Background Informed consent is a requirement for all research. It is not, however, clear how much information is sufficient to make an informed decision about participation in research. Information on an online questionnaire about childhood development was provided through an unfolding electronic participant sheet in three levels of information. Methods 552 participants, who completed the web-based survey, accessed and spent time reading the participant information sheet (PIS) between July 2008 and November 2009. The information behaviour of the participants was investigated. (...) The first level contained less information than might be found on a standard PIS, the second level corresponded to a standard PIS, and the third contained more information than on a standard PIS. The actual time spent on reading the information provided in three incremental levels and the participants' evaluation of the information were calculated. Results 77% of the participants chose to access the first level of information, whereas 12% accessed the first two levels, 6% accessed all three levels of information and 23% participated without accessing information. The most accessed levels of information were those that corresponded to the average reading times. Conclusion The brief information provided in the first level was sufficient for participants to make informed decisions, while a sizeable minority of the participants chose not to access any information at all. This study adds to the debate about how much information is required to make a decision about participation in research and the results may help inform the future development of information sheets by providing data on participants' actual needs when deciding about questionnaire surveys. (shrink)

The participation of vulnerable patients in clinical research poses apparent ethical dilemmas. Depending on the nature of the vulnerability, their participation may challenge the ethical principles of autonomy, non-maleficence, or justice. On the other hand, non-participation may preclude the building of a knowledge base that is a prerequisite for defining the optimal clinical management of vulnerable patients. Such clinical uncertainty may also incur substantial economic costs. We present the participation of pre-menopausal women with atrial fibrillation in trials of novel oral (...) anticoagulant drugs as a case study. Due to their non-participation in pivotal trials, it is uncertain whether for them, the risks that are associated with these drugs are outweighed by the advantages compared with conventional treatment. We addressed the question whether research of this new class of drugs in this subgroup would be appropriate from both, an ethical as well an economic perspective. We used the method of specifying norms as a wider framework to resolve the apparent ethical dilemma, while incorporating the question whether research of oral anticoagulants in premenopausal women with atrial fibrillation can be justified on economic grounds. For the latter, the results of a value-of-information analysis were used. Further clinical research on NOACs in premenopausal women with atrial fibrillation can be justified on both, ethical and economic grounds. Addressing apparent ethical dilemmas by invoking a method such as specifying norms can improve the quality of public practical reasoning. As such, the method should also prove valuable to committees that have formally been granted the authority to review trial protocols and proposals for scientific research. (shrink)

Cultural differences occur in the use of categories to aid accurate recall of information. This study investigated whether culture also contributed to false (erroneous) memories, and extended cross-cultural memory research to Turkish culture, which is shaped by Eastern and Western influences. Americans and Turks viewed word pairs, half of which were categorically related and half unrelated. Participants then attempted to recall the second word from the pair in response to the first word cue. Responses were coded as correct, as blanks, (...) or as different types of errors. Americans committed more categorical errors than did Turks, and Turks mistakenly recalled more non-categorically related list words than did Americans. These results support the idea that Americans use categories either to organize information in memory or to support retrieval strategies to a greater extent than Turks and suggest that culture shapes not only accurate recall but also erroneous distortions of memory. (shrink)

This article aims to deconstruct the concept of dignity in a way that is meaningful, in particular to nurses and other health workers who seek to promote the dignity of children in their care. Despite the emphasis in a variety of codes and policies to promote dignity, there is a lack of a clear definition of dignity in the literature. In particular there is little reference to dignity, theoretically or empirically, as it relates to children. Without clarity it is not (...) possible to act in an ethical way on behalf of children whose dignity could otherwise be compromised. The theoretical position taken has evolved from the medico-nursing and philosophical discourse concerning the nature of human dignity and more recent sociological texts that discuss the social construction of the child and childhood. The article is further influenced by additional insights derived from an ethnographic pilot study at a large district general hospital. This study was undertaken in an attempt to appreciate the subjective experience of dignity by children, and to begin to address the empirical gap in the literature and promote discussion. The concept of a macro and a micro dignity is discussed, together with the role of the nurse in articulating the relationship between the two. The importance of control and witnesses in the experience of dignity is discussed and, finally, also the ethical implications when seeking to promote the dignity of children. (shrink)

