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Science of Being - UBC 2012

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Talk for UBC students 3/2012

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Science of Being - UBC 2012

  1. 1. Stem Cells, Complexity, and the Science of Being Neil Theise MD Departments of Pathology & Medicine Beth Israel Medical Center – Albert Einstein College of Medicine New York City www.neiltheise.com
  2. 2. 1o Female RecipientMale Donor BM 48 Hours PKH26 Lin Deplete Label Elutriate Sort PKH-bright Transplant single cell into 2o Female Recipient
  3. 3. Bone Marrow One Adult CellEpithelia of Skin, Hair follicles• Liver• Lung• Gut, (Pancreas)
  4. 4. MESODERM One Adult Cell ENDODERM ECTODERMTrue clonality = True adult stem cell plasticity!
  5. 5. The Standard Paradigm: Restricted Plasticity
  6. 6. Embryology &Adult Tissue Reconstitution Self renewal Irreversible gene restrictions
  7. 7. BEWARE OFDOGMA
  8. 8. What if gene restrictionsare REVERSIBLE?
  9. 9. 3 Principles of Plasticity Theise & Krause BCMD, May 2001 Leukemia, April Fool’s Day 2002Comptes Rendus Biologies, December 2002
  10. 10. 1. Genomic Completeness2. Cellular Uncertainty3. Stochasticity of Cell Origins and Fates
  11. 11. 1. Genomic Completeness2. Cellular Uncertainty3. Stochasticity of Cell Origins and Fates
  12. 12. “…the internal and the external co-determine the cell.” Richard Lewontin, 2000
  13. 13. 2nd Principle: Cellular UncertaintyAny attempt to observe a cell alters the state of that cell at the time of characterization and potentially alters the likelihood of subsequent differentiation events.
  14. 14. 2nd Principle: Cellular UncertaintyAny attempt to observe a cell alters the state of that cell at the time of characterization and potentially alters the likelihood of subsequent differentiation events. ?
  15. 15. Meanwhile,back at the plasticity debates…
  16. 16. Controversy!!!
  17. 17. trivial... vs.ROBUST!!!
  18. 18. Conversations with Jane Prophet New Media Artist and Professor, Interdisciplinary StudiesUniversity of Westminster, London UKSciArt Award, Wellcome Trust 2002
  19. 19. Date: 9th May 2002 Location: Neils office, New YorkJane says: “Ideas about pathways are interesting. A lot of people who are involved in digital biology are interested in things like swarming people and so called ’soup organism’ behaviour. And one of the useful models to take forward is about ant colonies…”
  20. 20. Complex Adaptive Systems:1,21 Lewin R, Complexity: Life at the Edge of Chaos. 2nd ed. Chicago IL: University of Chicago Press; 2002.2 Johnson S, Emergence. New York NY: Scribner; 2001.
  21. 21. Complex Adaptive Systems: Interacting individuals that, if they fulfill 4 criteria,organize themselves from the bottom up, into larger structures…
  22. 22. Complex Adaptive Systems: Interacting individuals that, if they fulfill 4 criteria, organize themselves from the bottom up, into larger structures,which appear planned from the top, downward…
  23. 23. Complex Adaptive Systems: Interacting individuals that, if they fulfill 4 criteria, organize themselves from the bottom up, into larger structures,which appear planned from the top, downward, BUT ARE NOT!
  24. 24. Complex Adaptive Systems: Interacting individuals that, if they fulfill 4 criteria, organize themselves from the bottom up, into larger structureswhich appear planned from the top, downward, BUT ARE NOT! These structures are referred to as “emergent self-organization” and are ADAPTIVE.
