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Bacterial cytoplasmic membrane vesicles provide a unique experimental system for studying active transport. Vesicles are prepared by lysis of osmotically sensitized cells (i.e., protoplasts or spheroplasts) and comprise osmotically intact, unit-membrane-bound sacs that are approximately 0.5-1.0 μm in diameter and devoid of internal structure. Their metabolic activities are restricted to those provided by the enzymes of the membrane itself, and each vesicle is functional. The energy source for accumulation of a particular substrate can be determined by studying which compounds or experimental conditions drive solute accumulation, and metabolic conversion of the transported substrate or the energy source is minimal. These properties of the vesicle system constitute a considerable advantage over intact cells, as the system provides clear definition of the reactions involved in the transport process. This discussion is not intended as a general review but is concerned with respiration-dependent active transport in membrane vesicles from Escherichia coli . Emphasis is placed on experimental observations demonstrating that respiratory energy is converted primarily into work in the form of a solute concentration gradient that is driven by a proton electrochemical gradient, as postulated by the chemiosmotic theory of Peter Mitchell.

My career has been about discovering science and learning the joys of the discovery process itself. It has been a challenging but rewarding process filled with many exciting moments and wonderful colleagues and students. Although I went to college to become a French major, I ultimately stumbled into research while pursuing a Masters Degree in teaching. Thus, my research career began in graduate school where I was studying NAD kinase in the ovary as a possible regulator of steroidogenesis, a big issue in the late 1960s. After a short excursion of teaching in North Dakota, I became a postdoctoral fellow at the University of Michigan, where radio-immuno assays and radio receptor assays had just come on the scene and were transforming endocrinology from laborious bioassays to quantitative science and of course these assays related to the ovary. From there I went to Baylor College of Medicine, a mecca of molecular biology, cloning genes and generating mouse models. It has been a fascinating and joyous journey.

The invention of partition chromatography by the biochemists Archer Martin and Richard Synge in 1941 offered crucial insights into the structure and function of DNA, insights at least as important as those from X-ray crystallography. Even so, the role that partition chromatography played in molecular biological studies is far less well known. Using new archival material, this article describes the origins of Martin and Synge's work, arguing that their achievement was far more than a new technical innovation; it went on to have a profound impact on the development of molecular biology to an extent that scholars have insufficiently appreciated., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Between about 1951 and the early 1960s, the basic structure of molecular biology was revealed. Central to our understanding was the unraveling of the various roles of RNA, culminating in the identification of messenger RNA (mRNA) and the deciphering of the genetic code. We know a great deal about the role of Brenner, Crick, Jacob, and Nirenberg in these discoveries, but many others played important supporting parts. One of these is a little-known scientist, Martynas Yčas, who appears in histories, generally without explanation, as the "archivist of the RNA Tie Club." Yčas was born in Lithuania. His father helped write the Lithuanian Constitution in 1919. He studied Roman Law and served in the Lithuanian army before escaping from the Russians in 1940. The records of correspondence of Yčas with the physicist George Gamow and with Francis Crick throw some light on the genesis of our understanding of the role of mRNA. The story of the "RNA Tie Club" illustrates the difficulty in assigning credit for important discoveries and underscores the importance of a free exchange of information, even (or especially) among competitors., (Copyright © 2019 by the Genetics Society of America.)

