This paper argues that the biochemistry of memory consolidation provides valuable model systems for exploring the multiple realization of psychological states.

In the 1920s, scientists at the University of Cambridge’s Sir William Dunn Institute of Biochemistry made major contributions to the emerging discipline of biochemistry while also devoting considerable time and energy to the production of a humor journal entitled Brighter Biochemistry. Although humor is frequently regarded as peripheral to the work of science, the journal provides an opportunity to understand how it contributes to the social infrastructure of scientific communities as modern workplaces. Taking methodological cues from cultural (...) history, ethnography, and humor studies, this essay conducts a close and contextual reading of Brighter Biochemistry. This reading demonstrates how humor served as a central means through which members of the Dunn confronted workplace issues, including creating cooperative work teams, responding to gender discrimination, addressing funding anxiety, and defining professional identity. These conclusions provide a new perspective on the well-documented history of the Dunn and also offer a model for how historians of science can approach humor when its traces are encountered in other settings. (shrink)

In this essay we take creationist biochemist Michael Behe to task for failing to make an evidentially grounded case for the supernatural intelligent design of biochemical systems. In our earlier work on Behe we showed that there were dimensions to biochemical complexity---redundant complexity---that he appeared to have ignored. Behe has recently replied to that work. We show here that his latest arguments contain fundamental flaws.

With technical sophistication and innovation in the field of medical science, a considerable proportion of medical diagnosis now rely on laboratory analyses, which emphasises the crucial role of laboratory physicians in patient care. Sustaining high ethical standards remains crucial in both clinical biochemistry and laboratory medicine, and several ethical dilemmas are faced by laboratory physicians in day-to-day practice. In a low-resource country like Bangladesh, formal ethics education or ethical framework in laboratory practice is still absent; ethics has not received (...) that much attention it this field. This paper has considered ethical issues encountered during the daily routine work of laboratory physicians and specially focused on the ethical issues encountered during the pre-analytical, analytical and post-analytical phases of laboratory medicine practice and discuss those issues in light of ‘The Belmont Report’ (1978) perspective. It is not intended to be a comprehensive one, rather it aims to complement existing guidelines and documents that are available in some institutions and to offer a framework for addressing ethical issues encountered in the practice of clinical biochemistry and laboratory medicine in Bangladesh. (shrink)

To ensure their survival in natural habitats, plants must recognize and respond to a wide variety of insect herbivores. Aphids and other Hemiptera pose a particular challenge, because they cause relatively little direct tissue damage when inserting their slender stylets intercellularly to feed from the phloem sieve elements. Plant responses to this unusual feeding strategy almost certainly include recognition of aphid salivary components and the induction of phloem‐specific defenses. Due to the excellent genetic and genomic resources that are available for (...) Arabidopsis thaliana (Arabidopsis), this plant was chosen as a model system to study the metabolic and transcriptional responses to infestation by two aphids, Myzus persicae (green peach aphid, a broad generalist) and Brevicoryne brassicae (cabbage aphid, a crucifer‐feeding specialist). Future research on Arabidopsis–aphid interactions will lead to the identification of aphid‐specific elicitors, components of the defense‐signaling pathway, and additional metabolic responses that are induced by aphid infestation. BioEssays 29:871–883, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Biological dinitrogen fixation, the reduction of N2 to NH3, requires the enzyme nitrogenase, MgATP, a strongly reducing electron donor and an anaerobic environment. Reducing power for nitrogen fixation is generated by two particular mechanisms, while the mechanisms for protecting nitrogen fixation from oxygen show a greater diversity. Both the reduction and the protection aspects of nitrogen fixation, especially those of the legume root nodule, will be discussed.