Objectives—To evaluate a departmental computer system.Design—a. Direct comparison of the time taken to use a manual system with the time taken to use a computer system for lung function evaluation, loan of equipment and production of correspondence. b. Analysis of the accuracy of data capture before and after the introduction of the computer system. c. Analysis of the comparative running costs of the manual and computer systems.Setting—Within a department of respiratory medicine serving a hospital of 1323 beds.Main Outcome Measures—a. Time (...) taken to perform functions with the assistance of computerised methods, in comparison to the manual method used alone. b. Accuracy of data capture. c. Relative running costs.Results—a. The computer system (CS) was significantly faster than the manual system (MS) for lung function evaluation (CS=7.63 min/test, MS=12.25 min/test), loan of equipment (CS=0.40 min/loan, MS=2.07 min/loan), and checking for overdue equipment (CS=0.49 s/record, MS=9 s/record). The production of correspondence was slightly slower with the computer (CS=9.30 min/letter, MS=8.54 min/letter). b. All outpatient episodes, but only 43 of 65 (66%) of inpatient episodes, were captured. Lung function and managerial report data were accurate using both manual and computerised methods. The manual system for equipment loans was inefficient, and use of the computer resulted in the recovery of 221 nebulisers. c. Development costs for 1988–1990 were high (£72 178). Only £1200 to £1845 per year was recovered directly from staff time saved by the computer but larger savings resulted from changes in work practice (£4049–4765). After 10 years the projected deficit is £10 000 per annum in running costs.Conclusions—In comparison with the manual methods, the computer system has shown significant advantages which provide accurate information, with significant favourable effects on working practices. In evaluating computer systems used in clinical practice it is essential to ensure that the projected work practice benefits are achieved without unacceptable costs in staff time, inaccurate data and high financial outlay. (shrink)

Objectives—To evaluate a departmental computer system.Design—a. Direct comparison of the time taken to use a manual system with the time taken to use a computer system for lung function evaluation, loan of equipment and production of correspondence. b. Analysis of the accuracy of data capture before and after the introduction of the computer system. c. Analysis of the comparative running costs of the manual and computer systems.Setting—Within a department of respiratory medicine serving a hospital of 1323 beds.Main Outcome Measures—a. Time (...) taken to perform functions with the assistance of computerised methods, in comparison to the manual method used alone. b. Accuracy of data capture. c. Relative running costs.Results—a. The computer system was significantly faster than the manual system for lung function evaluation, loan of equipment, and checking for overdue equipment. The production of correspondence was slightly slower with the computer. b. All outpatient episodes, but only 43 of 65 of inpatient episodes, were captured. Lung function and managerial report data were accurate using both manual and computerised methods. The manual system for equipment loans was inefficient, and use of the computer resulted in the recovery of 221 nebulisers. c. Development costs for 1988–1990 were high. Only £1200 to £1845 per year was recovered directly from staff time saved by the computer but larger savings resulted from changes in work practice. After 10 years the projected deficit is £10 000 per annum in running costs.Conclusions—In comparison with the manual methods, the computer system has shown significant advantages which provide accurate information, with significant favourable effects on working practices. In evaluating computer systems used in clinical practice it is essential to ensure that the projected work practice benefits are achieved without unacceptable costs in staff time, inaccurate data and high financial outlay. (shrink)