  25. 25. Complex Adaptive Systems:Rise and fall of economic markets Urban development Immune systems Beatlemania Rise and fall of civilizations Evolution and speciation
  26. 26. Complex Adaptive Systems:Rise and fall of economic markets Urban development Immune systems Beatlemania Rise and fall of civilizations Evolution and speciation Conciousness
  27. 27. Complex Adaptive Systems: • Numbers matter
  28. 28. Complex Adaptive Systems: • Numbers matter • Negative feedback loops
  29. 29. Complex Adaptive Systems: • Numbers matter • Negative feedback loops• Interactions are local without global sensing
  30. 30. Complex Adaptive Systems: • Numbers matter • Negative feedback loops• Interactions are local without global sensing • Low level randomness
  31. 31. Complex Adaptive Systems: • Numbers matter • Negative feedback loops• Interactions are local without global sensing • “Quenched disorder”
  32. 32. Low level engraftment is not only NOT trivial, but it is VITAL – literally so.1-31 Theise ND. Exp Hematology 20032 D’Inverno M, Theise ND. BCMD 20043 D’Inverno M, Theise ND, Prophet J. In: Potten C, Wilson J, Clarke R, Renahan A: Tissue stem cells: Biology and applications
  33. 33. Implications of Cell Lineagesas Complex Adaptive Systems Mass extinctions.
  34. 34. “chaos”disorder order
  35. 35. “chaos”disorder complex adaptive systems order
  36. 36. Implications of Cell Lineagesas Complex Adaptive Systems Mass extinctions, eg: ? Aplastic anemia ? Fulminant liver failure
  37. 37. Implications of Cell Lineagesas Complex Adaptive Systems The price of adaptation, i.e. of LIFE, is DEATH
  38. 38. Implications of Cell Lineagesas Complex Adaptive SystemsHierarchies of complex systems…
  39. 39. Implications of Cell Lineagesas Complex Adaptive SystemsHierarchies of complex systems… thing vs. phenomenadepends on scale of observation
  40. 40. Communities Bodies Cells
  41. 41. e.g. cities, cultures, ecosystems, Gaia Bodies Cells
  42. 42. Communities Bodies Cells ?
  43. 43. Communities Bodies CellsBiomolecules ?
  44. 44. Communities Bodies CellsBiomolecules
  45. 45. Communities Bodies Cells BiomoleculesMore implications, of course.
  46. 46. 1. Genomic Completeness? Cellular Uncertainty3. Stochasticity of Cell Origins and Fates
  47. 47. Communities Bodies CellsBiomoleculesTheise ND.Now you see it, now you don’t.Nature, May 2005“Cell doctrine: modern biology and medicine see thecell as the fundamental building block of livingorganisms, but this concept breaks down at differentperspectives and scales.”
  48. 48. Communities Bodies CellsBiomolecules“The validity of cell doctrine depends on the scale atwhich the body is observed…
  49. 49. Communities Bodies CellsBiomolecules“The validity of cell doctrine depends on the scale atwhich the body is observed. To limit ourselves to theperspective of this model may mean that explications ofsome bodily phenomena remain outside the capacity ofmodern biology…
  50. 50. Communities Bodies CellsBiomolecules“The validity of cell doctrine depends on the scale atwhich the body is observed. To limit ourselves to theperspective of this model may mean that explications ofsome bodily phenomena remain outside the capacity ofmodern biology… e.g. Acupuncture
  51. 51. Communities Bodies CellsBiomolecules“The validity of cell doctrine depends on the scale atwhich the body is observed. To limit ourselves to theperspective of this model may mean that explications ofsome bodily phenomena remain outside the capacity ofmodern biology. It is perhaps time to dethrone thedoctrine of the cell, to allow alternative models of thebody for study and exploitation in this new, postmodernera of biological investigation.”
  52. 52. What kind of models?
  53. 53. for example, 2 models from Ancient Greece: Is the body made of…indivisible subunits or an endlessly divisible fluid
  54. 54. Models of the body are perspective/technique dependent Look at it this way (cell membranes): the body is made of cells Look at it that way (organelles): the body is an endlessly divisible fluid
  55. 55. Models are perspective/technique dependent Look at it this way (cell membranes): the body is made of cells Look at it that way (organelles): the body is an endlessly divisible fluid Yet another way (the genome):… overlapping spatial/temporal fields of molecular organization
  56. 56. Still more implications of complexity in life…
  57. 57. Communities Bodies CellsBiomolecules Atoms
  58. 58. Communities Bodies CellsBiomolecules Atoms
  59. 59. Communities Bodies CellsBiomolecules Atoms
  60. 60. Communities Bodies Cells Biomolecules AtomsWe are walking, talking Earth…
  61. 61. Communities Bodies Cells Biomolecules AtomsSubatomic Particles
  62. 62. Communities Bodies Cells Biomolecules AtomsSubatomic ParticlesStrings (or whatever)
  63. 63. Communities Bodies Cells Biomolecules AtomsSubatomic ParticlesStrings (or whatever)The Quantum Foam
  64. 64. We don’t live in the universe . . .
