Dear Pedro, Francesco, Bob, Joe and All,

we are approaching the end of this session (10.6) and I am going to make
some concluding remarks on it. This does not excludes the chance for
 submitting contributions until the end, but we have to follow our plan.
Your thoughts expanded significantly the scope of the  topic I began this
final chapter on medicine and phenomenology which was supposed to have more
applied character. As Pedro and I mentioned earlier, the focused base SOC
from the previous section ion physics is only one of the possible
underpinning theories that can be “adducted” (to use a medical term) in
solving modelling problems in medicine. Indeed, all themes in the previous
chapters on biology, mathematics, biosemiotics and physics were
representative samples of a study we made together reflecting on the
relation between natural sciences, mathematics and phenomenology. In a
private communication Joe Brenner suggested that the prefix “self” in SOC
should be opened up to allow for external processes to participate. This is
an interesting moment I wish to draw your attention to. I agreed with him
and noted that what we actually need is a kind of “membrane-like open close
*d*ness” of the processes to consider. I was really happy with this
expansion of the base which Alex may have implied in his chapter, but did
not came explicitly. Joe accepted this argument and noted that this kind of
models can be addressed by his constructive Logic in Reality (LIR) as a
novel perspective going beyond formal logical reasoning, ontology and
metaphysics that can be “basically seen in terms of change and stability,
being and becoming” (introduction to his 2008 Springer book). I have not
read this book yet, but I am certain it is a gem deserving our attention.
However, what is possibly missed there, and also in our agreed
“membrane-like open closedness” is the first-person phenomenological
perspective of Maxine Sheets-Johnstone, Shaun Gallagher, Steven M. Rosen
and others made explicit in our 2015 special issue. We are still too inert
in respect, judging by the reflections this forum. In de-fining such terms
we actually limit their application; Francesco, please correct me if I am
wrong in my Latin/Italian interpretation. This is what science is used to.
But in phenomenology we have this “mixture” between internal and external
perspectives, object and subject that perplex entirely our ontological
categories in science. So, how about such a "logic in a phenomenological
reality”? I think there is still a long way to go until we truly
internalise the phenomenological perspective in our scientific models. The
kind of reasoning we need should be flexible, adaptive, integrative and
recombinant, metaphorically following a scientific methodology close to the
molecular recognition principle of Emil Fischer and his successors that
Pedro addressed in one of his previous postings. This is indeed the other
kind of thinking that led Richard Feynman to the idea quantum computing.
Correct, the physics is embedded deeply into the architectural and
functional constraints of the living system. But living systems have
“personalities”, insight-out identities as such at all scales which enforce
the perpetuation of life. Perhaps we can try to better understanding this
by investigating the “first phenomenon”, the cell, which Howard Pattee
addressed in his paper in the 2015 JPBMB special issue. Pedro and his team
also reflected this in their contribution there. Interestingly that these
ideas are conform with those of Brian J. Ford on the intelligence of
the individual cell. This is a remarkable field which can be only enriched
by such metaphorical and poetic stimuli (necessary in science according to
Stu Kauffman) as those of Francesco from economy who regards stem cells as
a kind biological currency. There is pretty much to be discovered and
creatively recombined in our postings.

One last remark regarding the cancer modelling problem, which came from a
colleague, I recently met at a congress in Berlin. I am publishing his
comment in full length, assuming his permission, because I think it is
important to know about this phenomenon and about how far we can go when
trying to address such challenging issues in interdisciplinary circles like
the FIS forum.



   Tumor heterogeneity usually refers to divergent genotypes within cells
of one tumor.  But I think you are interested in tumors of different
patients, and what the shared characteristics are, that offset this from
normal tissues.  This is not a cancer discussion, but rather a precancer
definition.  We had a workshop about this several years ago, which I have
attached.  It took two days of interactive discussions between a dozen
experts to get this far.

    One of the barriers we are facing here is cultural - the unfiltered and
voluminous discussion format of e-communication favored by physical
scientists is uncommon amongst biologists.  There is just too much to say,
and the thread for biologists is always data.  This is why it is so
satisfying to meet in the real world, as we did in Berlin.