The 1940s and 1950s were marked by intense debates over the origin of drug resistance in microbes. Bacteriologists had traditionally invoked the notions of ‘training’ and ‘adaptation’ to account for the ability of microbes to acquire new traits. As the field of bacterial genetics emerged, however, its participants rejected ‘Lamarckian’ views of microbial heredity, and offered statistical evidence that drug resistance resulted from the selection of random resistant mutants. Antibiotic resistance became a key issue among those disputing physiological vs. genetic (...) explanations of variation in bacteria. Postwar developments connected with the Lysenko affair gave this debate a new political valence.Proponents of the neo-Darwinian synthesis weighed in with support for the genetic theory. However, certain features of drug resistance seemed inexplicable by mutation and selection, particularly the phenomenon of ‘multiple resistance’—the emergence of resistance in a single strain against several unrelated antibiotics. In the late 1950s, Tsutomu Watanabe and his collaborators solved this puzzle by determining that resistance could be conferred by cytoplasmic resistance factors rather than chromosomal mutation. These R factors could carry resistance to many antibiotics and seemed able to promote their own dissemination in bacterial populations. In the end, the vindication of the genetic view of drug resistance was accompanied by a recasting of the ‘gene’ to include extrachromosomal hereditary units carried on viruses and plasmids. (shrink)

This paper examines the US Atomic Energy Commission’s radioisotope distribution program, established in 1946, which employed the uranium piles built for the wartime bomb project to produce specific radioisotopes for use in scientific investigation and medical therapy. As soon as the program was announced, requests from researchers began pouring into the Commission’s office. During the first year of the program alone over 1000 radioisotope shipments were sent out. The numerous requests that came from scientists outside the United States, however, sparked (...) a political debate about whether the Commission should or even could export radioisotopes. This controversy manifested the tension between the aims of the Marshall Plan and growing US national security concerns after World War II. Proponents of international circulation of radioisotopes emphasized the political and scientific value of collaborating with European scientists, especially biomedical researchers. In the end, radioisotopes were shipped from the Commission’s Oak Ridge facility to many laboratories in England and continental Europe, where they were used in biochemical research on animals, plants, and microbes. However, the issue of radioisotope export continued to draw political fire in the United States, even after the establishment of national atomic energy facilities elsewhere. (shrink)

The recent historiography of molecular biology features key technologies, instruments and materials, which offer a different view of the field and its turning points than preceding intellectual and institutional histories. Radioisotopes, in this vein, became essential tools in postwar life science research, including molecular biology, and are here analyzed through their use in experiments on bacteriophage. Isotopes were especially well suited for studying the dynamics of chemical transformation over time, through metabolic pathways or life cycles. Scientists labeled phage with phosphorus-32 (...) in order to trace the transfer of genetic material between parent and progeny in virus reproduction. Initial studies of this type did not resolve the mechanism of generational transfer but unexpectedly gave rise to a new style of molecular radiobiology based on the inactivation of phage by the radioactive decay of incorporated phosphorus-32. These ‘suicide experiments’, a preoccupation of phage researchers in the mid-1950s, reveal how molecular biologists interacted with the traditions and practices of radiation geneticists as well as those of biochemists as they were seeking to demarcate a new field. The routine use of radiolabels to visualize nucleic acids emerged as an enduring feature of molecular biological experimentation. (shrink)

ABSTRACT Rosalind Franklin is best known for her informative X-ray diffraction patterns of DNA that provided vital clues for James Watson and Francis Crick's double-stranded helical model. Her scientific career did not end when she left the DNA work at King's College, however. In 1953 Franklin moved to J. D. Bernal's crystallography laboratory at Birkbeck College, where she shifted her focus to the three-dimensional structure of viruses, obtaining diffraction patterns of Tobacco mosaic virus (TMV) of unprecedented detail and clarity. During (...) the next five years, while making significant headway on the structural determination of TMV, Franklin maintained an active correspondence with both Watson and Crick, who were also studying aspects of virus structure. Developments in TMV research during the 1950s illustrate the connections in the emerging field of molecular biology between structural studies of nucleic acids and of proteins and viruses. They also reveal how the protagonists of the “race for the double helix” continued to interact personally and professionally during the years when Watson and Crick's model for the double-helical structure of DNA was debated and confirmed. (shrink)

