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From Quantum Physics to Quantum
Biology in 100 years
How long to Quantum Medicine?
Jack Tuszynski
University of Alberta
Ed...
Solvay Conference
Brussels 1927
Basics of Quantum Mechanics
 Classical mechanics (Newton's mechanics) and Maxwell's
equations (electromagnetic theory) ca...
Basics of Quantum Mechanics
 Microscopic physical systems can act as both particles
and waves  WAVE-PARTICLE DUALITY
 Q...
Heisenberg Uncertainty Principle
 One cannot unambiguously specify the values of
particle's position and its momentum for...
The Photoelectric Effect
A Photocell is Used to Study the Photoelectric Effect
Larger frequency, means smaller wavelength,...
Additional experiments demonstrating quantum
nature of the microscopic universe
 The Compton effect (photon-electron scat...
The First Postulate of QM
States of microscopic systems are represented by wave functions 
STATE FUNCTIONS (square integr...
The Second Postulate of Quantum Mechanics
If a system is in a quantum state represented by a wavefunction ,
then
is the p...
The Third Postulate of Quantum Mechanics -
Every observable in quantum mechanics is represented by an operator which is us...
Basics of Quantum Mechanics
- Fourth Postulate of Quantum
Mechanics -1926 Erwin Schrödinger proposed an equation that desc...
Describes well quantum vibrational modes of molecular gases
Describes well specific heats of solids
Macroscopic Quantum Effects
• Superconductivity
• Superfluidity
• Laser Action
• Crystal Vibrations (Phonons)
• Magnetism
Quantum Mechanics and Life
 Nature over 2B years of experimentation on Earth
must have taken advantage quantum mechanics
Quantum Mechanics and Life
• Where does quantum
weirdness fit in?
• Coherence
– superposition of states
• Entanglement
– “...
Quantum Mechanics and Life
 Five Gifts of Quantum Mechanics to
Nature
Stability
Countability
Information
Information Proc...
physicists think everything reduces to physics
But interactions matter:
hierarchies of systems form
Biochemistry
Chemistry
Condensed matter
Physics
Elementary particle
P...
Combinatorial Barriers
Elsasser’s immense number
I = 10110
I = atomic weight of the Universe measured in
proton’s mass (da...
Dimensions Matter, too
Organism
Cell
System
Biomolecule
Molecule
Atom
1020 Atoms
1010 Atoms
105 Atoms
103 Atoms
101 Atoms
...
Energy/Affinity Scale
 Covalent bond 90 kcal/mol at 1.5 Å
 Ion-Ion 60 kcal/mol at 5 Å
 Disulphide bond 40 kcal/mol at 2...
Many discounted QM in biology because…
• Life is big (cells) in comparison to photons/electrons where QM is
applicable
• L...
• Collective dynamics of many freedom degrees.
• Life – a metastable state.
• Various types of local and global order.
• S...
Quantum Mechanics and Life
 Quantum computers
use entanglement
and coherence
 These states are
fragile
 environmental
d...
Physiological Quantum Effects
• Light detection by the human eye
• Resonant recognition of aromatic
molecules in olfaction...
Quantum biology
• N.Bohr, W. Heisenberg, E. Schrodinger, J. von Neumann, C. von
Weizsacker, W. Elsasser, V. Weisskopf, E. ...
• Herbert Fröhlich postulated a dynamical order based on correlations
in momentum space, the single coherently excited pol...
Morphogenetic fields
• 1912:AlexanderGurwitsch introduced for the first time in biology the idea of a
field as a supracell...
Modern bioelectromagnetic field
concepts
• 1970 Presman:Review on Soviet research in bioelectromagnetism stimulated the
br...
Anatomy of the Intelligent Cell
Gunther Albrecht-Buehler, NWUniv Chicago
Centriole-Mitochondria Connection (G.
Albrecht-Buehler)
The control center detects objects and
other cells objects by puls...
Centrioles
Basal bodies and centrioles
consist of a 9-fold arrangement
of triplet microtubules. A molecular
cartwheel fill...
DNA
TF
MT
Free Tubulin Dimer
Nuclear Wall
Membrane
Cytoplasm
MT Bundle
Chromosome
Pair
Centrosome
Mitotic Cell
. . . . .
M...
Quantum Metabolism
Metabolic activity is localized in the biomembranes
(1.) Plasma membrane  Uni-cells
(2.) Thylakoid mem...
Evidence for quantum coherence
•Engel 2007: Quantum Beating: direct evidence of quantum
coherence
•Lee 2007: “correlated p...
Photosynthesis
Photosynthesis
 Light energy absorbed by light harvesting
complexes (LHC)
 LHCs transfer energy to photosynthetic reacti...
Photosynthesis
 LHCs are pigment-protein antennas,
 Densely packed chromophores efficient at
transporting excitation energ...
FMO Complex in C. Tepidum
 From a New Zealand
hot spring.
 Grow in dense mats
over hot springs that
contain sufficient
h...
FMO Complex in C. Tepidum
FMO Complex in C. Tepidum
Quantum Search Algorithms
 Mohseni et. al.
investigated
quantum
search
algorithms in
FMO based on
the Cho et. al.
Hamilto...
single-celled algae have a light-harvesting
system where quantum coherence is
present.
A UNSW Australia-led team has disco...
Quantum Entanglement
 Evidence for the existence of entanglement in
the FMO complex for picosecond timescales
 Predictio...
Quantum Beating and Coherence
 Superposition states formed during a fast
excitation event
 allows the excitation to reve...
Extensions
Penrose and Hameroff suggest quantum
computations in microtubules as playing a
role in higher brain functions
...
A lattice of seven tubulin dimers as found in the microtubule
lattice. Red lines connect tryptophans, and rectangles show
...
• In photosynthesis coherent energy transferred between
chromophoric chlorophyll molecules.
• Tubulin possesses a unique a...
Dipole Interactions in Tubulin
• Chromophores transfer energy via transition dipole moments.
• Tryptophan may be excited b...
Tryptophan excitations in
tubulin
In collaboration with Travis Craddock
Excitation Coherence in Tubulin
• Diagonalization of the Hamiltonian Matrix yields the excitation
energies and distributio...
Regulation of the Metabolic Pathway
Regulated by several Mechanisms:
•Product Inhibition
•Feedback Inhibition
•Reactant Ac...
Electron Transport Chain – Oxidative
Phosphorylation
•Movement of electrons from NADH to terminal electron acceptor throug...
Energy consumption in
organisms history
1. Laplace and Lavoisier (1780)
Respiration is a form of combustion
Metabolic rate...
Body Size – Metabolism
Allometric Relation
Y = α Wβ
W = body size
The Parameter Y
a) Measures of physiological time:
I. Re...
Problems
What is the mechanistic basis for these
scaling rules?
Issues to be addressed
1. Variation in proportionality con...
Quantum Metabolism
Metabolic activity has its origin in biochemical
processes which occur within biomembranes.
The theory ...
QM: molecular phenomena
1. Chemiosmotic coupling: Mitchell (1970)
Process with ADP phosphorylation
Coupling of electron tr...
Results – e vs. V0, T = 300 K
• Only Type IIB behaviour
below e of 7.8.
• A narrow range of
parameters are defined for
MTs...
L. Demetrius (2003) Quantum statistics and allometric scaling of organisms. Physica
A: Statistical Mechanics and its Appli...
