PhilInBioMed Summer School 2024

Preliminary program

Monday, June 3rd Tuesday, June 4th Wednesday, June 5th Thursday, June 6th Friday, June 7th
9.00 – 10.00
Lecture by course leader
Philosophy of neuroscience
Carl Craver
9.00 – 10.00
Lecture by course leader
Neuroscience
Serge Ahmed
9.00 – 10.00
Lecture by course leader
Evolution
Marie Vasse
9.00 – 10.15
Group session 7
Finalizing presentations
10.00 – 11.00
Tutorial
Applying philosophical tools in PinS
Fridolin Gross
10.00 – 11.00
Tutorial
What PinS is not: Situating PinS among other approaches
Maël Lemoine
10.00 – 11.00
Tutorial
Bringing scientists and philosophers together
Bertrand Daignan-Fornier
10.15 – 11.00
Presentation of group results
Group 1
11.00 – 11.30
Coffee Break
11.00 – 11.30
Coffee Break
11.00 – 11:30
Coffee Break
11.00 – 11.30
Coffee Break
11.30 – 13.00
Group session 1
11.30 – 13.00
Group session 3
11:30 – 13:00
Group session 5
Exchange with course leader from different group
11.30 – 13.00
Presentation of group results
Groups 2 and 3
13.00 – 14.00
Participant arrival
13.00 – 14.30
Lunch / Meet the speakers
13.00 – 14.30
Lunch / Meet the speakers
13.00 – 14.30
Lunch / Meet the speakers
13.00 – 14.30
Lunch / Meet the speakers
14.00 – 14:45
Welcome and participant self-introductions
14.30 – 15.30
Lecture by course leader
The impressive role of philosophy and theory in immunology
Thomas Pradeu
14:30 – 17:00
Group session 4
First draft
14.30 – 15.30
Lecture by course leader
Philosophy of evolution
Matt Haber
14.30 – 16.00
Presentation of group results
Groups 4 and 5
14.45 – 15.45
Tutorial
What is “philosophy in science”?
Jonathan Sholl
15.30 – 17.00
Group session 2
15.30 – 17.00
Group session 6
16.00 – 16.30
Closing session
15.45 – 16.15
Break
17.00 – 17.30
Break
17.00 – 17.30
Break
17.00 – 17.30
Break
16.15 – 17.15
Lecture by course leader
The immune system: current concepts and the need for theory change
Søren Paludan
17.30 – 19.00
Social activity
17.30 – 19.00
Speed dating
Rapid one-on-one discussions with course leaders (optional)
17.30 – 18.30
General discussion on PinS
Chair: Jan Pieter Konsman
17.15 – 18.15
Group meet-up
19.30
Apéro
Aux 4 coins du vin (all participants)
19.30
Speakers’ dinner

Group Projects

An important part of the Summer School is a group activity in which you will go through the steps of a philosophy in science project under the guidance of a scientist and a philosopher. To make sure that the group work is interesting and relevant, we have asked our guest speakers to propose topics in line with their research interests. Below you will find materials to help you prepare for the project. We have assigned you to one of the groups based on your application profile. Please check which group you have been assigned to and read the corresponding description.

The reading materials can be found here. The password has been sent to you by email.

Group 1: Causal bidirectionality in integrated systems involving the nervous system

Course leaders

Carl Craver, Jan Pieter Konsman

Group members

Héloïse Athéa, Doudja Boumaza, Éloi Demange, Sarah Diner, Rose Gatfield-Jeffries

Description
The scientific problem

The so-called gut–microbiota–brain axis has recently been put forward to describe “the network of connections involving multiple biological systems that allows bidirectional communication between gut bacteria and the brain …” (Morais et al. 2021, p. 242). In stress research, “[t]he connection between the brain and the gut microbiota is [considered as] bidirectional” with ‘psychological’ stress altering the composition of gut microbiota and gut microbiota influencing stress responses (Morais et al., 2021, p. 249; Misiak et al. 2021; Madison & Bailey 2024). The availability of techniques to characterize gut microbiota composition and tools to intervene on gut microbiota has favored explanations in terms of ‘upward’ causation, from the gut microbiota to brain function. This, in turn, has led to questions regarding neuroendocrine differences observed in mental disorders such as: “Can we shift the blame to gut microbiota?” (Misiak et al. 2021)

Questions regarding the relationship between stress and the microbiota-gut-brain axis can be seen as an illustration of the increasing awareness among life scientists that many of the biological systems they are studying seem to display bidirectional causality in the sense that some parts of these systems can cause effects in other parts (or in the whole system) as well as the latter being able to affect the former. Indeed, in neuroscience, brain structures are now often considered to be connected by reciprocal neuronal projections. Similarly, regarding the function of many of the peripheral organ systems that the brain can modulate, these organ systems can typically also influence brain function.