ABSTRACT Rosalind Franklin is best known for her informative X-ray diffraction patterns of DNA that provided vital clues for James Watson and Francis Crick's double-stranded helical model. Her scientific career did not end when she left the DNA work at King's College, however. In 1953 Franklin moved to J. D. Bernal's crystallography laboratory at Birkbeck College, where she shifted her focus to the three-dimensional structure of viruses, obtaining diffraction patterns of Tobacco mosaic virus (TMV) of unprecedented detail and clarity. During (...) the next five years, while making significant headway on the structural determination of TMV, Franklin maintained an active correspondence with both Watson and Crick, who were also studying aspects of virus structure. Developments in TMV research during the 1950s illustrate the connections in the emerging field of molecular biology between structural studies of nucleic acids and of proteins and viruses. They also reveal how the protagonists of the “race for the double helix” continued to interact personally and professionally during the years when Watson and Crick's model for the double-helical structure of DNA was debated and confirmed. (shrink)

The widespread adoption of radioisotopes as tools in biomedical research and therapy became one of the major consequences of the "physicists' war" for postwar life science. Scientists in the Manhattan Project, as part of their efforts to advocate for civilian uses of atomic energy after the war, proposed using infrastructure from the wartime bomb project to develop a government-run radioisotope distribution program. After the Atomic Energy Bill was passed and before the Atomic Energy Commission was formally established, the Manhattan Project (...) began shipping isotopes from Oak Ridge. Scientists and physicians put these reactor-produced isotopes to many of the same uses that had been pioneered with cyclotron-generated radioisotopes in the 1930s and early 1940s. The majority of early AEC shipments were radioiodine and radiophosphorus, employed to evaluate thyroid function, diagnose medical disorders, and irradiate tumors. Both researchers and politicians lauded radioisotopes publicly for their potential in curing diseases, particularly cancer. However, isotopes proved less successful than anticipated in treating cancer and more successful in medical diagnostics. On the research side, reactor-generated radioisotopes equipped biologists with new tools to trace molecular transformations from metabolic pathways to ecosystems. The U.S. government's production and promotion of isotopes stimulated their consumption by scientists and physicians, such that in the postwar period isotopes became routine elements of laboratory and clinical use. In the early postwar years, radioisotopes signified the government's commitment to harness the atom for peace, particularly through contributions to biology, medicine, and agriculture. (shrink)

When the Toxic Substances Control Act was passed by the US Congress in 1976, its advocates pointed to new generation of genotoxicity tests as a way to systematically screen chemicals for carcinogenicity. However, in the end, TSCA did not require any new testing of commercial chemicals, including these rapid laboratory screens. In addition, although the Environmental Protection Agency was to make public data about the health effects of industrial chemicals, companies routinely used the agency’s obligation to protect confidential business information (...) to prevent such disclosures. This paper traces the contested history of TSCA and its provisions for testing, from the circulation of the first draft bill in the Nixon administration through the debates over its implementation, which stretched into the Reagan administration. The paucity of publicly available health and environmental data concerning chemicals, I argue, was a by-product of the law and its execution, leading to a situation of institutionalized ignorance, the underside of regulatory knowledge. (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)

We argue that analyses of civil religious ideologies in civil rights contention must include the interplay of both movement and countermovement ideologies and must recognize the ways in which such discourse amplifies conflict as well as serves as a basis for unity. Based on in-depth interviews, archival research, and content analysis of civil religious language, this article examines how priestly and prophetic civil religious discourses, and the infusion of Black power ideologies, provided significant and dynamic resources for both movement and (...) countermovement ideologies during periods of civil rights contention in Cairo, Illinois, especially from 1969 to 1972. We compare the ways in which Cairo’s civil rights leaders mobilized prophetic versions of civil religion, and concomitantly, how white countermovement organizations used a priestly civil religion. On the prophetic side the themes of “equality,” “freedom,” “justice,” and the “right to revolt” against worldly socio-political arrangements were employed. On the priestly side, the theme of “law” and “order” was played up, with a secondary theme that connected religious acquiescence to worldly power with God’s will. The former rhetoric saw calls for economic and employment integration within God’s will and the nation’s destiny. The latter rhetoric contrasted civil rights claims as essentially “un-American.”. (shrink)

