This article examines the way in which public controversies affect regulatory science. It describes the controversy that unfolded in Europe around the use of the ninety-day rat-feeding tests for the risk assessment of genetically modified plants. This type of test had been criticized for almost two decades by toxicologists, nongovernmental organizations, and industry alike for its inability to capture the specific health effects of GM plants. But GM risk assessment experts showed great reluctance to move toward a more systematic use (...) of other tests, such as chronic two-year studies or toxicogenomic techniques, and made sure that official guidance continues to recommend the use of the ninety-day rat-feeding study. The article shows that these tactics of standardization are a defining feature of regulatory science, and a resource for toxicity experts to defend their authority and credibility against competing expertises that arise during controversies. (shrink)

If scientists rely on assumptions rather than logic, empirical confirmation, and falsification, they are no longer doing science but ideology – which is, by definition, unethical. As a recent US National Academy of Sciences report put it, “bad science is always unethical.”1 This article discusses several ways in which toxicologists can fall into ideology – bad, therefore unethical, science. In part because of the increasing expense of pollution control, some toxicologists have been reexamining pollution dose-response curves that are non-monotonic, that (...) is, curves in which the direction of some response changes with increasing or decreasing dose.2 Ethanol is a classic example of a non-monotonic dose-response curve because moderate drinking is associated with lower risks of heart disease, whereas heavy drinking is associated with higher risks.3,4 If some low-dose pollutants exhibit adaptive or “beneficial effects,”5 this might suggest re-thinking pollution regulations which presuppose linear no-threshold (LNT) dose-response curves. (shrink)

Inmaculada de Melo-Martín and Kristen Intemann consider whether, from the perspective of the argument from inductive risk, ethical and political values might be logically, epistemically, pragmatically, or ethically necessary in the “core” of scientific reasoning. In each case, they argue that there are significant conceptual problems. In this comment, employing regulatory uses of high-throughput toxicology at the US Environmental Protection Agency as a case study, I respond to some of their claims about the notion of “pragmatic necessity.” I conclude (...) that, while an inductive risk framework has some significant limitations, it is still conceptually and rhetorically valuable. (shrink)

Environmental risk assessment is often affected by severe uncertainty. The frequently invoked precautionary principle helps to guide risk assessment and decision-making in the face of scientific uncertainty. In many contexts, however, uncertainties play a role not only in the application of scientific models but also in their development. Building on recent literature in the philosophy of science, this paper argues that precaution should be exercised at the stage when tools for risk assessment are developed as well as when they are (...) used to inform decision-making. The relevance and consequences of this claim are discussed in the context of the threshold of the toxicological concern approach in food toxicology. I conclude that the approach does not meet the standards of an epistemic version of the precautionary principle. (shrink)

Hybrid scientific fields consist of a collection of knowledge-producing and -utilising organisations, fulfilling a dual role of providing specific knowledge services as well as contributing to increased scientific understanding. In this article, the processes that govern scientific knowledge production in hybrid scientific fields are explored. While such sets of organisations are targeted in science policy as receivers of resources, as well as providers of services and other knowledge products, attention in science studies is all but lacking. Data from a study (...) on toxicology as a representative of public health sciences are used. The author will focus on the effects on scientific research and its organisational relations by discussing three social processes relevant to knowledge production, problem choice, resource distribution, and reputational control. (shrink)

This essay explores how the enhanced sensitivity of chemical tests sometimes produced unforeseen and puzzling problems in nineteenth-century toxicology. It focuses on the earliest uses of the Marsh test for arsenic and the controversy surrounding “normal arsenic”—that is, the existence of traces of arsenic in healthy human bodies. The essay follows the circulation of the Marsh test in French toxicology and its appearance in the academy, the laboratory, and the courtroom. The new chemical tests could detect very small (...) quantities of poison, but their high sensitivity also offered new opportunities for imaginative defense attorneys to undermine the credibility of expert witnesses. In this context, toxicologists had to dispel the uncertainty associated with the new method and come up with arguments to refute the many possible criticisms of their findings, among them the appeal to normal arsenic. Meanwhile, new descriptions of animal experiments, autopsies, and cases of poisoning produced a steady flow of empirical data, sometimes supporting but in many cases questioning previous conclusions about the reliability of the chemical tests. This challenging scenario provides many clues about the complex interaction between science and the law in the nineteenth century, particularly how expert authority, credibility, and trustworthiness were constructed, and frequently challenged, in the courtroom. (shrink)

