IF THE WHOLE WORLD IS COMPLEX, WHY BOTHER?

1. IF THE WHOLE WORLD IS COMPLEX, WHY BOTHER? D. C. MIKULECKY PROFESSOR OF PHYSIOLOGY VIRGINIA COMMONWEALTH UNIVERSITY http://views.vcu.edu/~mikuleck/

2. WHAT I HOPE TO ACCOMPLISH • PROVIDE A UNIQUE, WORKABLE CONCEPT OF COMPLEXITY • MAKE A CLEAR DISTICTION BETWEEN THE REAL WORLD AND THOSE FORMAL THINGS WE DO TO TRY TO MODEL IT • SHOW HOW THE FORMAL DESCRIPTION OF THE REAL WORLD REDUCES IT TO SIMPLE MECHANISMS • PROVIDE EXAMPLES OF BOTH MECHANISTIC AND RELATIONAL MODELS OF THE WORLD • USE THE DEFINITION OF ORGANISM TO ILLUSTRATE WHAT CAN BE DONE BY STEPPING OUT OF THE TRADITIONAL FRAMEWORK

3. CAN WE DEFINE COMPLEXITY? Complexity is the property of a real world system that is manifest in the inability of any one formalism being adequate to capture all its properties. It requires that we find distinctly different ways of interacting with systems. Distinctly different in the sense that when we make successful models, the formal systems needed to describe each distinct aspect are NOT derivable from each other

4. COMPLEXITY VS COMPLICATION • Von NEUMAN THOUGHT THAT A CRITICAL LEVEL OF “SYSTEM SIZE” WOULD “TRIGGER” THE ONSET OF “COMPLEXITY” (REALLY COMPLICATION) • COMPLEXITY IS MORE A FUNCTION OF SYSTEM QUALITIES RATHER THAN SIZE • COMPLEXITY RESULTS FROM BIFURCATIONS -NOT IN THE DYNAMICS, BUT IN THE DESCRIPTION! • THUS COMPLEX SYSTEMS REQUIRE THAT THEY BE ENCODED INTO MORE THAN ONE FORMAL SYSTEM IN ORDER TO BE MORE COMPLETELY UNDERSTOOD

5. NATURAL VS FORMAL SYSTEMS • THE REAL WORLD IS COMPLEX • WE HAVE TREATED IT FORMALLY AS IF IT WERE SIMPLE • THE RESULT IS THE “DISCOVERY” OF COMPLEXITY, EMERGENCE,ETC. • THE IDEA IS BEST SEEN USING THE MODELING RELATION

6. THE MODELING RELATION: THE ESSENCE OF SCIENCE • ALLOWS US TO ASSIGN MEANING TO THE WORLD AROUND US • A “MODEL” OF OUR THINKING PROCESS • CAUSALITY IN THE NATURAL SYSTEM IS DEALT WITH THROUGH IMPLICATION IN A FORMAL SYSTEM • THERE IS AN ENCODING OF THE NATURAL SYSTEM INTO THE FORMAL SYSTEM AND A DECODING BACK • WHEN IT ALL HANGS TOGETHER WE HAVE A MODEL

7. THE MODELING RELATION: A MODEL OF HOW WE MAKE MODELS ENCODING NATURAL SYSTEM FORMAL SYSTEM CAUSAL EVENT IMPLICATION DECODING FORMAL SYSTEM NATURAL SYSTEM

8. WE HAVE A USEFUL MODEL WHEN AND ARE SATISFACTORY WAYS OF “UNDERSTANDING” THE CHANGE IN THE WORLD “OUT THERE”

9. THE MODELING RELATION: A MODEL OF HOW WE MAKE MODELS ENCODING NATURAL SYSTEM FORMAL SYSTEM CAUSAL EVENT MANIPULATION DECODING FORMAL SYSTEM NATURAL SYSTEM

10. WHAT “TRADITIONAL SCIENCE” DID TO THE MODELING RELATION FORMAL SYSTEM NATURAL SYSTEM MANIPULATION CAUSAL EVENT FORMAL SYSTEM NATURAL SYSTEM

11. WHAT “TRADITIONAL SCIENCE” DID TO THE MODELING RELATION FORMAL SYSTEM NATURAL SYSTEM MANIPULATION FORMAL SYSTEM NATURAL SYSTEM

