The existing literature on the development of recombinant DNA technology and genetic engineering tends to focus on Stanley Cohen and Herbert Boyer's recombinant DNA cloning technology and its commercialization starting in the mid-1970s. Historians of science, however, have pointedly noted that experimental procedures for making recombinant DNA molecules were initially developed by Stanford biochemist Paul Berg and his colleagues, Peter Lobban and A. Dale Kaiser in the early 1970s. This paper, recognizing the uneasy disjuncture between scientific authorship and legal invention (...) in the history of recombinant DNA technology, investigates the development of recombinant DNA technology in its full scientific context. I do so by focusing on Stanford biochemist Berg's research on the genetic regulation of higher organisms. As I hope to demonstrate, Berg's new venture reflected a mass migration of biomedical researchers as they shifted from studying prokaryotic organisms like bacteria to studying eukaryotic organisms like mammalian and human cells. It was out of this boundary crossing from prokaryotic to eukaryotic systems through virus model systems that recombinant DNA technology and other significant new research techniques and agendas emerged. Indeed, in their attempt to reconstitute 'life' as a research technology, Stanford biochemists' recombinant DNA research recast genes as a sequence that could be rewritten thorough biochemical operations. The last part of this paper shifts focus from recombinant DNA technology's academic origins to its transformation into a genetic engineering technology by examining the wide range of experimental hybridizations which occurred as techniques and knowledge circulated between Stanford biochemists and the Bay Area's experimentalists. Situating their interchange in a dense research network based at Stanford's biochemistry department, this paper helps to revise the canonized history of genetic engineering's origins that emerged during the patenting of Cohen-Boyer's recombinant DNA cloning procedures. (shrink)
In its last round of publications in September 2012, the Encyclopedia Of DNA Elements (ENCODE) assigned a biochemical function to most of the human genome, which was taken up by the media as meaning the end of ‘Junk DNA’. This provoked a heated reaction from evolutionary biologists, who among other things claimed that ENCODE adopted a wrong and much too inclusive notion of function, making its dismissal of junk DNA merely rhetorical. We argue that this criticism rests on misunderstandings concerning (...) the nature of the ENCODE project, the relevant notion of function and the claim that most of our genome is junk. We argue that evolutionary accounts of function presuppose functions as ‘causal roles’, and that selection is but a useful proxy for relevant functions, which might well be unsuitable to biomedical research. Taking a closer look at the discovery process in which ENCODE participates, we argue that ENCODE’s strategy of biochemical signatures successfully identified activities of DNA elements with an eye towards causal roles of interest to biomedical research. We argue that ENCODE’s controversial claim of functionality should be interpreted as saying that 80 % of the genome is engaging in relevant biochemical activities and is very likely to have a causal role in phenomena deemed relevant to biomedical research. Finally, we discuss ambiguities in the meaning of junk DNA and in one of the main arguments raised for its prevalence, and we evaluate the impact of ENCODE’s results on the claim that most of our genome is junk. (shrink)
Fred Sanger, the inventor of the first protein, RNA and DNA sequencing methods, has traditionally been seen as a technical scientist, engaged in laboratory bench work and not interested at all in intellectual debates in biology. In his autobiography and commentaries by fellow researchers, he is portrayed as having a trajectory exclusively dependent on technological progress. The scarce historical scholarship on Sanger partially challenges these accounts by highlighting the importance of professional contacts, institutional and disciplinary moves in his career, spanning (...) from 1940 to 1983. This paper will complement such literature by focusing, for the first time, on the transition of Sanger's sequencing strategies from degrading to copying the target molecule, which occurred in the late 1960s as he was shifting from protein and RNA to DNA sequencing, shortly after his move from the Department of Biochemistry to the Laboratory of Molecular Biology, both based in Cambridge (UK). Through a reinterpretation of Sanger's papers and retrospective accounts and a pioneering investigation of his laboratory notebooks, I will claim that sequencing shifted from the working procedures of organic chemistry to those of the emergent molecular biology. I will also argue that sequencing deserves a history in its own right as a practice and not as a technique subordinated to the development of molecular biology or genomics. My proposed history of sequencing leads to a reappraisal of current STS debates on bioinformatics, biotechnology and biomedicine. (shrink)