One way to do socially relevant investigations of science is through conceptual analysis of scientific terms used in special-interest science (SIS). SIS is science having welfare-related consequences and funded by special interests, e.g., tobacco companies, in order to establish predetermined conclusions. For instance, because the chemical industry seeks deregulation of toxic emissions and avoiding costly cleanups, it funds SIS that supports the concept of "hormesis" (according to which low doses of toxins/carcinogens have beneficial effects). Analyzing the hormesis concept of its (...) main defender, chemical-industry-funded Edward Calabrese, the paper shows Calabrese and others fail to distinguish three different hormesis concepts, H, HG, and HD. H requires toxin-induced, short-term beneficial effects for only one biological endpoint, while HG requires toxin-induced, net-beneficial effects for all endpoints/responses/subjects/ages/conditions. HD requires using the risk-assessment/regulatory default rule that all low-dose toxic exposures are net-beneficial, thus allowable. Clarifying these concepts, the paper argues for five main claims. (1) Claims positing H are trivially true but irrelevant to regulations. (2) Claims positing HG are relevant to regulation but scientifically false. (3) Claims positing HD are relevant to regulation but ethically/scientifically questionable. (4) Although no hormesis concept (H, HG, or HD) has both scientific validity and regulatory relevance, Calabrese and others obscure this fact through repeated equivocation, begging the question, and data-tri mm ing. Consequently (5) their errors provide some undeserved rhetorical plausibility for deregulating low-dose toxins. (shrink)

The ability of powerful and well-funded interest groups to steer scientific research in directions that advance their goals has become a significant social concern. This ability is increasingly being recognized in the peer-reviewed literature and in the findings of deliberative expert consensus committees. For example, there is increasing recognition that efforts to address climate change have been stymied in part by a powerful network of conservative foundations, which fund think tanks and other organizations that constitute a “climate change counter movement”. (...) Sociologist Robert Brulle recently found that the total annual income for 91 powerful.. (shrink)

Science des poisons, la toxicologie est une spécialité pluridisciplinaire dont l’enseignement est dispersé entre médecine, pharmacie et chimie. Les manuels de toxicologie soulèvent des enjeux disciplinaires et éditoriaux. Une première partie montre, à travers une approche sérielle et comparative, comment la publication de manuels constitue un moyen de promouvoir et de revendiquer la reconnaissance institutionnelle d’une discipline aux contours fluctuants. Une deuxième partie présente l’histoire éditoriale du Manuel complet de médecine légale (10 éditions : 1821-1880) de Briand & Chaudé et (...) les conséquences disciplinaires de l’insertion d’un Traité élémentaire de chimie légale écrit par des pharmaciens-chimistes. (shrink)

The Adverse Outcome Pathway (AOP) concept is a knowledge assembly and communication tool to facilitate the transparent translation of mechanistic information into outcomes meaningful to the regulatory assessment of chemicals. The AOP framework and associated knowledgebases (KBs) have received significant attention and use in the regulatory toxicology community. However, it is increasingly apparent that the potential stakeholder community for the AOP concept and AOP KBs is broader than scientists and regulators directly involved in chemical safety assessment. In this paper (...) we identify and describe those stakeholders who currently—or in the future—could benefit from the application of the AOP framework and knowledge to specific problems. We also summarize the challenges faced in implementing pathway-based approaches such as the AOP framework in biological sciences, and provide a series of recommendations to meet critical needs to ensure further progression of the framework as a useful, sustainable and dependable tool supporting assessments of both human health and the environment. Although the AOP concept has the potential to significantly impact the organization and interpretation of biological information in a variety of disciplines/applications, this promise can only be fully realized through the active engagement of, and input from multiple stakeholders, requiring multi-pronged substantive long-term planning and strategies. (shrink)

Des mortalités anormales frappent les ruchers d’Europe et d’autres continents depuis un peu plus de vingt ans. Depuis le début des troubles, des suspicions pèsent sur des insecticides d’un genre nouveau, utilisés en traitement de semences. La législation prescrivant l’évaluation des risques environnementaux de toute substance insecticide dès avant sa mise sur le marché, des apiculteurs sont allés consulter les dossiers portant sur les molécules suspectées, ce qui les a amenés à s’impliquer dans la critique et l’élaboration des règles d’évaluation, (...) et à côtoyer le monde des experts en toxicologie de l’abeille.Beehives across Europe and other continents have been affected by abnormal mortality for the last twenty years. Since these problems first appeared, suspicion has fallen on a new type of insecticide, which is used to treat seeds. The legislation prescribes environmental risk assessments of any insecticide substance before it reaches the market, and beekeepers therefore decided to consult the files concerning the suspect molecules. As a result, they became involved in critically reviewing and developing assessment rules, and thus came to rub shoulders with experts in bee toxicology. (shrink)