Biological “Planck constant”: E=kf
• Human energy production: 1021 ATP molecules per second
• There are on the order of 3....
The Microtubule Cytoskeleton
Hameroff et. al., In: Toward a Science of
Consciousness pp. 507-540 (1996)
• Microtubules (MT...
Dendritic spine has microtubules interacting with
membrane receptors.
Challenge: integration of various levels
in a hierarchy
Building a bridge between
 the molecular level (cytoskeleton)
 t...
Microtubule: structure
 is made of a- and b- tubulins
a
b
Source of UV Radiation
• Tryptophan requires UV radiation to be excited.
• Is there a UV source inside cells?
• Rahnama et...
Quantum link to function
• Mitochondria provide UV source.
• TRP excitations influenced by:
– C-terminal tail positions
– ...
Modes of
Communication/Signaling
C-termini oscillations
Electron hopping
Tryptophan excitations
Conformational changes
Brain questions
• What makes the brain special?
• What is consciousness?
• Where is memory stored?
• What is the computati...
The Human Brain:
a computer cluster of computers
• 1011 neurons in our brains
• 1015 synapses operating at about 10 impuls...
Potential for Memory Storage,
Computation and Signaling in MTs
 C-termini states (4 per dimer)
 Electron hopping (4 per ...
Energy limitations on information processing in
the brain
• P = 25 W but 60% used by ribosomes on protein synthesis alone
...
Fractal organization on time and
spatial scales
Ghosh S., et al. Information 2014, 5:28-100.
.
Hierarchical model of infor...
Brain has a bandwidth of 1030 Hz
(from 10-15 to 1015 Hz)
Anirban Bandhopadhyay.
Microtubules in neurons
Focusing on the Dendrite
Previous and
current study
future study
MTs and Neurodegenerative
diseases
 A common feature: a deteriorating cytoskeleton:
 Typical sequence of events:
DNA Mut...
Alzheimer’s disease
 Both the neuronal and cognitive consequences of cytoskeletal
protein disruption
 Cortical neurons i...
93
Alzheimer’s Disease (AD)
• Alzheimer’s disease (AD) characterized by b-Amyloid plaques
(bAPs) and neurofibrillary tangl...
MT’s in Parkinson’s and
Huntington’s diseases
 Mutations in genes for α-synuclein and parkin proteins lead to
familial Pa...
 Stroke and traumatic brain injury – The cytoskeleton is
disrupted following ischemia due to blood hemorrhage, occlusion,...
96
What is Memory?
 Ability to encode, store and
recall information.
 Postulated to be represented by
vastly interconnec...
Memory storage
Holographic: Lashley, Pribram: mouse studies
Fractal, resonant, tubulin: Anirban
Sheldrake: Memories not st...
• Is memory localized? Persistence of long-term
memory after head regeneration
Memory Storage
Shomrat & Levin, Journal of ...
• If we want to listen to our intuition or gut
feeling, what information are we accessing?
• Is this information holograph...
Capacity of Human Memory?
 Von Neumann (1950) – 3x1020 bits
Total life experience -we agree
 Anatomists (1970’s) – 1013-...
Historical Perspective
 1 Human = 1019 bytes
 # of Words ever written = about 1016 bytes
 # of Words ever spoken = abou...
102
Cytoskeletal Involvement in
Memory
 Synaptic plasticity:
 neuronal differentiation, movement,
synaptogenesis and reg...
Calmodulin kinase complex CaMKII as memory
read/write device
104
Information Storage
• Phosphorylation conveys
information.
• Each CaMKII – MT event
conveys 64 - 5218 bits.
• Each kin...
Memory storage
Long-term Potentiation (LTP):
synaptic strength
Craddock:
MT phosphorylation
“Cytoskeletal Signaling: Is Me...
106
Ca2+/Calmodulin Kinase II (CaMKII)
• Vital for memory (long term potentiation – LTP)
• Single point mutations cause me...
107
CaMKII Phosphorylates MT
• CaMKII phosphorylates S/T residues in many protein substrates.
• Tubulin one target of CaMK...
108
Geometric Matching
•Basic homology
models of CaMKII and
MT.
•Positional geometry
aligned.
•Kinase regions found to
clo...
109
Electrostatic Matching
• Field lines convergent
showing electrostatic
attraction.
• ~10 kT/e (6 kcal/mol at
310 K) att...
110
Information Storage
• Phosphorylation conveys
information.
• Each CaMKII – MT event
conveys 64 - 5218 bits.
• Each kin...
How does this affect neural function?
111
• PTMs may serve as tags
for MAPs to bind.
• Control:
• Neural structure
• Trans...
Potential base for Universal Logic
112
AND XOR
Computational predictions and partial experimental conformation
exists for the binding of psychoactive drugs to tubulin wh...
Caffeine THC Marijuana LSD Adrenaline
Nicotine MDMA Ecstasy Chocolate Methamphetamine
Xanax Heroin Rohypnol (Date rape) Al...
What about Consciousness?
• Much harder to define.
• Related to brain function and memory.
• Penrose-Hameroff “Orch OR” mo...
Anesthetic-Microtubule
Interactions?
 Hypothesis: The microtubule (MT)
network in dendrites is related to
memory, and int...
GAs Possess Dissimilar Structure
Inhaled Intravenous
Propofol
Ketamine
Etomidate
119
What about anesthetics?
119
• Anesthetics provide analgesia, hypnosis, paralysis
and amnesia.
• Volatile anesthetics r...
120
• 47 Distinct Sites found
• 9 sites found to persist for more than 70% of the 5 ns simulation.
• Of these 9, key sites...
Anesthetics and Tryptophan Excitation
• Anesthetics possess a large dipole moment.
• Putative anesthetic sites lie as clos...
Quantum Psychology
The Development of a New Formalism: Second Quantization:
Transitions between Normal States of Mind (Mas...
Psycho-Pathology
• The Development of a New Formalism: Q-Deformed Algebras and the
Distorted States of Mind in Mental Dise...
Connection to clinical psychiatry
• multidimensional classification systems taking account of quantum
statistics
• transit...
Future Goals
• To use quantum models to create a more adequate explanatory framework
for psychopathological phenomenology....
126
The Problem with Embryology
Egon Schiele
Kneeling Male Nude (Self-
Portrait). 1910.
http://www.moma.org/exhibitions/sc...
Staging of Axolotl Development
127
Top views 
Side views 
Bottom views 
Side view
L R
Bordzilovskaya, N.P.,
T.A. Dettla...
128
Staging of Axolotl Development
head
tail
right side
Timing, at 20oC:
Stage Time
in
hours
What’s
starting
2- 0 Synchron...
129
Stages 23-35 of Axolotl Development
130
Stages 36-44 of Axolotl Development
No increase in dry weight
since it was an egg!
131
The Cell State
Splitter
MF =
microfilament ring
MT =
annular apical
microtubule mat
IF =
intermediate
filament ring
132
The Unstable (Bistable) Mechanical Equilibrium
between the Microfilament Ring and the
Microtubule Mat in the Cell Stat...
133
The Differentiation Tree
Embryogenesis may be
modelled as a bifurcating
sequence of tissues
generated as each tissue
i...
134
The Differentiation Tree is the Physical Embodiment
of Conrad Waddington’s Epigenetic Landscape
Held Jr., L.I. (1992)....
