Experimentation in Science

Traditionally, in the literature on robustness analysis objects are classified as genuine phenomena (natural objects, events, and processes) or artifacts (results produced in error). But much of biological measurement requires the manipulation of local experimental conditions in order to produce new effects. These types of intervention-based regularities are neither natural objects nor artifacts; characterizing them as either fails adequately to address key ontological properties as well as their role in scientific practice. It is argued that a new classification, based on (...) methodological considerations, can be useful in order to characterize experimental productions. Experimentally-useful context-sensitive objects are referred to as ‘artefacts’. To show how the new classification works and why it is instructive for scientific practice, two case studies are discussed. First, the puzzle of arsenic-consuming living organisms is analyzed, where under a set of specific experimental conditions a given organism was found to replace phosphorous with arsenic in its DNA. Second, ecological epigenetic measurement is discussed to show the complexity of variant effects in the context of lab, field, and computer measurements. It is argued that the line between artifacts and artefacts is fluid because theoretical, experimental, and practical considerations vary. -/- . (shrink)

The numerous researches devoted to 'jaundice' during the Second World War have brought to light the existence of an infectious type of hepatic jaundice or 'homologous serum jaundice' following parenteral injection of vaccines containing human serum and blood transfusions, which were carried out on a large scale at the time. This type of serum jaundice was then gradually differentiated from 'catarrhal', contagious or epidemic jaundice by clinical trials along with large series of animal studies. Finally, the epidemiological, clinical and biological (...) data obtained made it possible to establish, between 1944 and 1954, the viral etiology of these two types of jaundice: the A virus, present in the patients' blood and stools, was considered to be the agent responsible for epidemic hepatitis; the B virus, present primarily in the blood, was held to be responsible for serum hepatitis. (shrink)

The episodes of cowpox inoculation (1798) and rabies preventive treatment (1885) are celebrated as the landmark of modern medicine. Paradoxically, these two advances have been accomplished without any theoretical breakthrough in the understanding of immunity. Going further, they were made possible by a long past of empirical procedures among which smallpox inoculation played an outstanding role. The paper explores the paradox of 'Immunization without Immunology' and Pasteur's reconstruction of the past, through his successful use of a metaphor. 'Vaccine', originally linked (...) to the jennerian method, was meant by Pasteur to designate a general program of virus attenuation. The paper investigates the scientific factors accounting for why viruses played such a leading role in immunization. The longlasting immunity, the easy transmission from man to man characteristic of smallpox allowing in vivo experimentation, may explain how crude procedures of early immunizers shaped scientific ideologies and strategies of public health and family initiated modern 'vaccinology'. (shrink)

Aims: The Research Diagnostic Criteria for Temporomandi¬bular Disorders (RDC/TMD) Axis I diagnostic algorithms were demonstrated to be reliable but below target sensitivity and specificity. Empirical data supported Axis I algorithm revisions that were valid. Axis II instruments were shown to be both reliable and valid. An international consensus workshop was convened to obtain recommendations and finalization of new Axis I diagnostic algorithms and new Axis II instruments. Methods: A comprehensive search of published TMD diagnostic literature was followed by review and (...) consensus via a formal structured process by a panel of experts for revision of the RDC/TMD. Results: The recommended Diagnostic Criteria for TMD (DC/TMD) Axis I protocol includes both a valid screener for pain diagnoses and valid criteria for the most common pain-related TMDs and for one intra-articular disorder. The Axis II protocol retains selected RDC/TMD screening instruments augmented with new instruments to better assess the interactions between pain and psychosocial functioning. A comprehensive classification system is also presented. Conclusion: The recommended evidence-based DC/TMD protocol is appropriate for use in both the clinical and research settings. Simple Axis I and II screening tests augmented by validated Axis I and Axis II instruments allow for identification of simple to complex TMD patients. (shrink)

Conducting research on animals is supposed to be valuable because it provides information on how human mechanisms work. But for the use of animal models to be ethically justified, it must be epistemically justified. The inference from an observation about an animal model to a conclusion about humans must be warranted for the use of animals to be moral. When researchers infer from animals to humans, it’s an extrapolation. Often non-human primates are used as animal models in laboratory behavioral research. (...) The target populations are humans and other non-human primates. I argue that the epistemology of extrapolation renders the use of non-human primates in laboratory behavioral research unreliable. If the model is relevantly similar to the target, then the experimental conditions introduce confounding variables. If the model is not relevantly similar to the target, then the observations of the model cannot be extrapolated to the target. Since using non-human primates in as animal models in laboratory behavioral research is not epistemically justified, using them as animal models in laboratory behavioral research is not ethically justified. (shrink)

