Biomedical Epistemology: Introduction

“Epistemology” is  that branch of Western philosophy referring to “what can be known” and “how do we know what we know.”  Modern biomedicine has effected major therapeutic interventions which affect many levels of biological systems. There have been dramatic technology-driven discoveries in basic biological research, most notably the “human genome project.” This led to “genomics” (and the other “-omics,”–e.g “proteomics,” “metabolomics,” etc) with “systems biology” as an overarching paradigm. There is unprecedented “therapeutic promise” in what is now often called the “post-genomic era.” (An overview of potential therapeutic applications–e.g. early intervention, personalized and “targeted” treatments (etc.)–is given in a popular format by Topol [32])

All this has granted biomedicine “scientific” status and public credibility commensurate with that of the so-called “physical sciences.” Indeed, intelligent lay commentators often conflate the achievements of the physical and biomedical sciences in the context of “modern scientific progress” in general.

Underlying issues here include whether there can be unique “laws” uncovered for biology (as in physics, for example) describing as yet undefined parameters; or, whether our focus should be entirely on an “engineering approach” (exploiting the findings of so-called “discovery science”) and routinely utilizing what Popper called “common sense knowledge” in our reasoning. This issue will be revisited later.

The related issue of what Kuhn called paradigmatic “maturity” of the physical sciences has been explored elsewhere and will be taken up again (notably with respect to a continuum rather than categorical perspective.

Presently, as we rush headlong into the “post-genomic” era,  two paradigms dominate biomedical thinking.  “Systems biology” (following upon the “genomic” revolution) attempts  whole system description via massive data collection (high throughput technologies) and computer-assisted simulation. “Evidence-based medicine” (EBM) stresses evaluation of therapeutic outcomes via “controlled-trial” methodologies. It would seem prudent, given the many “unknowns” to at least maintain an awareness of the issues posed by biomedical epistemology.

Interestingly, “epistemology” and related philosophical issues have been cited in the biomedical literature specifically with respect to issues around EBM [1-11] and “systems biology” (genomics, proteomics, metabolomics, etc.) [12-21]  These perspectives will be reviewed in detail in a forthcoming post or paper.

For now, I should say that both of the aforementioned lists of references reflect some degree of uncertainty with respect to, and a consequent willingness to re-examine, underlying meta-physical assumptions. For example, Boogerd et al state:

“…the philosophy of biology is still incomplete; we cannot as yet deal satisfactorily between a living system and its functional organization…Indeed, the existing philosophy of biology fails to address the rather profound issue of what distinguishes the living from the non-living…”   [21,  p.9].

There is then justification, even in their own literatures,  for considering alternative paradigms. These should be seen  as complementary, rather than competitive explanations. As noted below, biological systems may well require more than one approach to deriving explanatory principles.

Of particular interest are formulations which consider issues of “meaning” and “purpose,” not only as “emergent” properties of complex systems but as axiomatic to the process of life itself. Here we have biosemiotics and Gregory Bateson’s formulations whose interrelationship has been recently highlighted in the biosemiotics literature [22]. In this context, I take as “axiomatic” Barbieri’s intriguing definition of “meaning,” as “… an object which is related to another object via a code.” [23,  p.   5]. Of course, the significance of  “purpose” in the sense of Aristotelian “final cause” has been recognized, in the context of “feedback” from outcomes, since the earliest days of “cybernetics.” [24]

Another perspective to be considered here is the issue of “lawfulness” in biology, following upon Schrodinger’s original suggestion of “laws” unique to biological systems [25]. In this context, Kelso claims just such a status for his “coordination dynamics” equation in the realms of movement science and neuroscience [26, pp. 46-67] [27,  pp. 156-176] [28].  Kelso also broaches issues related to “agency” and “pattern.”

Then there is “fractal physiology” which postulates a “complexity measure” related to pathology and aging [29] [30].

These perspectives will be elaborated in subsequent posts or essays. Some were touched upon in a  recent essay in the context of Thomas Kuhn’s notion of “mature” sciences (physics being the common example) vs. “immature” “proto-sciences.” Here, I had begun by considering the juxtaposition of “Traditional Chinese Medicine” (TCM) and “epistemology.”  The general assumption was that TCM was “immature” compared to modern “scientific” biomedicine.  I was led then to briefly consider modern biomedicine from this Kuhnian perspective of “scientific maturity.” This blog continues a general epistemological examination of modern biomedicine and biology with respect to underlying assumptions.

My general attitude is that in the life sciences, diverse explanatory principles are likely to be complementary rather than competitive. At the beginning of his chapter “Part I; Principles: 3 Axioms, Definitions, and Laws Essential for Understanding the Phenomenon of Life.” semiotician Sungchul Ji [31] quotes American paleontologist Gaylord Simpson as follows:

“Physicists study the principles that apply to all phenomena;
biologists study phenomena to which all principles apply.”