The objectives will be

  1. to formulate a scientific problem relative to causation and the gut microbiota brain axis,
  2. to mobilize philosophy of science ideas, for example regarding levels, interventions, and mechanisms, which are all notions used by (neuro)scientists, and
  3. to put forward considerations and to formulate criteria regarding the clarification and the possibility of disentangling causal influences in integrated systems.

In addition, participants are encouraged to think about forms (based on spatial or part-whole relationships) of down- and upward causation.

Some philosophical notions

The life sciences frequently appeal to interventions based on hypothetical what-if questions. In the determination of what is often called counterfactual dependency (by philosophers) between a putative cause (C) and effect (E), the invariance (stability) of the relationship under the intervention given some background conditions as well as the absence of the reverse counterfactual relationship, (Woodward & Hitchcock 2003). Some of these criteria have been further refined by appealing to the notions of specificity and proportionality of cause and effect (including time and space considerations), and hence the importance of the choice of levels of explanation (Woodward 2010).

Debates about levels have been legion in philosophy and have resulted in many distinctions and some proposals to eliminate levels. Since scientists in many different domains employ some notion of levels, getting rid of a broad class of uses of levels may have many unforeseen consequences. Instead, promoting the use of distinction of levels may be more fruitful, even though local elimination or reformulation of levels may still be called for. One distinction that may be useful is to view mechanistic levels as levels of organization (Craver, in press). Appealing to mechanisms is widespread in causal explanations in the life sciences. Considering a minimal definition, according to which “[a] mechanism for a phenomenon consists of entities (or parts) whose activities and interactions are organized so as to be responsible for the phenomenon” (Glennan & Illari 2018, p. 92), this is not surprising as this definition can be applied to many situations. However, in mechanisms, one can often distinguish constitutional (vertical) part-whole relationships and etiological (horizontal) relationships. Applying these distinctions has been proposed to help in framing questions regarding up- and downward causation (Craver & Bechtel 2007). Here the challenge will be to apply these different notions in an attempt to tease apart possible bidirectional causation along the so-called microbiota-gut-brain axis. Indeed, here we will explore debates about the relationship between the gut and the brain as an example of a multilevel and dense causal mechanism, with a multitude of interactions and relations that run across and between multiple levels of organization and link in causal relations things that are in fact quite distinct from one another. Our goal is to disentangle the conceptual issues from the empirical ones so that the experimental focus can be on establishing important relations (whatever their form) that can be used for the purposes of understanding and controlling the relationships between the gut and the brain.

Scientific proposal based on mobilization of philosophical notions

The last challenge will be to formulate a proposal for (neuro)scientists based on these philosophical notions that would allow these scientists to tease apart causal influences in systems in which bidirectional (up- and downward) causation seems possible. This stage may, on the one hand, be expected to be relatively straightforward, but may, on the other hand, also be complicated by that fact scientists are already familiar with some notions of intervention, level and mechanisms.

