The new mechanists and the autonomy approach both aim to account for how biological phenomena are explained. One identifies appeals to how components of a mechanism are organized so that their activities produce a phenomenon. The other directs attention towards the whole organism and focuses on how it achieves self-maintenance. This paper discusses challenges each confronts and how each could benefit from collaboration with the other: the new mechanistic framework can gain by taking into account what happens outside individual mechanisms, (...) while the autonomy approach can ground itself in biological research into how the actual components constituting an autonomous system interact and contribute in different ways to realize and maintain the system. To press the case that these two traditions should be constructively integrated we describe how three recent developments in the autonomy tradition together provide a bridge between the two traditions: (1) a framework of work and constraints, (2) a conception of function grounded in the organization of an autonomous system, and (3) a focus on control. (shrink)

I consider recent strategies proposed by econometricians for extrapolating causal effects from experimental to target populations. I argue that these strategies fall prey to the extrapolator’s circle: they require so much knowledge about the target population that the causal effects to be extrapolated can be identified from information about the target alone. I then consider comparative process tracing as a potential remedy. Although specifically designed to evade the extrapolator’s circle, I argue that CPT is unlikely to facilitate extrapolation in typical (...) econometrics and evidence-based policy applications. To argue this, I offer a distinction between two kinds of extrapolation, attributive and predictive, the latter being prevalent in econometrics and evidence-based policy. I argue that CPT is not helpful for predictive extrapolation when using the kinds of evidence that econometricians and evidence-based policy researchers prefer. I suggest that econometricians may need to consider qualitative evidence to overcome this problem. (shrink)

The requirement that animals be used in research and testing in order to protect humans was formalized in the Nuremberg Code and subsequent national and international laws, codes, and declarations. We review the history of these requirements and contrast what was known via science about animal models then with what is known now. We further analyze the predictive value of animal models when used as test subjects for human response to drugs and disease. We explore the use of animals for (...) models in toxicity testing as an example of the problem with using animal models. We conclude that the requirements for animal testing found in the Nuremberg Code were based on scientifically outdated principles, compromised by people with a vested interest in animal experimentation, serve no useful function, increase the cost of drug development, and prevent otherwise safe and efficacious drugs and therapies from being implemented. (shrink)

Arguments for the inherent value, equality of interests,or rights of non-human animals have presented a strong challenge for the anthropocentric worldview. However, they have been met with criticism.One form of criticism maintains that,regardless of their theoretical consistency,these 'pro-animal arguments' cannot be accepted due to their absurdity. Often, particularly inter-species interest conflicts are brought to the fore: if pro-animal arguments were followed,we could not solve interest conflicts between species,which is absurd. Because of this absurdity, the arguments need to be abandoned. The (...) paper analyses the strength, background and relevance of this 'argument from absurdity'. It is claimed that in all of the three areas mentioned above, the argument faces severe difficulties. (shrink)

Animal ethics committees (AECs) appeal to utilitarian principles in their justification of animal experiments. Although AECs do not grant rights to animals, they do accept that animals have moral standing and should not be unnecessarily harmed. Although many appeal to utilitarian arguments in the justification of animal experiments, I argue that AECs routinely fall short of the requirements needed for such justification in a variety of ways. I argue that taking the moral status of animals seriously—even if this falls short (...) of granting rights to animals—should lead to a thorough revision or complete elimination of many of the current practices in animal experimentation. (shrink)

Many biological investigations are organized around a small group of species, often referred to as ‘model organisms’, such as the fruit fly Drosophila melanogaster. The terms ‘model’ and ‘modelling’ also occur in biology in association with mathematical and mechanistic theorizing, as in the Lotka–Volterra model of predator-prey dynamics. What is the relation between theoretical models and model organisms? Are these models in the same sense? We offer an account on which the two practices are shown to have different epistemic characters. (...) Theoretical modelling is grounded in explicit and known analogies between model and target. By contrast, inferences from model organisms are empirical extrapolations. Often such extrapolation is based on shared ancestry, sometimes in conjunction with other empirical information. One implication is that such inferences are unique to biology, whereas theoretical models are common across many disciplines. We close by discussing the diversity of uses to which model organisms are put, suggesting how these relate to our overall account. 1 Introduction2 Volterra and Theoretical Modelling3 Drosophila as a Model Organism4 Generalizing from Work on Model Organisms5 Phylogenetic Inference and Model Organisms6 Further Roles of Model Organisms6.1 Preparative experimentation6.2 Model organisms as paradigms6.3 Model organisms as theoretical models6.4 Inspiration for engineers6.5 Anchoring a research community7 Conclusion. (shrink)