A heated debate surrounds the significance of reproducibility as an indicator for research quality and reliability, with many commentators linking a "crisis of reproducibility" to the rise of fraudulent, careless and unreliable practices of knowledge production. Through the analysis of discourse and practices across research fields, I point out that reproducibility is not only interpreted in different ways, but also serves a variety of epistemic functions depending on the research at hand. Given such variation, I argue that the uncritical pursuit (...) of reproducibility as an overarching epistemic value is misleading and potentially damaging to scientific advancement. Requirements for reproducibility, however they are interpreted, are one of many available means to secure reliable research outcomes. Furthermore, there are cases where the focus on enhancing reproducibility turns out not to foster high-quality research. Scientific communities and Open Science advocates should learn from inferential reasoning from irreproducible data, and promote incentives for all researchers to explicitly and publicly discuss their methodological commitments, the ways in which they learn from mistakes and problems in everyday practice, and the strategies they use to choose which research component of any project needs to be preserved in the long term, and how. (shrink)

Novel therapeutics enter human testing after they show promise in animal and in vitro studies. They then begin a life cycle that extends from early phase trials without control groups, to randomized trials, to approval by regulatory authorities, to coverage by payers, to use in clinical practice. At each stage, scientific evidence is critical to determining whether to progress to the next step in this life cycle. Each of these decisions also implicitly involves issues of value and ethical norms based (...) on how the decision-makers weigh the risks of two types of errors: false positives and false negatives. For example, in determining whether to approve a new molecular entity based on evidence submitted by a.. (shrink)

The multiple detections of gravitational waves by LIGO (the Laser Interferometer Gravitational-Wave Observatory), operated by Caltech and MIT, have been acclaimed as confirming Einstein's prediction, a century ago, that gravitational waves propagating as ripples in spacetime would be detected. Yunes and Pretorius (2009) investigate whether LIGO's template-based searches encode fundamental assumptions, especially the assumption that the background theory of general relativity is an accurate description of the phenomena detected in the search. They construct the parametrized post-Einsteinian (ppE) framework in response, (...) which broadens those assumptions and allows for wider testing under more flexible assumptions. Their methods are consistent with work on confirmation and testing found in Carnap (1936), Hempel (1969), and Stein (1992, 1994), with the following principles in common: that confirmation is distinct from testing, and that, counterintuitively, revising a theory's formal basis can make it more broadly empirically testable. These views encourage a method according to which theories can be made abstract, to define families of general structures for the purpose of testing. With the development of the ppE framework and related approaches, multi-messenger astronomy is a catalyst for deep reasoning about the limits and potential of the theoretical framework of general relativity. (shrink)

Experimental randomization is defended as a procedure to select an allocation of treatments in comparative experiments. To be convincing, a comparative experiment should allow many alternative allocations of treatments over experimental units, that look equally informative "on paper," but may have underlying differences. Randomization prevents these underlying differences to be causally influential when an allocation is chosen for implementation. Randomization helps prevent bias. ;Both Bayesian criticisms of randomization and what seems to be the opinion of the early Fisher are rejected. (...) The Bayesian decision theoretic argument against randomization is shown to rest on a faulty analysis of experimental randomization that goes back, at least, to Abraham Wald. An improved decision theoretic framework is formulated in which randomization can indeed give higher expected utility. Against the early Fisher it is argued that the choice of a randomization scheme depends on the identification of equally informative, alternative allocations. Randomization alone can never validate a statistical analysis because what allocation is actually implemented, is relevant information that has to be taken into account in the statistical analysis. This does not, however, turn randomization into a useless ritual. The manner in which an allocation is obtained is equally relevant information. (shrink)

In light of the central role that medications play in medical progress, the declining rate of new drug development over the past decade is cause for concern . Without important breakthroughs in drug discovery, the future will not be auspicious for the many people suffering from chronic and incurable illnesses. The sluggish pace of pharmaceutical innovation has been particularly characteristic of the largest drug manufacturers, which have generally focused their energies on potential blockbuster medications, those that can generate over $1 (...) billion in annual revenue . Given Pharma’s struggles, the success of the country’s largest drug manufacturer in bringing the .. (shrink)

