Burt C. Hopkins presents the first in-depth study of the work of Edmund Husserl and Jacob Klein on the philosophical foundations of the logic of modern symbolic mathematics. Accounts of the philosophical origins of formalized concepts—especially mathematical concepts and the process of mathematical abstraction that generates them—have been paramount to the development of phenomenology. Both Husserl and Klein independently concluded that it is impossible to separate the historical origin of the thought that generates the basic concepts of mathematics from (...) their philosophical meanings. Hopkins explores how Husserl and Klein arrived at their conclusion and its philosophical implications for the modern project of formalizing all knowledge. (shrink)

First-in-human clinical trials represent a critical juncture in the translation of laboratory discoveries. However, because they involve the greatest degree of uncertainty at any point in the drug development process, their initiation is beset by a series of nettlesome ethical questions [1]: has clinical promise been sufficiently demonstrated in animals? Should trial access be restricted to patients with refractory disease? Should trials be viewed as therapeutic? Have researchers adequately minimized risks? The resolution of such ethical questions inevitably turns on claims (...) about future events like harms, therapeutic response, and clinical translation. Recurrent failures in clinical translation, like Eli Lilly's Alzheimer candidate semagacestat, highlight the severe limitations of current methods of prediction. In this case, patients in the active arm of the placebo-controlled trial had earlier onset of dementia and elevated rates of skin cancer [2]. Various authoritative accounts of human research ethics state that decision-making about risk and benefit should be careful, systematic, and non-arbitrary [3]–[5]. Yet, these sources provide little guidance about what kinds of evidence stakeholders should use to ensure their estimates of such events ground responsible ethical decisions. In this article, we suggest that investigators, oversight bodies, and sponsors often base their predictions on a flawed and inappropriately narrow preclinical evidence base. (shrink)

: "Therapeutic misconception" has been misconstrued, and some of the newer, mistaken interpretations are troublesome. They exaggerate the distinction between research and treatment, revealing problems in the foundations of research ethics and possibly weakening informed consent.

The sociogenomics revolution is upon us, we are told. Whether revolutionary or not, sociogenomics is poised to flourish given the ease of incorporating polygenic scores (or PGSs) as “genetic propensities” for complex traits into social science research. Pointing to evidence of ubiquitous heritability and the accessibility of genetic data, scholars have argued that social scientists not only have an opportunity but a duty to add PGSs to social science research. Social science research that ignores genetics is, some proponents argue, at (...) best partial and likely scientifically flawed, misleading, and wasteful. Here, I challenge arguments about the value of genetics for social science and with it the claimed necessity of incorporating PGSs into social science models as measures of genetic influences. In so doing, I discuss the impracticability of distinguishing genetic influences from environmental influences because of non-causal gene–environment correlations, especially population stratification, familial confounding, and downward causation. I explain how environmental effects masquerade as genetic influences in PGSs, which undermines their raison d’être as measures of genetic propensity, especially for complex socially contingent behaviors that are the subject of sociogenomics. Additionally, I draw attention to the partial, unknown biology, while highlighting the persistence of an implicit, unavoidable reductionist genes versus environments approach. Leaving sociopolitical and ethical concerns aside, I argue that the potential scientific rewards of adding PGSs to social science are few and greatly overstated and the scientific costs, which include obscuring structural disadvantages and cultural influences, outweigh these meager benefits for most social science applications. (shrink)

Many commentators have expressed concern that large investments in biomedical research over the past two decades have not been translated effectively into clinical applications. In its Critical Path Report, the Food and Drug Administration characterized the problem as a “technological disconnect between discovery and the product development process,” and documented that the number of investigational new drugs submitted to the agency had declined “significantly” since 2000. Along a similar vein, another study found that only five of 101 basic science studies (...) showing significant therapeutic promise were successfully translated into clinical applications.This perceived translational lag is stimulating a shift toward human testing of study interventions earlier in the drug development process. One indication of this trend is a recent guidance encouraging sponsors to pursue human “exploratory” studies before embarking on phase I trials. (shrink)

Many types of human research activities present risks and burdens to third parties (e.g., bystanders). Few human protection policies directly address the protection of research bystanders, though some address it in passing. In what follows, I re‐iterate reasons why bystanders are entitled to protections. I also argue that Institutional Review Boards (IRBs) are in the best position to signal to researchers and sponsors that bystanders should be protected in research. In some cases, IRB review would consist of evaluating bystander protection (...) strategies directly; in other cases, this might entail merely certifying that another institutions, like a drug regulator, has taken adequate measures to protect the welfare of research bystanders. (shrink)

