Search

In 1869, Johann Friedrich Miescher discovered a new substance in the nucleus of living cells. The substance, which he called nuclein, is now known as DNA, yet both Miescher's name and his theoretical ideas about nuclein are all but forgotten. This paper traces the trajectory of Miescher's reception in the historiography of genetics. To his critics, Miescher was a "contaminator," whose preparations were impure. Modern historians portrayed him as a "confuser," whose misunderstandings delayed the development of molecular biology. Each of these portrayals reflects the disciplinary context in which Miescher's work was evaluated. Using archival sources to unearth Miescher's unpublished speculations-including an analogy between the hereditary material and language, and a speculation that a series of asymmetric carbon atoms could account for hereditary variation-this paper clarifies the ways in which the past was judged through the lens of contemporary concerns. It also shows how organization, structure, function, and information were already being considered when nuclein was first discovered nearly 150 years ago.

I worked almost exclusively on nucleic acids and gene expression from the age of 19 as an undergraduate until the age of 38 as an associate professor. Mentors featured prominently in my choice of paths. My friendship with influential Brandeis colleagues then persuaded me that genetics was an important tool for studying gene expression, and I switched my experimental organism to yeast for this reason. Several years later, friendship also played a prominent role in my beginning work on circadian rhythms. As luck would have it, gene expression as well as genetics turned out to be important for circadian timekeeping. As a consequence, background and training put my laboratory in an excellent position to contribute to this aspect of the circadian problem. The moral of the story is, as in real estate, "location, location, location.", (Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.)

Francis' office window (at the Salk) commanded a panorama of the Pacific. "This grand natural scene was a physical correlate of Francis's intellectual world: wide-ranging, brilliantly lit, a little overawing, but also immensely inviting and above all an exciting place to be." (Mitchison, 2004)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The origins of genetics are to be found in Gregor Mendel's memoir on plant hybridization (1865). However, the word 'genetics' was only coined in 1906, to designate the new science of heredity. Founded upon the Mendelian method for analyzing the products of crosses, this science is distinguished by its explicit purpose of being a general 'science of heredity', and by the introduction of totally new biological concepts (in particular those of gene, genotype, and phenotype). In the 1910s, Mendelian genetics fused with the chromosomal theory of inheritance, giving rise to what is still called 'classical genetics'. Within this framework, the gene is simultaneously a unit of function and transmission, a unit of recombination, and of mutation. Until the early 1950s, these concepts of the gene coincided. But when DNA was found to be the material basis of inheritance, this congruence dissolved. Then began the venture of molecular biology, which has never stopped revealing the complexity of the way in which hereditary material functions., (Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.)

Jalal A. Aliyev was a distinguished and respected plant biologist of our time, a great teacher, and great human being. He was a pioneer of photosynthesis research in Azerbaijan. Almost up to the end of his life, he was deeply engaged in research. His work on the productivity of wheat, and biochemistry, genetics and molecular biology of gram (chick pea) are some of his important legacies. He left us on February 1, 2016, but many around the world remember him as he was engaged in international dialog on solving global issues, and in supporting international conferences on ''Photosynthesis Research for Sustainability" in 2011 and 2013.

Since the beginning of the last century, genetic research has been preoccupied with the dosage compensation question: What mechanism controls equal expression of chromosome X genes between females and males? In the 1950s, many discoveries occurred in the field of cytogenetics related to the sex chromatin of female mammals. Concomitantly, genetic information accumulated with regard to expression patterns of X-linked genes in female mice and the expression effect of translocations between chromosome X and autosomes. In addition, many case reports were published about families with sex-linked diseases. The lately deceased scientist Mary F. Lyon suggested a unifying theory of these findings. In her articles "Gene action in the X-chromosome of the mouse (Mus musculus L.T in 1961, and "Sex chromatin and gene action in the mammalian X-chromosome" in 1962, she suggested that: (1) the heteropyknotic chromosome X was genetically inactivated, (2) the inactivated chromosome X could be either paternal or maternal in origin in different cells of the same animal, and (3) the inactivation occurred early in embryonic development. This theory led to an immediate breakthrough in understanding the basic mechanisms responsible for X-linked diseases and solved many unexplained case studies. Moreover, the inquiry of the mechanism of the phenomenon promoted scientific understanding of a wide range of areas in molecular biology such as DNA methylation, the silencing mechanism by XIST, histone modifications, DNA replication timing and more. The current article deals with some biographical details about Mary F. Lyon, the background of her theory, her historical articles and the development of the field since.