12. MORE ON THE MODELING RELATION • THE FORMAL SYSTEM DOES NOT INCLUDE INFORMATION ABOUT ENCODING AND/OR DECODING • THEREFORE MODELING WILL ALWAYS BE AN ART • ONLY IN THE NEWTONIAN PARADIGM DOES THE FORMAL SYSTEM BECOME THE NATURAL SYSTEM (ENCODING AND DECODING ARE AUTOMATIC) AND ALL THAT IS LEFT TO DO IS TO MEASURE THINGS

13. SCIENCE REDUCED THE WORLD TO SIMPLE MECHANISMS • THE USUAL SCIENTIFIC PICTURE OF REALITY IS A MECHANISM • DEFICIENT IN CAUSAL RELATIONS • FRAGMENTABLE TO ATOMS AND MOLECULES • NOT “GENERIC” BUT TREATED AS IF THEY WERE

14. COMPLEXITY • REQUIRES A CIRCLE OF IDEAS AND METHODS THAT DEPART RADICALLY FROM THOSE TAKEN AS AXIOMATIC FOR THE PAST 300 YEARS • OUR CURRENT SYSTEMS THEORY, INCLUDING ALL THAT IS TAKEN FROM PHYSICS OR PHYSICAL SCIENCE, DEALS EXCLUSIVELY WITH SIMPLE SYSTEMS OR MECHANISMS • COMPLEX AND SIMPLE SYSTEMS ARE DISJOINT CATEGORIES

15. COMPLEX NO LARGEST MODEL WHOLE MORE THAN SUM OF PARTS CAUSAL RELATIONS RICH AND INTERTWINED GENERIC ANALYTIC  SYNTHETIC NON-FRAGMENTABLE NON-COMPUTABLE REAL WORLD SIMPLE LARGEST MODEL WHOLE IS SUM OF PARTS CAUSAL RELATIONS DISTINCT N0N-GENERIC ANALYTIC = SYNTHETIC FRAGMENTABLE COMPUTABLE FORMAL SYSTEM COMPLEX SYSTEMS VS SIMPLE MECHANISMS

16. GENERICITY AND SURROGACY • GENERIC PROPERTIES ARE THOSE POSSESED BY ALL THE MEMBERS OF A CLASS (AS OPPOSED TO SPECIAL PROPERTIES WHICH DISTINGUISH THE MEMBERS OF A CLASS) • SURROGACY IS THE ABILITY TO EXTRAPOLATE ONE’S MEASUREMENTS ON A FEW INDIVIDUALS TO THE GROUP

17. COMPLEXITY AND EMERGENCE • THE GENERIC ASPECT OF REAL SYSTEMS IS THAT THEY ARE ALL COMPLEX • THIS COMPLEXITY WORKS AGAINST SURROGACY AND LEADS TO THE NOTION OF EMERGENCE

18. WHY IS ORGANIZATION SPECIAL? BEYOND MERE ATOMS AND MOLECULES • IS THE WHOLE MORE THAN THE SUM OF ITS PARTS? • IF IT IS THERE IS SOMETHING THAT IS LOST WHEN WE BREAK IT DOWN TO ATOMS AND MOLECULES • THAT “SOMETHING” MUST EXIST

19. WHAT IS ORGANIZATION? DICTIONARY DEFINITION: NOUN: 1. THE ACT OR PROCESS OF BEING ORGANIZED 2.THE CONDITION OR MANNER OF BEING ORGANIZED (ALSO ASSOCIATION OR SOCIETY AND ITS PERSONNEL)

20. TO ORGANIZE DICTIONARY DEFINITION: VERB: 1. TO CAUSE OR DEVELOP AN ORGANIC STRUCTURE 2. TO ARRANGE OR FORM INTO A COHERENT UNITYOR FUNCTIONING WHOLE, TO INTEGRATE 3. TO ARRANGE ELEMENTS INTO A WHOLE OF INTERDEPENDENT PARTS

21. NOUN OR VERB OR ADJECTIVE? • AN ORGANIZED DESK • AN ORGANIZED CORPORATION • AN ORGANIZED AUTOMOBILE • AN ORGANIZED FROG • AN ORGANIZED ECOSYSTEM

