Plamen, Pedro --
It seems to me that perhaps Medicine should not look to mathematics for
support or underpinning so much as to SEMIOTICS (that is, Peircean
semiotics, being worked today as biosemiotics). Biosemiotics is, in the
verbal conceptual realm, almost as complex and messy as medicine, and so
the two might be matched up fruitfully!
STAN
On Tue, May 17, 2016 at 9:03 AM, Dr. Plamen L. Simeonov <
plamen.l.simeo...@gmail.com> wrote:
> Daer Pedro,
>
> thank you for your entertaining way of presenting my Sisyphus theme about
> medicine in a nutshell, which was mostly enjoyable to read. Actually, you
> are right, medicine is "messy", which qualifies it more like a liberal art
> discipline rather than science, full of workshop type of hustle and bustle,
> ad hoc insights of mystic adepts followed by faithful scholars and mixed
> with cutting edge technology wherever possible (in the Western world). It
> appears that every effort to organize it in the manner we know in
> mathematics and physics is doomed to failure. I realise that the subject's
> depth reflected in my presentation is indeed overwhelming. Yet, it was not
> my intention to put a Sisyphus rock upon this forum. Thank you for your and
> Koichiro's simplified pedestrian analysis of the theme. We can go with thes
> rephrased set of questions further.
>
>
> On Tue, May 17, 2016 at 12:51 PM, Pedro C. Marijuan <
> pcmarijuan.i...@aragon.es> wrote:
>
>> Dear Plamen,
>>
>> Thanks for the synthetic attempt. You have put together pretty complex
>> strands of thought that become too demanding for a general response. I will
>> concentrate in a few points.
>>
>> What is Medicine? In what extent is it amenable to "integration"? Is
>> reductionism an anathema in medicine? Can we regularly ascend from cellular
>> info flows to organs/systems, and to healthy individuals/environments?
>>
>>
> These are good general questions, but I'd rather wish to focus on one
> specific problem, e.g. the one of the metastatic melanoma that Koichiro
> addressed in his example and try to "dissect" it as in the article in his
> example. It is clear to me that I cannot focus on one single thing and
> brainstorm on it all the time. But the idea behind this concluding workshop
> was to be less philosophical and more practical in trying to investigate if
> we can reshape medicine as an extension of biology. After all, huge amounts
> of money are given for research here, more than in any other field, as far
> as I know. Are these investments justifyable in the way this "engineering
> science" is performing today? Is there anything that could make this
> discipline more predictable, at least at the curruculum level?
>
>
>> The history of Medicine shows messiness in the highest degree. To note
>> that it was not included in the Trivium/Quadrivium medieval scheme of
>> knowledge, and was only accepted within the "mechanical arts" after Hugh of
>> St. Victor compilation (XIII Century), many decades after the first
>> Faculties of Medicine were created in Italy. Why medicine is so messy? Just
>> go the wiki pages on the topic: hundreds of subspecialties are listed, and
>> under all those terms we imply all the internal and external ("natural")
>> phenomena that can derail and put out of track the advancement of a life
>> cycle. Each one of those specialties has to arrange its own world of
>> knowledge, with lots of analytical and synthetic avenues not amenable to
>> neat overall schemes and to formal approaches except in some reduced
>> pockets. Successful reductionist strategies and analytical techniques are
>> piled up with holistic views, and reams of tacit knowledge (indeed medicine
>> is a very stratified small world of "lords", "masters", "disciples",
>> "servants", and "beginners").
>>
>
> This is all true. But it is also true that medicine has been always very
> important for us human beings.
>
>
>>
>> So, like in engineering, one has to be suspicious of far reaching
>> implications for the term "integrative". Not necessarily in this case with
>> the "3φ" connotation.