This paper brings together the history of risk and the history of DNA repair, a biological phenomenon that emerged as a research field in between molecular biology, genetics, and radiation research in the 1960s. The case of xeroderma pigmentosum (XP), an inherited hypersensitivity to UV light and, hence, a disposition to skin cancer will be the starting point to argue that, in the 1970s and 1980s, DNA repair became entangled in the creation of new models of the human body at risk - what is here conceptually referred to as the vulnerability aspect of body history - and new attempts at cancer prevention and enhancement of the body associated with the new flourishing research areas of antimutagenesis and anticarcinogenesis. The aim will be to demonstrate that DNA repair created special attempts at disease prevention: molecular enhancement, seeking to identify means to increase the self-repair abilities of the body at the molecular level. Prevention in this sense meant enhancing the body's ability to cope with the environmental hazards of an already toxic world. This strategy has recently been adopted by the beauty industry, which introduced DNA care as a new target for skin care research and anti-aging formulas.

In 1953, Watson and Crick not only described the double-helix structure of DNA, but also embraced the idea that genes contained a code that expresses information and thereby changed our view of life. This article traces how these ideas entered biological thinking and highlights the connections between different branches of science at the time, exploring the power of metaphor in science., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The past 50 years have seen many changes in laboratory medicine, either as causes or consequences of increases in productivity and expansion of the range of information which can be provided. The drivers and facilitators of change in relation to clinical applications of molecular biology included the need for diagnostic tools for genetic diseases and technical advances such as PCR and sequencing. However, molecular biology techniques have proved to have far wider applications, from detection of infectious agents to molecular characterization of tumors. Journals such as Clinical Chemistry and Laboratory Medicine play an important role in communication of these advances to the laboratory medicine community and in publishing evaluations of their practical value.

This paper argues that the history of the computer, of the practice of computation and of the notions of 'data' and 'programme' are essential for a critical account of the emergence and implications of data-driven research. In order to show this, I focus on the transition that the investigations on the worm C. elegans experienced in the Laboratory of Molecular Biology of Cambridge (UK). Throughout the 1980s, this research programme evolved from a study of the genetic basis of the worm's development and behaviour to a DNA mapping and sequencing initiative. By examining the changing computing technologies which were used at the Laboratory, I demonstrate that by the time of this transition researchers shifted from modelling the worm's genetic programme on a mainframe apparatus to writing minicomputer programs aimed at providing map and sequence data which was then circulated to other groups working on the genetics of C. elegans. The shift in the worm research should thus not be simply explained in the application of computers which transformed the project from hypothesis-driven to a data-intensive endeavour. The key factor was rather a historically specific technology-in-house and easy programmable minicomputers-which redefined the way of achieving the project's long-standing goal, leading the genetic programme to co-evolve with the practices of data production and distribution., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The aim of this article is (1) to investigate the "neurosciences" as an object of study for historical and genealogical approaches and (2) to characterize what we identify as a particular "style of thought" that consolidated with the birth of this new thought community and that we term the "neuromolecular gaze." This article argues that while there is a long history of research on the brain, the neurosciences formed in the 1960s, in a socio-historical context characterized by political change, faith in scientific and technological progress, and the rise of a molecular gaze in the life sciences. They flourished in part because these epistemological and technological developments were accompanied by multiple projects of institution-building. An array of stakeholders was mobilized around the belief that breakthroughs in understanding the brain were not only crucial, they were possible by means of collaborative efforts, cross-disciplinary approaches and the use of a predominantly reductionist neuromolecular method. The first part of the article considers some of the different approaches that have been adopted to writing the history of the brain sciences. After a brief outline of our own approach, the second part of the article uses this in a preliminary exploration of the birth of the neurosciences in three contexts. We conclude by arguing that the 1960s constitute an important "break" in the long path of the history of the brain sciences that needs further analysis. We believe this epistemological shift we term the "neuromolecular gaze" will shape the future intellectual development and social role of the neurosciences.