Cells are cognitive entities possessing great computational power. DNA serves as a multivalent information storage medium for these computations at various time scales. Information is stored in sequences, epigenetic modifications, and rapidly changing nucleoprotein complexes. Because DNA must operate through complexes formed with other molecules in the cell, genome functions are inherently interactive and involve two-way communication with various cellular compartments. Both coding sequences and repetitive sequences contribute to the hierarchical systemic organization of the genome. By virtue of nucleoprotein complexes, (...) epigenetic modifications, and natural genetic engineering activities, the genome can serve as a read-write storage system. An interactive informatic conceptualization of the genome allows us to understand the functional importance of DNA that does not code for protein or RNA structure, clarifies the essential multidirectional and systemic nature of genomic information transfer, and emphasizes the need to investigate how cellular computation operates in reproduction and evolution. (shrink)
The short paper introduces the concept of possible branches of double-stranded DNA (later sometimes called palindromes): Certain sequences of nucleotides may be followed, after a short unpaired stretch, by a complementary sequence in reversed order, such that each DNA strand can fold back on itself, and the DNA assumes a cruciform or tree-like structure. This is postulated to interact with regulatory proteins. -/- .
Abstract: The discovery of DNA paternity tests has stirred a debate concerning the definition of paternity and whether the grounds for such a definition are legal or biological. According to the classical rules of Islamic law, paternity is established and negated on the basis of a valid marriage. Modern biomedical technology raises the question of whether paternity tests can be the sole basis for paternity, even independently of marriage. Although on the surface this technology seems to challenge the authority of (...) Islamic law in this area, the paper argues that classical Islamic rulings pertaining to paternity issues continue to hold higher authority even in cases of conflict with modern technology-based alternatives. Through closer analysis, the paper traces the emergence of a differentiation in the function of DNA tests between identity and paternity verification. While the former is accepted without reservation, the latter is approved only when it does not violate the rulings of Islamic law. (shrink)
Since its advent, predictive DNA testing has been perceived as a technology that may have considerable impact on the quality of people’s life. The decision whether or not to use this technology is up to the individual client. However, to enable well considered decision making both the negative as well as the positive freedom of the individual should be supported. In this paper, we argue that current professional and public discourse on predictive DNA-testing is lacking when it comes to supporting (...) positive freedom, because it is usually framed in terms of risk and risk management. We show how this ‘risk discourse’ steers thinking on the good life in a particular way. We go on to argue that empirical research into the actual deliberation and decision making processes of individuals and families may be used to enrich the environment of personal deliberation in three ways: (1) it points at a richer set of values that deliberators can take into account, (2) it acknowledges the shared nature of genes, and (3) it shows how one might frame decisions in a non-binary way. We argue that the public sharing and discussing of stories about personal deliberations offers valuable input for others who face similar choices: it fosters their positive freedom to shape their view of the good life in relation to DNA-diagnostics. We conclude by offering some suggestions as to how to realize such public sharing of personal stories. (shrink)
I begin with a description of the benefits and limits of DNA barcoding as presented by its advocates not its critics. Next, I argue that due to the mutually dependent relationship between defining and delimiting species, all systems of classification are grounded in theory, even if only implicitly. I then proceed to evaluate DNA barcoding in that context. In particular, I focus on the barcoders’ use of a sharp boundary by which to delimit species, arguing that this boundary brings along (...) additional theoretical commitments inconsistent with the way taxonomists conceive of species, viz., as entities that have vague boundaries and that cannot be defined by any single attribute other than ancestry. Given these inconsistencies, I conclude that even if groupings based on DNA barcodes match those of an existing taxonomy, the two systems of classification are not necessarily tracking the same entities, i.e., species. (shrink)