It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one (...) empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics. (shrink)

This article tracks the transformation of beagle dogs from a common breed in mid-twentieth century American laboratories to the de jure standard in global toxicological research by the turn of the twenty-first. The breed was dispersed widely due to the expanding use of dogs in pharmacology in the 1950s and a worldwide crisis around pharmaceutical safety following the thalidomide scandal of the 1960s. Nevertheless, debates continued for decades over the beagle’s value as a model of carcinogenicity, even as the dogs (...) became legislated stand-ins for human beings in multiple countries. Situating beagles as a biocommodity, the article calls for more sustained attention to the “political economy” of laboratory organism breeding, use, and production. The story of American commercial breeder Marshall Farms offers insight into the role of for-profit companies in contemporary laboratory animal provision, as the article makes a case for the value of a global perspective on transnational corporations as key sites of scientific practice and collaboration. (shrink)

In this paper we argue for a naturalistic solution to some of the methodological controversies in regulatory science, on the basis of two case studies: toxicology and health claim regulation. We analyze the debates related to the scientific evidence that is considered necessary for regulatory decision making in each of those two fields, with a particular attention to the interactions between scientific and regulatory aspects. This analysis allows us to identify two general stances in the debate: a) one that (...) argues for more permissive standards of evidence and for methodological pluralism, and b) an opposing one that not only defends strict evidence requirements but also stipulates the use of one particular scientific methodologies for data generation. We argue that the real-world outcomes produced by alternative regulatory options are a vital piece of information that allows for the empirical assessment of these two stances. In particular, this information on outcomes makes it possible to analyze which standards of evidence and scientific methods generate the most useful knowledge as input for regulatory decision making. Our conclusion is that instead of an a priori selection of methodologies and standards, such decisions ought to be based on empirical evidence related to real-world outcomes. (shrink)

Today, human pluripotent stem cell technologies find widespread application across biomedical research, as models for early human development, as platforms for functional human genomics, as tools for the study of disease, drug screening and toxicology, and as a renewable source of cellular therapeutics for a range of intractable diseases. The foundations of this human pluripotent stem cell revolution rest on advances in a wide range of disciplines, including cancer biology, assisted reproduction, cell culture and organoid technology, somatic cell nuclear (...) transfer, primate embryology, single‐cell biology, and gene editing. This review surveys the slow emergence of the study of human pluripotency and the exponential growth of the field during the past several decades. (shrink)

The controversy over glyphosate-based herbicides, where there is extreme divergences in health and environmental assessments, is rooted in several methodological and normative factors. Foremost among them are the differences found in testing pure glyphosate compared to the testing of glyphosate formulations. The adjuvant chemicals found in formulations can be more toxic than the so-called “active ingredient.” Other factors can also account for why scientists reach different conclusions on the toxicological effects of GBH including the preconceptions and methodological choices they bring (...) into the study. Lack of consensus on the science can be problematic for policymakers. The paper argues that the toxicological science behind the GBH assessments is embedded in a normative substratum, which must be considered in policy decisions. (shrink)

Cancer—and scientific research on cancer—raises a variety of compelling philosophical questions. This entry will focus on four topics, which philosophers of science have begun to explore and debate. First, scientific classifications of cancer have as yet failed to yield a unified taxonomy. There is a diversity of classificatory schemes for cancer, and while some are hierarchical, others appear to be “cross-cutting,” or non-nested. This literature thus raises a variety of questions about the nature of the disease and disease classification. Second, (...) philosophers of science have historically taken the aim of science to be arriving at true theories. However, scientists studying cancer come from a variety of disciplines, with different scientific as well as practical aims. Perhaps it is not surprising, then, that historians and philosophers of science do not seem to agree on how best to characterize the aim and structure of cancer research; it is far from clear whether the appropriate characterization of the aim is arriving at true theories, or even whether the proper units of analysis are “theories”, or instead, “models”, “explanatory frameworks”, “research programs”, “paradigms”, or perhaps, “experimental traditions”. With the rise of “big data” science—such as the Cancer Genome Atlas Project (or TCGA)—and “systems” approaches to the study of disease, both philosophers and historians of science are rethinking how best to describe and explain these distinctive kinds of scientific inquiry. -/- Third, cancer is in part a byproduct of our developmental and life history, as well as our evolutionary history. Cancer progression can be compared to a reversion of development, or, to the evolution of multicellularity. Thus, cancer raises intriguing questions about how we conceive of “functions”, “development”, and the role of our evolutionary history and particularly, selective trade-offs, in vulnerability to disease. -/- Last but not least, cancer research provides a case study for consideration of the roles of values at the science-policy interface. Epidemiological and toxicological research on cancer’s causes informs toxics law and regulatory policy, which raises a variety of questions about the nature of evidence and inductive risk in such contexts. (shrink)