Understanding how scientific activities use naming stories to achieve disciplinary status is important not only for insight into the past, but for evaluating current claims that new disciplines are emerging. In order to gain a historical understanding of how new disciplines develop in relation to these baptismal narratives, we compare two recently formed disciplines, systems biology and genomics, with two earlier related life sciences, genetics and molecular biology. These four disciplines span the twentieth century, a period in which the processes of disciplinary demarcation fundamentally changed from those characteristic of the nineteenth century. We outline how the establishment of each discipline relies upon an interplay of factors that include paradigmatic achievements, technological innovation, and social formations. Our focus, however, is the baptism stories that give the new discipline a founding narrative and articulate core problems, general approaches and constitutive methods. The highly plastic process of achieving disciplinary identity is further marked by the openness of disciplinary definition, tension between technological possibilities and the ways in which scientific issues are conceived and approached, synthesis of reductive and integrative strategies, and complex social interactions. The importance--albeit highly variable--of naming stories in these four cases indicates the scope for future studies that focus on failed disciplines or competing names. Further attention to disciplinary histories could, we suggest, give us richer insight into scientific development.

The paper aims at reconstructing the scientific career of Adriano Buzzati-Traverso, a prominent character in Italian biology after the Second World War. In the Fifties and the Sixties, he was able to introduce the new molecular approaches in life sciences. A great scientific manager, much ahead of his times (at least in Italy), he successfully organized the first postgraduate courses of genetics and molecular biology in Pavia, and later created the International Laboratory of Genetics and Biophysics in Naples. Between 1962 and 1969, this institution gained the greatest respect in the scientific community, but the political turmoil in 1969 abruptly ended this fascinating attempt to modernize Italian science. Buzzati-Traverso's personal archive allows us to reconstruct the detailed history of his scientific enterprises, focusing particularly on the hard struggle to modernize management and policies of Italian science.

The classical Mendelian genetics forged the development of biomedical sciences in the twentieth century. However, the classical works that allowed the sequencing of human genoma, have not received the recognition that they deserve. The author does a historical revision of works, considered classic in genetics and its specialties such as cytogenetics, biochemical genetics, immunogenetics and molecular genetics, published between 1990 and 1999. Authors that received the Nobel Prize are identified and the works are sorted in chronological order. Most founders of genetics specialties, have not received the Nobel Prize. Only 26 of 80 classical works have been awarded with such distinction. Almost all founders of Mendelian genetics and human cytogenetics, have been unrewarded. The author proposes to create the "Johan Gregory Mendel Prize" for geneticists.

I have tried to unpack the polysemy of the word epigenetics by adopting a historical point of view and by focusing on the models that were proposed at the beginning of the 1960s to explain variations in gene activity during cell differentiation and development. Most of the questions that were or are at the core of epigenetics were posed in this period. This was due to the fact that the regulatory models and their extension to the notion of the genetic program were proposed as genetic answers to the questions raised by Waddington when he defined epigenetics in the 1940s. Studies of DNA methylation and chromatin structure, which became increasingly important in the 1960s and 1970s, were seen as alternative explanations to the regulatory mechanisms that had been previously proposed. This historical detour shows that epigenetics cannot be defined per se, but only as an evolving opposition to the piecemeal, reductionist approach of genetics.

The classical view of the gene prevailing during the 1910s and 1930s comprehended the gene as the indivisible unit of genetic transmission, genetic recombination, gene mutation and gene function. The discovery of intragenic recombination in the early 1940s led to the neoclassical concept of the gene, which prevailed until the 1970s. In this view the gene or cistron, as it was now called, was divided into its constituent parts, the mutons and recons, materially identified as nucleotides. Each cistron was believed to be responsible for the synthesis of one single mRNA and concurrently for one single polypeptide. The discoveries of DNA technology, beginning in the early 1970s, have led to the second revolution in the concept of the gene in which none of the classical or neoclassical criteria for the definition of the gene hold strictly true. These are the discoveries concerning gene repetition and overlapping, movable genes, complex promoters, multiple polyadenylation sites, polyprotein genes, editing of the primary transcript, pseudogenes and gene nesting. Thus, despite the fact that our comprehension of the structure and organization of the genetic material has greatly increased, we are left with a rather abstract, open and general concept of the gene. This article discusses past and present contemplations of genes, genomes, genotypes and phenotypes as well as the most recent advances of the study of the organization of genomes.