George L. Mutter, MD

Professor of Pathology, Harvard Medical School

Elsevier Cancer Detection and Prevention 30 (2006) 387–394


Precancer: A conceptual working definition

Results of a Consensus Conference

Jules J. Berman MDa, Jorge Albores-Saavedra MDb,*, David Bostwick MDc,
Ronald DeLellis MDd, John Eble MDe, Stanley R. Hamilton MDf, Ralph H.
Hruban MDg, George L. Mutter MD, PhDh, David Page MDi, Thomas Rohan PhDj,
William Travis MDk, Donald E. Henson MDl

a Cancer Diagnosis Program, National Cancer Institute, NIH, Bethesda, MD,
United States b Department of Pathology, Louisiana State University Health
Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, United
States c Bostwick
Laboratories, Richmond, VA, United States d Department of Pathology, Brown
University, Providence, RI, United States e Department of Pathology,
Indiana School of Medicine, Indianapolis, IN, United States f Divison of
Pathology and Laboratory Medicine, The University of Texas M.D. Anderson
Cancer Center, Houston, TX, United States g Department of Pathology, The
Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Hospital,
Baltimore, MD, United States h Department of Pathology, Brigham and Women’s
Hospital, Boston, MA, United States i Department of Pathology, Vanderbilt
University Medical Center, Nashville, TN, United States j Department of
Epidemiology and Population Health, Albert Einstein College of Medicine,
NY, United States k Department of Pathology, Memorial Sloan Kettering
Cancer Center, New York, NY, United States l The George Washington
University Cancer Institute, Washington, DC, United States

Accepted 1 September 2006

*Abstract *

Background: Precancers are lesions that precede the appearance of invasive
cancers. The successful prevention or treatment of precancers has the
potential to eliminate deaths due to cancer. Methods: A National Cancer
Institute-sponsored Conference on Precancer was convened on November 8–9,
2004, at The George Washington University Medical Center, Washington, DC. A
definition of precancers was developed over 2 days of Conference
discussions. Results: The following five criteria define a precancer: (1)
evidence must exist that the precancer is associated with an increased risk
of cancer; (2) when a precancer progresses to cancer, the resulting cancer
arises from cells within the precancer; (3) a precancer differs from the
normal tissue from which it arises; (4) a precancer differs from the cancer
into which it develops, although it has some, but not all, of the molecular
and phenotypic properties that characterize the cancer; (5) there is a
method by which the precancer can be diagnosed. Conclusions: The Conference
participants developed a general definition for precancers that would
provide a consistent and clinically useful way of distinguishing precancers
from all other types of lesions. It was recognized that many precancerous
lesions may not meet this strict definition, but the group felt it was
necessary to define criteria that will help standardize clinical and
biological studies. Furthermore, a set of defining criteria for putative
precancer lesions will permit pathologists to build a diagnostically useful
taxonomy of precancers based on specified clinical and biological
properties. Precancers thus characterized can be classified into clinically
relevant sub-groups based on shared properties (i.e. biomarkers, oncogenes,
common metabolic pathways, responses to therapy, etc.). Publications that
introduce newly described precancer entities should describe how each of
the five defining criteria apply. This manuscript reviews the proposed
definition of precancers and suggests how pathologists, oncologists and
cancer researchers may determine when these criteria are satisfied. # 2006
International Society for Preventive Oncology. Published by Elsevier Ltd.
All rights reserved.

Keywords: Precancer; Premalignant; In situ carcinoma; Severe dysplasia;
Atypical hyperplasia; Intraepithelial neoplasia; Incipient neoplasia;
Preinvasive; Classification; Definition; Cytologic atypia; Immunosuppression;
Regression; Chronologic precedence; Taxonomy; Criteria

*   Corresponding author. Tel.: +1 318 675 5860; fax: +1 318 675 7662. E-mail
address: (J. Albores-Saavedra).


Indeed, nothing can replace face-to-face meetings in finding a consensus
and devising a strategy to tackle a practical problem.

All the best.