Preparation
Essential readings
Craver, Carl F. Forthcoming. “Defending levels by trading waves for trees.” Synthese.
Craver, Carl F., and William Bechtel. 2006. “Top-down Causation Without Top-down Causes.” Biology & Philosophy 22 (4): 547–63. https://doi.org/10.1007/s10539-006-9028-8.
Misiak, Błażej, Jerzy Samochowiec, Wojciech Marlicz, and Igor Łoniewski. 2021. “Gut Microbiota in Psychiatric Disorders: Better Understanding or More Complexity to Be Resolved?” Progress in Neuro-Psychopharmacology and Biological Psychiatry 110 (August):110302. https://doi.org/10.1016/j.pnpbp.2021.110302.
Woodward, James, and Christopher Hitchcock. 2003. “Explanatory Generalizations, Part I: A Counterfactual Account.” Noûs 37 (1): 1–24.
Background readings
Glennan, Stuart, and Phyllis Illari. 2017. “Varieties of Mechanisms.” In The Routledge Handbook of Mechanisms and Mechanical Philosophy. Routledge.
Madison, Annelise A., and Michael T. Bailey. 2024. “Stressed to the Core: Inflammation and Intestinal Permeability Link Stress-Related Gut Microbiota Shifts to Mental Health Outcomes.” Biological Psychiatry, The Microbiome at the Interface of the Exposome and Risk for Psychiatric Disorders, 95 (4): 339–47. https://doi.org/10.1016/j.biopsych.2023.10.014.
Morais, Livia H., Henry L. Schreiber, and Sarkis K. Mazmanian. 2021. “The Gut Microbiota–Brain Axis in Behaviour and Brain Disorders.” Nature Reviews Microbiology 19 (4): 241–55. https://doi.org/10.1038/s41579-020-00460-0.
Woodward, James. 2010. “Causation in Biology: Stability, Specificity, and the Choice of Levels of Explanation.” Biology & Philosophy 25 (3): 287–318. https://doi.org/10.1007/s10539-010-9200-z.

Group 2: Is the chronic brain disease model of addiction challenged by the possibility of spontaneous remission?

Course leaders

Serge Ahmed, Maël Lemoine, Jonathan Sholl

Group members

Garance Castino, Jeremy Guttman, Yingying Han, Stephen Rowe

Description

If addiction is explained by a permanent change in major functional circuits of the brain, the possibility of spontaneous remission from addiction (e.g., following single life events) sounds implausible. Yet, since such remissions are documented, they seem to question the chronic brain disease model of addiction. Is it really the case? What would remain of that model, if spontaneous remission was taken seriously?

Preparation

Participants should read, in the following order:

Leshner, Alan I. 1997. “Addiction Is a Brain Disease, and It Matters.” Science 278 (5335): 45–47. https://doi.org/10.1126/science.278.5335.45.
Volkow Nora D., Koob George F., and McLellan A. Thomas. 2016. “Neurobiologic Advances from the Brain Disease Model of Addiction.” New England Journal of Medicine 374 (4): 363–71. https://doi.org/10.1056/NEJMra1511480.
Heilig, Markus, James MacKillop, Diana Martinez, Jürgen Rehm, Lorenzo Leggio, and Louk J. M. J. Vanderschuren. 2021. “Addiction as a Brain Disease Revised: Why It Still Matters, and the Need for Consilience.” Neuropsychopharmacology 46 (10): 1715–23. https://doi.org/10.1038/s41386-020-00950-y.
Hall, Wayne, Adrian Carter, and Cynthia Forlini. 2015. “The Brain Disease Model of Addiction: Is It Supported by the Evidence and Has It Delivered on Its Promises?” The Lancet Psychiatry 2 (1): 105–10. https://doi.org/10.1016/S2215-0366(14)00126-6.

Group 3: Early immune defenses: How and Why?

Course leaders

Hannah Kaminski, Søren Riis Paludan, Thomas Pradeu

Group members

Carla Feliciano, Coral González Martínez, Jacob Hamel-Mottiez, Kristina Humphreys

Description
Why is this question important and timely in today’s immunology?

Early host defense barriers eliminate many viruses before infections are established, and clear others so they remain subclinical or cause only mild disease. As such the first immunological reactions to invading pathogens are of utmost importance but remain incompletely understood. Immunology is a field that has historically been shaped by broad concepts, including the pattern recognition theory that currently dominates innate immunology, and which proposes that pattern recognition receptors should be considered as “the first line of defense” against pathogens (Medzhitov and Janeway 2002). However, the responses evoked by pattern recognition receptors potently induces inflammation, and although we are frequently exposed to viruses, we do not often have fever. Moreover, some organs and cell types are highly sensitive to inflammation, and are unlikely to mount inflammatory response as the immediate response to viruses. Therefore, it can be argued that there is currently no unifying and broadly accepted theory for the biological principles that govern the first line of host defense. This is needed to explain clinically important phenomena such as: (i) Subclinical elimination of infections, (ii) Transmission of infections, (iii) Zoonotic “hosting” of viral reservoirs, (iv) Antiviral defense by inflammation-sensitive organs/cells. It is hence important to build a theory that can explain the first line of defense against infections.