Behavioral genetic (BG) research has yielded many important discoveries about the origins of human behavior, but offers little insight into how we might improve outcomes. We posit that this gap in our knowledge base stems in part from the epidemiologic nature of BG research questions. Namely, BG studies focus on understanding etiology as it currently exists, rather than etiology in environments that could exist but do not as of yet (e.g., etiology following an intervention). Put another way, they focus exclusively (...) on the etiology of “what is” rather than “what could be”. The current paper discusses various aspects of this field-wide methodological reality, and offers a way to overcome it by demonstrating how behavioral geneticists can incorporate an experimental approach into their work. We outline an ongoing study that embeds a randomized intervention within a twin design, connecting “what is” and “what could be” for the first time. We then lay out a more general framework for a new field—experimental BGs—which has the potential to advance both scientific inquiry and related philosophical discussions. (shrink)

_The New Yearbook for Phenomenology and Phenomenological Philosophy_ provides an annual international forum for phenomenological research in the spirit of Husserl's groundbreaking work and the extension of this work by such figures as Scheler, Heidegger, Sartre, Levinas, Merleau-Ponty and Gadamer.

The paper argues for three things. First, that the abstract concepts of ancient Greek and modern mathematics are fundamentally different. The general treatment of mathematical things in ancient Greek mathematics manifestly does not presuppose a general mathematical object, while in modern mathematics the generality of the method presupposes precisely such a general mathematical object. Two, that this difference in abstract concepts of mathematics makes a difference in our understanding of a discipline other than mathematics, specifically, in the discipline of history. (...) And, three, that what is at issue in this difference is whether it is necessary for human beings to understand themselves from the perspective of history in order to understand themselves properly as human. (shrink)

The last two decades have witnessed a crescendo of allegations that clinical translation is rife with waste and inefficiency. Patient advocates argue that excessively demanding regulations delay access to life‐saving drugs, research funders claim that too much basic science languishes in academic laboratories, journal editors allege that biased reporting squanders public investment in biomedical research, and drug companies (and their critics) argue that far too much is expended in pharmaceutical development.But how should stakeholders evaluate the efficiency of translation and proposed (...) reforms to drug development? Effective reforms require an accurate model of the systems they aspire to improve—their components, their proper functions, and their pathologies. However, there is currently no explicit and well‐developed model of translation for evaluating such criticisms.In what follows, we offer an explicit model of clinical translation. Many discussions of clinical translation and its pathologies presume that its main output is tangible: new drugs, vaccines, devices, and diagnostics. We disagree. We argue that the principal output of clinical translation is information—in particular, information about the coordinated set of materials, practices, and constraints needed to safely unlock the therapeutic or preventive activities of drugs, biologics, and diagnostics. To develop this information calls for a process far different from a simple linear progression of clinical trials; it requires exploratory sampling of many different elements in this set. Our model points to some limitations and liabilities of influential proposals for reforming research. It also reveals some underrecognized opportunities for improving the efficiency of clinical translation. (shrink)

: Despite its mandate on minimizing harms in clinical trials, the Common Rule provides little guidance as to how IRBs should evaluate risk. The Common Rule and derivative commentaries tend to conceptualize risk review as an expert-based endeavor aimed at an objective and universal evaluation of possible harm; they also have tended to locate risk in the research activity itself rather than in the context of the research. These views of risk conflict with scholarship showing that risk evaluations are socially (...) determined even among experts, that the context of harms can influence how persons evaluate risks, and that forums that approach risk assessment as a technical endeavor bracket from discussion the numerous values that ground risk judgments. Possible reforms are proposed for clinical trial risk review that would render it more inclusive of the different types of risks encountered and more attuned to the priorities of trial subjects. (shrink)

Abstractabstract:Expectations about future events underlie practically every decision we make, including those in medical research. This paper reviews five studies undertaken to assess how well medical experts could predict the outcomes of clinical trials. It explains why expert trial forecasting was the focus of study and argues that forecasting skill affords insights into the quality of expert judgment and might be harnessed to improve decision-making in care, policy, and research. The paper also addresses potential criticisms of the research agenda and (...) summarizes key findings from the five studies of trial forecasting. Together, the studies suggest that trials frequently deliver surprising results to expert communities and that individual experts are often uninformative when it comes to forecasting trial outcome and recruitment. However, the findings also suggest that expert forecasts often contain a "signal" about whether a trial will be positive, especially when forecasts are aggregated. The paper concludes with needs for further research and tentative policy recommendations. (shrink)