135
Nouri, C., R. Luppes, A.E.P. Veldman,
J.A. Tuszynski & R. Gordon (2008).
Rayleigh instability of the inverted one-
cel...
136
Cortical Rotation
• Forced Cortical Rotation:
Direction of the last forced rotation determines the left-right symmetry...
137
When an egg is inverted:
• 1. The egg will not develop at all.
• 2. It will develop but with colors of dorsal and vege...
138
Working Hypothesis
• Cortical rotation aligns microtubules attached
to the inner surface of the cortex via global
torq...
139
ComFlo Computational Fluid
Dynamics Simulation
Symmetric sloshing of the heavier liquid (yolk) in the inverted egg. Th...
140
Summary
• Memory depends on the neuronal cytoskeleton.
• This basis yields:
– A molecular mechanism of synaptic plasti...
Implications for Health and
Disease
Quantum coherence= a healthy state
Decoherence=transition to disease
Location of decoh...
• Already doing this with EKG, EEG for
diagnostic purposes
Body: Bioelectric medicine
142
• Is this an avenue for non-invasive signals?
– Yes
• Able to deliver quality information on the
health of the body?
– Yes...
• Bioelectric signals
• Morphogenesis
• Cell membrane (cancer depolarized)
Michael Levin
144
Morphogenesis and cancer
Levin, BioSystems 109:243-261, 2012
145
• Hypothesized by Dr. James Oschman
• High-speed electric communication system
made up of biological wires in the body:
ne...
Microtubule conductivity
Friesen et al. BioSystems 127:14-27, 2015
Coherent
Energy
Transfer
147
• Flexible, transient electronics
Nanotechnology advances
John A. Rogers Group
University of Illinois
148
• NanoFET (Nano Field Effect
Transistor)
• Intracellular electrical
recordings
• Charles M. Lieber group
(Harvard)
Nanotec...
• Nanosensors to measure health of body, in
terms of communication within cells and
between cells and between organs and t...
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?
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Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?

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Jack Tuszynski presents "From Quantum Physics to Quantum Biology in 100 Years. How long to Quantum Medicine?" March 17 and 22, 2016 University of Alberta, Edmonton, Canada.

Publié dans : Santé & Médecine
  • Light and its nature have caused a lot of ink to flow during these last decades. Its dual behavior is partly explained by (1)Double-slit experiment of Thomas Young - who represents the photon’s motion as a wave - and also by (2)the Photoelectric effect in which the photon is considered as a particle. A Revolution: SALEH THEORY solves this ambiguity and this difficulty presenting a three-dimensional trajectory for the photon's motion and a new formula to calculate its energy. More information on https://youtu.be/mLtpARXuMbM
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Jack Tuszynski From Quantum Physics to Quantum Biology in 100 Years. How long to quantum medicine?

  1. 1. From Quantum Physics to Quantum Biology in 100 years How long to Quantum Medicine? Jack Tuszynski University of Alberta Edmonton, Canada
  2. 2. Solvay Conference Brussels 1927
  3. 3. Basics of Quantum Mechanics  Classical mechanics (Newton's mechanics) and Maxwell's equations (electromagnetic theory) can explain MACROSCOPIC phenomena such as motion of billiard balls or rockets.  Quantum mechanics is used to explain MICROSCOPIC phenomena such as photon-atom scattering and flow of the electrons in a semiconductor. But there are macroscopic quantum effects in: superfluids, superconductors, lasers and crystal dynamics (phonons)  QUANTUM MECHANICS developed postulates based on a huge number of experimental observations. It has a precise mathematical formalism of Hermitian operators in Hilbert spaces
  4. 4. Basics of Quantum Mechanics  Microscopic physical systems can act as both particles and waves  WAVE-PARTICLE DUALITY  Quantum state is a superposition of a number of possible outcomes of measurements of physical properties  Quantum mechanics uses the language of PROBABILITY theory  An observer cannot observe a microscopic system without altering some of its properties (an observer problem)  QUANTIZATION of energy is yet another property of "microscopic" particles.
  5. 5. Heisenberg Uncertainty Principle  One cannot unambiguously specify the values of particle's position and its momentum for a microscopic particle, i.e.  Position and momentum are, therefore, considered as incompatible variables (same for angle and angular momentum; time and energy)   22 1 00 )()( h x tptx
  6. 6. The Photoelectric Effect A Photocell is Used to Study the Photoelectric Effect Larger frequency, means smaller wavelength, and larger Energy=hf.
  7. 7. Additional experiments demonstrating quantum nature of the microscopic universe  The Compton effect (photon-electron scattering)  Atomic absorption/emission spectra  Double slit experiments (electrons and photons)  Stern-Gerlach experiment (magnetic spin)
  8. 8. The First Postulate of QM States of microscopic systems are represented by wave functions  STATE FUNCTIONS (square integrable). First postulate of Quantum mechanics: Every physically-realizable state of the system is described in quantum mechanics by a state function  that contains all accessible physical information about the system in that state.  State function  function of position, momentum, energy that is spatially localized.  If 1 and 2 represent two physically-realizable states of the system, then so is their linear combination
  9. 9. The Second Postulate of Quantum Mechanics If a system is in a quantum state represented by a wavefunction , then is the probability that in a position measurement at time t the particle will be detected in the infinitesimal volume dV. Note:  position and time probability density According to the second postulate of quantum mechanics, the integrated probability density can be interpreted as a probability that in a position measurement at time t, we will find the particle anywhere in space (i.e one= certainty) dVPdV 2  2 ),( tx
  10. 10. The Third Postulate of Quantum Mechanics - Every observable in quantum mechanics is represented by an operator which is used to obtain physical information about the observable from the state function. For an observable that is represented in classical physics by a function Q(x,p), the corresponding operator is ),( pxQ  . Observable Operator Position x  Momentum xi p     Energy )( 2 )( 2 2 222 xV xm xV m p E      
  11. 11. Basics of Quantum Mechanics - Fourth Postulate of Quantum Mechanics -1926 Erwin Schrödinger proposed an equation that describes the evolution of a quantum- mechanical system  SWE which represents quantum equations of motion, and is of the form: t itxxV xm txxV xm                     ),()( 2 ),()( 2 2 22 2 22 This work of Schrödinger was stimulated by a 1925 paper by Einstein on the quantum theory of ideal gas, and the de Broglie theory of matter waves. Note: Examining the time-dependent SWE, one can also define the following operator for the total energy: t iE     
  12. 12. Describes well quantum vibrational modes of molecular gases
  13. 13. Describes well specific heats of solids
  14. 14. Macroscopic Quantum Effects • Superconductivity • Superfluidity • Laser Action • Crystal Vibrations (Phonons) • Magnetism
  15. 15. Quantum Mechanics and Life  Nature over 2B years of experimentation on Earth must have taken advantage quantum mechanics
  16. 16. Quantum Mechanics and Life • Where does quantum weirdness fit in? • Coherence – superposition of states • Entanglement – “spooky action at a distance”: distant particles affecting one another without energy transfer
  17. 17. Quantum Mechanics and Life  Five Gifts of Quantum Mechanics to Nature Stability Countability Information Information Processing Randomness
  18. 18. physicists think everything reduces to physics
  19. 19. But interactions matter: hierarchies of systems form Biochemistry Chemistry Condensed matter Physics Elementary particle Physics nucleic acids  proteins ions  molecules (valence is important) quarks  nucleons electrons & protons  solids
  20. 20. Combinatorial Barriers Elsasser’s immense number I = 10110 I = atomic weight of the Universe measured in proton’s mass (daltons) time the age of the Universe in picoseconds (10-12 s) No conceivable computer could store a list of I objects, and even if it could, there would be no time to inspect it !