Studies of learning in marine invertebrates have yielded new information, implicating protein kinase C and calmodulin‐dependent protein kinase as critical components in pathways for learning and memory that are shared with higher vertebrates. Recent advances correlating in vitro biochemical and biophysical measurements with in vivo learning have begun to elaborate the roles in memory storage for these two kinases, their substrates, and signaling proteins such as calexcitin and calmodulin. Other studies have implicated transcription factors associated with kinases such as the (...) cyclic AMP response element binding protein (CREB). These experiments have resulted in a greater understanding of the role of second messengers, principally calcium and cyclic AMP (cAMP), as vehicles for transforming memory‐specific effects occurring at the membrane into permanent DNA‐mediated cellular and structural changes. (shrink)

This essay discusses the wartime work of one of the world’s leading biochemists, the Nobel Prize winner, Adolf Butenandt. It describes the influence of the war on Butenandt’s Institute, and considers his role as a representative figure in the collusion of science, government, and the military in Nazi Germany.

Causal selection has to do with a distinction between mere background conditions and the "true" causes of some outcome of interest. Mainstream philosophical views claim that causal selection is "groundless" in the sense that it lacks any type of principled rationale. I argue against this position in the context of biochemistry where causal factors are selected in explanations of metabolic processes. These factors are selected on the basis of a principled rationale, which is best understood in terms of the (...) causal control that they provide over an outcome of interest. (shrink)

The recombinational repair of chromosomal double‐strand breaks (DSBs) is of critical importance to all organisms, who devote considerable genetic resources to ensuring such repair is accomplished. In Saccharomyces cerevisiae, DSB‐mediated recombination can be initiated synchronously by the conditional expression of two site‐specific endonucleases, HO or I‐Scel. DNA undergoing recombination can then be extracted at intervals and analyzed. Recombination initiated by meiotic‐specific DSBs can be followed in a similar fashion. This type of ‘in vivo biochemistry’ has been used to describe (...) several discrete steps in two different homologous recombination pathways: gene conversion and single‐strand annealing. The roles of specific proteins during recombination can be established by examining DNA in strains deleted for the corresponding gene. These same approaches are now becoming available for the study of recombination in both higher plants and animals. Physical monitoring can also be used to analyze nonhomologous recombination events, whose mechanisms appear to be conserved from yeast to mammals. (shrink)

The flipped classroom is becoming a popular new instructional model in higher education capable of increasing student performance in higher-order learning outcomes. However, the success of a flipped classroom model depends on various supporting elements, and it may not be appropriate for all students and courses. In this study, a new blended Biochemistry classroom model based on Massive Open Online Courses and a “semi-flipped” environment was applied to Biochemistry instruction of Nursing and Clinical Medicine majors. The students’ academic (...) performance and perceptions of self-cognition were used to assess the blended Biochemistry classroom. Students who participated in the blended classroom model achieved higher academic performance and reported a significant improvement in their perceptions of self-cognition compared to the control group. Moreover, the effectiveness of the blended Biochemistry classroom on the small size class was stronger than on the large size class. (shrink)

The evolution of research on the biochemistry of virus multiplication cannot be understood without knowing something of the structure of biochemistry and of virology before, during and immediately after World War II. My own research on virus multiplication began after studies on plant viruses and wartime research on the rickettsial components of the typhus vaccine, all of which involved work on the nucleic acids. Interest in the chemotherapy of virus disease led to a search for a model system. (...) A simple methodology for handling phage systems enabled biochemists to examine infected cells. The fortuitous use of an extremely virulent phage group (the T‐even phages) which evoke marked changes in polymeric products without affecting the production of energy and small building blocks facilitated these studies. An exaggerated synthesis of viral DNA by these phages concentrated our attention on the origins of this substance, which proved to contain a new pyrimidine deoxyribonucleotide, synthesized by a novel virus‐determined enzyme. The generality of the existence of virus‐induced enzymes and other proteins may be the key to a chemotherapy of virus infection. (shrink)

Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to understanding the (...) role of the mitochondrion and its component parts in cellular respiration. In particular, by developing techniques for localizing enzymes or enzyme systems in specific cellular components, cell biologists provided crucial information about the organized structures in which the biochemical reactions occurred. Although the idea that biochemical operations are intimately related to and depend on cell structures was at odds with the then-dominant emphasis on systems of soluble enzymes in biochemistry, a reconceptualization of energetic processes in the 1960s and 1970s made it clear why cell structure was critical to the biochemical account. This paper examines how numerous excursions between biochemistry and cell biology contributed a new understanding of the mechanism of cellular respiration. (shrink)