This paper focuses on the question of whether DNA patents help or hinder scientific discovery and innovation. While DNA patents create a wide variety of possible benefits and harms for science and technology, the evidence we have at this point in time supports the conclusion that they will probably promote rather than hamper scientific discovery and innovation. However, since DNA patenting is a relatively recent phenomena and the biotechnology industry is in its infancy, we should continue to gather evidence about (...) the effects of DNA patenting on scientific innovation and discovery as well the economic, social, and legal conditions relating to intellectual property in biotechnology. We should give the free market, the courts, researchers, and patent offices a chance to settle issues related to innovation and discovery, before we seek legislative remedies, since new laws proposed at this point would lack adequate foresight and could do more harm than good. However, we should be open to new laws or regulations on DNA patents if they are required to in order to deal with some of the biases and limitations of the free market. (shrink)
Technology has provided state and federal governments with huge collections of DNA samples and identifying profiles stored in databanks. That information can be used to solve crimes by matching samples from convicted felons to unsolved crimes, and has aided law enforcement in investigating and convicting suspects, and exonerating innocent felons, even after lengthy incarceration. Rights surrounding the provision of DNA samples, however, remain unclear in light of the constitutional guarantee against unreasonable searches and seizures and privacy concerns. The courts have (...) just begun to consider this issue, and have provided little guidance. It is unclear whether the laws governing protected health information are applicable to the instant situation, and if so, the degree to which they apply. DNA databanks are not uniformly regulated, and it is possible that DNA samples contained in them may be used for purposes unintended by donors of the samples. As people live their lives, they leave bits of their DNA behind. They cannot be assured that these tiny specimens will not be taken or used against their will or without their knowledge for activities such as profiling to measure tendencies such as thrill-seeking, aggressiveness, or crimes with threatening behavior. Existing racial or ethnic discrimination and profiling may also encompass genetic discrimination and profiling, creating societal class distinctions. This article will explore the constitutionality of collecting genetic materials, the ethics of such activities, and balance the social good in solving crime and deterrence against the individual's security, liberty, and privacy. (shrink)
DNA profiling is a well-established technology for use in the criminal justice system, both in courtrooms and elsewhere. The fact that DNA profiles are based on non-coding DNA and do not reveal details about the physical appearance of an individual has contributed to the acceptability of this type of evidence. Its success in criminal investigation, combined with major innovations in the field of genetics, have contributed to a change of role for this type of evidence. Nowadays DNA evidence is not (...) merely about identification, where trace evidence is compared to a sample taken from a suspect. An ever-growing role is anticipated for DNA profiling as an investigative tool, a technique aimed at generating a suspect where there is none. One of these applications is the inference of visible traits. As this article will show, racial classifications are at the heart of this application. The Netherlands and its legal regulation of 'externally visible traits' will serve as an example. It will be shown that, to make this technology work, a large number of actors has to be enrolled and their articulations invited. This indicates that instead of a 'silent witness', a DNA profile should rather be seen as an 'articulate collective'. Based on two cases, I argue that the normativity of visible traits is context-dependent. Taking into account the practices in which technology is put to use alerts us to novel ethical questions raised by their application. (shrink)