I believe there is a good chance that this may turn out to  be literally true and compatible with the uniqueness of the life process.

NOTE: For an approach to these issues from the perspective of “Complementary and Alternative” or “Integrative Medicine,” see “EPISTEMOLOGY AND CHINESE MEDICINE: COMMENTARY AND ELABORATION ON TWO ARTICLES.”

REFERENCES & NOTES:

[1] Djulbegovic B., et al, “Epistemologic inquiries in evidence-based medicine,” Cancer Control, 2009 Apr;16(2):158-168

http://www.ncbi.nlm.nih.gov/pubmed/19337202

http://europepmc.org/abstract/MED/19337202

http://www.moffitt.org/CCJRoot/v16n2/pdf/158.pdf

Note: This article represents the views of arguably the founding proponents of EBM—see addendum under the heading “Competing Interests”: ” Dr Guyatt coined the term “evidence-based medicine” and has been intimately involved in its development ever since. Dr Djulbegovic has devoted a better part of his career to the issues of evidence and decision-making. The authors hope they continue to be open-minded to the topic explored in this paper and that their presentation is fair, balanced, and respectful of opposing views.” [1, p. 167]]

[2]  Ashcroft, R.E., “Current epistemological problems in evidence based medicine,” J Med Ethics 2004;30:131–135

http://jme.bmj.com/content/30/2/131.full

http://jme.bmj.com/content/30/2/131.full.pdf+html

[3]  Sehon S.R., & Stanley, D.E., “A philosophical analysis of the evidence-based medicine debate,” BMC Health Serv Res. 2003 Jul 21;3(1):14

http://www.biomedcentral.com/1472-6963/3/14

http://www.biomedcentral.com/content/pdf/1472-6963-3-14.pdf

[4]  Sestini P., “Epistemology and ethics of evidence-based medicine: putting goal-setting in the right place,” J Eval Clin Pract. 2010 Apr;16(2):301-5

http://www.ncbi.nlm.nih.gov/pubmed/20367852

[5]  Goldenberg MJ. “From Popperian science to normal science. Commentary on Sestini (2009) ‘Epistemology and ethics of evidence-based medicine,'” J Eval Clin Pract. 2010 Apr;16(2):306-9

http://www.ncbi.nlm.nih.gov/pubmed/20367853

http://www.uoguelph.ca/~mgolden/JECP_PopperianScienceCommentary.pdf

[6] Couto J.S., “Evidence-based medicine: a Kuhnian perspective of a transvestite non-theory,” J Eval Clin Pract. 1998 Nov;4(4):267-75

http://www.ncbi.nlm.nih.gov/pubmed/9927237

[7] Shahar E. “A Popperian perspective of the term ‘evidence-based medicine,'” J Eval Clin Pract. 1997 Apr;3(2):109-16.

[8] Marshall T., “Scientific knowledge in medicine: a new clinical epistemology?” J Eval Clin Pract. 1997 Apr;3(2):133-8.
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2753.1997.00075.x/abstract

http://www.ncbi.nlm.nih.gov/pubmed/11990882

[9] Harari E., “Whose evidence? Lessons from the philosophy of science and the epistemology of medicine,” Aust N Z J Psychiatry. 2001 Dec;35(6):724-30.

http://anp.sagepub.com/content/35/6/724.short

http://www.ncbi.nlm.nih.gov/pubmed/11990882

[10] Marshall T.”Scientific knowledge in medicine: a new clinical epistemology?” J Eval Clin Pract. 1997 Apr;3(2):133-8.

http://www.ncbi.nlm.nih.gov/pubmed/9276588
http://philpapers.org/rec/MARSKI

[11] Goodman, N.W., “Evidence-Based Medicine Needs Proper Critical Review,” Letter to the Editor, Anesthesia & Analgesia: December 2002 – Volume 95 – Issue 6 – p 1817

http://journals.lww.com/anesthesia-analgesia/Fulltext/2002/12000/Evidence_Based_Medicine_Needs_Proper_Critical.65.aspx

[12] Dougherty, E.R., “On the Epistemological Crisis in Genomics,” Current Genomics, 2008, 9, 69-79

http://www.ncbi.nlm.nih.gov/pubmed/19440447[32]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674806/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674806/pdf/CG-9-69.pdf

[13] Dougherty, E.R., & Bittner, M.L., “Epistemology of the Cell: A Systems Perspective on Biological Knowledge,” IEEE Press, Wiley & Sons, 2011

[14] Bittner, M.L., & Dougherty, E.R.,”Newton, Laplace, and The Epistemology of Systems Biology,” Cancer Inform. 2012; 11: 185–190.

http://www.ncbi.nlm.nih.gov/pubmed/23170064

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493142/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493142/pdf/cin-11-2012-185.pdf

