We address Turkheimer’s argument that genome-wide association studies of behaviors and psychiatric traits will fail to produce coherent explanations. We distinguish two major sources of potential i...

Lucas Matthews and I substantially revised my SEP entry on Heritability. This version includes discussion of the missing heritability problem and other issues that arise from the use of Genome Wide Association Studies by Behavioral Geneticists.

Simple idealized models seem to provide more understanding than opaque, complex, and hyper-realistic models. However, an increasing number of scientists are going in the opposite direction by utilizing opaque machine learning models to make predictions and draw inferences, suggesting that scientists are opting for models that have less potential for understanding. Are scientists trading understanding for some other epistemic or pragmatic good when they choose a machine learning model? Or are the assumptions behind why minimal models provide understanding misguided? In (...) this paper, using the case of deep neural networks, I argue that it is not the complexity or black box nature of a model that limits how much understanding the model provides. Instead, it is a lack of scientific and empirical evidence supporting the link that connects a model to the target phenomenon that primarily prohibits understanding. (shrink)

There is currently no viable alternative to the Bayesian analysis of scientific inference, yet the available versions of Bayesianism fail to do justice to several aspects of the testing and confirmation of scientific hypotheses. Bayes or Bust? provides the first balanced treatment of the complex set of issues involved in this nagging conundrum in the philosophy of science. Both Bayesians and anti-Bayesians will find a wealth of new insights on topics ranging from Bayes’s original paper to contemporary formal learning theory.In (...) a paper published posthumously in 1763, the Reverend Thomas Bayes made a seminal contribution to the understanding of "analogical or inductive reasoning." Building on his insights, modem Bayesians have developed an account of scientific inference that has attracted numerous champions as well as numerous detractors. Earman argues that Bayesianism provides the best hope for a comprehensive and unified account of scientific inference, yet the presently available versions of Bayesianisin fail to do justice to several aspects of the testing and confirming of scientific theories and hypotheses. By focusing on the need for a resolution to this impasse, Earman sharpens the issues on which a resolution turns. John Earman is Professor of History and Philosophy of Science at the University of Pittsburgh. (shrink)

The discovery and ongoing investigation of microRNAs suggest important conceptual and methodological lessons for philosophers and historians of biology. This paper provides an account of miRNA research and the shift from viewing these tiny regulatory entities as minor curiosities to seeing them as major players in the post-transcriptional regulation of genes. Conceptually, the study of miRNAs is part of a broader change in understandings of genetic regulation, in which simple switch-like mechanisms were reinterpreted as aspects of complex cellular and genome-wide (...) processes. Among them are the activities of small RNAs, previously regarded as non-functional. Methodologically, the miRNA story suggests new ways of characterizing biological research that should prove helpful to philosophers of science who seek to develop more pluralistic, pragmatic models of scientific inquiry. miRNA research displays iterative movements between multiple modes of investigation that include not only the proposal and testing of hypotheses but also exploratory, technology-oriented and question-driven modes of research. As an exemplary story of scientific discovery and development, the miRNA case illustrates transitions from genetics to genomics and systems biology, and it shows how diverse configurations of research practice are related to major scientific advances. (shrink)

This book presents the concept of “complementary science” which contributes to scientific knowledge through historical and philosophical investigations. It emphasizes the fact that many simple items of knowledge that we take for granted were actually spectacular achievements obtained only after a great deal of innovative thinking, painstaking experiments, bold conjectures, and serious controversies. Each chapter in the book consists of two parts: a narrative part that states the philosophical puzzle and gives a problem-centred narrative on the historical attempts to solve (...) the puzzle; and the analysis part which provides in-depth analyses of certain scientific, historical, and philosophical aspects of the story. (shrink)

This paper is devoted to an examination of the discovery, characterization, and analysis of the functions of microRNAs, which also serves as a vehicle for demonstrating the importance of exploratory experimentation in current (post-genomic) molecular biology. The material on microRNAs is important in its own right: it provides important insight into the extreme complexity of regulatory networks involving components made of DNA, RNA, and protein. These networks play a central role in regulating development of multicellular organisms and illustrate the importance (...) of epigenetic as well as genetic systems in evolution and development. The examination of these matters yields principled arguments for the historicity of the functions of key biological molecules and for the indispensability of exploratory experimentation in contemporary molecular biology as well as some insight into the complex interplay between exploratory experimentation and hypothesis-driven science. This latter result is not only important for philosophy of science, but also of practical importance for the evaluation of grant proposals, although the elaboration of this latter claim must be left for another occasion. (shrink)

Philosophers of experiment have acknowledged that experiments are often more than mere hypothesis-tests, once thought to be an experiment's exclusive calling. Drawing on examples from contemporary biology, I make an additional amendment to our understanding of experiment by examining the way that `wide' instrumentation can, for reasons of efficiency, lead scientists away from traditional hypothesis-directed methods of experimentation and towards exploratory methods.