Assignment

Laying the foundations of a rigorous and useful conceptual and theoretical account of early immune defenses.

Guiding Question

How can we collectively build a novel conceptual and theoretical framework to shed light on early immune defenses, and how can philosophical tools be useful for achieving this goal?

More specific guiding questions
  • Why are the current accounts of early immune defenses unsatisfactory?
  • What goals should an alternative account of early immune defenses achieve?
  • Which immunological phenomena should be included in a novel conceptual and theoretical account of early immune defenses? For example, should this account include only responses to viruses, or responses to other microbes as well? Should it include other situations, such as cancer and autoimmunity? Should we include the early immune responses to the microbiome and to viruses that belong to the virome (e.g., TTV)? Can we figure out whether early immune response are involved in virus latency?
  • Are early immune responses that do not come with inflammation the product of a specific form of homeostasis? If so, which one?
  • Why and how did anti-inflammatory early immune responses evolve? Both excessive inflammation and insufficient inflammation can be extremely costly in terms of fitness, so how was a balance reached with regard to such fundamental trade-offs?
  • Epistemologically, when exactly must a novel theoretical framework emerge in a given scientific domain? What are the most central components of a satisfactory theory? How can philosophers of science help in building a novel scientific theory?
Preparation
Essential
Paludan SR, Pradeu T, Masters SL, Mogensen TH (2021) Constitutive immune mechanisms: mediators of host defence and immune regulation. Nat Rev Immunol 21:137–150. https://doi.org/10.1038/s41577-020-0391-5
Medzhitov R, Janeway CA (2002) Decoding the patterns of self and nonself by the innate immune system. Science 296:298–300. https://doi.org/10.1126/science.1068883
Additional
McNab F, Mayer-Barber K, Sher A, et al (2015) Type I interferons in infectious disease. Nat Rev Immunol 15:87–103. https://doi.org/10.1038/nri3787
Zhang Q, Bastard P, Liu Z, et al (2020) Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370:eabd4570. https://doi.org/10.1126/science.abd4570

If you have no background in immunology, please read pages 3-13 of Pradeu’s Philosophy of Immunology, which give a very basic introduction:

Pradeu, Thomas. 2019. Philosophy of Immunology. Cambridge: Cambridge University Press. https://doi.org/10.4324/9780415249126-q138-1.

Group 4: The Emergence of Individuals in Microbiology

Course leaders

Matt Haber, Marie Vasse

Group members

Aurore Aymerie dit Eymeric, Yasmin Bar-Tzlil, Jonah Branding, Ge Fang, Cassandra Zie Yang

Description
Background/Sample Case

Knowing that groups of bacteria virtually inhabit and are key components of all types of ecosystems have fostered vast empirical and theoretical research. The very object of such research, however, may be elusive: are we investigating the behavior, ecology and/or evolution of single cells? Of populations? Of communities? And which of those can function as individuals?

Here we propose to explore the concept of (transition to) individuality in bacterial groups. While selection and co-option have been traditionally presented as causes of collective-level reproduction, Black et al (2020) examine how ecological conditions may shape the emergence of the cell collectives. They propose a model in which ecological cycles of cell growth, dispersal, and colonization on discrete resource patches lead to two fundamentally different evolutionary outcomes depending on the dispersal regime. Only in the slow regime cells evolve restrained growth rate (and even cell differentiation and division of labor). This work is an example of an alternative narrative to understand the evolution of collectivity.

Assignment

Consider the guiding questions below as applied to the case described above.  How are the empirical and conceptual questions intrinsically bound to one another?

Guiding Questions:

  • When should we regard groups of bacteria as individuals?
  • More precisely, what sorts of behaviors do bacteria display that generate a collective identity as a new biological individual?

This is not merely an empirical question, but a conceptual one as well.  Namely, what sort of criteria ought we employ to determine when groups of bacteria may be regarded as a biological individual?