This essay explores connections between bacteriology and the disciplinary evolution of biochemistry in this country during the 1930s. Many features of intermediary metabolism, a central component of biochemistry, originated as attempts to answer fundamental bacteriological questions. Thus, many bacteriologists altered their research programs to answer these questions. In so doing they changed their disciplinary focus from bacteriology to biochemistry. Chester Hamlin Werkman's (1893-1962) Iowa State career illustrates the research perspective that many bacteriologists adopted. As a junior faculty (...) member in the Bacteriology Department in the late 1920s, Werkman faced a powerful professional dilemma: establishing a research identity that distinguished him from his colleagues with flourishing national and international reputations. His solution was to radically alter his research program from traditional bacteriology to a biochemistry program, which reflected the influence of the Dutch microbiologist/biochemist, Albert Jan Kluyver (1888-1956). Werkman was extremely successful in this career change. His laboratory made significant contributions to biochemistry, and Werkman achieved a notable degree of personal success. His career began in the shadow of his departmental bacteriological colleagues; within a decade he became the department's dominant research figure, as a biochemist. Werkman's personal success, however, had profound consequences for the disciplinary future of bacteriology at Iowa State. (shrink)

The confluence of protein engineering techniques and delivery protocols are providing new opportunities in cell biology. In particular, techniques that render the membrane of cells transiently permeable make the introduction of nongenetically encodable macromolecular probes into cells possible. This, in turn, can enable the monitoring of intracellular processes in ways that can be both precise and quantitative, ushering an area that one may envision as cellular biochemistry. Herein, the author reviews pioneering examples of such new cell‐based assays, provides evidence (...) that challenges the paradigm that cell penetration is a necessarily damaging and stressful event for cells, and highlights some of the challenges that should be addressed to fully unlock the potential of this nascent field. (shrink)

This paper investigates the interface between philosophy and biochemistry. While it is problematic to justify the application of a particular philosophical model to biochemistry, it seems to be even more difficult to develop a special “Philosophy for Biochemistry”. Alternatively, philosophy can be used in biochemistry based on an alternative approach that involves an interdependent iteration process at a philosophical and (bio)chemical level (“Exeter Method”). This useful iteration method supplements more abstract approaches at the interface between philosophy (...) and natural sciences, and serves the biochemical community to systematically locate logical inconsistencies that arise from more theoretical aspects of the scientific process. Initial cycles of this iteration process identify the in vitro–in vivo problem as a central epistemological difficulty in biochemical research. While previous attempts have generated ad hoc rules to mend the gap between chemistry, biochemistry and biology in order to justify in vitro experimentation, this paper concludes that in vitro experimentation is heavily based on chemistry and cannot derive definite statements about biological processes. It can, however, generate results that will influence the direction of future biological research. The consequence is that the relationship between in vitro and in vivo experimentation is more of a psychological or social one than of a logical nature. Apart from highlighting these inconsistencies in biochemical thinking (“problem awareness”), the Exeter Method demands an improvement of biochemical terminology that contains separate and unequivocally defined terms for in vitro and in vivo systems. (shrink)

The multiple activities of the RecA protein in DNA metabolism have inspired over a decade of research in dozens of laboratories around the world. This effort has nevertheless failed to yield an understanding of the mechanism of several RecA protein‐mediated processes, the DNA strand exchange reactions prominent among them. The major factors impeding progress are the invalid constraints placed upon the problem by attempting to understand RecA protein‐mediated DNA strand exchange within the context of an inappropriate biological paradigm – namely, (...) homologous genetic recombination as a mechanism for generating genetic diversity. In this essay I summarize genetic and biochemical data demonstrating that RecA protein evolved as the central component of a recombinational DNA repair system, with the generation of genetic diversity being a sometimes useful byproduct, and review the major in vitro activities of RecA protein from a repair perspective. While models proposed for both recombination and recombinational repair often make use of DNA strand cleavage and transfer steps that appear to be quite similar, the molecular and thermodynamic requirements of the two processes are very different. The recombinational repair function provides a much more logical and informative framework for thinking about the biochemical properties of RecA and the strand exchange reactions it facilitates. (shrink)