  65. 65. . . . we are the universe
  66. 66. Implications of Everything as Complex Adaptive System Science-Metaphysics Interface  Complementarity  Consciousness Studies
  67. 67. Implications of Everything as Complex Adaptive System Science-Metaphysics Interface  Complementarity  Consciousness Studies
  68. 68. The Relative
  69. 69. The Absolute
  70. 70. Implications of Everything as Complex Adaptive System3. “thingness” is dependent on scale
  71. 71. Implications of Everything as Complex Adaptive System3. Emptiness of inherent existence
  72. 72. Implications of Everything as Complex Adaptive System3. Emptiness of inherent existence 2. Inevitable mass extinction
  73. 73. Implications of Everything as Complex Adaptive System3. Emptiness of inherent existence 2. Impermanence
  74. 74. Implications of Everything as Complex Adaptive System 3. Emptiness of inherent existence 2. Impermanence3. Systems depend on EVERY member
  75. 75. Implications of Everything as Complex Adaptive System3. Emptiness of inherent existence 2. Impermanence 3. Interdependence
  76. 76. Implications of Everything as Complex Adaptive System 3. Emptiness of inherent existence 2. Impermanence 3. Interdependence4. The fact of emergence is predictable, the nature of it is not.
  77. 77. Implications of Everything as Complex Adaptive System3. Emptiness of inherent existence 2. Impermanence 3. Interdependence 4. Karmic law (cause and effect)
  78. 78. Implications of Everythingas Complex Adaptive System Buddhist Metaphysics
  79. 79. Implications of Everythingas Hierarchical Complex Systems Jewish Mysticism
  80. 80. Implications of Everythingas Complex Adaptive Systems Hindu Mysticism
  81. 81. Implications of Everything as Complex Adaptive System Science-Metaphysics Interface  Biological Complementarity  Consciousness Studies
  82. 82. Bohr, Delbruck, Menas Kafatos
  83. 83. Implications of Everything as Complex Adaptive System Science-Metaphysics Interface  Complementarity  Consciousness Studies
  84. 84. HUMBERT R. MATURANA and FRANCISCO J. VARELA All living systems are autopoietic systems. AUTOPOIESIS AND COGNITION The Realization of the Living With a preface on “Autopoiesis” by SIR STAFFORD BEERS 1. Boundary: open to energy but closed to foreign materials – i.e. is semi-porous.
  85. 85. HUMBERT R. MATURANA and FRANCISCO J. VARELA All living systems are autopoietic systems. AUTOPOIESIS AND COGNITION The Realization of the Living With a preface on “Autopoiesis” by SIR STAFFORD BEERS 1. Boundary: open to energy but closed to foreign materials – i.e. is semi-porous. 2. Processes: the boundary is the ’being’ and the processes are the ‘doing’ of a living system.
  86. 86. HUMBERT R. MATURANA and FRANCISCO J. VARELA All living systems are autopoietic systems. AUTOPOIESIS AND COGNITION The Realization of the Living With a preface on “Autopoiesis” by SIR STAFFORD BEERS 1. Boundary: open to energy but closed to foreign materials – i.e. is semi-porous. 2. Processes: the boundary is the ’being’ and the processes are the ‘doing’ of a living system. 3. Nervous System: the connection between external events and the internal processes of the living system.
  87. 87. HUMBERT R. MATURANA and FRANCISCO J. VARELA All living systems are autopoietic systems. AUTOPOIESIS AND COGNITION The Realization of the Living With a preface on “Autopoiesis” by SIR STAFFORD BEERS 1. Boundary: open to energy but closed to foreign materials – i.e. is semi-porous. 2. Processes: the boundary is the ’being’ and the processes are the ‘doing’ of a living system. 3. Nervous System: the connection between external events and the internal processes of the living system. 4. Communication Channels: between the living system and its external environment.