We argue that the recommendations made by the Institute of Medicine’s 2011 report, Chimpanzees in Biomedical and Behavioral Research : Assessing the Necessity, are methodologically and ethically confused. We argue that a proper understanding of evolution and complexity theory in terms of the science and ethics of using chimpanzees in biomedical research would have had led the committee to recommend not merely limiting but eliminating the use of chimpanzees in biomedical research. Specifically, we argue that a proper understanding of the (...) difference between the gross level of examination of species and examinations on finer levels can shed light on important methodological and ethical inconsistencies leading to ignorance of potentially unethical practices and policies regarding the use of animals in scientific research. (shrink)

Within this paper, I critique the history of the modification of the broiler chicken through selective breeding and possible future genetic modification. I utilize Margaret Atwood’s fictitious depiction of genetically engineered chickens, from her novel Oryx and Crake , in order to forward the argument that modifications that eliminate animal telos either move beyond the range of current ethical frameworks or can be ethically defended by them. I then utilize the work of feminist epistemologists to argue that understanding what it (...) means to be a chicken shapes our conceptions of what modifications are or are not acceptable. Taking into account justifications stemming from practical knowledge when making ontological claims can help to shift our understanding of what animal modifications can or cannot be justified. The paper ends by addressing three possible problems brought about by accepting such justifications. (shrink)

This paper provides a historical analysis of a shift in the way animal models of mental disorders were conceptualized: the shift from the mid-twentieth-century view, adopted by some, that animal models model syndromes classified in manuals such as the Diagnostic and Statistical Manual of Mental Disorders (DSM), to the later widespread view that animal models model component parts of psychiatric syndromes. I argue that in the middle of the twentieth century the attempt to maximize the face validity of animal models (...) sometimes led to the pursuit of the ideal of an animal model that represented a behaviorally defined psychiatric syndrome as described in manuals such as the DSM. I show how developments within psychiatric genetics and related criticism of the DSM in the 1990s and 2000s led to the rejection of this ideal and how researchers in the first decade of the twenty-first century came to believe that animal models of mental disorders should model component parts of mental disorders, adopting a so-called endophenotype approach. (shrink)

Extrapolating causal effects is becoming an increasingly important kind of inference in Evidence-Based Policy, development economics, and microeconometrics more generally. While several strategies have been proposed to aid with extrapolation, the existing methodological literature has left our understanding of what extrapolation consists of and what constitutes successful extrapolation underdeveloped. This paper addresses this lack in understanding by offering a novel account of successful extrapolation. Building on existing contributions pertaining to the challenges involved in extrapolation, this more nuanced and comprehensive account (...) seeks to provide tools that facilitate the scrutiny of specific extrapolative inferences and general strategies for extrapolation. Offering such resources is important especially in view of the increasing amounts of real-world decision-making in policy, development, and beyond that involve extrapolation. (shrink)

The ways in which other animal species can be informative about human biology are not exhausted by the traditional picture of the animal model. In this paper, I propose to distinguish two roles which laboratory organisms can have in biomedical research. In the more traditional case, organisms act as surrogates for human beings, and as such are expected to be more manageable replicas of humans. However, animal models can inform us about human biology in a much less straightforward way, by (...) being used as measuring devices—what I call their instrumental role. I first characterize this role and provide criteria for it, before illustrating it with some examples from biomedical research, especially cancer research. In such an instrumental role, phenotypes are not expected to phenocopy human phenomena, but instead have the purely instrumental value of detecting or measuring differences. I argue that the instrumental role is more prevalent than might first be suspected, and that some characteristics of contemporary biomedical research are increasingly shifting the use of laboratory organisms to the instrumental role. Finally, in light of the distinction proposed, I discuss the meaning of the expression “animal model”. (shrink)

Through an examination of the actual research strategies and assumptions underlying the Human Genome Project, it is argued that the epistemic basis of the initial model organism programs is not best understood as reasoning via causal analog models. In order to answer a series of questions about what is being modeled and what claims about the models are warranted, a descriptive epistemological method is employed that uses historical techniques to develop detailed accounts which, in turn, help to reveal forms of (...) reasoning that are explicit, or more often implicit, in the practice of a particular field of scientific study. It is suggested that a more valid characterization of the reasoning structure at work here is a form of case-based reasoning. This conceptualization of the role of model organisms can guide our understanding and assessment of these research programs, their knowledge claims and progress, and their limitations, as well as how we educate the public about this type of biomedical research. (shrink)