There is a middle ground of imperfect knowledge in fields like medicine and the social sciences. It stands between our day-to-day relatively certain knowledge obtained from ordinary basic observation of regularities in our world and our knowledge from well-validated theories in the physical sciences. -/- The latter enable reliable prediction a great deal of the time of the happening of events never before experienced. The former enable prediction only of what has happened before and beyond that of educated guesses which (...) may sometimes prove right and others not when we test them. -/- The imperfection of our knowledge between those limits is a consequence of complexity. -/- Reductionist empiricism fails when faced with complexity but we all still have to live in a complex world where reductionist science cannot help us devise reliable theories from which we can predict the behaviour of the world around us. We cannot predict reliably. We can only monitor actively and manage actively the world around us if we want to try to control our environment. We have a limited prediction horizon. -/- Science and empiricism work well if we want to send Voyager I and II over 3 billion miles away but not for most other things. -/- In medicine how and when to apply probabilistic, conjectural, incomplete medical theories and explanations requires professional expertise, intuition and judgement (non scientific knowledge) which is essential. Medical diagnosis is a skill of predicting from knowledge of what has happened before that the past will recur in the current patient applying expertise and intuition from knowledge and experience of prior cases and probabilistic medical research and theory. The physician is left to an educated guess as to how the future will develop for the particular individual patient the focus of his or her current attention. (shrink)

An apparent ethical dilemma arises when physicians consider enrolling their patients in randomized clinical trials. Suppose that a randomized clinical trial comparing two treatments is in progress, and a physician has an opinion about which treatment is better. The physician has a duty to promote the patient's best medical interests and therefore seems to be obliged to advise the patient to receive the treatment that the physician prefers. This duty creates a barrier to the enrollment of patients in randomized clinical (...) trials.1-10 Two strategies are often used to resolve the dilemma in favor of enrolling patients in clinical trials. (shrink)

I have previously argued that stem cell experiments cannot demonstrate that a single cell is a stem cell. Laplane and others dispute this claim, citing experiments that identify stem cells at the singlecell level. This paper rebuts the counterexample, arguing that the alleged ‘crucial stem cell experiments’ do not measure self-renewal for a single cell, do not establish a single cell’s differentiation potential, and, if interpreted as providing results about single cells, fall into epistemic circularity. I then discuss the source (...) of the dispute, locating it in differences between philosophical and experimental perspectives. (shrink)

This is a book that is much easier to read than to review. For its originality and charm lie chiefly in the luminous, lively style and the choice of illustrative material garnered with great skill from an impressive array of authors ancient and modern. In these respects this long essay, which is as much philosophical and literary as scientific, is clearly in the distinguished tradition of French critical and philosophical writing although the language is English. It is easy to imagine (...) the shades of Montaigne, of the seventeenth-century Encyclopedists, of Renan, of Claude Bernard hovering in the corners of the author's study as he wrote. The two major theses conform also with the classical French essay. The first is a denial ofthe possibility of utopias—past, present, or future—and the corollary affirmation, "Complete freedom from disease and from struggle is almost incompatible with the process of living." As support is marshalled for this premise, the second is soon developed: While man cannot hope to refashion and dwell forever in a new Garden of Eden, he may, if he uses wisely all his intellectual and emotional resources, look forward to bettering his condition to such a degree that he may approximate at least for a time a true state of health and happiness. (shrink)

The modern history of experimentation with human beings is notable for its ethical lacunae. In 1865, in his great work, An Introduction to the Study of Experimental Medicine, Dr. Claude Bernard, the French physician who first established the use of the scientific method in medicine, echoed the earlier injunctions of physician-moralist Moses Maimonides in counseling his fellow physicians not to treat their patients solely as a means of advancing knowledge. Yet such cautions had no apparent effect on the physicians who, (...) at the end of the 19th century, studied the transmission of venereal diseases by intentionally infecting poor and institutionalized people without their knowledge, much less their consent. In response... (shrink)