  21. 21. Dimensions Matter, too Organism Cell System Biomolecule Molecule Atom 1020 Atoms 1010 Atoms 105 Atoms 103 Atoms 101 Atoms 1 Atom Thermodynamics Mesoscale: Quantum Biology? Quantum Chemistry Quantum Physics
  22. 22. Energy/Affinity Scale  Covalent bond 90 kcal/mol at 1.5 Å  Ion-Ion 60 kcal/mol at 5 Å  Disulphide bond 40 kcal/mol at 2.2 Å  Salt bridge 4-7 kcal/mol at 2.8 Å  Ion-dipole 6 kcal/mol at 5 Å  Hydrogen bond 0.5-12 kcal/mol at 3-5 Å  VdW 1-4 kcal/mol at 3.5 Å  kT at 310K is ~0.6 kcal/mol  GTP/ATP hydrolysis (biological energy quanta): 3 kcal/mol-60 kcal/mol
  23. 23. Many discounted QM in biology because… • Life is big (cells) in comparison to photons/electrons where QM is applicable • Life is hot (and active) in comparison to where QM works best in cold isolated environments where it is currently studied [to keep QM coherence] • Life is wet in comparison to controlled QM experimental environments where it is studied in a vacuum to avoid environmental influences which decoheres QM effects • Life is slow in comparison to QM events where it is measured in milliseconds or less • Life is complex, requiring billions of particle relationships/bonds in comparison to simple QM relationships/entanglements involving < 100 particles • Life is not fuzzy (yes/no) and real in comparison to the QM random world which is probablistic multi value/states superpositions • Life is real, local, and stable in comparison to Heisenberg QM uncertainty and non-local realism • Life brings out discrete realism/information and QM always reverts to its fuzzy world • … BUT Nature is the nanotech MASTER!!!!! … so it was soon found out that IT can!! since QM works in the nano-world of BIO
  24. 24. • Collective dynamics of many freedom degrees. • Life – a metastable state. • Various types of local and global order. • Structural and dynamic hierarchy, successive levels. • Biological complexity – order without repetition. • Short- and long-range correlations and interactions. • Living organisms are open, irreversible, disipative systems. • They are self-organized, optimal systems (->homeostasis), with cooperative interactions. • Nonlinear interactions, highly integrated dynamics. • Such features – to some degree in various complex non-living systems – but only organisms join them altogether. Features of life unsolved by molecular biology
  25. 25. Quantum Mechanics and Life  Quantum computers use entanglement and coherence  These states are fragile  environmental decoherence  keep cold & isolated  Biological systems  too “warm and wet”  Or are they?
  26. 26. Physiological Quantum Effects • Light detection by the human eye • Resonant recognition of aromatic molecules in olfaction (sense of smell) • Bird navigation • Photosynthesis • Mitochondrial Metabolism • Consciousness (?)
  27. 27. Quantum biology • N.Bohr, W. Heisenberg, E. Schrodinger, J. von Neumann, C. von Weizsacker, W. Elsasser, V. Weisskopf, E. Wigner, F. Dyson, A. Kastler, and others – QM essential for understanding life. • Quantum biology (QB): “speculative interdisciplinary field that links quantum physics and the life sciences” (Wikipedia) –Some directions : – Quantum metabolism. – “Biophoton” (ultraweak emission) statistics. – Photosynthesis, light harvesting – Solitons (Davydov), phonons, conformons, plasmons, etc. – Decoherence, entanglement, quantum computation. – Long-range coherent excitations – Froehlich. – QED coherence in cellular water – Vitiello,Preparata, Del Giudice.
  28. 28. • Herbert Fröhlich postulated a dynamical order based on correlations in momentum space, the single coherently excited polar mode, as the basic living vs. non-living difference. Assumptions: • (1) pumping of metabolic energy above a critical threshold; • (2) presence of thermal noise due to physiologic temperature; • (3) a non-linear interaction between the freedom degrees. Physical image and biological implications: • A single collective dynamic mode excited far from equilibrium. • Collective excitations have features of a Bose-type condensate. • Coherent oscillations of 1011-1012 Hz of electric dipoles arise. • Intense electric fields allow long-range Coulomb interactions. • The living system reaches a metastable minimum of energy. • This is a terminal state for all initial conditions (e.g. Duffield 1985); thus the genesis of life may be much more probable. Fröhlich’s long-range coherence in living systems
  29. 29. Morphogenetic fields • 1912:AlexanderGurwitsch introduced for the first time in biology the idea of a field as a supracellular ordering principle corresponding to spatial but immaterial factors of morphogenesis. • Kraftfeld,a field in which a force is exerted. • Gurwitsch tried to solve the biological problem of morphogenesis: How living tissues transform and transfer information about the size and shape of different organs. • Chemical reactions do not contain spatial or temporal patterns a priori, and that is why Gurwitsch looked for a "morphogenetic field". • Geschehensfeld,afield in which events, occur in an integrated, coordinated manner.Gurwitsch, A.G. (1912). Die Vererbung als Verwirklichungsvorgang, Biologisches Zentralblatt, vol. 32, no. 8, pp. 458-486.
  30. 30. Modern bioelectromagnetic field concepts • 1970 Presman:Review on Soviet research in bioelectromagnetism stimulated the breakthrough and beginning of modern theories • Non-equilibrium thermodynamics Organisms as open systems that exchange energy, matter and information –how they establish a stable state far from equilibrium A.Gurwitsch, E.Bauer, V.Vernadsky, and L.Bertalanffy. • Contributions to modern concepts • Negative entropy Organisms preserve their high order by feeding on negentropy (highly-organized energy) from the environment Erwin Schrodinger, Albert Szent Gyorgyi, Ilya Prigogine. • Ilya Prigogine introduced his theory of dissipative structures, a discovery that won him the Nobel Prize in Chemistry in 1977 • •Herbert Frohlich introduced his concept of biological coherence.
  31. 31. Anatomy of the Intelligent Cell Gunther Albrecht-Buehler, NWUniv Chicago
  32. 32. Centriole-Mitochondria Connection (G. Albrecht-Buehler) The control center detects objects and other cells objects by pulsating near infrared signals. Cells have ‘eyes’ in the form of centrioles. They are able to detect infrared signals and steer the cell movements towards their source. Percentage of cells that removed the light scattering particle as a function of wavelength. The near infrared wavelength, between 800 and 900 nm, is most attractive. Extension of surface projections towards the pulsating light source.
  33. 33. Centrioles Basal bodies and centrioles consist of a 9-fold arrangement of triplet microtubules. A molecular cartwheel fills the minus end of the cylinder; it is involved in initiating the assembly of the structure. The cylinders – now called cetrioles – are always found in pairs orientated at right angles. Dense clouds of sattelite material associated with the outer cylinder surfaces are responsible for the initiation of cytoplasmatic microtubules.