The Bermuda Principles for DNA sequence data sharing are an enduring legacy of the Human Genome Project (HGP). They were adopted by the HGP at a strategy meeting in Bermuda in February of 1996 and implemented in formal policies by early 1998, mandating daily release of HGP-funded DNA sequences into the public domain. The idea of daily sharing, we argue, emanated directly from strategies for large, goal-directed molecular biology projects first tested within the "community" of C. elegans researchers, and were introduced and defended for the HGP by the nematode biologists John Sulston and Robert Waterston. In the C. elegans community, and subsequently in the HGP, daily sharing served the pragmatic goals of quality control and project coordination. Yet in the HGP human genome, we also argue, the Bermuda Principles addressed concerns about gene patents impeding scientific advancement, and were aspirational and flexible in implementation and justification. They endured as an archetype for how rapid data sharing could be realized and rationalized, and permitted adaptation to the needs of various scientific communities. Yet in addition to the support of Sulston and Waterston, their adoption also depended on the clout of administrators at the US National Institutes of Health (NIH) and the UK nonprofit charity the Wellcome Trust, which together funded 90% of the HGP human sequencing effort. The other nations wishing to remain in the HGP consortium had to accommodate to the Bermuda Principles, requiring exceptions from incompatible existing or pending data access policies for publicly funded research in Germany, Japan, and France. We begin this story in 1963, with the biologist Sydney Brenner's proposal for a nematode research program at the Laboratory of Molecular Biology (LMB) at the University of Cambridge. We continue through 2003, with the completion of the HGP human reference genome, and conclude with observations about policy and the historiography of molecular biology.

The article shortly describes the life path of Erwin Chargaff, one of the most famous figures in the history of molecular biology and genetics. Chargaff was born in Chernivtsi (Austria-Hungary, now Ukraine) but during the First World War his family was forced to move to Vienna. After graduating from the University of Vienna, Chargaff worked in Berlin, where he studied bacterial lipids. Due to Nazis coming to power in Germany, Chargaff moved to Paris and later (1935) emigrated to the USA and obtained a position at Columbia University, where he initially investigated the role of phospholipids in blood clotting. In 1944, applying novel methods Chargaff initiated intensive investigation of the chemical composition of nucleic acids from taxonomically distant species and established two rules which were later named after him. The first Chargaff's rule provided a significant support to Watson and Crick in construction of their double helical DNA model. The explosion of atomic bombs over Hiroshima and Nagasaki forced Chargaff to think about the moral responsibility of researchers and science to mankind. He begins to raise these issues in the press and manifests himself as a talented journalist, who criticized the bureaucratization of science and its transformation into a way of earning money. Despite decades of life in America, spiritually Erwin Chargaff always remained a European, who never forgot his roots and always remembered his native land.

In 1960, J. Anthony Morris, a molecular biologist at the US National Institutes of Health conducted one of the only non-therapeutic clinical studies of the cancer virus SV40. Morris and his research team aimed to determine whether SV40 was a serious harm to human health, since many scientists at the time suspected that SV40 caused cancer in humans based on evidence from in vivo animal studies and experiments with human tissue. Morris found that SV40 had no significant effect but his claim has remained controversial among scientists and policymakers through the present day--both on scientific and ethical grounds. Why did Morris only conduct one clinical study on the cancer-causing potential of SV40 in healthy humans? We use the case to explain how empirical evidence and ethical imperatives are, paradoxically, often dependent on each other and mutually exclusive in clinical research, which leaves answers to scientific and ethical questions unsettled. This paper serves two goals: first, it documents a unique--and uniquely important--study of clinical research on SV40. Second, it introduces the concept of "the stowaway," which is a special type of contaminant that changes the past in the present moment. In the history of science, stowaways are misfortunes that nonetheless afford research that otherwise would have been impossible specifically by creating new pasts. This case (Morris' study) and concept (the stowaway) bring together history of science and philosophy of history for productive dialog., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Joshua Lederberg (1925-2008), was one of the pioneers of molecular genetics perhaps best known for his discovery of genetic recombination in bacteria which earned him a Nobel Prize in 1958 (shared with George Beadle and Edward Tatum). Lederberg's interests were broad including the origin of life, exobiology (a term that he coined) and emerging diseases and artificial intelligence in his, later years. This article contains the transcription of an interview in excerpts, docu- menting the interactions between Lederberg and fellow biologist J.B.S. Haldane wlich lasted from 1946 until Haldane's death in Kolkata (then Calcutta) in 1964.