>>
>
> Indeed, there coud be a "3φ", a "4φ", or a "3φ+ 1ψ", ... etc. Greek
> alphabet built polynomial connotations encoded in this prefix. The question
> is wether we can use such kind of combination from the known natural
> science disciplines and extend them by some humanitarian fields in order to
> address key issues in an organised and diligent manner in medicine. We know
> well that there are both serios conflicts between some branches and efforts
> to reconcile them. The prefix I used was to make clear that we are asking
> for a novel kind of integration, if possible. Yet this prefix definition
> should not be considered "fixed" once for ever.
>
> But the strong reliance on criticality could be subject to scrutiny. Quite
>> many cellular / biomolecular phenomena do not especially rely on
>> criticality --perhaps the most essential ones, related to "codes", genomic
>> maintenance, protein synthesis, protein degradation, signaling, apoptosis,
>> etc. Why the integrative strategy should rely on a term that
>> notwithstanding strong physical grounds, has relatively thin explanatory
>> capability in the biological?
>>
>
> Criticality is a phenomenon that holds both for living and non-living
> matter. This is something that "matters". Of course, one could take
> "autopoiesis" instead, which is also a good choice. I am not sure how far
> we can go with this this "criticality" bus. I had to start somewhere my
> talk, and I made this choice to facilitate the transition to medicine. If
> anyone has a better suggestion, I do not mind.
>
>
>> It is a long story of looking for responses "where the physical/math
>> light is" and not where the biol. problems are.
>>
>>
> I agree. This is the real issue. How can ""3φ", "4φ", or "3φ+ 1ψ + µ "
> help us is the question.
>
> My view, I can be wrong but I have worked considerably on the matter, is
>> that cellular signaling, the crisscrossing of info flows that provide the
>> singular intelligence and adaptability of organisms, is not well
>> articulated yet. Neither in evo-devo, nor in physiology, medicine and
>> health. In this regard all the present parlance on information processing
>> that accompanies the tremendous technological info-tech revolution does not
>> represent a help, maybe the opposite.
>>
>
> Unfortunately, you appear to be right. I am also not convinced that Big
> Data is blessing rather than a curse.
>
>
>> The deep info problems are taken as already solved and articulated
>> synthesis are undertaken as mere agglutinations. Maybe the problem is too
>> deeply complex, and medicine is as always too messy.
>>
>
> The question we could try to answer here is: can we do something to
> disentangle the spaghetti dish of medicine?
>
>>
>> Sorry if seemingly I have joined the "Cassandra" club!
>>
>
> I don't think so. Yours are fair concerns.
>
> Best,
>
> Plamen
>
>
>
>> Best--Pedro
>>
>>
>>
>>
>> El 14/05/2016 a las 9:49, Dr. Plamen L. Simeonov escribió:
>>
>> Dear Colleagues,
>>
>>
>>
>> My contribution will finalize the discussion on phenomenology in the
>> domains of biology, mathematics, cyber/biosemiotics and physics by the
>> previous speakers (Maxine, Lou, Sœren and Alex) with a “challenging topic”
>> in *3φ integrative medicine*. *You may wish to skip the small font text
>> notes following each underscored phrase like the one below.*
>>
>>
>>
>> *Note 1:* Although this term is often used as synonym for holistic
>> healing (s. ref. list A), its meaning in this context with the prefix 3φ
>> goes much “deeper” into the disciplines’ integration leaving no room for
>> speculations by mainstream scientists. The concept is a linguistic choice
>> of mine for the intended merge of the complexity sciences *ph*ysics and
>> *ph*ysiology with *ph*enomenology for application in modern medicine
>> along the line of integral biomathics (s. ref. list B).
>>
>>
>>
>> It is rooted in the last presentation of Alex Hankey, since it naturally
>> provides the link from physics to physiology and medicine, and thus to an
>> anthropocentric domain implying a leading part of phenomenological studies.
>> To begin, I compiled a précis of Alex’ thesis about self-organized
>> criticality (s. ref. list C) from his paper “A New Approach to Biology and
>> Medicine” -- the download link to it was distributed in a previous email of
>> him -- and extended it with my reflections including some questions I hope
>> you will resonate on.
>>
>>
>> I am curious of your opinion about how to apply the scientific method,
>> and in particular mathematics and information science, to study illness and
>> recovery as complex phenomena.