First the ‘Weismann barrier’ and later on Francis Crick’s ‘central dogma’ of molecular biology nourished the gene-centric paradigm of life, i.e., the conception of the gene/genome as a ‘central source’ from which hereditary specificity unidirectionally flows or radiates into cellular biochemistry and development. Today, due to advances in molecular genetics and epigenetics, such as the discovery of complex post-genomic and epigenetic processes in which genes are causally integrated, many theorists argue that a gene-centric conception of the organism has become problematic. (...) Here, we first explore the causal implications of the following two central dogma-related issues: (1) widespread reverse transcription—arguing for an extension from ‘DNA-genome’ to RNA-encompassing ‘NA-genome’ and, thus, from traditional DNA-centrism to a broader ‘NA-centrism’; and (2) the absence of a mechanism of reverse translation—arguing for the ‘structural primacy’ of NA-sequence over protein in cellular biochemistry. Secondly, we explore whether this latter conclusion can be extended to a ‘functional primacy’ of NA-sequence over protein in cellular biochemistry, which would imply a limited kind of ‘gene/NA-centrism’ confined to the subcellular level of NA/protein-based biochemistry. Finally, we explore the conditions—and their (non)fulfilment—for a more generalised form of gene-centrism extendable to higher levels of biological organisation. We conclude that the higher we go in the biological hierarchy, the more dubious gene-centric claims become. (shrink)
Major problems in cancer chemotherapy are toxicity, resistance, and cancer heterogeneity. A new theranostic paradigm has been proposed by the authors. Many million small molecules (SM) are bound to the proteins extracted from a patient's cancer. SM that also bind proteins extracted from normal human tissues are subtracted from the cancer protein bound SM leaving a large array of SM targeting many sites on each of the cancer biomarkers. Targeting many more than the conventional 1 – 4 cancer biomarkers will (...) reduce development of tumor resistance. After several cycles of selection and counter selection, DNA codes appended to the SM will be PCR amplified to provide templates for restricted libraries of the SM to improve selectivity and sensitivity. The large array of selected and counter selected SM assures that many of the compounds in the array will penetrate the cell membrane and bind to intracellular targets, low tumor resistance, low background for imaging, low therapeutic toxicity, and targeting of the diverse biomarkers present in the heterogeneous mixture of cells in primary and metastatic cancer. Theranostic use of radiolabeled SM binding many sites on many, not necessarily critical, biomarkers provides high cancer cell killing. Experiments to provide proof of principle of this novel concept suggested by the authors. -/- . (shrink)
Transcription is a fundamental cellular process and the first step in gene regulation. Although RNA polymerase (RNAP) is highly processive, in growing cells the progression of transcription can be hindered by obstacles on the DNA template, such as damaged DNA. The authors recent findings highlight a trade‐off between transcription fidelity and DNA break repair. While a lot of work has focused on the interaction between transcription and nucleotide excision repair, less is known about how transcription influences the repair of DNA (...) breaks. The authors suggest that when the cell experiences stress from DNA breaks, the control of RNAP processivity affects the balance between preserving transcription integrity and DNA repair. Here, how the conflict between transcription and DNA double‐strand break (DSB) repair threatens the integrity of both RNA and DNA are discussed. In reviewing this field, the authors speculate on cellular paradigms where this equilibrium is well sustained, and instances where the maintenance of transcription fidelity is favored over genome stability. (shrink)
To decode the function and molecular recognition of several recently discovered cytosine derivatives in the human genome – 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine – a detailed understanding of their effects on the structural, chemical, and biophysical properties of DNA is essential. Here, we review recent literature in this area, with particular emphasis on features that have been proposed to enable the specific recognition of modified cytosine bases by DNA-binding proteins. These include electronic factors, modulation of base-pair stability, flexibility, and radical changes (...) in duplex conformation. We explore these proposals and assess whether or not they are supported by current biophysical data. This analysis is focused primarily on the properties of epigenetically modified DNA itself, which provides a basis for discussion of the mechanisms of recognition by different proteins. 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine have recently been discovered in mammalian DNA and appear to have essential regulatory roles. Here, we summarize recent investigations into their effects on the structural, chemical, and biophysical properties of DNA, an understanding of which is essential to decoding their behavior in the genome. (shrink)