Starting with some illustrative examples, I develop a systematic account of a specific type of experimentation--an experimentation which is not, as in the "standard view", driven by specific theories. It is typically practiced in periods in which no theory or--even more fundamentally--no conceptual framework is readily available. I call it exploratory experimentation and I explicate its systematic guidelines. From the historical examples I argue furthermore that exploratory experimentation may have an immense, but hitherto widely neglected, epistemic significance.

Genome-wide association studies of human complex traits have provided us with new estimates of heritability. These estimates foreground the question of genetic causation. After having presen...

Genetic explanation of complex human behavior presents an excellent test case for pluralism. Although philosophers agree that successful scientific investigation of behavior is pluralistic, there remains disagreement regarding integration and elimination—is the plurality of approaches here to stay, or merely a waystation on the road to monism? In this paper we introduce an issue taken very seriously by scientists yet mostly ignored by philosophers—the missing heritability problem—and assess its implications for disagreement among pluralists. We argue that the missing heritability problem, (...) which isn’t going anywhere any time soon, implies that pluralism in behavior genetics is both practically ineliminative and theoretically non-integrative. (shrink)

With In Search of Mechanisms, Carl F. Craver and Lindley Darden offer both a descriptive and an instructional account of how biologists discover mechanisms. Drawing on examples from across the life sciences and through the centuries, Craver and Darden compile an impressive toolbox of strategies that biologists have used and will use again to reveal the mechanisms that produce, underlie, or maintain the phenomena characteristic of living things. They discuss the questions that figure in the search for mechanisms, characterizing the (...) experimental, observational, and conceptual considerations used to answer them, all the while providing examples from the history of biology to highlight the kinds of evidence and reasoning strategies employed to assess mechanisms. At a deeper level, Craver and Darden pose a systematic view of what biology is, of how biology makes progress, of how biological discoveries are and might be made, and of why knowledge of biological mechanisms is important for the future of the human species. (shrink)

In the last few years, biologists and computer scientists have claimed that the introduction of data science techniques in molecular biology has changed the characteristics and the aims of typical outputs (i.e. models) of such a discipline. In this paper we will critically examine this claim. First, we identify the received view on models and their aims in molecular biology. Models in molecular biology are mechanistic and explanatory. Next, we identify the scope and aims of data science (machine learning in (...) particular). These lie mainly in the creation of predictive models which performances increase as data set increases. Next, we will identify a tradeoff between predictive and explanatory performances by comparing the features of mechanistic and predictive models. Finally, we show how this a priori analysis of machine learning and mechanistic research applies to actual biological practice. This will be done by analyzing the publications of a consortium—The Cancer Genome Atlas—which stands at the forefront in integrating data science and molecular biology. The result will be that biologists have to deal with the tradeoff between explaining and predicting that we have identified, and hence the explanatory force of the ‘new’ biology is substantially diminished if compared to the ‘old’ biology. However, this aspect also emphasizes the existence of other research goals which make predictive force independent from explanation. (shrink)

There is currently no viable alternative to the Bayesian analysis of scientific inference, yet the available versions of Bayesianism fail to do justice to several aspects of the testing and confirmation of scientific hypotheses. Bayes or Bust? provides the first balanced treatment of the complex set of issues involved in this nagging conundrum in the philosophy of science. Both Bayesians and anti-Bayesians will find a wealth of new insights on topics ranging from Bayes's original paper to contemporary formal learning theory. (...) In a paper published posthumously in 1763, the Reverend Thomas Bayes made a seminal contribution to the understanding of "analogical or inductive reasoning." Building on his insights, modem Bayesians have developed an account of scientific inference that has attracted numerous champions as well as numerous detractors. Earman argues that Bayesianism provides the best hope for a comprehensive and unified account of scientific inference, yet the presently available versions of Bayesianisin fail to do justice to several aspects of the testing and confirming of scientific theories and hypotheses. By focusing on the need for a resolution to this impasse, Earman sharpens the issues on which a resolution turns. John Earman is Professor of History and Philosophy of Science at the University of Pittsburgh. (shrink)