>>
>>
>>
>> *Alex Hankey: self-organized criticality and regulation in living systems*
>>
>>
>>
>> *There is a continuous growth and change at the end of a phase transition
>> in an organism, i.e. at its critical point, which is the end point of phase
>> equilibrium.*
>>
>>
>>
>> *Both endo and exo, genetics and epigenetics are important for life.*
>>
>>
>>
>> *Self-organized criticality* is a characteristic state of a system at
>> its critical point generated by self-organization during a long transient
>> period at the complexity edge between order/stability/predictability and
>> disorder/chaos/unpredictability.
>>
>>
>>
>> *Regulation of growth, form and function as a balance between health and
>> illness.* The role of regulation and homeostasis in maintaining the
>> structure and function of living systems is critical. Every deviation from
>> a regulated state of being leads to imbalances, failures and subsystem
>> dysfunction that is usually transitory, but could also become
>> life-threatening, if the organism cannot find a way to restore quickly to a
>> balanced, healthy state. Living beings are robust and fault-tolerant with
>> respect to hazards; they possess multiple alternative pathways for
>> supplying and maintaining their existential functions. However, some state
>> transitions in response to severe harms can become practically
>> irreversible, because of the deep evolutionary interlocking between the
>> participating entities and processes. Sometimes the normal functioning of
>> the organism cannot be easily restored by its natural repair processes,
>> especially when adversities reoccur frequently, and the organism fails ill.
>>
>>
>>
>> *Synchronicity of action and information between the building blocks of a
>> living system.* There is a need for every physiological function to be
>> correctly coordinated with all other “peer” functions. Information flows
>> within a living system interconnect all physiological functions and organs
>> at multiple levels into a single mesh of regulatory interconnections.
>> Multiple feedback-control loops enable the cross-functional interlocking of
>> both healthy and ill state changes of the organism.
>> Adjacent/peripheral/secondary homeostasis processes act as fine-tuning
>> catalyzers of substrate ratios and process rates exchanged within the
>> living system. Imbalances of these quantities lead to excess/blockage or
>> scarcity/draining of essential nourishment and information exchange
>> pathways.
>>
>>
>>
>> *Regulation at criticality* not only fine-tunes a process, it *optimizes*
>> it for survival: with respect to a given generation’s available
>> possibilities in the light of the past generations’ possibilities. To
>> survive an organism or a species needs to develop optimal
>> *response-ability* to environmental distress.
>>
>>
>> *New ecological definition of life according to Hankey: self-regulating,
>> self-reproducing systems that maximize efficiency of function to maximize
>> competitiveness in their chosen environment. *
>>
>>
>>
>> *Summary: Elements of self-organized criticality*
>>
>>
>>
>> 1. Criticality
>> 2. Edge of the chaos
>> 3. Self-organized criticality
>> 4. 1/f fractal patterns of response
>>
>>
>>
>> *… and beyond*
>>
>>
>>
>> I wish to add a 5th aspect to this definition from the perspective of
>> integral biomathics:
>>
>>
>>
>> 1. *Phenomenology*
>>
>>
>>
>> The latter is a largely studied matter in contemporary medicine (s. ref.
>> list D), at least at the macro, interpersonal *level*.
>>
>>
>>
>> *Note 2*: A level refers to the compositional hierarchy defining levels
>> by scale.
>>
>>
>>
>> *The key question in such a “deep holistic” physically-phenomenological
>> physiology (*3φ*)** is how to define or comprehend (self-organized)
>> criticality operationally within the unifying framework of biomathematics
>> and biocomputation*. Indeed, a single temporary imbalance within a
>> living system regarded as disease involves multiple agents, perspectives
>> and interpretations at all levels altogether, moreover *simultaneously*.
>>
>>
>>
>> *Note 3*: Simultaneously at different levels involves very different
>> sized 'moments' at the different scales.
>>
>>
>>
>> So, how should we approach and take into account the other levels/scales
>> in order to derive a reliable diagnosis and *therapy*?