The Belmont Report is a totem of human research ethics. Its principles have provided a sustained and organizing vision for human protections and have been endorsed by various subsequent human protections policies. Besides its influence, the Belmont Report rewards multiple reads and abounds in insights, many of which have been under-attended in research ethics. Above all, the principles articulated in Belmont have proven adaptable to the many novel research strategies, approaches, settings, and challenges that have emerged in the 40 years (...) since... (shrink)

Cesario provides a compelling critique of the use of experimental social psychology to explain real-world group disparities. We concur with his targeted critique and extend “the problem of missing information” to another common measures of bias. We disagree with Cesario's broader argument that the entire enterprise be abandoned, suggesting instead targeted utilization. Finally, we question whether the critique is appropriately directed at experimental social psychologists.

The problem of ‘collective unity’ in the transcendental philosophies of Kant and Husserl is investigated on the basis of number’s exemplary ‘collective unity’. To this end, the investigation reconstructs the historical context of the conceptuality of the mathematics that informs Kant’s and Husserl’s accounts of manifold, intuition, and synthesis. On the basis of this reconstruction, the argument is advanced that the unity of number – not the unity of the ‘concept’ of number – is presupposed by each transcendental philosopher in (...) their accounts of the transcendental foundation of manifold, intuition, and synthesis. This presupposition is ultimately traced to Kant’s and Husserl’s responses to Hume’s philosophy of human understanding and the critical limits of what Kant calls the ‘qualitative’ unity of transcendental consciousness. These critical limits are exposed in both philosophers’ attempts to account for that ‘qualitative’ unity on the basis of the ‘quantitative’ unity of number. (shrink)

ABSTRACTRelatively little has been written about the ethics of conducting early phase clinical trials involving subjects from the developing world. Below, I analyze ethical issues surrounding one of gene transfer’s most widely praised studies conducted to date: in this study, Italian investigators recruited two subjects from the developing world who were ineligible for standard of care because of economic considerations. Though the study seems to have rendered a cure in these two subjects, it does not appear to have complied with (...) various international guidelines that require that clinical trials conducted in the developing world be responsive to their populations’ health needs. Nevertheless, policies devised to address large scale, late stage trials, such as the AZT short‐course placebo trials, map somewhat awkwardly to early phase studies. I argue that interest in conducting translational research in the developing world, particularly in the context of hemophilia trials, should motivate more rigorous ethical thinking around clinical trials involving economically disadvantaged populations. (shrink)

Developments in the last several years have sparked renewed interest in the ethics of research involving humans. Issues relating to the global extent of research and its guiding principles are of particular importance to researchers, health officials, and individual ethics committees who want a deeper and more encompassing inquire regarding the foundation and evolution of human research. This department of CQ launches a long overdue effort to explore these wider issues. Readers are invited to submit papers to Charles MacKay, 5011 (...) Worthington Drive, Bethesda, MD 20816, USA. E-mail: mackaycharles@yahoo.com. a. (shrink)

Volume XVIII Special Issue: Gian-Carlo Rota and The End of Objectivity, 2019 Aim and Scope: The New Yearbook for Phenomenology and Phenomenological Philosophy provides an annual international forum for phenomenological research in the spirit of Husserl's groundbreaking work and the extension of this work by such figures as Scheler, Heidegger, Sartre, Levinas, Merleau-Ponty and Gadamer. Contributors: Gabriele Baratelli, Stefania Centrone, Giovanna C. Cifoletti, Jean-Marie Coquard, Steven Crowell, Deborah De Rosa, Daniele De Santis, Nicolas de Warren, Agnese Di Riccio, Aurélien Djian, (...) Yuval Dolev, Mirja Hartimo, Burt C. Hopkins, Talia Leven, Ah Hyun Moon, Luis Niel, Fabrizio Palombi, Mario Ariel González Porta, Gian-Carlo Rota, Michael Roubach, Franco Trabattoni and Michele Vagnetti. Submissions: Manuscripts, prepared for blind review, should be submitted to the Editors electronically via e-mail attachments. (shrink)

Over ten years have elapsed since Virginia passed the nation's first criminal DNA banking law, which authorized law enforcement authorities to collect DNA samples from certain categories of offenders for the purposes of performing profile analysis. Within nine years, Rhode Island became the fiftieth state to enact a similar statute. The passage of a decade since the first enactment provides a convenient opportunity to assess the strengths and weaknesses of ethical safeguards under present law as well as predict the likely (...) direction of future developments.DNA forensics are merely the latest in a long line of biologically based identifying law enforcement technologies that include fingerprints and serotyping. Nevertheless, DNA has properties that make it significantly different than its predecessors with respect to the ethical and social concerns it raises. (shrink)

