Charles Darwin’s studies. Small inherited variations were at the core of his theory of organic evolution by means of natural selection. He put forward a developmental theory of heredity (pangenesis) based on the assumption of the existence of material hereditary particles. However, unlike his proposition of natural selection as a new mechanism for evolutionary change, Darwin’s highly speculative and contradictory hypotheses on heredity were unfruitful for further research. They attempted to explain many complex biological phenomena at the same time, disregarded the then modern developments in cell theory, and were, moreover, faithful to the widespread conceptions of blending and so-called Lamarckian inheritance. In contrast, Mendel’s approaches, despite the fact that features of his ideas were later not found to be tenable, proved successful as the basis for the development of modern genetics. Mendel took the study of the transmission of traits and its causes (genetics) out of natural history; by reducing complexity to simple particulate models, he transformed it into a scientific field of research. His scientific approach and concept of discrete elements (which later gave rise to the notion of discrete genes) also contributed crucially to the explanation of the existence of stable variations as the basis for natural selection.

The concepts of hierarchical organization, genetic determinism and biological specificity have played a crucial role in biology as a modern experimental science since its beginnings in the nineteenth century. The idea of genetic information and genetic determination was at the basis of molecular biology that developed in the 1940s with macromolecules, viruses and prokaryotes as major objects of research often labelled “reductionist”. However, the concepts have been marginalized or rejected in some of the research that in the late 1960s began to focus additionally on the molecularization of complex biological structures and functions using systems approaches. This paper challenges the view that ‘molecular reductionism’ has been successfully replaced by holism and a focus on the collective behaviour of cellular entities. It argues instead that there are more fertile replacements for molecular ‘reductionism’, in which genomics, embryology, biochemistry, and computer science intertwine and result in research that is as exact and causally predictive as earlier molecular biology.