The potential for financial conflicts of interest to influence scientific research in problematic ways has recently become a significant topic of discussion across numerous fields. The chemical, petroleum, pharmaceutical, and tobacco industries have all been accused of suppressing evidence that their products are harmful, producing studies with questionable methodologies, generating questionable reinterpretations of studies that challenge their products, and working with public relations firms and front groups to mislead the public about relevant science. In an effort to address these influences, (...) government... (shrink)

Dr. Henry Beecher, a renowned Harvard Medical School anesthesiologist, sent shock waves through the medical research community and the lay press when he described 22 examples of “unethical or questionably ethical studies” by reputable researchers at major institutions in his now well-known 1966 New England Journal of Medicine article. Beecher concluded this exposé by noting: “The ethical approach to experimentation in man has several components: two are more important than the others, the first being informed consent.... Secondly, there is the (...) more reliable safeguard provided by the presence of an intelligent, informed, conscientious, compassionate, responsible investigator”. Beecher’s... (shrink)

On June 16, 1966, the New England Journal of Medicine published “Ethics and Clinical Research” by Henry K. Beecher. Beecher’s account of 22 examples of unethical contemporary clinical research shook up the medical profession and helped pave the way for U.S. federal regulation of research involving human subjects. Five decades later, in this issue of Perspectives in Biology and Medicine, we pay tribute to the lasting significance of this whistle-blowing article and to the remarkable contributions of Henry Beecher. Beecher was (...) a pioneer in anesthesiology as an academic discipline and in research on pain and the placebo effect. He was an early and influential champion of randomized placebo-controlled... (shrink)

“You are interested in ethics,” the clinician said, “there are problems with medical ethics in Taiwan.” It was 2005, shortly after I had moved to Taiwan. A little later, a professor told me of a university hospital that served as a site for a transnational clinical trial run by a pharmaceutical company. He said that since no informed consent procedure was in place at that time, the hospital had simply obtained employer consent. “That’s why companies want to come to Taiwan (...) to do clinical testing, because you can do anything here—things that can’t be done in the US. That’s why everyone wants to come to Taiwan.” These statements may seem, at first, to indicate a lack of concern in Taiwan for medical and scientific... (shrink)

Evidence-based policy has support in many areas of government and in public affairs more generally. In this paper we outline what evidence-based policy is, then we discuss its strengths and weaknesses. In particular, we argue that it faces a serious challenge to provide a plausible, over-arching account of evidence. We contrast evidence-based policy with evidence-based medicine, especially the role of evidence in assessing the effectiveness of medicines. The evidence required for policy decisions does not easily lend itself to randomized controlled (...) trials, nor, for that matter, being listed in a single all-purpose hierarchy. (shrink)

Despite the conceptual problems in identifying the placebo effect, an increasing number of multidisciplinary inquiries rest on the assumption that there is a distinct class of effects, placebo effects. In this chapter, I argue against this assumption. I present cases and characterizations of the placebo effect as offered in the literature, and argue that the latter are subject to insurmountable problems. Moreover, I argue that identification of placebo effects as such is not useful for the three main purposes offered in (...) the literature. I then offer suggestions for why it may remain intuitive that some effects are placebo effects and close by noting the potential benefits of ultimately explaining away these intuitions. (shrink)

With an eye towards a potential scientific ethics curriculum, this paper examines four contrasting discourses regarding the ethics of using human subjects in science. The first two represent official statements regarding ethics. These include the U.S.’s National Science Education Standards, that identify ethics with a professional code, and the Belmont Report, that conceptualizes ethics in three principles to guide research oversight boards. Contrasting this view of ethics as decorum and practice in line with a priori principles is the conception of (...) ethics from unofficial sources representing populations who have been human subjects. The first counter-discourse examined comes from Guinea Pig Zero, an underground magazine for professional human subjects. Here ethics emerges as a question of politics over principle. The good behavior of the doctors and researchers is an effect of the politics and agency of the communities that supply science with subjects. The second counter-discourse is a comic book called Truth, which tells the story of Black soldiers who were used as guinea pigs in World War II. Ethics is both more political and more uncertain in this narrative. Science is portrayed as complicit with the racism of NAZI Germany; at the same time, and in contrast to the professional guinea pigs, neither agency nor politics are presented as effective tools for forcing the ethical conduct of the scientific establishment. The conclusion examines the value of presenting all of these views of scientific ethics in science education. (shrink)