Dear Editor,The April 2014 issue of Theoretical Medicine and Bioethics [1] presented eight essays regarding the use of nonhuman animals in biomedical research. While I appreciate the essays concerning contemporary research—which were well written and offered new thinking from the fields of ethics and ethology—I believe the journal, via the topics and the authors chosen, failed to communicate the most important fact regarding the current science pertinent to the use of nonhuman animals in research.The foundational reason for using chimpanzees and (...) other animals in research is their predictive value for human response to drugs and disease. This was alluded to by several of the authors when they discussed the necessity of using nonhuman animals. For example, Smith writes: “A common assumption in the selection of nonhuman animal subjects for research and the approval of research is that, if the risks of a procedure are too great for humans, and if there is a so-called scientific necessity, .. (shrink)

Health policy frameworks usually construe environmental protection and human health as harmonious values. Policies that protect the environment, such as pollution control and pesticide regulation, also benefit human health. In recent years, however, it has become apparent that promoting human health sometimes undermines environmental protection. Some actions, policies, or technologies that reduce human morbidity, mortality, and disease can have detrimental effects on the environment. Since human health and environmental protection are sometimes at odds, political leaders, citizens, and government officials need (...) a way to mediate and resolve conflicts between these values. Unfortunately, few approaches to applied bioethics have the conceptual tools to do accomplish this task. Theories of health care ethics have little to say about the environment, and theories of environmental ethics don’t say much about human health. In this essay, I defend an approach to ethical decision-making that gives policy-makers some tools for balancing promotion of human health and protection of the environment. (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)

P.F. Strawson’s work on moral responsibility is well-known. However, an important implication of the landmark “Freedom and Resentment” has gone unnoticed. Specifically, a natural development of Strawson’s position is that we should understand being morally responsible as having externalistically construed pragmatic criteria, not individualistically construed psychological ones. This runs counter to the contemporary ways of studying moral responsibility. I show the deficiencies of such contemporary work in relation to Strawson by critically examining the positions of John Martin Fischer and Mark (...) Ravizza, R. Jay Wallace, and Philip Pettit for problems due to individualistic assumptions. (shrink)

This article identifies some of the important issues that underlie student-teacher conflicts regarding animal experimentation and dissection in psychology education. Understanding the reasons why students object to animal laboratories, why some teachers may refuse students access to non-animal alternatives, and why other teachers support student choice is an important first step in resolving student-teacher disputes regarding the use of animals in the psychology classroom. The article discusses why establishing an openly declared student choice policy at schools that use animals in (...) psychology education is a reasonable thing to do and describes how a student choice policy works in practice. (shrink)

This chapter provides an introduction to the study of the philosophical notions of mechanisms and causality in biology and economics. This chapter sets the stage for this volume, Mechanism and Causality in Biology and Economics, in three ways. First, it gives a broad review of the recent changes and current state of the study of mechanisms and causality in the philosophy of science. Second, consistent with a recent trend in the philosophy of science to focus on scientific practices, it in (...) turn implies the importance of studying the scientific methods employed by researchers. Finally, by way of providing an overview of each chapter in the volume, this chapter demonstrates that biology and economics are two fertile fields for the philosophy of science and shows how biological and economic mechanisms and causality can be synthesized. (shrink)

According to the hypothesis-generator account, valid extrapolations from a source to a target system are circular, since they rely on knowledge of relevant similarities and differences that can onl...

Francesco Guala once wrote that ‘The problem of extrapolation is a minor scandal in the philosophy of science’. This paper agrees with the statement, but for reasons different from Guala’s. The scandal is not, or not any longer, that the problem has been ignored in the philosophy of science. The scandal is that framing the problem as one of external validity encourages poor evidential reasoning. The aim of this paper is to propose an alternative—an alternative which constitutes much better evidential (...) reasoning about target systems of interest, and which makes do without consideration of external validity. (shrink)

Extrapolation from a well-understood base population to a less-understood target population can fail if the base and target populations are not sufficiently similar. Differences between laboratory mice and humans, for example, can hinder extrapolation in medical research. Mice that carry a partial or complete human physiological system, known as humanized mice, are supposed to make extrapolation more reliable by simulating a variety of human diseases. But what justifies our belief that these mice are similar enough to their human counterparts to (...) simulate human disease? I argue that, unless three requirements are met in the process of humanizing mice, very little does. My requirements are not meant to provide necessary and sufficient conditions that guarantee a particular outcome. Instead, they serve as a heuristic for guiding scientific judgments involving extrapolation. In developing each requirement, I engage with philosophical issues concerning the nature of model-based science and the mechanistic approach (and its limits) to making generalizations in the life sciences. (shrink)