The structures of protein and DNA were discovered primarily by means of synthesizing component-level information about bond types, lengths, and angles, rather than analyzing X-ray diffraction photographs of these molecules. In this paper, I consider the synthetic and analytic approaches to exemplify alternative heuristics for approaching mid-twentieth-century macromolecular structure determination. I argue that the former was, all else being equal, likeliest to generate the correct structure in the shortest period of time. I begin by characterizing problem solving in these cases (...) as proceeding via the elimination of candidate structures through the successive application of component-level information and interpretations of X-ray diffraction photographs, each of which serves as a kind of constraint on structure. Then, I argue that although each kind of constraint enables the elimination of a considerable proportion of candidate structures, component-level constraints are significantly more likely to do so correctly. Thus, considering them before X-ray diffraction photographs is a better heuristic than one that reverses this order. Because the synthetic approach that resulted in the determination of the protein and DNA structures exemplifies such a heuristic, its use can help account for these discoveries. (shrink)
DNA glycosylases remove aberrant DNA nucleobases as the first enzymatic step of the base excision repair (BER) pathway. The alkyl‐DNA glycosylases AlkC and AlkD adopt a unique structure based on α‐helical HEAT repeats. Both enzymes identify and excise their substrates without a base‐flipping mechanism used by other glycosylases and nucleic acid processing proteins to access nucleobases that are otherwise stacked inside the double‐helix. Consequently, these glycosylases act on a variety of cationic nucleobase modifications, including bulky adducts, not previously associated with (...) BER. The related non‐enzymatic HEAT‐like repeat (HLR) proteins, AlkD2, and AlkF, have unique nucleic acid binding properties that expand the functions of this relatively new protein superfamily beyond DNA repair. Here, we review the phylogeny, biochemistry, and structures of the HLR proteins, which have helped broaden our understanding of the mechanisms by which DNA glycosylases locate and excise chemically modified DNA nucleobases. (shrink)
DNA helicases are a class of molecular motors that catalyze processive unwinding of double stranded DNA. In spite of much study, we know relatively little about the mechanisms by which these enzymes carry out the function for which they are named. Most current views are based on inferences from crystal structures. A prominent view is that the canonical ATPase motor exerts a force on the ssDNA resulting in “pulling” the duplex across a “pin” or “wedge” in the enzyme leading to (...) a mechanical separation of the two DNA strands. In such models, DNA base pair separation is tightly coupled to ssDNA translocation of the motors. However, recent studies of the Escherichia coli RecBCD helicase suggest an alternative model in which DNA base pair melting and ssDNA translocation occur separately. In this view, the enzyme‐DNA binding free energy is used to melt multiple DNA base pairs in an ATP‐independent manner, followed by ATP‐dependent translocation of the canonical motors along the newly formed ssDNA tracks. Repetition of these two steps results in processive DNA unwinding. We summarize recent evidence suggesting this mechanism for RecBCD helicase action. (shrink)
The astonishing efficiency and accuracy of DNA replication has long suggested that refined rules enforce a single highly reproducible sequence of molecular events during the process. This view was solidified by early demonstrations that DNA unwinding and synthesis are coupled within a stable molecular factory, known as the replisome, which consists of conserved components that each play unique and complementary roles. However, recent single-molecule observations of replisome dynamics have begun to challenge this view, revealing that replication may not be defined (...) by a uniform sequence of events. Instead, multiple exchange pathways, pauses, and DNA loop types appear to dominate replisome function. These observations suggest we must rethink our fundamental assumptions and acknowledge that each replication cycle may involve sampling of alternative, sometimes parallel, pathways. Here, we review our current mechanistic understanding of DNA replication while highlighting findings that exemplify multi-pathway aspects of replisome function and considering the broader implications. Recent single-molecule studies have revealed that replisome function is dominated by stochastic sampling of multiple molecular pathways. In the context of these new findings, we re-examine the foundational assumptions and seminal experiments that have guided our understanding of replication mechanism and reconcile several long-debated coordination models. (shrink)