The genetically manipulated organism crisis demonstrated that technological development based solely on the law of the marketplace and State protection against serious risks to health and safety is no longer a warrant of ethical acceptability. In the first part of our paper, we critique the implicitly individualist social-acceptance model for State regulation of technology and recommend an interdisciplinary approach for comprehensive analysis of the impacts and ethical acceptability of technologies. In the second part, we present a framework for the analysis (...) of impacts and acceptability, devised—with the goal of supporting the development of specific nanotechnological applications—by a team of researchers from various disciplines. At the conceptual level, this analytic framework is intended to make explicit those various operations required in preparing a judgement about the acceptability of technologies that have been implicit in the classical analysis of toxicological risk. On a practical level, we present a reflective tool that makes it possible to take into account all the dimensions involved and understand the reasons invoked in determining impacts, assessing them, and arriving at a judgement about acceptability. (shrink)

In this article we discuss two divergent accounts of non-human animals as analog models of human biomedical phenomena. Using a classical account of analogical reasoning, toxicologists and teratologists claim that if the model and subject modeled are substantially similar, then test results in non-human animals are likely applicable to humans . However, the same toxicologists report that different species often react very differently to the same chemical stimuli . The best way to understand their findings is to abandon the classical (...) view of analogical - i.e., linear - reasoning, and replace it with a version informed by chaos theory. We briefly outline the current understanding of chaos, and trace its implications for toxicology and teratology. (shrink)

In this case study from litigation, I examine the origin of Monsanto-sponsored articles published in toxicology journals and the lay media that were designed to create doubt in critical evaluations of the herbicide, glyphosate. The role of ghostwriting and the use of third-party academics in the corporate defense of glyhphosate reveal that this practice extends beyond the corruption of medical journals and persists in spite of efforts to enforce transparency in industry manipulation of the scientific literature.

Risk assessment is an evidence-based analytical framework used to evaluate research findings related to environmental and public health decision-making. Different routines have been adopted for assessing the potential risks posed by substances and products to human health. In general, the traditional paradigm is a hazard-driven approach, based on a monocausal toxicological perspective. Questions have been raised about the applicability of the general chemical risk assessment approach in the specific case of nanomaterials. Most scientists and stakeholders assume that the current standard (...) methods are in principle suitable, but point out that experimental aspects and practical guidelines need specific adaptations. Beyond this laboratory level, risk assessment of nanomaterials also faces a number of substantive and procedural limitations, which are intrinsically attributed to the general orthodoxy of the risk assessment concept. Moreover, the developed formalism used to organize scientific knowledge is closely interlinked with the underlying governance design and the mode of interaction between the two spheres of ‘science’ and ‘decisions’. This contribution will provide a closer look at the evolution of different institutional settings for risk assessment in the context of decision-making. Improved risk governance frameworks with different narratives, process designs and procedural elements will be compared. The question of a general principle of enhanced organization of risk assessment will be discussed taking account of the barriers of substantive and procedural limitations in the special case of nanomaterials. (shrink)

In vitro experimental approaches are of central importance to contemporary molecular and cellular biology and toxicology. However, the scientific value or impact of in vitro results depends on their relevance in vivo. In vitro effect studies address inobservable in vivo phenomena through experiments on analogous in vitro phenomena. We present a theoretical basis developed to evaluate the in vivo relevance of in vitro effect studies. As a case study, the procedure for measuring specific gene transcription in isolated cell nuclei (...) (nuclear run-off method) is analyzed It is concluded that current evidence fails to justify in vivo interpretations of nuclear run-off experiments within the framework of theoretical models of transcription, implying that quantitative in vivo interpretations are unwarranted. Qualitative interpretations of nuclear run-off experiments may be justified by inferring the best explanation, especially when significant in vitro effects follow in vivo perturbations.Elements of a general theory are proposed. It is concluded that quantitative in vivo interpretations are warranted primarily in biochemical quantitation of biomolecules, while studies on biological function should be interpreted qualitatively in terms of causal explanations. Inferences to the best explanations are strengthened through additional evidence and the creation of experimental differences (effects). (shrink)