Replicability is widely taken to ground the epistemic authority of science. However, in recent years, important published findings in the social, behavioral, and biomedical sciences have failed to replicate, suggesting that these fields are facing a “replicability crisis.” For philosophers, the crisis should not be taken as bad news but as an opportunity to do work on several fronts, including conceptual analysis, history and philosophy of science, research ethics, and social epistemology. This article introduces philosophers to these discussions. First, I (...) discuss precedents and evidence for the crisis. Second, I discuss methodological, statistical, and social-structural factors that have contributed to the crisis. Third, I focus on the philosophical issues raised by the crisis. Finally, I discuss proposed solutions and highlight the gaps that philosophers could focus on. (shrink)

. Scientists, for the most part, want to get it right. However, the social structures that govern their work undermine that aim, and this leads to nonreplicable findings in many fields. Because the social structure of science is a decentralized system, it is difficult to intervene. In this article, I discuss how we might do so, focusing on self-corrective-labor schemes. First, I argue that we need to implement a scheme that makes replication work outcome independent, systematic, and sustainable. Second, I (...) use these three criteria to evaluate extant proposals, which place the responsibility for replication on original researchers, consumers of their research, students, or many labs. Third, on the basis of a philosophical analysis of the reward system of science and the benefits of the division of cognitive labor, I propose a scheme that satisfies the criteria better: the professional scheme. This scheme has two main components. First, the scientific community is organized into two groups: discovery researchers, who produce new findings, and confirmation researchers, whose primary function is to do confirmation work. Second, a distinct reward system is established for confirmation researchers so that their career advancement is separated from whether they obtain positive experimental results. (shrink)

Examining the historical development of scientific concepts is important for understanding the structured routines within which these concepts are currently used as goal-directed tools in experiments. To illustrate this claim, I will outline how the concepts of mental imagery and hallucinations each draw on an older interdependent set of associations that, although nominally-discarded, continues to structure their current independent uses for pursuing discrete experimental goals. In doing so, I will highlight how three strands of literature offer mutually instructive insights for (...) understanding how the uses of our current scientific concepts contribute to experimental practices. The first strand of literature includes recent scholarship examining how the uses of scientific concepts can enable scientific practices (e.g., Boon 2012; Brigandt 2012; Feest 2010; Steinle 2012). In this context, scientific concepts have been described as tools that function in ways that contribute to empirical knowledge; contributions that extend beyond their traditionally recognized roles in mental and linguistic representation. The second strand of literature can be glimpsed within the technoscientific studies focus on non-human agency; a focus that supports an account of the disciplined routines within which concepts are used as acting in analogous ways to the routinized participation of machines in experiments (Pickering 1995). The third strand of the literature draws attention to how the functions of concepts are grounded by the set of historically-contingent experimental practices (e.g., Canguilhem 2008; Tiles 1984). Although maintaining valuable differences, the focus of these three strands of literature are mutually instructive. Together, they offer a view of the uses of concepts as taken-for-granted tools that function within networks of subterranean associations; associations that are grounded by historically contingent experimental practices that structure how they act (in concert with human and material participants) within the temporally dynamic processes of scientific practice. Through examples drawn from a comparison of the concepts of mental imagery and hallucinations, I aim to demonstrate the value that the converging insights of these three strands of literature offer for studying the role of scientific concepts in experimental practices. (shrink)

Historians of biology have argued that much of the dynamics of experimental disciplines such as genetics or molecular biology can be understood from studying experimental systems and model organisms alone . Such accounts contrast sharply with more traditional philosophies of science which viewed scientific research essentially as a process of inventing and testing theories. I present a case from the history of biochemistry which can be viewed from both the experimental systems perspective and from the methodology of theory testing. I (...) argue that not only are the two perspectives fully compatible, but they are both necessary for a complete account of the research process. (shrink)

The article presents some conclusions arising from an educational experiment conducted by the University Centre for Distance Learning. The aim of the experiment was to verify the applicability of Second Life for educational purposes. The most important conclusion of the experiment is that SL is not as much productive as an e-learning platform but it is quite efficient for the realization of multi-disciplinary projects. It is also effective as a tool for creating digital animations and simulations. Moreover, the article presents (...) some factors indispensable for the successful application of SL observed during the realization of the project. (shrink)