  34. 34. DNA TF MT Free Tubulin Dimer Nuclear Wall Membrane Cytoplasm MT Bundle Chromosome Pair Centrosome Mitotic Cell . . . . . Microtubule: function
  35. 35. Quantum Metabolism Metabolic activity is localized in the biomembranes (1.) Plasma membrane  Uni-cells (2.) Thylakoid membrane  Chloroplasts in plants (3.) Inner membrane  Mitochondria in animals
  36. 36. Evidence for quantum coherence •Engel 2007: Quantum Beating: direct evidence of quantum coherence •Lee 2007: “correlated protein environments preserve electronic coherence in photosynthetic complexes and allow the excitation to move coherently in space” •Sarovar 2009: “a small amount of long-range and multipartite entanglement exists even at physiological temperatures.” •What does this mean for other biological systems?
  37. 37. Photosynthesis
  38. 38. Photosynthesis  Light energy absorbed by light harvesting complexes (LHC)  LHCs transfer energy to photosynthetic reaction centers (RCs)  RCs chemically store some energy (ie. ATP)  Remaining energy removes electrons from water or sulphates.  Electrons used to turn CO2 into organic compounds.
  39. 39. Photosynthesis  LHCs are pigment-protein antennas,  Densely packed chromophores efficient at transporting excitation energy in disordered environments (~99%)  Chromophore number and spacing vary but separations on the scale of 15˚A
  40. 40. FMO Complex in C. Tepidum  From a New Zealand hot spring.  Grow in dense mats over hot springs that contain sufficient hydrogen sulfide  LHCs made of bacterio -chlorophylls (Bchls)
  41. 41. FMO Complex in C. Tepidum
  42. 42. FMO Complex in C. Tepidum
  43. 43. Quantum Search Algorithms  Mohseni et. al. investigated quantum search algorithms in FMO based on the Cho et. al. Hamiltonian
  44. 44. single-celled algae have a light-harvesting system where quantum coherence is present. A UNSW Australia-led team has discovered how cryptophytes that survive in very low levels of light are able to switch on and off a weird quantum phenomenon that occurs during photosynthesis.
  45. 45. Quantum Entanglement  Evidence for the existence of entanglement in the FMO complex for picosecond timescales  Prediction of entanglement is experimentally verifiable because of these timescales.  Evidence for the beneficial role of quantum coherence in LHC excitation transport.  Entanglement a by-product of quantum coherence.
  46. 46. Quantum Beating and Coherence  Superposition states formed during a fast excitation event  allows the excitation to reversibly sample relaxation rates from all component exciton states,  efficiently directs the energy transfer to find the most effective sink.  The system is essentially performing a single quantum computation  Analogous to Grover’s algorithm,  Hamiltonian describing both relaxation to the lowest energy state and coherence transfer
  47. 47. Extensions Penrose and Hameroff suggest quantum computations in microtubules as playing a role in higher brain functions “Aromatic" ring structures provide regions of delocalizable/ polarizable electrons and electronic excited states. Tryptophan has an "indole ring" giving it a high electron resonance and fluorescence  indole rings may take part in energy transfer (photon exchange). Unexplained 8 MHz non-thermal radiation from microtubules. Tryptophan path in tubulin and MT Spacing ~ 20 Ang
  48. 48. A lattice of seven tubulin dimers as found in the microtubule lattice. Red lines connect tryptophans, and rectangles show four possible winding patterns. (The work of Alexander Nip, Université de Montréal.)
  49. 49. • In photosynthesis coherent energy transferred between chromophoric chlorophyll molecules. • Tubulin possesses a unique arrangement of chromophoric tryptophan amino acids. • Spacing comparable to photosynthetic units. Chromophore Network in Tubulin 55
  50. 50. Dipole Interactions in Tubulin • Chromophores transfer energy via transition dipole moments. • Tryptophan may be excited by 260 - 305 nm light (UV range) • Possesses a transition dipole moment of ~ 5.5 - 6 Debye • Non-negligible dipole coupling strengths Vmn = ((5.04m2 ) ( ˆmm × ˆmn -3( ˆmm × ˆRmn )( ˆmn × ˆRmn )) Rmn 3 H = emam t am + Vmn ( n<m 8 å m=1 8 å am t an + an t am ) 56
  51. 51. Tryptophan excitations in tubulin In collaboration with Travis Craddock
  52. 52. Excitation Coherence in Tubulin • Diagonalization of the Hamiltonian Matrix yields the excitation energies and distribution. • Values indicate a significant delocalization of the excitation over several tryptophan residues. • Quantum and local field corrections of protein environment taken into account. 58 DecreasingEnergy <10% 10-20% 20-30% 30-40% 40-50% 50-60% 60-70% 70-80% 80-90% 90-100%
  53. 53. Regulation of the Metabolic Pathway Regulated by several Mechanisms: •Product Inhibition •Feedback Inhibition •Reactant Activation A lot of redundancy among pathways
  54. 54. Electron Transport Chain – Oxidative Phosphorylation •Movement of electrons from NADH to terminal electron acceptor through Redox reactions •Release of energy as electron moves from high to low Redox potential facilitates movement of H+ across the mitochondrial inner membrane •Movement of H+ back across membrane through ATPase results in ATP synthesis from ADP
  55. 55. Energy consumption in organisms history 1. Laplace and Lavoisier (1780) Respiration is a form of combustion Metabolic rate could be measured by the amount of heat produced by the organism • Rubner (1904) i. Body size and metabolic rate of domesticated animals ii. Body size and life span 1. Kleiber (1940) Systematic study of the relation between basal metabolic rate and body size
  56. 56. Body Size – Metabolism Allometric Relation Y = α Wβ W = body size The Parameter Y a) Measures of physiological time: I. Respiratory Cycle II. Cardiac Cycle b) Measures of metabolic activity: I. Basal metabolic Rate II. Field metabolic Rate III. Maximal metabolic Rate Y = Physiological time : β ~ 1/4 Y = Basal metabolic rate: uni-cells: β = 3/4 plants: 2/3 < β < 1 animals: 2/3 < β < 3/4
  57. 57. Problems What is the mechanistic basis for these scaling rules? Issues to be addressed 1. Variation in proportionality constant α (Birds) > β (Mammals) 1. Variation in scaling exponents β (Plants) > β (Animals) β (Large mammals) > β (Small birds)
  58. 58. Quantum Metabolism Metabolic activity has its origin in biochemical processes which occur within biomembranes. The theory integrates three classes of phenomena: i. The chemiosmotic coupling between the electron transfer process and ADP phosphorylation ii. The storage of this metabolic energy in vibrational modes among the molecular components of the membrane iii. The quantization of the energy stored in the membrane
  59. 59. QM: molecular phenomena 1. Chemiosmotic coupling: Mitchell (1970) Process with ADP phosphorylation Coupling of electron transport • Energy storage: Froehlich (1968) Storage of metabolic energy in the dipolar oscillation modes among the molecular components • Energy quantization: After Debye (1912) Analogies between: coupled oscillations of atoms in crystalline solids and coupled oscillations of molecules in biomembranes
  60. 60. Results – e vs. V0, T = 300 K • Only Type IIB behaviour below e of 7.8. • A narrow range of parameters are defined for MTs capable of information processing.
  61. 61. L. Demetrius (2003) Quantum statistics and allometric scaling of organisms. Physica A: Statistical Mechanics and its Applications 322:477-490.