In lieu of an abstract, here is a brief excerpt of the content:When Is Enough, Enough?Megan HomsyThis was a case that stuck with many members of our transplant team for a long time. The patient was a 44-year-old Caucasian male evaluated for a liver transplant with a diagnosis of hepatitis C virus (HCV), originally diagnosed 11 years before the transplant evaluation. The patient met the criteria for the following substance use diagnoses: alcohol use disorder moderate in sustained remission, in a (...) controlled environment, opioid use disorder, severe, in sustained remission, on maintenance therapy, in a controlled environment, stimulant use disorder, amphetamine-type, severe, in early remission, in a controlled environment and stimulant use disorder, cocaine-type, severe in early remission, in a controlled environment.The patient had been living in a sober living housing program for approximately ten months prior to his transplant evaluation with me, his social worker. He had also been diagnosed with depression and bipolar disorder. He had been intermittently linked with mental health services and had participated in numerous detox and substance abuse programs over the last ten years, with varying degrees of success. He was in dual diagnosis treatment (i.e., treatment for co-occurring substance use and mental health disorders) through his Suboxone clinic and was completing toxicology screenings on a biweekly basis.After concluding the minimum three months of drug and alcohol treatment set forth by the state's Organ Transplantation Consortium, the patient graduated from his sober living program, moved in with his sister, and was listed for a liver transplant.The patient was transplanted five months after his clinic evaluation. At the time of the surgery, the patient's Suboxone was abruptly discontinued and replaced with IV Dilaudid. Within days of his transplant, the patient frequently expressed concerns about his pain. Several medical services attempted to manage the pain medications, resulting in his pain management plan being changed repeatedly and much confusion over his current medication regimen. During his liver transplant hospitalization, the RN found the patient with a needle in his arm, and after a search of the patient's hospital room, the hospital police found drug paraphernalia and illicit substances. The patient was eventually discharged to an inpatient substance abuse program, which he left before completing the program and against medical advice.During his first year post-transplant, I attempted to arrange other various treatment programs for him (most of which he did not follow through with) and to find housing for him (as he had been forced to leave his sister's home after his relapse). Eventually, the patient was incarcerated on drug-related charges. Numerous times, the patient missed completing his labs and his post-transplant appointments. He did not refill his immunosuppressant medications, and for lengthy periods of time, he was unreachable by the transplant care team, which resulted in my team members and I calling the patient's family, other providers, and the police for safety checks.In the aftermath of these issues, my colleagues and I had to reckon with the realization that we had failed the patient. As a team, our transplant center created a task force to review this case and what to do in the future to prevent such breakdowns in patient care. We created protocols for managing patients who, at the time of their transplant, are on Medication Assisted Treatment (MAT) such as Suboxone and methadone. Staff across the multidisciplinary team attended trainings regarding addiction, pain management, and best practices for MAT services. Additionally, our transplant center collaborated with our hospital's addiction treatment program for a streamlined referral process for transplant patients to addiction services.This patient's case and its sensational nature resulted in many conversations, both professional and unprofessional. Members of the social worker department became aware that personnel within transplant, though not involved in patient care, were inappropriately discussing this patient's case and engaging in unprofessional behavior. Said actions led to the termination of a member of the transplant team. I was placed in the unenviable [End Page E3] position of having to report this behavior to hospital management and legal teams to protect a vulnerable patient.The ethical challenge behind this case really stems from the transplant team attempting to balance two... (shrink)

It is widely recognized that endocrine disrupting compounds, such as Bisphenol A, pose challenges for traditional paradigms in toxicology, insofar as these substances appear to have a wider range of low-dose effects than previously recognized. These compounds also pose challenges for ethics and policymaking. When a chemical does not have significant low-dose effects, regulators can allow it to be introduced into commerce or the environment, provided that procedures and rules are in place to keep exposures below an acceptable level. (...) This option allows society to maximize the benefits from the use of the chemical while minimizing risks to human health or the environment, and it represents a compromise between competing values. When it is not possible to establish acceptable exposure levels for chemicals that pose significant health or environmental risks, the most reasonable options for risk management may be to enact either partial or complete bans on their use. These options create greater moral conflict than other risk management strategies, leaving policymakers difficult choices between competing values. (shrink)

The aim of this paper is to present the modes of action of venom as construed by Abū 'Uthmān 'Amr ibn Ba[hdotu]r al-Jā[hdotu]i[zdotu] in his Kitāb al-[Hdotu]ayawān. The toxicological information presented by Jā[hdotu]i[zdotu] is a synthesis of data available in his time, but Jā[hdotu]i[zdotu] complemented these early conceptions by his personal theoretical views. Jā[hdotu]i[zdotu]'s fundamental idea is that venoms act through their specific natures; this idea in a way is reminiscent of present-day theory of enzymes.