BackgroundCurrent policies regulating the use of animals for scientific purposes are based on balancing between potential gain of knowledge and suffering of animals used in experimentation. The balancing process is complicated, on the one hand by plurality of views on our duties towards animals, and on the other hand by more recent discussions on uncertainty in the probability of reaching the final aim of the research and problems of translational failure.MethodsThe study combines ethical analysis based on a literature review with (...) neuropsychiatry-related preclinical research as a case study.ResultsBased on the analysis and the case study we show that neuropsychiatry-related preclinical research is an especially interesting case from an ethical perspective. The 3R principles are used to minimize the negative consequences for the animals used in research. However, neuropsychiatric research is characterized by specific challenges in assessing the probability of success of reaching the final aim, due to our limited mechanistic knowledge of human neuropsychiatric illness. Consequently, the translational value of the currently used animal models may be difficult to prove, which undermines the validity of these models and complicated the ethical assessment.ConclusionsWe conclude that a combined approach that deals with both science and the ethical dimensions is necessary to address the problems of validity and translation in neuropsychiatry-related preclinical research. We suggest this approach to comprise first, improved experimental methods, e.g. by using systematic reviews, second, a more patients-based approach that leads to models that reflect interindividual variation better, and third, more interdisciplinary cooperation. (shrink)

Prejudice in the selection of the subjects of scientific research is morally unacceptable. Indeed, the occurrence of prejudice in the Tuskegee Syphilis Study prompted the production of the Belmont Report, setting out the basic ethical principles for the protection of human subjects of biomedical and behavioral research. The relevance of the Belmont Report to the protection of all animal subjects of scientific research is discussed.

For animal research that causes sentient nonhuman animal suffering to be justifiable, I believe that two conditions must be met. First, harming animals for human benefit must be morally justified; this is the speciesism justification. Second, animal research must have utility—that is, it must produce useful, empirically valid knowledge that successfully increases our understanding of human illness and treatments and that could not reasonably be obtained through other means; this is the utility justification. In other words, (some) animals must be (...) sufficiently different from humans in morally relevant ways to allow the morality of speciesism, and (some) animals must be sufficiently similar to humans biologically for cross‐species extrapolation to have utility. Both conditions are necessary, and neither by itself is sufficient to justify animal experimentation. I focus exclusively on the utility justification. I do not defend the morality of using animals in experiments, nor do I review the alternatives and refinements that can minimize laboratory animal suffering. I will argue that I and the medical scientists with whom I work have a sound rationale to continue the work we do. (shrink)

Animal research is a challenging issue for the animal advocate because of what, besides animal well-being, is considered to be at stake, namely, human health. This article seeks to vindicate the antivivisectionist position. The standard defense of animal research as promoting the overwhelming good of human health is refuted on both factual and logical, or normative-theoretical, grounds. The author then attempts to clinch the case by arguing that animal research violates a deontic principle. However, this principle falls to counterexample. The (...) author concludes, nevertheless, that the principle retains force as a presumption that the current state of affairs fails to overthrow. This does suggest, though, that the antivivisection movement would be well advised to keep ahead of the curve. The author proposes it do so by emulating the vegan movement against animal agriculture with the active promotion of alternatives to animal research. (shrink)

Many people find the manipulation of the human germline—editing the DNA of sperm or egg cells such that these genetic changes are passed to the resulting offspring—to be morally impermissible. In this paper, I argue for the claim that editing the human germline is morally permissible. My argument starts with the claim that outcome uncertainty regarding the effects of germline editing shows that the duty to not harm cannot ground the prohibition of germline editing. Instead, if germline editing is wrong, (...) it is wrong because it violates a duty to protect. However, we also have an epistemic duty to gather evidence regarding the effects of editing the human germline which overrides any moral duty to protect future generations. Thus, we have a duty to gather evidence regarding the effects of editing the human germline, which is to say that we have a duty to edit the human germline. (shrink)

Inconsistencies in science take several forms. Some occur at the level of substantive claims about the world. Others occur at the level of methodology, and take the form of dilemmas, or cases of conflicting epistemic or cognitive values. In this article, I discuss how methodological dilemmas arise. I then consider how scientists resolve them. There are strong grounds for thinking that emotional judgement plays an important role in resolving methodological dilemmas. Lastly, I discuss whether and under what conditions this reliance (...) on emotional judgement is rationally warranted. I consider two possible mechanisms, based on coherence and induction, able to ensure that scientists’ emotional responses to methodological dilemmas are rationally warranted. (shrink)

Ethics, Policy & Environment, Volume 15, Issue 2, Page 234-236, June 2012.