On Thu, Jun 2, 2016 at 8:04 PM, Francesco Rizzo <
> wrote:

> Caro Plamen e cari Tutti,
> circa dieci giorni fa ho composto e inviato un messaggio in-centrato sul
> rapporto antagonista tra riduzionismo (specialismo) e armonia (olismo), ma
> non ha riscosso tanto successo, e non solo perché scrivo in lingua
> italiana. Non ripeto quel che ho già comunicato, ma mi limito a confessare
> che andando avanti negli anni la specializzazione professionale o
> settorializzazione del sapere mi attrae e convince sempre di meno. Da
> economista, invece, divento sempre più consapevole dell'armonia
> (dell'equilibrio e del dis-equilibrio) che domina il mondo.Tutto ciò è
> provato anche dall'ultimo mio libro che è uscito il 1 aprile scorso: "Una
> scienza non può non essere umana, civile, sociale, ECONOMI(C)A,enigmatica,
> nobile, profetica"(Aracne editrice, Roma, 2016).
> Allora in questa circostanza desidero spendere qualche parola sulla terna:
> asimmetria/simmetria, auto-similarità o geometria frattale, legge di
> potenza o sviluppo esponenziale che vale sia per le cellule sane sia per le
> cellule malate. Tuttavia, questa terna vale di più per le cellule malate di
> cancro, il cui sviluppo è molto più intenso ed esponenziale di quello che
> caratterizza le cellule sane. Interessante sarebbe in questa prospettiva
> indagare in modo specifico le cellule staminali, più o meno potenti o
> pluri-potenti, ma non sono un esperto di queste cose. Dico solo che le
> cellule staminali sono una forma di moneta biologica.
> Ragionando per schemi  simmetria e asimmetria si alternano e/o convivono
> contemporaneamente e continuamente. La simmetria si ad-dice ai momenti di
> conservazione e stabilità, l'asimmetria invece caratterizza i momenti di
> rottura o discontinuità che si verificano tra uno stato di simmetria e/o di
> equilibrio e l'altro. Tutta l'attività economica, essendo dinamica,non è
> altro che il passare irreversibile da uno stato di dis-equilibrio
> all'altro. La natura della fisica di tutto ciò che è stato creato o si è
> formato ci fa capire o sapere che se immediatamente dopo il Big Bang non si
> fosse rotta la simmetria tra materia e antimateria, creandosi un'asimmetria
> vitale (solo materia perché l'anti-materia pareche sia sparita), noi e il
> resto non saremmo a questo mondo. Anzi, non ci sarebbe nemmeno il mondo
> stesso. La stessa particella di Dio o il Bosone di Higgs senza la rottura
> della simmetria di gauge non avrebbe interagito con se stessa formandosi la
> massa nè con le altre particelle altrettanto bisognose di massa. Il
> discorso potrebbe continuare con i buchi neri, ma mi fermo qui per questo
> punto.
> L'auto-similarità contrassegna la geometria frattale e la rende
> irregolare, discontinua, disordinata e imprevedibile.
> La legge di potenza o esponenziale vale per i sistemi complessi, non
> lineari e lontani dall'equilibrio.
> Ho il sospetto che oggi le parole di un economista non valgano molto. Ma
> bisogna stare attenti a non confondere la teoria economica, con l'attività
> o la pratica economica e, comunque, non è nè teoria o pratica economica la
> professione dei ladri, dei briganti e dei pirati , ad es. della finanza.La
> chiamano economia, ma è solo ruberia o ladrocinio. Beninteso, la finanza
> speculativa.
> In ogni caso, ormai, posso ben dire di avere scoperto una nuova scienza o
> conoscenza economica, come i miei testi dimostrano, proprio aprendomi alla
> conoscenza delle scienze dell'uomo e della natura.
> Non sono un presuntuoso e so quel che affermo.
> Vi saluto con un grazie e un abbraccio affettuoso a Tutti.
> Francesco.
> 2016-06-02 18:00 GMT+02:00 Pedro C. Marijuan <>:
>> Dear Plamen, Bob, and FIS Colleagues,
>> I respond to ideas previously expressed on the connection of living cells
>> with physics. SOC may be one of the ways, but there are other instances, eg
>> "constructal law", catastrophe theory, tensegrity (at least, all of these
>> are well related to development), and many others... My own bet regarding
>> the centrality and potential extension of the construct is "molecular
>> recognition". Elevating beyond heterogeneity, its conflation with symmetry
>> makes sense on the polymerization and supramolecular strategies of life.