The debate between A.I. Oparin's heterotrophic proposal of the origin of life and H.J. Muller's suggestion that what may be considered a posteriori the beginning of life, was an autocatalytic, replicative gene, is analyzed. Although both recognized that what was needed was an interacting system contiguous in space and time, it is now rarely mentioned that this scientific confrontation went on for several decades against the background of intense ideological issues, political tensions, and scientific developments that include the rise and demise of Lysenkoism, on the one hand, and, on the other, the establishment of neoDarwinism and the birth of molecular biology. Whereas for Oparin life was the outcome of the step-wise slow process of precellular evolution in which membrane-bounded polymolecular systems played a key role, Muller argued that life started with the appearance of the first nucleic-acid (DNA) molecule in the primitive oceans. Oparin and Muller came from different scientific backgrounds and almost opposite intellectual traditions, so their common interest in the origin of life did nothing to assuage their opposing views, which as argued soon became part of the debates that took place within the framework of intense ideological confrontations.

George Palade, a founding father of cell biology and of the American Society for Cell Biology (ASCB), established the ultrastructural framework for an analysis of how proteins are secreted and membranes are assembled in eukaryotic cells. His vision inspired a generation of investigators to probe the molecular mechanisms of protein transport. My laboratory has dissected these pathways with complementary genetic and biochemical approaches. Peter Novick, one of my first graduate students, isolated secretion mutants of Saccharomyces cerevisiae, and through cytological analysis of single and double mutants and molecular cloning of the corresponding SEC genes, we established that yeast cells use a secretory pathway fundamentally conserved in all eukaryotes. A biochemical reaction that recapitulates the first half of the secretory pathway was used to characterize Sec proteins that comprise the polypeptide translocation channel in the endoplasmic reticulum (ER) membrane (Sec61) and the cytoplasmic coat protein complex (COPII) that captures cargo proteins into transport vesicles that bud from the ER.

This essay looks backward on the past three decades of research toward understanding the mechanism of macromolecular traffic through and within the Golgi apparatus with an eye to the future. I also explain why I feel the Golgi should continue to hold the attention of molecular cell biologists.

I describe my wanderings from the United States to East Germany and back. I hope this gives a glimpse of science in East Germany and encourages people who do science under less than favorable conditions. Although elements of my story are unique, the main points are general: don't be afraid to start something new; it pays to be persistent; and science is a passion--if it feels like fun, you've probably got it right.

Biologists in the 1960s witnessed a period of intense intra-disciplinary negotiations, especially the positioning of organismic biologists relative to molecular biologists. The perceived valorization of the physical sciences by "molecular" biologists became a catalyst creating a unified front of "organismic" biology that incorporated not just evolutionary biologists, but also students of animal behavior, ecology, systematics, botany - in short, almost any biological community that predominantly conducted their research in the field or museum and whose practitioners felt the pinch of the prestige and funding accruing to molecular biologists and biochemists. Ernst Mayr, Theodosius Dobzhansky, and George Gaylord Simpson took leading roles in defending alternatives to what they categorized as the mechanistic approach of chemistry and physics applied to living systems - the "equally wonderful field of organismic biology." Thus, it was through increasingly tense relations with molecular biology that organismic biologists cohered into a distinct community, with their own philosophical grounding, institutional security, and historical identity. Because this identity was based in large part on a fundamental rejection of the physical sciences as a desirable model within biology, organismic biologists succeeded in protecting the future of their field by emphasizing deep divisions that ran through the biological sciences as a whole.

There is a growing perception that modern medicine is approaching a state of crisis characterized by creative inertia, non-innovation, and non-productivity. Compared to the remarkable progress during the first 30 years after World War II, the last 30 years have been characterized by a self-congratulatory illusion of progress, the fruits of which have failed to reach our patients. The problem may lie with the fact that the (often lone) clinical innovator of the past who made all the difference to the spectacular progress of medicine during the golden age has been marginalized to the extent that he is now an endangered species. The two definable forces that have led to his alienation are the hegemony of molecular science and the primacy accorded to the randomized clinical trial in biomedical research. Both these stifle creative originality-the former by an overdependence on complex and technology-driven "big science" and a flawed founding philosophy, and the latter by putting limits on our intellectual expectations and a bureaucratic approach to scientific research.