The homeopathic principle of similitude is not based on the principle of vaccination but on the more general principle of inversion of effects, a widespread medical phenomenon. Based on the systemic networks which play an important role in response to stress, this principle concerns the reorganization of regulation systems, through a coherent response to the medicine. This model is backed by a large number of published studies from our laboratory and others, by toxicological evidence such as the emerging fields of (...) ‘hormesis’, of neuropharmacology, and of systems biology. The immune system is just one example of the possible application of this law of similitude, which constitutes the true ‘heart’ of the homeopathic idea, and again ethically justifies the attempt to apply it to experimental pharmacology. (shrink)

The Safe by Design conceptual initiative being developed for nanomaterials offers a template for a new sustainable innovation approach for advanced materials with four important sustainability characteristics. Firstly, it requires potential toxicity risks to be evaluated earlier in the innovation cycle simultaneously with its chemical functionality and possible commercial applications. Secondly, it offers future options for reducing animal laboratory testing by early assessment using in silico predictive toxicological approaches, minimizing the number that reaches in vitro and in vivo trials. Thirdly, (...) it promotes a culture of shared responsibility for ethical and sustainable outcomes in the innovation process by promoting early dialogue between groups with vested interests. Finally, it offers the prospect of a more democratized innovation process by including civil society actors in decisions on product safety, commercial applications, and social utility. Collectively, these four characteristics offer the prospect for a new social contract between science, technology, and society for the societal alignment and sustainable innovation of advanced materials. (shrink)

This article investigates the question of how forensic toxicologists established the credibility of chemical analytical methods in poisoning lawsuits in the nineteenth century. After encountering the problem of laypersons in court, forensic toxicologists attempted to find strategies to make their evidence compelling to an untrained audience. Three of these strategies are discussed here: redundancy, standard methods, and intuitive comprehensibility. Whereas redundancy was not very practical and legally prescribed standard methods were not very popular with most forensic toxicologists, intuitive comprehensibility proved (...) effective and popular. This strategy relied on employing methods which did not require chemical knowledge to be understandable. The methods aimed to generate a visual aid and to be obvious in their results. Two forms of this strategy are discussed here: the presentation of the actual material and explicit comparison. I argue that this shift towards presenting forensic toxicology expertise as evident represents an important step in the history of forensic expertise. (shrink)

This issue of the Kennedy Institute of Ethics Journal continues two conversations that have been developing in this journal over the last few years, and introduces a new and timely one. Kevin Elliot and Paul Mushak’s paper, “Structured Development and Promotion of a Research Field: Hormesis in Biology, Toxicology, and Environmental Regulatory Science,” continues an ongoing debate in this journal over the role of values in shaping scientific methodology and communication, and how this role should be managed at the (...) level of policy. We inaugurated this discussion in our June 2012 special issue on Science, Expertise, and Democracy, and have followed up with multiple articles on science and values. David.. (shrink)

Much of the focus of the published 2011 symposium that inspired this work focused on the question, “When have you reduced risk enough to move from bench/animal studies to ‘first in-human’ studies?” Building applied research ethics related to nanotherapeutics requires bench and clinical scientists to have a clear vision about how to test nanotherapeutic safety, and it is clear that there is still much to be considered at the steps before “in-human” assessment. Herein, the perspective of the bench scientist is (...) brought to bear on using in vivo and in vitro models to assess the safety of nanotherapeutics. Much of this work falls under the purview of the field of nanotoxicology that aims to understand the toxicological impact of engineered nanoscale materials. Engineered nanomaterials include a wide variety of materials that are manipulated and controlled on the nanoscale level where, typically, the nanoparticle or nanomaterial has some dimension that is less than 100 nm. (shrink)

This essay argues that Freud’s case of Little Hans, while complicated by Hans’ father’s dual role in the analysis and in the Oedipal drama itself, provides valuable insight into the nature of psychoanalytic evidence and argument. The case provides direct, if sometimes ambiguous, evidence concerning primal phantasies and infantile sexuality--issues of universality, the role of experience, and the nature of phantasy are explored. Four strands of Freud’s analysis of Little Hans’ horse phobia are also explored. While the toxicological theory of (...) anxiety is problematical and was subsequently abandoned by Freud himself, the other strands have great explanatory power and offer advantages over behaviorist and other alternative accounts. A kind of theoretical rigor in the concepts employed is argued to be among those advantages. The inevitably theory-laden character of observation is emphasized throughout, and it is argued that psychoanalysis provides a far more powerful theory than certain critiques would allow. (shrink)