DNA methylation can be considered a component of epigenetic memory with a critical role during embryo development, and which undergoes dramatic reprogramming after fertilization. Though it has been a focus of research for many years, the reprogramming mechanism is still not fully understood. Recent results suggest that absence of maintenance at DNA replication is a major factor, and that there is an unexpected role for TET3-mediated oxidation of 5mC to 5hmC in guarding against de novo methylation. Base-resolution and genome-wide profiling (...) methods are enabling more comprehensive assessments of the extent to which ART might impair DNA methylation reprogramming, and which sequence elements are most vulnerable. Indeed, as we also review here, studies showing the effect of culture media, ovarian stimulation or embryo transfer on the methylation pattern of embryos emphasize the need to face ART-associated defects and search for strategies to mitigate adverse effects on the health of ART-derived children. DNA methylation, critical for embryo development, suffers significant changes after fertilization, including demethylation, remethylation and TET3-mediated oxidation of 5 mC to 5 hmC. In addition to infertility and environmental insults, ART could impact DNA methylation and ART related consequences in the offspring have been reported. (shrink)
Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress tolerance, (...) and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment. PTEN is a guardian of the genome. However, the role of PTEN in guarding the genome has not been revealed until recently. PTEN controls multiple fundamental processes of genomic transmission. By physically interacting with key molecules in DNA replication, DNA repair/decatenation, and chromosome segregation during the cell cycle, PTEN maintains genomicintegrity and fitness. (shrink)
Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. MYC is a potent oncogene, which is upregulated in the majority of cancers; thus numerous studies have focused on detailed understanding of its regulation. Dissection (...) of regulatory regions within the MYC promoter provided the first hint that intimate feedback between DNA topology and associated DNA remodeling proteins is critical for moderating transcription. As evidence of such regulation is also found in the context of many other genes, here we expand on the prototypical example of the MYC promoter, and also explore DNA architecture in a genome-wide context as a global mechanism of transcriptional control. Torsional stress, and supercoiling generated by transcription, shape the topology of DNA. Furthermore, the resultant secondary DNA structures and their interacting partners provide feedback to regulate gene expression. Emerging evidence suggests these mechanisms, identified through analysis of the MYC promoter, are applicable genome-wide. (shrink)
This paper investigates which of the variouslegal notions proposed for human DNA is themost appropriate from an ontological viewpoint – unique legal status, private property, commonproperty, person, or information. The focus is onthe difficulties that private property, commonproperty and person present. By usingHarré''s notion of ``file-self'''' we arguethat, ontologically, the most appropriate legalnotion to be applied is information. This hasconsequences for storage, control and use ofgenetic information as well as identifiablehuman body material.
In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break-induced replication, lead to the deleterious large-scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA microsatellites in eukaryotes. We suggest that the negative mutagenic outcomes of these pathways, exemplified by repeat expansion diseases, are likely outweighed by their positive role in (...) maintaining functional repetitive regions of the genome such as telomeres and centromeres. Break-induced replication and template switching are conserved mechanisms of replication fork restart. They do not cause microsatellite instability in prokaryotes, but promote repeat expansion in eukaryotes. We suggest that TS and BIR persisted in eukaryotes despite their mutagenic potential because they help maintain long repetitive telomeres and centromeres. (shrink)
Definition of the problem:The frequency and scope of human genetic banking has increased significantly in recent years and is set to expand still further. Two of the major growth areas in medical research, pharmacogenomics and population genetics, rely on large DNA banks to provide extensive, centralised and standardised genetic information as well as clinical and personal data. This development raises ethical concerns. Arguments and conclusion: Our article focuses on the appropriateness of informed consent as a means to safeguard both research (...) subjects’ rights and their good will. It will be argued that information requirements are extensive, with regard to non-therapeutic research, feedback, type of consent and possible breaches of confidentiality as well as possible implications for third parties. Given the demand of these requirements and the danger that research facilitated by these huge DNA banks may not reflect public priorities, it is argued that the research needs be steered by trustees to ensure that the altruistic act of sample donation contributes to the public good. (shrink)