  62. 62. Biological “Planck constant”: E=kf • Human energy production: 1021 ATP molecules per second • There are on the order of 3.5 × 1013 cells in the human body • each cell has on the order of 103 mitochondria, so there are approximately 3.5 x10 16 mitochondria in the human body • hence approximately 3 × 104 ATP production events per mitochondrion per second. • net effect: conversion of 1 molecule of glucose into 38 molecules ATP. • each ATP synthase operates at a rate of 600 ATP molecules/s, we estimate that each mitochondrion has on average 50 ATP synthase enzymes. • Consequently, the frequency of the oxidative phosphorylation reaction is approximately 1,000 cycles per second for each complex. • Using: E0 = κf where E0 ~ 10 -20 J is the biological energy quantum we conclude that the biological equivalent of Planck’s constant is κ = 10-24 J s which, when compared to the physical Planck’s constant h = 6.6 × 10−34 J/s, gives a ratio of κ/h = 1.8 × 1011. • The physical Planck’s constant corresponds to a single atom, the biological constant corresponds to a mitochondrion. There are approximately 1.9 × 1014 atoms per cell and approximately 1000 mitochondria per cell, which gives 1.9 × 1011 atoms per mitochondrial “sphere of influence” within the cell.
  63. 63. The Microtubule Cytoskeleton Hameroff et. al., In: Toward a Science of Consciousness pp. 507-540 (1996) • Microtubules (MTs) form elaborate networks in neurons • Learning/memory involves reordering of the MT cytoskeleton. • Cognitive diseases (Alzheimer ’ s, Dementias, Bipolar Disorder, Schizophrenia) show dysfunction in the neuronal MT cytoskeleton. 76
  64. 64. Dendritic spine has microtubules interacting with membrane receptors.
  65. 65. Challenge: integration of various levels in a hierarchy Building a bridge between  the molecular level (cytoskeleton)  the membrane level (synaptic activity, AP)
  66. 66. Microtubule: structure  is made of a- and b- tubulins a b
  67. 67. Source of UV Radiation • Tryptophan requires UV radiation to be excited. • Is there a UV source inside cells? • Rahnama et. al. 2010 (arxiv.org/pdf/1012.3371) points out: – Absorption/emisison of tryptophan dependent on tubulin conformation – Microtubule polymerization is sensitive to UV (Staxén et al. 1993) – Mitochondria are sources of biophotons at this wavelength (Vladimirov and Proskurnina 2009, Hideg et al. 1991, Batyanov 1984) – Microtubules co-localize with mitochondria (Tuszynski, Microtubule Plenary, TSC 2011) http://www.mitochondrion.info/
  68. 68. Quantum link to function • Mitochondria provide UV source. • TRP excitations influenced by: – C-terminal tail positions – Microtubule associated proteins (MAPs) – Post-translational modifications • Resulting TRP dipole could affect: – C-terminal tail position – MAP attachment – Ionic currents around MTs • Quantum computation in TRPs could couple to MT-MAP computations 81
  69. 69. Modes of Communication/Signaling C-termini oscillations Electron hopping Tryptophan excitations Conformational changes
  70. 70. Brain questions • What makes the brain special? • What is consciousness? • Where is memory stored? • What is the computational power of the brain? • Is information processing in the brain classical, quantum, or fractal resonant (or something else)? • How can the brain work with so low power compared to computers?
  71. 71. The Human Brain: a computer cluster of computers • 1011 neurons in our brains • 1015 synapses operating at about 10 impulses/second (CPUs have 108 transistors) • Approximately 1016 synapse operations per second i.e. at least 10 PF ( Blue Gene performs at 1015 FLOPS=1 PETAFLOP) • Total energy consumption of the brain is about 25 watts (Blue Gene requires 1.5 MW) • Is there anything special inside each neuron? • YES, probably another computer that has both classical and quantum processors http://www.merkle.com/brainLimits.html
  72. 72. Potential for Memory Storage, Computation and Signaling in MTs  C-termini states (4 per dimer)  Electron hopping (4 per dimer)  Conformational changes/GTP states (2 per dimer) Phosphorylation states: 4 per dimer Total: 128 states/ dimer 100 kB/MT or 1 GB/neuron 100 billion neurons: 1020 bits/brain At microsecond transitions: 1026 flops= 100 yottaflops!!! BlueGene 1015 flops = 1 Petaflop
  73. 73. Energy limitations on information processing in the brain • P = 25 W but 60% used by ribosomes on protein synthesis alone • Approximately 70% of the rest used to maintain temperature, so we assume that 3 W at most is used for information processing • Cost of 1 bit is at least 3 10 -21 J, if ATP used, then 5 10 -20 J • The amount of information processed then depends on the clocking rate but ranges from 109 to to 10 10 bits/neuron/sec. • The clocking time ranges from 1 ns for a microtubule exciton to 1 ms for protein conformational changes to 1 ms for action potentials to 1 s for brain’s Libet pre-processing times. So: the number of bits per time step per neuron can vary between: 1-10 (ns), 1000-10,000 (ms), 1,000,000-10,000,000 (ms) to billions (s) Hierarchical model of information processing: Few fast transitions but many processing units ( 1018 tubulins in brain) Many slow transitions but few processing units (1011 neurons per brain)
  74. 74. Fractal organization on time and spatial scales Ghosh S., et al. Information 2014, 5:28-100. . Hierarchical model of information processing: Few fast (ns) transitions but many processing units ( 1018 tubulins in brain) Many slow (s) transitions but few processing units (1011 neurons per brain)
  75. 75. Brain has a bandwidth of 1030 Hz (from 10-15 to 1015 Hz) Anirban Bandhopadhyay.
  76. 76. Microtubules in neurons
  77. 77. Focusing on the Dendrite Previous and current study future study
  78. 78. MTs and Neurodegenerative diseases  A common feature: a deteriorating cytoskeleton:  Typical sequence of events: DNA Mutation or PTM ->misfolding->aggregation ->loss of function-> Neurodegenration Examples: AD, PD, CJD, ALS, HD, TBI  Bioengineered cytoskeletal protein products or pharmacological agents can stabilize, or destabilize the existing cytoskeletal matrix, and prevent neuronal degeneration resulting from multiple causes.
  79. 79. Alzheimer’s disease  Both the neuronal and cognitive consequences of cytoskeletal protein disruption  Cortical neurons in AD brain accumulate hyperphosphorylated tau, a MAP, which triggers the formation of neurofibrillary tangles.  Neurons in AD demonstrate impaired axonal transport and compromised MT matrixes, even in the absence of neurofibrillary tangles.  Beta amyloid protein accumulates in the ECM
  80. 80. 93 Alzheimer’s Disease (AD) • Alzheimer’s disease (AD) characterized by b-Amyloid plaques (bAPs) and neurofibrillary tangles (NFTs). • NFTs formed from hyperphosphorylated MAP-tau. • bAPs correlate with cell death, NFTs with memory impairment. • Link between these unknown. 93
  81. 81. MT’s in Parkinson’s and Huntington’s diseases  Mutations in genes for α-synuclein and parkin proteins lead to familial Parkinson’s, and contribute to sporadic cases  Altered α-synuclein and parkin proteins result in impaired axonal transport of dopamine-containing vesicles. Dopamine is released and degraded into toxic by-products that kill dopamine-containing neurons.  Huntington’s chorea: an autosomal dominant disorder caused by mutations in huntingtin protein, characterized by polyglutamine repeat expansion. Polyglutamine repeats in huntingtin protein disrupt its binding to microtubules resulting in impaired axonal transport.