More specific guiding questions:

  • Is there a single set of criteria that we ought to employ in the case of microbes, or are there multiple different criteria we might employ? If the latter, does that mean we are employing different notions of biological individuality, or are we capturing different facets of a complex notion?
  • If there are different criteria of individuality we might employ, how do we determine which criteria are the correct ones to use for the research problem at hand?
  • Are the criteria we ought to use to assess microbial individuality distinctive from other levels of biological organization, or are we discovering general criteria that applies generally across biology.
  • How do the criteria of individuality that we employ direct empirical research questions? For example, how do competing criteria change the way we think about a biological individual’s boundaries, identity, or composition?  What, if anything, is at stake in these competing claims (e.g., do we end up with competing ‘counts’ of the number of individuals)?
  • Do biological individuals come in degrees? What sort of persistence criteria do we expect of individuals, e.g., may biological individuals persist only ephemerally, may they exist intermittently with gaps, or must they persist without interruption over a relevantly meaningful amount of time?
Preparation
Essential readings
Black, Andrew J., Pierrick Bourrat, and Paul B. Rainey. 2020. “Ecological Scaffolding and the Evolution of Individuality.” Nature Ecology & Evolution 4 (3): 426–36. https://doi.org/10.1038/s41559-019-1086-9.
The authors balance classic approaches to questions about the emergence of multicellularity/individuality (in selectionist terms) while also expanding how we might frame those questions. This offers a good example of the utility of identifying and expanding traditional conceptual frameworks.
Santelices, Bernabé. 1999. “How Many Kinds of Individual Are There?” Trends in Ecology & Evolution 14 (4): 152–55. https://doi.org/10.1016/S0169-5347(98)01519-5.
Santelices identifies what he calls three classic attributes of individuality, then precedes to ask what happens if we were to relax those as criteria of individuality. This permits an expansion of candidate biological individuals—and the sorts of features we associate with individuals—rather than ruling those out by definition.
Additional readings
Haber, M.H. “Biology’s Einstein Moment: Specifying Lineal Frames of Reference & Rejecting Absolute Biological History” (Draft—Under Review).
Haber argues that we ought to reject the idea of an absolute, invariant biological history, much as physicists have rejected the idea of absolute, invariant space. In place, we get richer accounts of biology by specifying relevant lineal frames of reference and paying attention to how they interact with one another.
Pradeu, Thomas. 2018. “Genidentity and Biological Processes.” In Everything Flows: Towards a Processual Philosophy of Biology, edited by Daniel J. Nicholson and John Dupré, 0. Oxford University Press. https://doi.org/10.1093/oso/9780198779636.003.0005.
Pradeu provides an account of process ontology, focusing on its epistemological utility. Viewed through this lens and employing the genidentity view, Pradeu offers a compelling account of how processes have a claim of priority in generating biological boundaries and individuals.

Group 5: Division of labor across the tree of life

Course leaders

Bertrand Daignan-Fornier, Fridolin Gross

Group members

Claudio Davini, Claudia Gadaleta, Jokūbas Janušauskas, Tianqin Ren, Sebastian Sander Oest

Description

Division of labor is of central importance in biology and an idea that is increasingly used in relation to a variety of phenomena in different taxa, from microbes (e.g. West & Cooper 2016) to social insect colonies to the evolution of modularity in plants and animals (e.g. Rueffler et al. 2012) and the evolution of human societies (e.g. Nakahashi & Feldman 2014). On closer inspection, however, this concept appears to be used in very different ways in different biological contexts. This raises the crucial question of whether division of labor in biology is a unified concept at all and whether similar reasoning and modeling can be used in the different contexts in which it is applied. Are there different forms of division of labor and should we reconsider and redefine it based on the different forms it takes in the tree of life? Are there common underlying features of the division of labor in different biological contexts? Do the molecular mechanisms involved in the division of labor tell us more than just how it happens?