22. WHAT MAKES BIOLOGICAL ORGANIZATION UNIQUE? • SELF-REFERENCE • CONTINGENCY • PARALLEL DISTRIBUTION • MAPPINGS ARE MANY TO MANY RATHER THAN ONE TO ONE • CAUSALITY IS INTERTWINED • CATABOLISM AND ANABOLISM ARE BOTH IMPORTANT • MECHANISMS ARE SPECIAL

23. EVEN IN THE WORLD OF MECHANISMS THERE ARETHE SEEDS OF COMPLEXITY THEORY • THERMODYNAMIC REASONING • OPEN SYSTEMS THERMODYNAMICS • NETWORK THERMODYNAMICS

24. THE NATURE OF THERMODYNAMIC REASONING • THERMODYNAMICS IS ABOUT THOSE PROPERTIES OF SYSTEMS WHICH ARE TRUE INDEPENDENT OF MECHANISM • THEREFORE WE CAN NOT LEARN TO DISTINGUISH MECHANISMS BY THERMODYNAMIC REASONING

25. THERMODYNAMICS OF OPEN SYSTEMS • THE NATURE OF THERMODYNAMIC REASONING • HOW CAN LIFE FIGHT ENTROPY? • WHAT ARE THERMODYNAMIC NETWORKS?

26. NETWORKS IN NATURE • NATURE EDITORIAL: VOL 234, DECEMBER 17, 1971, pp380-381 • “KATCHALSKY AND HIS COLLEAGUES SHOW, WITH EXAMPLES FROM MEMBRANE SYSTEMS, HOW THE TECHNIQUES DEVELOPED IN ENGINEERING SYSTEMS MIGHT BE APPLIED TO THE EXTREMELY HIGHLY CONNECTED AND INHOMOGENEOUS PATTERNS OF FORCES AND FLUXES WHICH ARE CHARACTERISTIC OF CELL BIOLOGY”

27. MY BOOK: • APPLICATION OF NETWORK THERMODYNAMICS TO PROBLEMS IN BIOMEDICAL ENGINEERING, NYU PRESS, 1993 • PREFACE, CONTENTS AND REFERENCES ARE ON MY WEB PAGE • http://views.vcu.edu/~mikuleck/

28. SR (BRIGGS,FEHER) GLOMERULUS (OKEN) ADIPOCYTE GLUCOSE TRANSPORT AND METABOLISM (MAY) FROG SKIN MODEL (HUF) TOAD BLADDER (MINZ) KIDNEY (FIDELMAN,WATTLINGTON) FOLATE METABOLISM (GOLDMAN, WHITE) ATP SYNTHETASE (CAPLAN, PIETROBON, AZZONE) SOME PUBLISHED NETWORK MODELS OF PHYSIOLOGICAL SYSTEMS

29. AN EXAMPLE: SODIUM TRANSPORTING EPITHELIA • CAN BE GROWN IN CULTURE • HAVE A DISTINCT ORGANIZATION WHICH IS NECESSARY AND SUFFICIENT FOR THEIR FUNCTION • UNDERGO A TRANSFORMATION AS THE EPITHELIUM DEVELOPS IN CULTURE

30. An Epithelial Membrane in Cartoon Form:

31. A Network Model of Coupled Salt and Volume Flow Through an Epithelium

32. WHAT IS THE NETWORK THERMODYNAMIC MODEL? • IT CAPTURES ORGANIZATION AS THE NETWORK’S TOPOLOGY • SPHERICAL CELL - SIMPLE TOPOLOGY • FUNCTIONAL EPITHELIUM - SAME CELL DEVELOPS A MORE COMPLICATED TOPOLOGY

33. LIMITS OF THE NETWORK THERMODYNAMIC MODEL • IT CAN MODEL EITHER CASE, BUT THESE MODELS CONTAIN NO INFORMATION ABOUT WHY ONE TRANSFORMS INTO THE OTHER • IT CAN NOT MODEL THE TRANSITION AS WELL • THE REAL SYSTEM IS COMPLEX

34. MISSING ASPECTS OF THE TRANSITION TO BE MODELED • CELL SIGNALLING EVENTS • NUCLEAR EVENT • MECHANICAL EVENTS • ONSET OF “EMERGENT” FUNCTION

35. WHAT HAVE WE LEARNED? • FORMALISMS HAVE LIMITS (GÖDEL) • THEREFORE ONE FORMALISM IS NOT ENOUGH • MECHANISTIC FORMALISMS ARE INADEQUATE FOR CERTAIN PROPERTIES, IN PARTICULAR CHANGES IN ORGANIZATION

36. WHAT ABOUT OTHER FORMALISMS? • RELATIONAL • OTHERS

37. THE RELATIONAL APPROACH TO A COMPLEX REALITY • FOCUS ON THE ORGANIZATION • DEVELOP A SET OF FUNCTIONAL COMPONENTS WHICH CAPTURE THAT ORGANIZATION • UTILIZE THE CAUSAL RELATIONS RESULTING FROM ANSWERING “WHY?”