Physicists regularly invoke universal laws, such as those of motion and electromagnetism, to explain events. Biological and medical scientists have no such laws. How then do they acquire a reliable body of knowledge about biological organisms and human disease? One way is by repeatedly returning to, manipulating, observing, interpreting, and reinterpreting certain subjects—such as flies, mice, worms, or microbes—or, as they are known in biology, “model systems.” Across the natural and social sciences, other disciplinary fields have developed canonical examples that (...) have played a role comparable to that of biology’s model systems, serving not only as points of reference and illustrations of general principles or values but also as sites of continued investigation and reinterpretation. The essays in this collection assess the scope and function of model objects in domains as diverse as biology, geology, and history, attending to differences between fields as well as to epistemological commonalities. Contributors examine the role of the fruit fly Drosophila and nematode worms in biology, troops of baboons in primatology, box and digital simulations of the movement of the earth’s crust in geology, and meteorological models in climatology. They analyze the intensive study of the prisoner’s dilemma in game theory, ritual in anthropology, the individual case in psychoanalytic research, and Athenian democracy in political theory. The contributors illuminate the processes through which particular organisms, cases, materials, or narratives become foundational to their fields, and they examine how these foundational exemplars—from the fruit fly to Freud’s Dora—shape the knowledge produced within their disciplines. Contributors Rachel A. Ankeny Angela N. H. Creager Amy Dahan Dalmedico John Forrester Clifford Geertz Carlo Ginzburg E. Jane Albert Hubbard Elizabeth Lunbeck Mary S. Morgan Josiah Ober Naomi Oreskes Susan Sperling Marcel Weber M. Norton Wise. (shrink)

The three cycles of cell division immediately following theformation of the cellular blastoderm during Drosophila embryogenesis display an invariant pattern(1,2). Bursts of transcription of a gene called string are required and sufficient to trigger mitosis at this time during development(3). The activator of mitosis encoded by the string gene is a positive regulator of cdc2 kinase and a Drosophila homologue of the Saccharomyces pombe cdc25 tyrosine phosphatase(4,5). Evidence presented in a recent paper(6) demonstrates that transcription of string, and hence the (...) timing and pattern of mitosis in the postblastoderm embryo, is under complex developmental control. Several lines of evidence support this interpretation, including the analysis of string transcription in pattern formation mutants, cell cycle arrest mutants, and the preliminary characterization of an extensive cis‐acting regulatory region. (shrink)

Many enzymes are inhibited by their own substrates, leading to velocity curves that rise to a maximum and then descend as the substrate concentration increases. Substrate inhibition is often regarded as a biochemical oddity and experimental annoyance. We show, using several case studies, that substrate inhibition often has important biological functions. In each case we discuss, the biological significance is different. Substrate inhibition of tyrosine hydroxylase results in a steady synthesis of dopamine despite large fluctuations in tyrosine due to meals. (...) Substrate inhibition of acetylcholinesterase enhances the neural signal and allows rapid signal termination. Substrate inhibition of phosphofructokinase ensures that resources are not devoted to manufacturing ATP when it is plentiful. In folate metabolism, substrate inhibition maintains reactions rates in the face of substantial folate deprivation. Substrate inhibition of DNA methyltransferase serves to faithfully copy DNA methylation patterns when cells divide while preventing de novo methylation of methyl‐free promoter regions. (shrink)