This paper presents the manner in which the DNA, the molecule of life, was discovered. Unlike what many people, even biologists, believe, it was Johannes Friedrich Miescher who originally discovered and isolated nuclein, currently known as DNA, in 1869, 75 years before Watson and Crick unveiled its structure. Also, in this paper we show, and above all demonstrate, the serendipity of this major discovery. Like many of his contemporaries, Miescher set out to discover how cells worked by means of studying (...) and analysing their proteins. During this arduous task, he detected an unexpected substance of unpredicted properties. This new substance precipitated when he added acid to the solution and it dissolved again when adding alkali. Unexpectedly and by a mere fluke, Miescher was the first person to obtain a DNA precipitate. The paper then presents the term serendipity and discusses how it has influenced the discovery of other important scientific milestones. Finally, we address the question of whether serendipitous discoveries can be nurtured and what role the computer could play in this process. (shrink)
Mortal and immortal DNA : Craig Venter and the lure of "lamia" -- Homeopathy : Holmes, hogwarts, and the Prince of Wales -- Citizen Pinel and the madman at Bellevue -- The experimental pathology of stress : Hans Selye to Paris Hilton -- Gore's fever and Dante's Inferno : Chikungunya reaches Ravenna -- Giving things their proper names : Carl Linnaeus and W.H. Auden -- Spinal irritation and fibromyalgia : Lincoln's surgeon general and the three graces -- Tithonus and the (...) fruit fly : new science and old myths -- Swiftboating "America the beautiful" : Katharine Lee Bates and a Boston marriage -- Nothing makes sense in medicine except in the light of biology -- Apply directly to the forehead : Holmes, Zola, and Hennapecia -- Elizabeth Blackwell breaks the bonds -- Chronic lyme disease and medically unexplained syndromes -- Eugenics and the immigrant : Rosalyn Yalow and Rita Levi-Montalcini -- Science in the Middle East : Robert Koch and the cholera war -- How to win a Nobel prize : thinking inside and outside the box -- Homer Smith and the lungfish : the last gasp of intelligent design -- DDT is back : let us spray! -- Academic boycotts and the Royal Society -- Teach evolution, learn science : John William Draper and the "bone bill" -- Diderot and the yeti crab : the encyclopedias of life -- Dengue fever in Rio : Macumba versus Voltaire. (shrink)
Writers, philosophers, and theologians have oft made the comparison between being a mature human being and a masterpiece work of art or design. Employing the analogy between the creation of artistic value and the creation of full-fledged human value, this paper stakes out a middle ground between pro-choice and pro-life by considering a more general account of value and the relationship between being a potential X and a mature implementation of X's potential. I argue that the value of a potential (...) X is a function of a number of factors, most importantly, what I call the "accessibility relation" between a potential X and a full-fledged instantiation of this potential. The value is as much intrinsic to the “seed” as to some future implementation of the seed’s potential. This approach inclines even a secular humanist to reasonably confer a significant degree of moral value to a human conceptus, and even more to an early term fetus. (shrink)
The repair of chromosomal double‐strand breaks (DSBs) by homologous recombination is essential to maintain genome integrity. The key step in DSB repair is the RecA/Rad51‐mediated process to match sequences at the broken end to homologous donor sequences that can be used as a template to repair the lesion. Here, in reviewing research about DSB repair, I consider the many factors that appear to play important roles in the successful search for homology by several homologous recombination mechanisms.
Definition of the problem: The development of molecular genetics has provided tools not only for the diagnosis of genetic diseases and disease dispositions in affected individuals, but also for the detection of healthy carriers of recessive hereditary traits. The resulting, ethically controversial option of genetic population screening used to be restricted to a small number of rather rare diseases by methodological limitations which are now about to be overcome.