More specifically, we propose in this project

  1. to gain an overview of the different explanations and models of division of labor and the different molecular mechanisms proposed at the level of microorganisms or multicellular organisms
  2. to systematically investigate the similarities and differences within and between these levels and to ask whether these differences are in degree or in kind
  3. to propose a meaningful classification of the cellular division of labor across the tree of life on this basis.
We realize that this is probably too ambitious for a one-week project, so it should be understood as an initial roadmap that can be adapted and refined as we proceed.
Preparation

In preparation we would like all of you to read the following paper:

West, Stuart A., and Guy A. Cooper. 2016. “Division of Labour in Microorganisms: An Evolutionary Perspective.” Nature Reviews Microbiology 14 (11): 716–23. https://doi.org/10.1038/nrmicro.2016.111.

In addition, each member of the group should pick one among the following papers and prepare a small summary of the main ideas. Please note that some of them can be a little technical. So it would be good if you coordinate among yourselves who chooses which paper, depending on your respective interests and background.

Adler, Miri, Yael Korem Kohanim, Avichai Tendler, Avi Mayo, and Uri Alon. 2019. “Continuum of Gene-Expression Profiles Provides Spatial Division of Labor within a Differentiated Cell Type.” Cell Systems 8 (1): 43-52.e5. https://doi.org/10.1016/j.cels.2018.12.008.
Arendt, Detlev, Jacob M. Musser, Clare V.H. Baker, Aviv Bergman, Connie Cepko, Douglas H. Erwin, Mihaela Pavlicev, et al. 2016. “The Origin and Evolution of Cell Types.” Nature Reviews Genetics 17 (12): 744–57. https://doi.org/10.1038/nrg.2016.127.
Beshers, Samuel N., and Jennifer H. Fewell. 2001. “MODELS OF DIVISION OF LABOR IN SOCIAL INSECTS.” Annual Review of Entomology 46 (Volume 46, 2001): 413–40. https://doi.org/10.1146/annurev.ento.46.1.413.
D’Hombres, Emmanuel. 2012. “The ‘Division of Physiological Labour’: The Birth, Life and Death of a Concept.” Journal of the History of Biology 45 (1): 3–31. https://doi.org/10.1007/s10739-010-9256-2.
Gestel, Jordi Van, Hera Vlamakis, and Roberto Kolter. 2015. “Division of Labor in Biofilms: The Ecology of Cell Differentiation.” In Microbial Biofilms, 67–97. John Wiley & Sons, Ltd. https://doi.org/10.1128/9781555817466.ch4.
Gordon, Deborah M. 2016. “From Division of Labor to the Collective Behavior of Social Insects.” Behavioral Ecology and Sociobiology 70 (7): 1101–8. https://doi.org/10.1007/s00265-015-2045-3.
Page Jr, Robert E., and Sandra D. Mitchell. 1998. “Self-Organization and the Evolution of Division of Labor.” Apidologie 29 (1–2): 171–90. https://doi.org/10.1051/apido:19980110.
Kirk, David L. 2005. “A Twelve-Step Program for Evolving Multicellularity and a Division of Labor.” BioEssays 27 (3): 299–310. https://doi.org/10.1002/bies.20197.
Nakahashi, Wataru, and Marcus W. Feldman. 2014. “Evolution of Division of Labor: Emergence of Different Activities among Group Members.” Journal of Theoretical Biology 348 (May):65–79. https://doi.org/10.1016/j.jtbi.2014.01.027.
Rueffler, Claus, Joachim Hermisson, and Günter P. Wagner. 2012. “Evolution of Functional Specialization and Division of Labor.” Proceedings of the National Academy of Sciences 109 (6): E326–35. https://doi.org/10.1073/pnas.1110521109.
Smith, Chris R., Amy L. Toth, Andrew V. Suarez, and Gene E. Robinson. 2008. “Genetic and Genomic Analyses of the Division of Labour in Insect Societies.” Nature Reviews Genetics 9 (10): 735–48. https://doi.org/10.1038/nrg2429.
Ulrich, Y., J. Saragosti, C. K. Tokita, C. E. Tarnita, and D. J. C. Kronauer. 2018. “Fitness Benefits and Emergent Division of Labour at the Onset of Group Living.” Nature 560 (7720): 635–38. https://doi.org/10.1038/s41586-018-0422-6.
West-Eberhard, Mary Jane. 1979. “Sexual Selection, Social Competition, and Evolution.” Proceedings of the American Philosophical Society 123 (4): 222–34.