Scientific practices have been changed by the increasing use of computer simulations. A central question for philosophers is how to characterize computer simulations. In this paper, we address this question by analyzing simulations in biochemistry. We propose that simulations have been used in biochemistry long before computers arrived. Simulation can be described as a surrogate relationship between models. Moreover, a simulative aspect is implicit in the classical dichotomy between in vivo–in vitro conditions. Based on a discussion about how (...) to characterize a simulative aspect in this dichotomy, we will argue that an adequate understanding of computer simulations in biochemistry requires a previous understanding of simulations in experimental contexts. (shrink)

The discovery of RNA interference in 1998 has made a lasting impact on biological research. Identifying the regulatory role of small RNAs changed the modes of molecular biological inquiry as well as biologists' understanding of genetic regulation. This article examines the early years of small RNA biology's success story. I query which factors had to come together so that small RNA research came into life in the blink of an eye. I primarily look at scientific repertoires as facilitators of rapid (...) scientific change. I show that for a short period of time, between the years 1998 and 2002, different model organism communities, investigative strategies, technological innovations, and research interests could be successfully aligned to take small RNA research off the ground. I discuss how the keystone discoveries were situated in specific experimental traditions and what strategies were employed to establish these discoveries as more general phenomena. Providing thus a practice-based approach of rapid scientific change, I ask how to relate the change in propositional bits of scientific knowledge with changes in scientific practice. (shrink)

Philosophers of science diverge on the question what drives the growth of scientific knowledge. Most of the twentieth century was dominated by the notion that theories propel that growth whereas experiments play secondary roles of operating within the theoretical framework or testing theoretical predictions. New experimentalism, a school of thought pioneered by Ian Hacking in the early 1980s, challenged this view by arguing that theory-free exploratory experimentation may in many cases effectively probe nature and potentially spawn higher evidence-based theories. Because (...) theories are often powerless to envisage workings of complex biological systems, theory-independent experimentation is common in the life sciences. Some such experiments are triggered by compelling observation, others are prompted by innovative techniques or instruments, whereas different investigations query big data to identify regularities and underlying organizing principles. A distinct fourth type of experiments is motivated by a major question. Here I describe two question-guided experimental discoveries in biochemistry: the cyclic adenosine monophosphate mediator of hormone action and the ubiquitin-mediated system of protein degradation. Lacking underlying theories, antecedent data bases, or new techniques, the sole guides of the two discoveries were respective substantial questions. Both research projects were similarly instigated by theory-free exploratory experimentation and continued in alternating phases of results-based interim working hypotheses, their examination by experiment, provisional hypotheses again, and so on. These two cases designate theory-free, question-guided, stepwise biochemical investigations as a distinct subtype of the new experimentalism mode of scientific enquiry. (shrink)