38. FUNCTIONAL COMPONENTS • MUST POSSESS ENOUGH IDENTITY TO BE CONSIDERED A “THING” • MUST BE ABLE TO ACQUIRE PROPERTIES FROM LARGER SYSTEMS TO WHICH IT MAY BELONG • ITS FORMAL IMAGE IS A MAPPING f: A -----> B • THIS INTRODUCES A NEW KIND OF “DYNAMICS” : RELATIONAL

39. THE FOUR BECAUSES: WHY A HOUSE? • MATERIAL: THE STUFF IT’S MADE OF • EFFICIENT: IT NEEDED A BUILDER • FORMAL: THERE WAS A BLUEPRINT • FINAL: IT HAS A PURPOSE

40. METABOLISM/REPAIR SYSTEMS • BASED ON INPUT/OUTPUT REPRESENTATIONS OF SYSTEMS • MORE ABSTRACT • ALLOW CAUSALITY TO BE REPRESENTED • LEAD TO NEW INFORMATION • ARE BASED ON RECOGNITION THAT BUILDING UP AND TEARING DOWN ARE PART OF THE LIFE PROCESS

41. THE IMPORTANCE OF CATABOLISM AND ANABOLISM • NO STRUCTURE IS PERMANENT • ADAPTABILITY AND CHANGE INHERENT • NEEDS SPECIAL TYPE OF ORGANIZATION • IMPORTANT FOR UNDERSTANDING EVOLUTION, DEVELOPMENT, AND HEALING

42. THE RELATIONAL REPRESENTATION • INVOLVES MAPPINGS • METABOLISM IS f: A  B • A REPRESENTS METABOLITES WHICH CAN ALSO EXCHANGE WITH THE ENVIRONMENT • B REPRESENTS THE RESULTS OF METABOLISM • f IS A MAPPING FROM A TO B

43. THE CAUSAL RELATIONSHIPS • A IS THE MATERIAL CAUSE OF B (DOTTED ARROW) • f IS THE EFFICIENT CAUSE OF B • OTHER COMPONENTS FOR REPAIR AND REPLICATION COME IN BECAUSE THESE COMPONENTS HAVE A FINITE LIFETIME: CATABOLISM AND ANABOLISM OR “TURNOVER”

44. f  A B ROSEN’S RELATIONAL MODEL OF THE ORGANISM

45.  f  A B ROSEN’S RELATIONAL MODEL OF THE ORGANISM

46. f  A B ROSEN’S RELATIONAL MODEL OF THE ORGANISM

47. ORGANISMS • ARE COMPLEX SYSTEMS • ARE CLOSED TO EFFICIENT CAUSE • ARE AUTOPOIETIC UNITIES

48. SOME CONSEQUENCES • REDUCTIONISM DID SERIOUS DAMAGE TO THERMODYNAMICS • THERMODYNAMICS IS MORE IN HARMONY WITH TOPOLOGICAL MATHEMATICS THAN IT IS WITH ANALYTICAL MATHEMATICS • THUS TOPOLOGY AND NOT MOLECULAR STATISTICS IS THE FUNDAMENTAL TOOL

49. EXAMPLES: • CAROTHEODRY’S PROOF OF THE SECOND LAW OF THERMODYNAMICS • THE PROOF OF TELLEGEN’S THEOREM AND THE QUASI-POWER THEOREM • THE PROOF OF “ONSAGER’S” RECIPROCITY THEOREM

50. RELATIONAL NETWORKS • THROW AWAY THE PHYSICS, KEEP THE ORGANIZATION • DYNAMICS BECOMES A MAPPING BETWEEN SETS • TIME IS IMPLICIT • USE FUNCTIONAL COMPONENTS-WHICH DO NOT MAP INTO ATOMS AND MOLECULES 1:1 AND WHICH ARE IRREDUCABLE