Brazil is the biggest market for pesticides in the world. In the registration process, a pesticide must be authorized by the Institute of the Environment, Health Surveillance Agency and Ministry of Agriculture. Evaluations follow a package of toxicological studies submitted by the companies and also based on the Brazilian law regarding pesticides. We confronted data produced by private laboratories, submitted to the Institute of the Environment for registration, with data obtained from scientific databases, corresponding to mutagenicity, carcinogenicity and teratogenicity of (...) pesticides. All studies submitted by the companies were carried out by private laboratories. From 247 pesticide formulations analyzed, none showed positive results for mutagenicity, carcinogenicity or teratogenicity. From 574 articles in the scientific literature, 84% published by public laboratories showed positive results, while 79% of those showing negative results came from private laboratories. There is an ethical concern about a conflict of interest between public/independent laboratories and private laboratories that produce data for registering pesticides. We demonstrated that there is a clear contradiction between public and private laboratories. Brazilian regulatory authorities have approved the registration of pesticides based almost exclusively on the monographs provided by the pesticide industry, because the use of scientific articles or information from the independent literature is strongly belittled by the industry. Pesticide companies argue that scientific articles cannot be trusted. Also, according to the industry, pesticide registration cannot be refused based on results from scientific articles. Thus, the registration of pesticides with mutagenic, carcinogenic and teratogenic risks has been approved in Brazil. (shrink)

Claude Bernard, the father of scientific physiology, believed that if medicine was to become truly scientiifc, it would have to be based on rigorous and controlled animal experiments. Bernard instituted a paradigm which has shaped physiological practice for most of the twentieth century. ln this paper we examine how Bernards commitment to hypothetico-deductivism and determinism led to (a) his rejection of the theory of evolution; (b) his minima/ization of the role of clinical medicine and epidemiological studies; and (c) his conclusion (...) that experiments on nonhuman animals were, "entirely conclusive for the toxicology and hygiene of man". We examine some negative consequences of Bernardianism for twentieth century medicine, and argue that physio/ogy's continued adherence to Bernardianism has caused it to diverge from the other biological sciences which have become increasingly infused with evolutionary theory. (shrink)

: This paper examines the epistemological warrant for a toxicological phenomenon known as chemical hormesis. First, it argues that conceptual confusion contributes significantly to current disagreements about the status of chemical hormesis as a biological hypothesis. Second, it analyzes seven distinct concepts of chemical hormesis, arguing that none are completely satisfactory. Finally, it suggests three ramifications of this analysis for ongoing debates about the epistemological status of chemical hormesis. This serves as a case study supporting the value of philosophical methodologies (...) such as conceptual clarifica-tion for addressing contemporary scientific disputes, including policy-related scientific disputes that may be heavily in(integral)uenced by social and political factors. (shrink)

Despite their growing usage in commercial and industrial applications, nanomaterials have yet to be been thoroughly researched as to their potential health, safety, and environmental risk to human life after incorporation into new product improvement, development, design, and manufacturing processes. Identifying the appropriate governance framework for effective risk assessment analysis of toxicological risk to human beings—specifically manufacturing employees and consumers—and other living organisms, resulting from the development and application of these nanotechnology-based products, has yet to be scientifically determined. With major (...) regulatory gaps in the public regulation framework at national and international levels of governance, a proposed private governance framework is needed to assist the existing public regulatory framework with the proliferation of products and manufacturing processes utilizing nanomaterials. There are three distinct (yet complimentary) approaches available to develop a private governance framework to complement existing national public regulatory frameworks: responsible innovation, risk management, and voluntary guidelines/industry standards. The case for supporting a hybrid governance framework, combining public and private governance mechanisms, for nanotechnology is reflective of the current public policy environment that has emerged to best address health, safety, and environmental risk assessment issues concerning nanotechnology and nanomaterials. (shrink)