[15] Dougherty, E.R., & Shmulevich, I., “On the limitations of biological knowledge,” Curr Genomics. Nov 2012; 13(7): 574–587

http://www.ncbi.nlm.nih.gov/pubmed/23633917

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468890/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468890/pdf/CG-13-574.pdf

[16] Edward R. Dougherty, E.R., “Translational Science: Epistemology and the Investigative Process,” Current Genomics. 2009 Apr;10(2):102-9

http://www.ncbi.nlm.nih.gov/pubmed/19794882

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699826/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699826/pdf/CG-10-102.pdf

[17] Dougherty, E.R., & Bittner, M.L., “Causality, Randomness, Intelligibility, and the Epistemology of the Cell,” Curr Genomics. 2010 June; 11(4): 221–237–link at:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699826/

[18] Edward R Dougherty, E.R., et al, “The Illusion of Distribution-Free Small-Sample Classification in Genomics, Curr Genomics,” 2011 August; 12(5): 333–341,
http://www.ncbi.nlm.nih.gov/pubmed/22294876

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145263/

http://www.ee.tamu.edu/~ulisses/public/Dougherty_CG_2011_preprint.pdf

http://www.researchgate.net/publication/221796067_The_illusion_of_distribution-free_small-sample_classification_in_genomics/file/9fcfd50f83ff70687b.pdf

[19] Mehta, T., et al, “Towards sound epistemological foundations of
statistical methods for high-dimensional biology,” Nat. Genet. 2004 Sep;36(9):943-7

http://www.ncbi.nlm.nih.gov/pubmed/15340433

http://www.soph.uab.edu/statgenetics/research/epistemology.pdf

[20] Boogerd et al, “Systems Biology: Philosophical Foundations,” Elsevier, 2007

[21]  Boorgerd, F.C., et al, Chap. 1: “Towards Philosophical Foundations of Systems Biology: Introduction,” in ibid., pp. 3-19

[22] Hoffemeyer, J., “A Legacy for Living Systems: Gregory Bateson as Precursor to Biosemiotics,” Springer, 2008

[23] Barbieri, M., “The Organic Codes: An Introduction to Semantic Biology,” Cambridge Univ. Press, 2003

[24] Rosenblueth, A., et al, “Behavior, Purpose and Teleology,” Philosophy of Science, 10(1943), S. 18–24

[25]  Schrodinger, I., “What is Life” Cambridge Univ. Press, 1944; reprinted in “What is Life? Mind and Matter,” Cambridge Univ. Press 1967

[26] Kelso, J.A.S., “Dynamic Patterns: The Self-Organization of Brain and Behavior,” MIT Press 1995

[27] Kelso, J.A.S., & Engstrom, D.A., “The Complementary Nature,” MIT Press, 2006.

[28] Additional referenecs to Kelso’s work:

A useful account of basic principles and early work (Haken-Kelso-Bunz Model) can be found at::

http://www.scholarpedia.org/article/Haken-kelso-bunz_model

Basic Neuroscience article  “Cortical Coordination Dynamics and Cognition” (“Box I” gives basic summary of coordination dynamics & “metastability” is discussed)—links at:

http://119.93.223.179/ScienceDirect/Cognitive%20Sciences/05-01/sdarticle_010.pdf

and

http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.11.318&rep=rep1&type=pdf

Also see

Kelso, J.A.S., & Tognoli1, E., “Toward a Complementary Neuroscience: Metastable Coordination Dynamics of the Brain,” in Kozma, R., & Perlovsky, L., eds., “Neurodynamics of Higher-level Cognition and Consciousness,” Springer, Heidelberg, 2007—links at:
http://adsabs.harvard.edu/abs/2009dcnf.book..103K


http://www.ccs.fau.edu/~tognoli/BrainDyn/index_files/ComplementaryNeuroscience.pdf

[29] West, B.J., Chap. 7, “Disease as Loss of Complexity,,” in  West B.J., “Where Medicine Went Wrong: Rediscovering the Path to Complexity,” World Scientific Publ. Co., 2006,  pp.283-314

[30] Goldberger, A.L., et al, “Fractal dynamics in physiology: Alterations with disease and aging,” PNAS, February 19, 2002 vol. 99 no. Suppl 1 2466-2472—link at:
http://www.pnas.org/content/99/suppl_1/2466.full
http://www.pnas.org/content/99/suppl_1/2466.full.pdf+html

[31]  Sungchul Ji,Semiotics of Life: A Unified Theory of Molecular Machines, Cells, the Mind, Peircean Signs, and the Universe based on the Principle of Information Energy Complementarity,” 2003

http://www.conformon.net/wp-content/uploads/2012/12/SOLManuscriptsubmitted_final_downloaded_from_Taragona_09032011_modified_07282012.pdf

[32] Topol, E., Chapter 5: “Biology: Sequencing the Genome,” in Toplol, E., “The Creative Destruction of Medicine: How the Digital Revolution Will Create better health Care,” Basic Books, 2012