  82. 82.  Stroke and traumatic brain injury – The cytoskeleton is disrupted following ischemia due to blood hemorrhage, occlusion, or injury.  Epilepsy – Microtubule-associated protein, MAP2, shows decreased phosphorylation in parts of brain where epileptic seizure activity is prevalent. This is indicative of impaired cytoskeletal dynamics.  Amyotropic lateral sclerosis (ALS) – Axonal transport is compromised in this movement disorder as a result of cytoskeletal disruption.  Charcot-Marie-Tooth disease – A cause of impaired axonal transport may be stalled microtubules that assume a hyperstabilized state due to mutated dynamin2 protein.  Multiple sclerosis – This demyelinating disease also involves disruption of axonal cytoskeleton.
  83. 83. 96 What is Memory?  Ability to encode, store and recall information.  Postulated to be represented by vastly interconnected networks of synapses in the brain.  Memories formed by changing synaptic strengths (Hebbian Theory / Synaptic Plasticity)  Supported by the paradigm of Long-Term Potentiation (LTP)  How is this achieved on the molecular level?  What is the underlying substrate? 96
  84. 84. Memory storage Holographic: Lashley, Pribram: mouse studies Fractal, resonant, tubulin: Anirban Sheldrake: Memories not stored in the brain at all caterpillar study, slime mold, ants Plants that learn. Bacteria that learn. Mice descendants that do mazes more quickly
  85. 85. • Is memory localized? Persistence of long-term memory after head regeneration Memory Storage Shomrat & Levin, Journal of Experimental Biology 216:3799-3810, 2013 98
  86. 86. • If we want to listen to our intuition or gut feeling, what information are we accessing? • Is this information holographic or localized? Are microtubules involved to access it? • Can we measure this ability? – Galvanic skin response (lie detector) – Heart rate variability – Noninvasive nanosensor biofeedback Memory, Intuition, Gut feeling 99
  87. 87. Capacity of Human Memory?  Von Neumann (1950) – 3x1020 bits Total life experience -we agree  Anatomists (1970’s) – 1013-1015 synapses allowing 1016 syn-ops/sec  Landauer (1986*) – 109 bits  assumed we retain 2 bits/sec of visual, verbal, tactile, musical memory!  Human lifetime ~ 2.5 billion seconds Thomas K. Landauer "How Much Do People Remember? Some Estimates of the Quantity of Learned Information in Long-term Memory" Cognitive Science 10, 477-493, 1986
  88. 88. Historical Perspective  1 Human = 1019 bytes  # of Words ever written = about 1016 bytes  # of Words ever spoken = about 1019 bytes  Data on all Digital Media = 3x1019 bytes http://www.lesk.com/mlesk/ksg97/ksg.html
  89. 89. 102 Cytoskeletal Involvement in Memory  Synaptic plasticity:  neuronal differentiation, movement, synaptogenesis and regulation.  All involve cytoskeletal remodeling.  Assembly/reorganization of Microtubules (MTs) and MAP cross bridges  Directing motor proteins transporting molecular cargo along MTs  MT-MAP alterations correlate with memory formation.  Dysfunction affects learning/memory.  MT disrupting agents affect memory. 102
  90. 90. Calmodulin kinase complex CaMKII as memory read/write device
  91. 91. 104 Information Storage • Phosphorylation conveys information. • Each CaMKII – MT event conveys 64 - 5218 bits. • Each kinase event releases ~20 kT • Robust encoding 104
  92. 92. Memory storage Long-term Potentiation (LTP): synaptic strength Craddock: MT phosphorylation “Cytoskeletal Signaling: Is Memory Encoded in Microtubule Lattices by CaMKII Phosphorylation?” by Craddock, Tuszynski, Hameroff (2012).
  93. 93. 106 Ca2+/Calmodulin Kinase II (CaMKII) • Vital for memory (long term potentiation – LTP) • Single point mutations cause memory impairment. • Suggested as a molecular switch for memory. • Records synaptic activity, retaining a ‘memory’ of past Ca2+ influx events in terms of activated phosphorylation states. 106
  94. 94. 107 CaMKII Phosphorylates MT • CaMKII phosphorylates S/T residues in many protein substrates. • Tubulin one target of CaMKII. • a,b-tubulin phosphorylated on S/T beyond residue 306. • Phosphorylation alters MT interactions with MAPs. 107 Serine Threonine Positive Negative
  95. 95. 108 Geometric Matching •Basic homology models of CaMKII and MT. •Positional geometry aligned. •Kinase regions found to closely match MT lattice geometry with multiple forms. 108
  96. 96. 109 Electrostatic Matching • Field lines convergent showing electrostatic attraction. • ~10 kT/e (6 kcal/mol at 310 K) attraction for single kinase. • Considerable binding energy. 109
  97. 97. 110 Information Storage • Phosphorylation conveys information. • Each CaMKII – MT event conveys 64 - 5218 bits. • Each kinase event releases ~20 kT • Robust encoding 110
  98. 98. How does this affect neural function? 111 • PTMs may serve as tags for MAPs to bind. • Control: • Neural structure • Transport • Synapse structure • TRP excitation
  99. 99. Potential base for Universal Logic 112 AND XOR
  100. 100. Computational predictions and partial experimental conformation exists for the binding of psychoactive drugs to tubulin which suggests enhancement of cognitive functions by the action of these drugs This is consistent with the Hameroff hypothesis of the quantum states of tubulin being involved (if not responsible) for mental processes. Anesthetics quench quantum hopping Psychoactive drugs enhance quantum transitions Our hypothesis: these compounds interact with the quantum information processing in MTs Mental Activity, Microtubules and Quantum Biology
  101. 101. Caffeine THC Marijuana LSD Adrenaline Nicotine MDMA Ecstasy Chocolate Methamphetamine Xanax Heroin Rohypnol (Date rape) Alcohol
  102. 102. What about Consciousness? • Much harder to define. • Related to brain function and memory. • Penrose-Hameroff “Orch OR” most comprehensive extended thcory • Quantum computation in brain MTs. • Anesthetics inhibit quantum states. • But, isn’t biology too “warm and wet” for quantum effects? • Recently, quantum coherent energy transfer shown photosynthetic systems. • Can microtubules support similar phenomena? • Could anesthetics inhibit this phenomena? 116
  103. 103. Anesthetic-Microtubule Interactions?  Hypothesis: The microtubule (MT) network in dendrites is related to memory, and interaction with anesthetics can influence consciousness and alter memory formation.  Anesthetics natural probe for functional sites of consciousness  Memory formation and learning rely on normal MT cytoskeleton functioning  Postoperative Cognitive Dysfunction (POCD)  Exacerbation of diseases (Alzheimer’s, FTD, Schizophrenia) following anesthesia http://www.brainleadersandlearners.com/wp- content/uploads/2008/09/blog-brain-business2.