Machine learning (ML) has been praised as a tool that can advance science and knowledge in radical ways. However, it is not clear exactly how radical are the novelties that ML generates. In this article, I argue that this question can only be answered contextually, because outputs generated by ML have to be evaluated on the basis of the theory of the science to which ML is applied. In particular, I analyze the problem of novelty of ML outputs in the (...) context of molecular biology. In order to do this, I first clarify the nature of the models generated by ML. Next, I distinguish three ways in which a model can be novel (from the weakest to the strongest). Third, I dissect the way ML algorithms work and generate models in molecular biology and genomics. On these bases, I argue that ML is either a tool to identify instances of knowledge already present and codified, or to generate models that are novel in a weak sense. The notable contribution of ML to scientific discovery in the context of biology is that it can aid humans in overcoming potential bias by exploring more systematically the space of possible hypotheses implied by a theory. (shrink)

Heritability estimates obtained from genome-wide association studies are much lower than those of traditional quantitative methods. This phenomenon has been called the “missing heritability problem.” By analyzing and comparing GWAS and traditional quantitative methods, we first show that the estimates obtained from the latter involve some terms other than additive genetic variance, while the estimates from the former do not. Second, GWAS, when used to estimate heritability, do not take into account additive epigenetic factors transmitted across generations, while traditional quantitative (...) methods do. Given these two points we show that the missing heritability problem can largely be dissolved. (shrink)

Graphical AbstractThere are four major hypotheses (H1, H2, H3, and H4) as to the source of missing heritability. We propose that estimates obtained from GWAS underestimate heritability by not taking into account non-DNA (epigenetic) sources of heritability. Taking those factors into account (H4) should result in increased heritability estimates.

A number of scholars have recently drawn attention to the importance of iteration in scientific research. This paper builds on these previous discussions by drawing a distinction between epistemic and methodological forms of iteration and by clarifying the relationships between them. As defined here, epistemic iteration involves progressive alterations to scientific knowledge claims, whereas methodological iteration refers to an interplay between different modes of research practice. While distinct, these two forms of iteration are related in important ways. Contemporary research on (...) the biological effects of nanomaterials illustrates that methodological iteration can help to “initiate,” “equip,” and “stimulate” epistemic iteration. (shrink)

In the last few years, biologists and computer scientists have claimed that the introduction of data science techniques in molecular biology has changed the characteristics and the aims of typical outputs (i.e. models) of such a discipline. In this paper we will critically examine this claim. First, we identify the received view on models and their aims in molecular biology. Models in molecular biology are mechanistic and explanatory. Next, we identify the scope and aims of data science (machine learning in (...) particular). These lie mainly in the creation of predictive models which performances increase as data set increases. Next, we will identify a tradeoff between predictive and explanatory performances by comparing the features of mechanistic and predictive models. Finally, we show how this a priori analysis of machine learning and mechanistic research applies to actual biological practice. This will be done by analyzing the publications of a consortium—The Cancer Genome Atlas—which stands at the forefront in integrating data science and molecular biology. The result will be that biologists have to deal with the tradeoff between explaining and predicting that we have identified, and hence the explanatory force of the ‘new’ biology is substantially diminished if compared to the ‘old’ biology. However, this aspect also emphasizes the existence of other research goals which make predictive force independent from explanation. (shrink)

Recently, biologists have argued that data - driven biology fosters a new scientific methodology; namely, one that is irreducible to traditional methodologies of molecular biology defined as the discovery strategies elucidated by mechanistic philosophy. Here I show how data - driven studies can be included into the traditional mechanistic approach in two respects. On the one hand, some studies provide eliminative inferential procedures to prioritize and develop mechanistic hypotheses. On the other, different studies play an exploratory role in providing useful (...) generalizations to complement the procedure of prioritization. Overall this paper aims to shed light on the structure of contemporary research in molecular biology. (shrink)

Ten years after the Human Genome Project’s completion the life sciences stand in a moment of uncertainty, transition, and contestation. The postgenomic era has seen rapid shifts in research methodology, funding, scientific labor, and disciplinary structures. Postgenomics is transforming our understanding of disease and health, our environment, and the categories of race, class, and gender. At the same time, the gene retains its centrality and power in biological and popular discourse. The contributors to Postgenomics analyze these ruptures and continuities and (...) place them in historical, social, and political context. Postgenomics, they argue, forces a rethinking of the genome itself, and opens new territory for conversations between the social sciences, humanities, and life sciences. Contributors. Russ Altman, Rachel A. Ankeny, Catherine Bliss, John Dupré, Michael Fortun, Evelyn Fox Keller, Sabina Leonelli, Adrian Mackenzie, Margot Moinester, Aaron Panofsky, Sarah S. Richardson, Sara Shostak, Hallam Stevens. (shrink)