>>
>>
>>
>> *Note 4*: The notion of “subject” becomes plural (“subjects”) as
>> superposition of quantum states to survive the integration of the multiple
>> first-person subjective descriptions and the standard third-person
>> objective one.
>>
>>
>>
>> Until now criticality has been *non-phenomenological*.
>>
>>
>> *Note 5:* In their 2012 paper “No entailing laws, but enablement in the
>> evolution of the biosphere” Longo, Montévil and Kauffman claim that
>> biological evolution “marks the end of a physics world view of law entailed
>> dynamics” ( <http://arxiv.org/abs/1201.2069>
>> http://arxiv.org/abs/1201.2069). They argue that the evolutionary phase
>> space or space of possibilities constituted of interactions between
>> organisms, biological niches and ecosystems is “ever changing,
>> intrinsically indeterminate and even (mathematically) unprestatable”.Hence,
>> the authors' claim that it is impossible to know “ahead of time the
>> 'niches' which constitute the boundary conditions on selection” in order to
>> formulate laws of motion for evolution. They call this effect “radical
>> emergence”, from life to life. Yet this applies to abiotic dissipative
>> structures like tornadoes as well. Living beings are not radically
>> different in this respect. In their study of biological evolution, Longo
>> and colleagues carried close comparisons with physics. They investigated
>> the mathematical constructions of phase spaces and the role of symmetries
>> as invariant preserving transformations, and introduced the notion of
>> “enablement” to restrict causal analyses to Batesonian differential cases
>> (1972: “the difference that makes a difference”). The authors have shown
>> that mutations or other “causal differences” at the core of evolution
>> enable the establishment of non-conservation principles, in contrast to
>> physical dynamics, which is largely based on conservation principles as
>> symmetries. Their new notion of “extended criticality” also helps to
>> understand the distinctiveness of the living state of matter when compared
>> to the non-animal one. However, their approach to both physics and biology
>> is also *non-phenomenological*. The possibility for endo states that can
>> trigger the “(genetic/epigenetic) switches of mutation” has not been
>> examined in their model. This is intended to be different in 3φ*
>> integrative medicine*.
>>
>> If we split a human body into macro (patient), mezzo (systems) and micro
>> levels (cells) three distinct questions regarding phenomenology arise: i)
>> *how* these levels pervade into each other with larger scale providing
>> context (boundary conditions) and lowest scale providing raw materials for
>> middle scale to function, monitor and control vital processes, ii)
>> *who/which* are the agents taking care for this to happen spontaneously,
>> and iii) *what kind and role* plays information in the context of i) and
>> ii). After all what we are concerned about is modeling the agency of the
>> systems in the mezzo level.
>>
>>
>>
>> Where should we go from here?
>>
>>
>> In particular, I am interested to know *what kind of
>> scientific-phenomenological methodology can be developed and applied for
>> investigating *the following three major groups of ailments:
>>
>>
>>
>> 1. *oncological diseases* with a particular focus on spatial and
>> temporal heterogeneity both in terms of flawed histological structures and
>> biochemical reactions;
>>
>>
>> 1. *neuro-degenerative disorders* such as vascular dementia,
>> Parkinson and Alzheimer diseases:
>>
>>
>> 1. *altered organ and physiological system failures* such as the
>> Multiple Organ Dysfunction Syndrome (MODS), cardiovascular and autoimmune
>> diseases.
>>
>>
>>
>> In the first group, the *extreme diversity of cancer tissue structures
>> and circulating tumor cells (CTC) concentrations over both spatial and
>> temporal scales* makes the reliable classification, diagnosis,
>> model/hypothesis generation, forecast and treatment of individual patients
>> very difficult. This is a real challenge for modern pathology. Another
>> problem is that pathologists are actually dealing with random tissue and
>> blood samples over irregular periods, which hinder the exact 3D
>> histological reconstruction of the tumor formations and tracing their
>> development over time and space. Using additional means such as diagnostic
>> sonography, CT, MRT and PET images do not improve sufficiently the
>> hypotheses about the individual cancer morphology and development. All this
>> makes tumor classification and diagnosis, even when analyzing
>> high-resolution digital images from biopsy slices by means of virtual
>> microscopy, very difficult and often a guesswork also for experts. The
>> recent advances in high-performance medical scanning and automation
>> systems, computerized visualization and graphical modeling tools, as well
>> the collection of huge amounts of anonymous patient data in specialized
>> medical databases make the impression that the solution of these problems
>> is only a question of more automation, performance, investment and time.