In order to make scientific results relevant to practical decision making, it is often necessary to transfer a result obtained in one set of circumstances—an animal model, a computer simulation, an economic experiment—to another that may differ in relevant respects—for example, to humans, the global climate, or an auction. Such inferences, which we can call extrapolations, are a type of argument by analogy. This essay sketches a new approach to analogical inference that utilizes chain graphs, which resemble directed acyclic graphs (...) (DAGs) except in allowing that nodes may be connected by lines as well as arrows. This chain graph approach generalizes the account of extrapolation I provided in my (2008) book and leads to new insights that integrate the contributions of the other participants of this symposium. More specifically, this approach explicates the role of “fingerprints,” or distinctive markers, as a strategy for avoiding an underdetermination problem having to do with spurious analogies. Moreover, it shows how the extrapolator’s circle, one of the central challenges for extrapolation highlighted in my book, is closely tied to distinctive markers and the Markov condition as it applies to chain graphs. Finally, the approach suggests additional ways in which investigations of a model can provide information about a target that are illustrated by examples concerning nanomaterials in sunscreens and Wendy Parker’s discussion of fingerprints in climate science. (shrink)

The call for a planned phase-out is at the forefront of the political debate about animal experimentation. While authorities like the European Commission start taking a strategic approach to regulatory animal testing, they refuse to develop specific roadmaps for the phase-out of animal research. I articulate the central argument that is advanced against phase-out planning in animal research, the argument from avoidable harms: By restricting research, we may incur avoidable future harms and thus, while we may regret having to use (...) animals in ways that harm them, for the sake of avoiding future harms we must not phase out animal research. The discussion of this argument yields two Conclusions: First, it applies only to ban-based phase-out plans, but not to plans consisting of a range of other interventions known from the literature on transformative governance. Second, the premises of the argument construe animal research as a necessary evil, thus as a conflict of unequal duties. But we have a duty not just to avoid avoidable harms, but also to avoid avoidable moral conflicts. This we can only do by taking a strategic approach. Thus, what initially looks like an argument against phase-out planning is in truth an argument for ban-free phase-out planning. This finding is important for practice because it shows that while government authorities’ reluctance to issue bans may be justified, their refusal to undertake strategic planning for the phase-out of animal research is not. (shrink)

For animal research, the precautionary principle was written into public policy through the so-called three R’s of replacement, reduction, and refinement. These guidelines, as developed by Russell and Burch six decades ago, aimed to establish safeguards against the abuse of animals in the pursuit of science. While these safeguards, which started from the basic premise that science itself would benefit from a reduction of animal suffering, seem compelling at first, the three R’s have in practice generated a degree of confusion (...) while opening up loopholes that have enabled researchers to effectively dismiss some of the more inconvenient aspects of ethical concerns. Such problems have been discussed in detail by multiple authors. Here, we suggest a different approach by arguing that a clear parallel can be drawn between the shortcomings evident in the current three R’s model and the flawed practice of early modern judicial torture, in which a set of elaborate safeguards that were designed to prevent abuses served instead to create the same combination of confusion and easily exploited loopholes. In the case of judicial torture, attempts to refine the system from within produced limited results, and effective change only took place when individual legal systems succeeded in enforcing clear absolutes. We explore the implications of this for the regulation of animal research by pointing to the need for achievable absolutes, based on a clear, evidence-based, and publicly deliberated rationale, in order to facilitate and improve research ethics. (shrink)

What role do nonhuman animals play in the construction of medical knowledge? Animal researchers typically claim that their use has been essential to progress – but just how have animals fitted into the development of biomedicine? In this article, I trace how nonhuman animals, and their body parts, have become incorporated into laboratory processes and places. They have long been designed to fit into scientific procedures – now increasingly so through genetic design. Animals and procedures are closely connected – animals (...) in science are disassembled and reassembled in various ways. Indeed, biomedical knowledge can be said to rest on a large pile of animal bodies and body parts. The process of producing animal body parts to order has implications for how we conceptualize the body (human or nonhuman), which I discuss in the final section. (shrink)