For centuries in the UK and elsewhere, charities have been widely regarded as admirable and virtuous organisations. Business corporations, by contrast, have been characterised in the popular imagination as entities that lack a capacity for moral judgement. Drawing on the philosophical literature on the moral agency of organisations, we examine how the law shapes the ability of charities and business corporations headquartered in England to exercise moral agency. Paradoxically, we find that charities are legally constrained in exercising moral agency in (...) ways in which business corporations are not. Implications for charities and business corporations are then explored. (shrink)

Hopkins begins his study with Plato's written and unwritten theories of eidê and Aristotle's criticism of both. He then traces Husserl's early investigations into the formation of mathematical and logical concepts, charting the critical necessity that leads from descriptive psychology to transcendentally pure phenomenology. An investigation of the movement of Husserl's phenomenology of transcendental consciousness to that of monadological intersubjectivity follows. Hopkins then presents the final stage of the development of Husserl's thought, which situates monadological intersubjectivity within the context of (...) the historical a priori constitutive of all meaning. An exposition of the unwarranted historical presuppositions that guide Heidegger's fundamental ontological and Derrida's deconstructive criticisms of Husserl's transcendental phenomenology concludes the book. By following Husserl's personal trajectory Hopkins is able to show the unity of Husserl's philosophical enterprise, challenging the prevailing view that Husserl's late turn to history is inconsistent with his earlier attempts to establish phenomenology as a pure science. Contents: Introduction Part I Descriptive Psychology 1. Investigation of the Origin of Number 2. Investigation of the Origin of Logical Signification Part II Cartesian Transcendental Phenomenology 3. Investigation of the Origin of Objective Transcendence 4. Investigation of the Origin of Subjective Transcendence Part III Historical Transcendental Phenomenology 5. The Crisis of Meaning in Contemporary European Science 6. Historical Investigation of the Phenomenological Origin Part IV Husserl and his Critics 7. Fundamental Critiques of Transcendental Phenomenology 8. A Husserlian Response to the Critics. (shrink)

I compare Plato’s and Husserl’s accounts of the non-original appearance and the original with a focus on their methodologies for distinguishing between them and the phenomenological—i.e., the answer to the question of the what and how of their appearance—criteria that drive their respective methodologies. I argue that Plato’s dialectical method is phenomenologically superior to Husserl’s reflective method in the case of phantasmata that function as apparitions. Plato’s method has the capacity to discern the apparition on the basis of criteria that (...) appeal solely to its appearance, whereas Husserl’s method presupposes a non-apparent primitive distinction between the original qua primal impression and the phantasm as its reproductive modification. On the basis of Plato’s methodological superiority in this regard, I sketch a reformulation of the Husserlian approach to appearances guided by the original interrogative context of Plato’s dialectical account of the distinction between true and false appearances, eikones and phantasmata. (shrink)

A growing number of clinical trials use invasive research procedures to obtain tissue for disease screening and to monitor the effects of drugs. These procedures can be ethically contentious because they often have neither therapeutic nor diagnostic value, and because research participants may not realize this, which could compromise the validity of their consent to the procedure. In the first section of this paper, we describe the burdens, risks, and benefits associated with certain common invasive, nondiagnostic research procedures. We next (...) offer a series of arguments about the general properties of a valid consent for such procedures, and we close by examining what is currently known about consent quality for invasive research procedures when measured against the standards laid out in the second section. We conclude that there is little evidence to either confirm or dispel concerns about participants’ consent quality for protocols involving invasive, nondiagnostic research procedures. (shrink)

Clinical trials of novel agents often present several layers of ethical challenge. Because time and resources for ethical and safety review are limited, how investigators, IRBs, and regulators allocate attention to a trial's various safety dimensions itself represents a critical ethical question. In what follows, I use the example of a Parkinson's disease gene transfer trial to show how risks involving unknown probabilities or outcomes (ambiguity), might sometimes draw attention away from risks that involve known probabilities or outcomes. This potentially (...) undermines the goal of ‘systematic and nonarbitrary analysis of risk’ during ethical review. To counteract the possible effects of such attention biases, I propose that reviewers develop ‘cognitive aids’ like lists and, where appropriate, set aside time to discuss non-ambiguous risks. I also propose further research for addressing and understanding how attention allocation, emotion, and ambiguity influence ethical decision-making. (shrink)