Scientists and historians have often presumed that the divide between biochemistry and molecular biology is fundamentally epistemological.100 The historiography of molecular biology as promulgated by Max Delbrück's phage disciples similarly emphasizes inherent differences between the archaic tradition of biochemistry and the approach of phage geneticists, the ur molecular biologists. A historical analysis of the development of both disciplines at Berkeley mitigates against accepting predestined differences, and underscores the similarities between the postwar development of biochemistry and the emergence (...) of molecular biology as a university discipline. Stanley's image of postwar biochemistry, with its focus on viruses as key experimental systems, and its preference for following macromolecular structure over metabolism pathways, traced the outline of molecular biology in 1950.Changes in the postwar political economy of research universities enabled the proliferation of disciplines such as microbiology, biochemistry, biophysics, immunology, and molecular biology in universities rather than in medical schools and agricultural colleges. These disciplines were predominantly concerned with investigating life at the subcellular level-research that during the 1930s had often entailed collaboration with physicists and chemists. The interdisciplinary efforts of the 1930s (many fostered by the Rockefeller Foundation) yielded a host of new tools and reagents that were standardized and mass-produced for laboratories after World War II. This commercial infrastructure enabled “basic” researchers in biochemistry and molecular biology in the 1950s and 1960s to become more independent from physics and chemistry (although they were practicing a physicochemical biology), as well as from the agricultural and medical schools that had previously housed or sponsored such research. In turn, the disciplines increasingly required their practitioners to have specialized graduate training, rather than admitting interlopers from the physical sciences.These general transitions toward greater autonomy for biochemistry and allied disciplines should not mask the important particularities of these developments on each campus. At the University of Caliornia at Berkeley, agriculture had provided, with medicine, significant sponsorship for biochemistry. The proximity of Lawrence and his cyclotrons supported the early development of Berkeley as a center for the biological uses of radioisotopes, particularly in studies of metabolism and photosynthesis. Stanley arrived to establish his department and virus institute before large-scale federal funding of biomedical research was in place, and he courted the state of California for substantial backing by promising both national prominence in the life sciences and virus research pertinent to agriculture and public health. Stanley's venture benefited significantly from the expansion of California's economy after World War II, and his mobilization against viral diseases resonated with the concerns of the Cold War, which fueled the state's rapid growth. The scientific prominence of contemporary developments at Caltech and Stanford invites the historical examination of the significance of postwar biochemistry and molecular biology within the political and cultural economy of the Golden State.In 1950, Stanley presented a persuasive picture of the power of biochemistry to refurbish life science at Berkeley while answering fundamental questions about life and infection. In the words of one Rockefeller Foundation officer,There seems little doubt in [my] mind that as a personality Stanley will be well able to dominate the other personalities on the Berkeley campus and will be able to drive his dream through to completion, which, incidentally, leaves Dr. Hubert [sic] Evans and the whole ineffective Life Sciences building in the somewhat peculiar position of being by-passed by much of the truly modern biochemistry and biophysics research that will be carried out at Berkeley. Furthermore, it seems likely that Dr. S's show will throw Dr. John Lawrence's Biophysics Department strongly in the shade both figuratively and literally, but should make the University of California pre-eminent not only in physics but in biochemistry as well.101Stanley, Sproul, Weaver, and this officer (William Loomis) all testified to a perceptible postwar opportunity to capitalize on public support for biological research that relied on the technologies from physics and chemistry without being captive to them, and that addressed issues of medicine and agriculture without being institutionally subservient. What is striking, given the expectation by many that Stanley would ‘be able to drive his dream through to completion,” was that in fact he did not. Biochemists who had succeeded in making their expertise valued in specialized niches were resistant to giving up their affiliations to joint Stanley's “liberated” organization. Stanley's failure was not simply due to institutional factors: researchers as well as Rockefeller Foundation officers faulted him for his lack of scientific imagination, which made it difficult for him to gain credibility in leading the field. Moreover, many biochemists did not share Stanley's commitment to viruses as the key material for the “new biochemistry.”In the end, Stanley's free-standing department did become a first-rate department of biochemistry, but only after freeing itself from Stanley's leadership and his single-minded devotion to viruses. Nonetheless, the falling-out with the Berkeley biochemists was rapidly followed by the establishment of a Department of Molecular Biology, attesting to the unabating economic and institutional possibilities for an authoritative “general biology” (or two, for that matter) to take hold. In each case, following Stanley's dream sheds light on how the possible and the real shaped the (re)formation of biochemistry and molecular biology as postwar life sciences. (shrink)

The historiography of the ‘dark age’ of biochemistry between 1910–1930 is examined. The biochemistry of the period is located within a larger contemporary debate on the interrelationship between structure and function on a submicroscopic level. It is suggested that biocolloid science was an understandable part of the historical development of biochemistry, representing a conceptual bridge between the cell biology of the late nineteenth century, and the era of structural macromolecular studies of proteins that began after 1930.

Kincaid argues that molecular biology provides little support for the reductionist program, that biochemistry does not reveal common mechanisms, indeed that biochemical theory obstructs discovery. These assertions clash with biologists' stated advocacy of reductionist programs and their claims about the consequent unity of experimental biology. This striking disagreement goes beyond differences in meaning granted to the terms. More significant is Kincaid's misunderstanding of what biochemists do, for a closer look at scientific practice-- and one of Kincaid's examples--reveals substantial progress (...) toward explaining biological function with biochemical models. With the molecular detail emerge unifying generalizations as well as further aspects of the functional processes. (shrink)