In September 2012, Gilles-Eric Séralini and seven coauthors published an article in Food and Chemical Toxicology claiming that rats fed Roundup©-resistant genetically modified maize alone, genetically modified maize with Roundup©, or Roundup© for 2 years had a higher percentage of tumors and kidney and liver damage than normal controls. Shortly after this study was published, numerous scientists and several scientific organizations criticized the research as methodologically and ethically flawed. In January 2014, the journal retracted the article without the authors’ (...) consent on the grounds that the research was inconclusive. In June 2014, Environmental Sciences Europe published a slightly modified version of the retracted paper. The publication, retraction and subsequent republication of the Séralini study raise important scientific and ethical issues for journal editors. Decisions to retract an article should be made on the basis of well-established policies. Articles should be retracted only for serious errors that undermine the reliability of the data or results, or for serious ethical lapses, such as research misconduct or mistreatment of animal or human subjects. Inconclusiveness, by itself, is not a sufficient reason for retracting an article, though a flawed study design might be. Retracted articles that are submitted for republication should undergo scientific review to ensure that they meet appropriate standards. Republished articles should be linked to the original, retracted publication. Journals that are reviewing studies with significant scientific and social implications should take special care to ensure that peer review is rigorous and fair. (shrink)

Information is usually supposed to be a prerequisite for people making decisions on whether or not to participate in a clinical trial. Previously conducted studies and research ethics scandals indicate that participants have sometimes lacked important pieces of information. Over the past few decades the quantity of information believed to be adequate has increased significantly, and in some instances a new maxim seems to be in place: the more information, the better the ethics in terms of respecting a participant’s autonomy. (...) The authors hypothesise that the dose-response curve from pharmacology or toxicology serves as a model to illustrate that a large amount of written information does not equal optimality. Using the curve as a pedagogical analogy when teaching ethics to students in clinical sciences, and also in engaging in dialogue with research institutions, may promote reflection on how to adjust information in relation to the preferences of individual participants, thereby transgressing the maxim that more information means better ethics. (shrink)

Nanotechnology is the latest in a growing list of emerging technologies that includes nuclear technologies, genetics, reproductive biology, biotechnology, information technology, robotics, communication technologies, surveillance technologies, synthetic biology, and neuroscience. As was the case for many of the technologies that came before, a key question facing nanotechnology is what type of regulatory oversight is appropriate for this emerging technology. As two of us wrote several years ago, the question facing nanotechnology is not whether it will be regulated, but when and (...) how.Yet, appropriate regulation of nanotechnology will be challenging. The term “nanotechnology” incorporates a broad, diverse range of materials, technologies, and products, with an even greater spectrum of potential risks and benefits. This technology slashes across the jurisdiction of many existing regulatory statutes and regulatory agencies, and does so across the globe. Nanotechnology is developing at an enormously rapid rate, perhaps surpassing the capability of any potential regulatory framework to keep pace. Finally, the risks of nanotechnology remain largely unknown, both because of the multitude of variations in the technology and because of the limited applicability of traditional toxicological approaches such as structure-activity relationship to nanotechnology products. (shrink)

The assessment of nanotechnology applications such as nanocarrier-based targeted drug delivery has historically been based mostly on toxicological and safety aspects. The use of nanocarriers for TDD, a leading-edge nanomedical application, has received little study from the angle of experts’ perceptions and acceptability, which may be reflected in how TDD applications are developed. In recent years, numerous authors have maintained that TDD assessment should also take into account impacts on ethical, environmental, economic, legal, and social issues in order to lead (...) to socially responsible innovation. Semi-structured interviews were conducted with French and Canadian researchers and research trainees with diverse disciplinary backgrounds and involved in research related to emerging technologies. The interviews focussed on scenarios presenting two types of TDD nanocarriers in two contexts of use. Content and inductive analyses of interviews showed how facets of perceived impacts such as health, environment, social cohabitation, economy, life and death, representations of the human being and nature, and technoscience were weighed in acceptability judgments. The analyses also revealed that contextual factors related to device, to use, and to user influenced the weighting assigned to perceived impacts and thus contributed to variability in interviewees’ judgments of acceptability. Giving consideration to researchers’ perspective could accompany first steps of implementation and development of nanomedicine by producing a first, but wide, picture of the acceptability of nanocarrier-based TDD. (shrink)

I examine how Heather Douglas’ account of values in science applies to the assessment of actual cases of scientific practice. I focus on the case of applied toxicologists’ acceptance of molecular evidence-gathering methods and evidential sources. I demonstrate that a set of social and institutional processes plays a philosophically significant role in changing toxicologists’ inductive risk judgments about different kinds of evidence. I suggest that Douglas’ inductive risk framework can be integrated with a suitable account of evidence, such as Helen (...) Longino’s contextual empiricism, to address the role of social context in the cases like the one examined here. I introduce such an integrated account and show how Longino’s contextual empiricism and inductive risk framework fruitfully complement each other in analyzing the novel aspects of the toxicology case. (shrink)