>> However, many pathologists begin to realize a third problem, namely that
>> *tumors
>> appear to be unique in their histological structure and development*,
>> related to the personal history and the overall state of health of the
>> individual patients. This argument reveals the need for developing a more
>> personalized and differentiated medicine that goes over scales without
>> becoming purely symptomatic, causality-driven and reductionistic.
>>
>>
>>
>> Recent research in the other two fields leads to the same conclusion.
>> Therefore, I think that we may be able to develop and test hypotheses about
>> emergence and development of deficiency and illness that will lead to
>> individual therapies in *3φ* integrative medicine. Your ideas regarding
>> this assumption are very welcome.
>>
>>
>>
>> Some interesting questions bridging the previous discussion sessions to
>> this one are:
>>
>>
>>
>> - Why does a human embryo repeat the evolutionary history of its
>> species when going through its development stages? Is it because it is more
>> secure to project and set up the execution of a future life plan by tracing
>> and bodily memorizing a series of evolutionary encoded (successful) “locks”
>> through equilibrium states at the edge of criticality?
>>
>>
>>
>> - Which is the *vital *role of recursion and repetition of life
>> processes including their material and information exchange flows in the
>> criticality driven self-regulation for recovery from imbalances and the
>> reversibility and healing of diseases? How can we effectively model such
>> processes?
>>
>> - Do we make difference between a physicist’s time and a
>> biologist’s time in complex living systems?
>>
>>
>>
>> * I look forward to your feedback and notes on the subject.*
>>
>>
>>
>> *References:*
>>
>> *A. **Integrative Medicine*
>>
>> Integrative Medicine: https://en.wikipedia.org/wiki/Integrative_medicine
>> <http://www.wikiwand.com/en/Integrative_medicine>
>>
>> What Is Integrative Medicine?:
>>
>>
>> <http://www.webmd.com/a-to-z-guides/features/alternative-medicine-integrative-medicine>
>> http://www.webmd.com/a-to-z-guides/features/alternative-medicine-integrative-medicine
>>
>>
>>
>> Integrative Medicine Research:
>>
>> http://www.journals.elsevier.com/integrative-medicine-research/
>>
>>
>>
>> Advances in Integrative Medicine
>>
>> http://www.journals.elsevier.com/advances-in-integrative-medicine
>>
>>
>>
>> *B. **Integral Biomathics*
>>
>> Integral Biomathics:
>>
>> <http://www.wikiwand.com/en/Integral_Biomathics>
>> https://en.wikipedia.org/wiki/Integral_Biomathics
>>
>> Integral Biomathics: A Post-Newtonian View into the Logos of Bios
>>
>> <https://arxiv.org/ftp/cs/papers/0703/0703002.pdf>
>> https://arxiv.org/ftp/cs/papers/0703/0703002.pdf
>>
>> On Some Recent Insights in Integral Biomathics:
>>
>> <https://arxiv.org/ftp/arxiv/papers/1306/1306.2843.pdf>
>> https://arxiv.org/ftp/arxiv/papers/1306/1306.2843.pdf.