The history of modern genetics in Germany during the 20th century is a story of missed chances. In the USA the genetic revolution opened a fascinating new field for ambitious scientists and created a rapidly growing new industry. Meanwhile Germany stood aside, combating with political and social restrictions. Promising young scientists who wanted to work in the field left Germany for the US, and big companies moved their facilities out of the country. Up until the middle of the 1990s molecular biology in Germany remained a "sleeping beauty" even though many brilliant scientists did their jobs very well. Then a somewhat funny idea changed everything: the German minister for education and science proclaimed the BioRegio contest in order to award the most powerful biotechnology region in Germany concerning academia and especially industry. Since then Germany's biotechnology industry has grown constantly and rapidly due to the foundation of a number of small biotech companies; big companies have returned their interests and their investments to Germany, paralleled by an improvement in academic research because of more funding and better support especially for younger scientists. In respect to biotechnology and molecular biology, Germany is still a developing country, but it has started to move and to take its chances in an exciting global competition.

The problem of gene function--of the relationships between hereditary material and the characteristics of organisms--preceded the rediscovery of Mendel's laws and accompanied the development of genetics in the XXth century. Molecular biologists replaced the simple gene-character relationship by two relationships: the first, between genes and proteins, was well defined, whereas the second between proteins and the complex structural and functional characteristics of organisms remained unknown. I will describe in this article the experimental approaches which helped to characterize during the last twenty years the relationships between proteins and characters. Four principles of macromolecular organization emerged from these studies: conservation of the elementary components during evolution, existence of pathways and networks, pleiotropy and redundancy. These principles are the explanation of the surprising experimental observations that have been made in recent years. The existence of these principles makes problematic any prediction on the consequences of gene modification. It both sounds the death-knell of the simplistic reductionist approach of many biologists, whereby genes were considered as responsible for specific functions, and definitely prevents the distribution of genes in separate, well defined categories.

In the first half-century of genetics, 1900 to 1953, the main techniques were breeding experiments and microscopy. Emphasis was on transmission genetics and cytogenetics, and during the half-century these became mature sciences. But the gene remained elusive. In 1953, thanks to Watson and Crick, the nature of the gene was no longer a mystery. In the second half of the century, the techniques became more chemical and computers played an indispensable role. The emphasis was then on gene action and, in the human, on increasingly accurate gene mapping and the soon-to-be-completed DNA sequence. During the first half-century, human genetics was very primitive, but by the end of the century it was comparable to that of the best-studied species. This trend will surely extend to the next century. The humanitarian possibilities of new techniques are enormous, but social judgments about their use and the problems of an increasingly crowded planet temper our optimism.

Although molecular biology is a young discipline, it originated in the second half of the 19th century with the simultaneous discoveries of the laws of heredity by Mendel and of nucleic acid by Miescher. It was not until about 1950 that the structure of DNA was determined and it was proved that DNA governs the hereditary properties. Subsequently, the developments followed in rapid succession with the unravelling of the hereditary code, the elucidation of the mechanism of the translation of DNA into proteins, the discovery of the structure of genes and the finding of the methods for genetic manipulation. These have proved essential for the evolution of modern biotechnology.

The first cognitive-theoretical model in genetics developed by Morgan and his disciples on the basis of physicochemical reductionism is reviewed. The pathway of the gene theory remains unfinished due to many reasons, nevertheless, Morgan left it open for further development and integration with other disciplines.

French genetics had unusual beginnings. There are clear indications that the French biological establishment resisted Mendelian genetics strenuously from about 1910 to 1940. From about 1930 to 1950 several unconventional research programs with a strongly physiological orientation paved the way for the full entrance of French biology into genetics after World War II. This review examines some salient features of this history to clarify the strengths, weaknesses, and distinctive features of French genetics until about 1965. We suggest that after that data French genetics slowly merged into the international mainstream as genetics has become a largely molecular discipline.