  88. 88. HUMBERT R. MATURANA and FRANCISCO J. VARELA All living systems are cognitive systems. AUTOPOIESIS AND COGNITION The Realization of the Living With a preface on “Autopoiesis” by SIR STAFFORD BEERS
  89. 89. HUMBERT R. MATURANA and FRANCISCO J. VARELA All living systems are cognitive systems. AUTOPOIESIS AND COGNITION The Realization of the Living With a preface on “Autopoiesis” by SIR STAFFORD BEERS
  90. 90. All living systems are cognitive systems.Conciousness <> Sense Making <> Sentience
  91. 91. They’ve found that some of the key molecularbuilding blocks of neurons predate even the firstmulticellular organisms. By looking down the treeof life, they are concluding that assembling thesecomponents into a cell a modern neuroscientistwould recognize as a neuron probably happenedvery early in animal evolution, more than 600million years ago. Most scientists agree thatcircuits of interconnected neurons probably arosesoon thereafter, first as diffuse webs and later as acentralized brain and nerves. G. Miller, Science, 2009
  92. 92. s g s nes akin ce ciou se M tienCo n Sen Sen Communities Bodies Cells Biomolecules Atoms Subatomic Particles Strings (or whatever)
  93. 93. s g s nes akin ce ciou se M tienCo n Sen Sen Communities Bodies Cells Biomolecules Only living (biological) Atoms systems ??? Subatomic Particles Strings (or whatever)
  94. 94. s g s nes akin ce ciou se M tienCo n Sen Sen Communities Bodies Cells Biomolecules ? Atoms Subatomic Particles Strings (or whatever)
  95. 95. Biomolecules!!!
  96. 96. Only biomolecules???
  97. 97. Atoms!!!
  98. 98. Only atoms???
  99. 99. Subatomic particles!!! 10-18m Strings 10-35m (or whatever)
  100. 100. Conclusion:While one may argue that sense makingand therefore some form of conciousness islimited, extending downward in scale onlyto the smallest, autopoietic elements of life– namely the cell – a complexity analysis ofthe universe (as a unified, self-organizingand emergent system) reveals that theuniverse is sentient throughout; thatsentience is inherent and universal in thestructures of existence.
  101. 101. Conclusion:While one may argue that sense makingand therefore some form of conciousness islimited, extending downward in scale onlyto the smallest, autopoietic elements of life– namely the cell – a complexity analysis ofthe universe (as a unified, self-organizingand emergent system) reveals that theuniverse is sentient throughout; thatsentience is inherent and universal in thestructures of existence.
  102. 102. Conclusion:While one may argue that sense makingand therefore some form of conciousness islimited, extending downward in scale onlyto the smallest, autopoietic elements of life– namely the cell – a complexity analysis ofthe universe (as a unified, self-organizingand emergent system) reveals that theuniverse is sentient throughout; thatsentience is inherent and universal in thestructures of existence.
  103. 103. Conclusion:While one may argue that sense makingand therefore some form of conciousness islimited, extending downward in scale onlyto the smallest, autopoietic elements of life– namely the cell – a complexity analysis ofthe universe (as a unified, self-organizingand emergent system) reveals that theuniverse is sentient throughout; thatsentience is inherent and universal in thestructures of existence.
  104. 104. s g s nes akin ce ciou se M tienCo n Sen Sen Communities Bodies Cells Biomolecules? ? Atoms Subatomic Particles Strings (or whatever)
  105. 105. Single cell multiorgan plasticity Diane Krause MD PhDSaul Sharkis MD PhD, Michael Collector Octavian Henegariu MD Sonya Hwang MD, Rebekah Gardner Sarah Neutzel
  106. 106. Cell Team Jane Prophet Mark D’Inverno Rob Saunders Peter Ride Neil TheiseDiscussions were part of the production of "Cell", a collaboration across art and science funded by a Wellcome Trust SciArt Award and an award from Future Physical. "Cell" is coordinated by Peter Ride and is a DA2 Digital Arts Agency production.

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