>>
>> Integral Biomathics Reloaded: 2015 (free access until July 19th 2016):
>>
>> <http://www.sciencedirect.com/science/article/pii/S0079610715001509>
>> http://www.sciencedirect.com/science/article/pii/S0079610715001509
>>
>>
>>
>> *C. **Self-organized criticality**:*
>>
>>
>>
>> Self-organized criticality:
>>
>> <http://www.wikiwand.com/en/Self-organized_criticality>
>> https://en.wikipedia.org/wiki/Self-organized_criticality
>>
>>
>>
>> Self-organized criticality (SOC):
>>
>> <http://www.johnboccio.com/courses/SOC26/15-SOC.pdf>
>> http://www.johnboccio.com/courses/SOC26/15-SOC.pdf
>>
>>
>>
>> Self-organized criticality:
>>
>>
>> <http://web.mit.edu/8.334/www/grades/projects/projects12/V.%20A.%20Golyk.pdf>
>> http://web.mit.edu/8.334/www/grades/projects/projects12/V.%20A.%20Golyk.pdf
>>
>>
>>
>> Self-organized criticality – what it is and what it isn’t
>>
>>
>> <http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.96.8017&rep=rep1&type=pdf>
>> http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.96.8017&rep=rep1&type=pdf.
>>
>>
>>
>>
>> *D. **Phenomenology in Medicine*
>>
>>
>>
>> The meaning of illness: a phenomenological approach to the
>> physician/patient relationship:
>> https://baylor-ir.tdl.org/baylor-ir/handle/2104/8286 ;
>> http://hdl.handle.net/2104/8286.
>>
>>
>>
>> Body Matters: A Phenomenology of Sickness, Disease, and Illness:
>>
>> <http://philpapers.org/rec/AHOBMA>http://philpapers.org/rec/AHOBMA.
>>
>>
>>
>> Suffering Transfigured: Phenomenological Personalism In the
>> Doctor-Patient Relationship:
>> http://elischolar.library.yale.edu/cgi/viewcontent.cgi?article=1658&context=ymtdl
>> .
>>
>> The challenge of neuroscience: Psychiatry and phenomenology today:
>> <https://www.klinikum.uni-heidelberg.de/fileadmin/zpm/psychatrie/fuchs/Challenge_of_Neuroscience.pdf>
>> https://www.klinikum.uni-heidelberg.de/fileadmin/zpm/psychatrie/fuchs/Challenge_of_Neuroscience.pdf
>> .
>>
>>
>>
>> Rediscovering Psychopathology: The Epistemology and Phenomenology of the
>> Psychiatric Object:
>> http://cfs.ku.dk/staff/zahavi-publications/Rediscovering_Psychopathology.pdf
>> .
>>
>> PHENOMENOLOGY IN PSYCHIATRY:
>> http://www.wpanet.org/uploads/Sections/Philosopy_and_Humanities/Phenomenology-in-Psychiatry.pdf.
>>
>>
>> *Plamen*
>> ____________________________________________________________
>> 2015 JPBMB Special Issue on Integral Biomathics: Life Sciences,
>> Mathematics and Phenomenological Philosophy
>> <http://www.sciencedirect.com/science/journal/00796107/119/3>
>> (note: free access to all articles until July 19th, 2016)
>>
>> 2013 JPBMB Special Issue on Integral Biomathics: Can Biology Create a
>> Profoundly New Mathematics and Computation?
>> <http://www.sciencedirect.com/science/journal/00796107/113/1>
>>
>> 2012 Integral Biomathics: Tracing the Road to Reality
>> <http://www.springer.com/engineering/computational+intelligence+and+complexity/book/978-3-642-28110-5>
>>
>> 2011 INtegral BIOmathics Support Action (INBIOSA) <http://www.inbiosa.eu>
>>
>> ____________________________________________________________
>>
>>
>>
>> --
>> -------------------------------------------------
>> Pedro C. Marijuán
>> Grupo de Bioinformación / Bioinformation Group
>> Instituto Aragonés de Ciencias de la Salud
>> Centro de Investigación Biomédica de Aragón (CIBA)
>> Avda. San Juan Bosco, 13, planta X
>> 50009 Zaragoza, Spain
>> Tfno. +34 976 71 3526 (&
>> 6818)pcmarijuan.iacs@aragon.eshttp://sites.google.com/site/pedrocmarijuan/
>> -------------------------------------------------
>>
>>
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