>> Molecular recognition appears as the key element from which the whole
>> biochemical and evolutionary universe is constructed. Like any other
>> chemical reaction, recognition between molecules is based on the “making
>> and breaking of bonds”. This ––and only this–– is what makes possible the
>> mutual recognition and the formation of complexes between biomolecular
>> partners. The big problem with biomolecular recognition instances is that
>> they involve an amazing variety and combinatorics of almost any type of
>> chemical interaction: hydrogen bonds, hydrophobic / hydrophilic forces,
>> dipole forces, van der Waals forces, ionic Coulombian forces, etc. Dozens
>> or even hundreds of weak bonds participate, for instance, in the formation
>> of a protein-protein specific complex. Quite probably, measuring molecular
>> recognition and establishing its crucial parameters and variables can only
>> be realized biologically on a case-by-case basis. At least this is the
>> current trend in most molecular biological and molecular dynamic
>> approaches. But a few "classic" references have provided some interesting
>> insights about molecular-recognition generalities. First, *W. Meggs*
>> about “biological homing”, mainly from a Coulombian “lock and key”
>> combinatory point of view; then *Shu-Kun Lin* about the changes in
>> thermodynamic entropy of mixing derived from molecular similarity changes;
>> and finally *M. Carlton*, with original proposals for measuring the
>> information content of any complex molecular system.
>> Anyhow, the result of the whole organization of molecular recognition
>> instances would remind our artificial computers--is it interesting to
>> connect them "meaningfully" with physics? Yes, the physics is all around,
>> but it is submerged very deep into the architectural and functional
>> constraints of the living system. No royal road, no "camino real" to
>> explain the entirety, a pleiad of disciplines has to be involved. For
>> cancer, or for biomaterial engineering, recombination of multiple
>> disciplines becomes the basic research enterprise of our times. We have to
>> combine the surfing of many disciplines with the occasional fundamental
>> insights (from physics, maths, symmetry, information science, etc.). But
>> neither reductionism, nor wholism, nor phenomenology, nor perspectivism,
>> nor... are going very far making sense of the whole social intelligence
>> caught into action (blind spots included). We made the "artistic" drawing
>> below.
>> Enough for today. Greetings to all, and congratulations to Xueshan for
>> his Magnus Opus! --Pedro
>> *Disciplines involved in modern biomaterial research. The representation
>> is based on the description made by bioengineer **James Kirkpatrick
>> (2009) and also del Moral et al., (2011).*
>> El 02/06/2016 a las 13:20, Pedro C. Marijuan escribió:
>> On Tue, May 31, 2016 at 6:54 PM, Robert E. Ulanowicz < <>
>>> wrote:
>>> > Dear Bob,
>>> >
>>> > thank you for your response. What you said in the core - heterogeneity
>>> -
>>> > resonated with the first suggested example I began this session with:
>>> the
>>> > puzzle of registering the heterogeneity of cancer, both in the
>>> > molecular-biological and histological level, both in space and time. It
>>> > appears that exactly this elusive property of matter, liveness, from
>>> the
>>> > single cell to entire eco-systems, which implies intelligence
>>> throughout
>>> > all scales (as Brian Ford states) is what we still cannot in system(s)
>>> > biology put on the feet of statistical mechanics and classical
>>> > physics.Aren't tumors such intelligent clusters of heterogeneous cell
>>> > computers interacting within internaly secured invasive networks that
>>> > escape our medical enigma code breakers placed in our synthetic drugs
>>> and
>>> > radiation devices? Also such undesired life is not easy to kill.  And
>>> yet
>>> > cancer cannot win the battle unless our own internal systems surrender
>>> and
>>> > become allies of the invador.
>> --
>> -------------------------------------------------
>> 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.es
>> -------------------------------------------------
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