In Vivo, ex Vivo, in Vitro, in Silico: Models in the Life Sciences

This topic is very broad, timely, and of theoretical and methodological interest for philosophers as well as for medical researchers and biologists.   As mathematician, economist and physicist John von Neumann put it in a provocative way 60 years ago: "The sciences do not try to explain, they hardly even try to interpret, they mainly make models." All sciences indeed make models of phenomena, in order to describe them in a way which makes salient their most explanatory features regarding at least the questions we are asking. Models can take many forms, including analytical models, viz., sets of ordinary or partial differential equations (e.g., the Lotka-Volterra equations in population genetics), or computer models (e.g., cellular automata, agent based models, logical approaches to computation, etc.), i.e., in silico models. But in the life sciences there are also "in vivo models" — organisms whose study is supposed to provide an understanding of much more encompassing phenomena. Most famous is the Drosophila melanogaster used by geneticists and molecular biologists; mice, nematodes (e.g., Caenorhabditis elegans), the plant Aradobipsis thaliana, and all the bacteria used for experimenting on long term evolution are other prominent “model organisms.” These raise specific epistemological problems. Medicine appeals to model organisms constantly as clinical trials on human beings should be the last step only of a methodical set of experiments on non-human subjects, so that the risk of the human trials are maximally minimized. There are also in vitro studies, which isolate specific living processes and reproduce them in laboratory conditions — a common method in biochemistry, cell biology, molecular genetics, etc. Here, what is going on in test tubes is supposed to model the real processes taking place in organisms, or in nature in general, whereas many conditions of these real processes are simply neglected — above all, the fact that they take place in a living organism. This method stimulated criticisms from the beginnings of physiology in the 18th century, where vitalist physicians accused experimental biologists of studying mere artifacts, since those phenomena are part of the whole organism in its natural environment, from which the scientist abstracts away. However, countless are the results acquired since two centuries thanks to those models.

For a long time philosophy of science focused on theories – and whether they find out ‘laws of nature’ – according to the framework defined by logical positivism in the 1930s. Since the 1970s, many doubts have been cast on this framework. Alternative views of science flourished, and many philosophers of science turned to studying the epistemological nature of scientific modeling. They made significant advances about the kind of knowledge models do provide, their relationships with theories, laws of nature or experiments, as well as the consequences of a conception of models for the debates about realism vs. instrumentalism, the criteria and importance of reasonable assumptions in designing models, etc. They distinguished mathematical and simulated models, they identified epistemic values such as genericity, realism or precision, which may not be reachable at the same time (as ecologist Richard Levins pointed out in 1966), triggering a considerable amount of debates in the field. They questioned cases where one has several different models for the same phenomenon, and what this means for explanatory pluralism. They also considered inverse cases where several different phenomena have a common model, like in the case of behavioral ecology and microeconomics, which can both be modeled through game theory. Robustness analysis, as a way to cope with the plurality of models has been scrutinized.

However, the use of the four kinds of models — in vitro, in vivo, ex vivo, in silico — in the life sciences brings to the fore many particular issues, because the scientific knowledge in this case is produced through the entanglement of those four kinds of models. Model organisms raise, for sure, specific problems, such as: how can we generalize from experiments on this organism, to teachings about a genus, a family, a clade, or even (as it is the case on molecular genetics) to all living beings? Given that the living world has been shaped by evolution, and that the key properties of being which evolve under natural selection are diversity and variety, it would not be reasonable to expect many universally shared properties across living families; therefore this issue of the scope of what we learn from model organisms is crucial. Much work still needs to be done in order to understand how model organisms interact with in silico, ex vivo, and biochemical models, as well as with computer simulation and mathematical frameworks, in order to produce knowledge.  

PhD students and early career researchers from a large spectrum of disciplines and interests in history and philosophy of biology as well as life sciences are invited to submit an application, by sending a letter of motivation, CV and abstract in a single file:

name-easpls2012.pdf to Philippe Hunemann at [email protected]  

Deadline for applications: March 19, 2012

Applications will be evaluated and applicants will be notified acceptance before the end of May.   EASPLS: General presentation The European Advanced School for the Philosophy of Life Sciences is organized by six top level institutions in the philosophy and history of life sciences and aims at fostering research, advancement of students and collaborations in the field of the philosophy of biomedical sciences. After a preliminary meeting of the EASPLS in Gorino Sullam (Italy) in 2008, the first EASPLS "Causation and disease in the post-genomic era" was held at the Brocher Foundation in September 2010, as the 2012 will be. Meetings are planned to be held every other year. The Brocher Foundation is located in Hermance, near Geneva, in a beautiful setting along the Lake Léman. The accommodation will be a hotel situated next to the Foundation.  

Registration fee: 550 Chf, including room and board . The Brocher Foundation provides a limited number of fellowships to support junior participants. Those wishing to apply for these fellowships should do so in a separate letter and include it in their application file. The schedule mixes presentations of senior researchers, postdoctoral researchers and PhD students. The selected contributors will be either asked to give a paper on the topic they propose, or asked to comment on one of the senior researchers' presentations, according to decision of the committee based on the examination of the set of applications. Each presentation lasts 40mn with a 20mn comment and discussion. People who do not want to comment on a paper should make this clear in the application.  

Some papers resulting from the meeting will be selected for submission to a special issue of History and Philosophy of the Life Sciences, as it was the case for papers of the last EASPLS. Publication will be subject to the normal peer review process of the journal.