  104. 104. GAs Possess Dissimilar Structure Inhaled Intravenous Propofol Ketamine Etomidate
  105. 105. 119 What about anesthetics? 119 • Anesthetics provide analgesia, hypnosis, paralysis and amnesia. • Volatile anesthetics reduce polymerized MTs • MT to macrotubule transformation by halothane. • Halothane modifies colchicine-tubulin binding. • Tubulin altered out to 3 days by desflurane. • Tubulin altered out to 28 days by sevoflurane in rat. • Halothane binds specifically to tubulin in humans • Tubulin is changed by halothane and isoflurane in rat. • Of ~500 detectable proteins, tubulin among the ~2% affected by halothane, and ~1% altered by isoflurane (1 of 3 affected by both) • Location/ mechanism of interaction unknown
  106. 106. 120 • 47 Distinct Sites found • 9 sites found to persist for more than 70% of the 5 ns simulation. • Of these 9, key sites of interaction include: – GTP binding site (responsible for dimer stability) – Colchicine binding site (a MT depolymerizing agent) – Vinca Alkaloid binding site (a MT depolymerizing agent) – Putative zinc binding sites (involved in MT polymerization) • Findings indicate only longitudinal/intradimer interactions are affected. Putative Anesthetic Binding Sites 120
  107. 107. Anesthetics and Tryptophan Excitation • Anesthetics possess a large dipole moment. • Putative anesthetic sites lie as close as 7 Å to tryptophan residues. • Anesthetic dipole can influence tryptophan transition dipoles. • Plausible that anesthetics interfere with potential energy transfer. 121
  108. 108. Quantum Psychology The Development of a New Formalism: Second Quantization: Transitions between Normal States of Mind (Maslow’s hierarchy of needs) Bosons and Fermions Creation and annihilation operators Commutator and anti-commutator algebras Quantum energy states and the action of creators and annihilators on energy eigenstates (excitation and de-excitation processes) In mental states, the processes that either spontaneously or by external intervention take the subject either to a higher level of mental excitation or towards depression Excitation in affective or psychotic terms Coherent states and squeezed states
  109. 109. Psycho-Pathology • The Development of a New Formalism: Q-Deformed Algebras and the Distorted States of Mind in Mental Diseases • q-bosons and q-fermions • q-statistics • the number of q deformations and the strength of deformation • examples: an extension to quaternion values of the deformation parameter • I= affective polarization (Fermi-Dirac statistics) • J=cognitive efficacy (Superpositional probability) • K=social integration (Bose-Einstein statistics) • defining mental state axes in stages, (1) psychotic-non psychotic; (2) affective-euthymic: (3) impulsive-controlled, (4) anxious – not anxious: (5) autononous – enmeshed;
  110. 110. Connection to clinical psychiatry • multidimensional classification systems taking account of quantum statistics • transitional states between normality and illness (even healthy people at times can experience psychiatric problems • transitional states grading severity of illness and predicting clinical course • predictable and random effects determining clinical course and catastrophic events
  111. 111. Future Goals • To use quantum models to create a more adequate explanatory framework for psychopathological phenomenology. • To enlist quantum-formal actuarial tools for rigorous prospective estimation of the impact of random and potentially predictable events on the evolution of illness states and catastrophic events • To use quantum statistics in actual risks assessments in a prospective and hence more realistic context.
  112. 112. 126 The Problem with Embryology Egon Schiele Kneeling Male Nude (Self- Portrait). 1910. http://www.moma.org/exhibitions/schiele/artistwork. html Nikas, G., T. Paraschos, A. Psychoyos & A.H. Handyside (1994). The zona reaction in human oocytes as seen with scanning electron microscopy. Hum. Reprod. 9(11), 2135-2138. ? How did your spherically symmetrical egg turn into such a highly asymmetrical shape? 1,000,000 µm = 1 meter
  113. 113. Staging of Axolotl Development 127 Top views  Side views  Bottom views  Side view L R Bordzilovskaya, N.P., T.A. Dettlaff, S.T. Duhon & G.M. Malacinski (1989). Developmental-stage series of axolotl embryos. In: Armstrong, J.B. & G.M. Malacinski, Developmental Biology of the Axolotl, New York: Oxford University Press, p. 201-219.
  114. 114. 128 Staging of Axolotl Development head tail right side Timing, at 20oC: Stage Time in hours What’s starting 2- 0 Synchronous cleavage 2 0.6 2 cells 3 2 4 cells 8 16 Blastulation, asynchronous cleavage 10 26 Gastrulation 14 36 Neurulation 19 69 Neural tube, eyes, somites 44 340 = 14 days Mouth opens, hatching 16
  115. 115. 129 Stages 23-35 of Axolotl Development
  116. 116. 130 Stages 36-44 of Axolotl Development No increase in dry weight since it was an egg!
  117. 117. 131 The Cell State Splitter MF = microfilament ring MT = annular apical microtubule mat IF = intermediate filament ring
  118. 118. 132 The Unstable (Bistable) Mechanical Equilibrium between the Microfilament Ring and the Microtubule Mat in the Cell State Splitter Gordon, R., N.K. Björklund & P.D. Nieuwkoop (1994). Dialogue on embryonic induction and differentiation waves. Int. Rev. Cytol. 150, 373- 420. MF ring is a torus of radius r and cross sectional area A, empirically of constant volume V Force F A V = 2πrA, so F 1/r, a hyperbola
  119. 119. 133 The Differentiation Tree Embryogenesis may be modelled as a bifurcating sequence of tissues generated as each tissue is split into two new tissues by pairs of contraction and expansion waves. Unsolved problems: 1. What launches these waves at specific times and locations? 2. What confines their trajectories? 3. What stops them?
  120. 120. 134 The Differentiation Tree is the Physical Embodiment of Conrad Waddington’s Epigenetic Landscape Held Jr., L.I. (1992). Models for Embryonic Periodicity, Basel: Karger.
  121. 121. 135 Nouri, C., R. Luppes, A.E.P. Veldman, J.A. Tuszynski & R. Gordon (2008). Rayleigh instability of the inverted one- cell amphibian embryo [In: "Physical Aspects of Developmental Biology" special issue]. Physical Biology 5, 015006. in collaboration with: Institute of Mathematics & Computing Science University of Groningen
  122. 122. 136 Cortical Rotation • Forced Cortical Rotation: Direction of the last forced rotation determines the left-right symmetry. Gerhart et al (1989) Many observers report the alignment of microtubules during and after the cortical rotation
  123. 123. 137 When an egg is inverted: • 1. The egg will not develop at all. • 2. It will develop but with colors of dorsal and vegetal . regions exchanged. We suggest that it has to do with the way the heavy fluid on top sloshes down the inverted egg’s volume, Case 1 corresponds to symmetric fluid flow. Case 2 to asymmetric flow. One of the following happens: Wakahara, et al (1984), Neff, et al (1986), Malacinski and Neff (1989),
  124. 124. 138 Working Hypothesis • Cortical rotation aligns microtubules attached to the inner surface of the cortex via global torque T • Microtubules drive the cortical rotation by polymerization and/or motor molecules attached to them, each contributing torque Ti, with T = Ti • This can be represented as a mean field Ising model in which the mean field is precisely the same as the local field
  125. 125. 139 ComFlo Computational Fluid Dynamics Simulation Symmetric sloshing of the heavier liquid (yolk) in the inverted egg. This particular case has too low a viscosity.
  126. 126. 140 Summary • Memory depends on the neuronal cytoskeleton. • This basis yields: – A molecular mechanism of synaptic plasticity and memory encoding. – A link between the hallmarks of Alzheimer’s Disease. – A mechanism for the amnesiac affect of anesthetics. • Quantum phenomena in microtubules could serve as a basis for consciousness, and anesthetics could potentially inhibit this phenomena. 140
  127. 127. Implications for Health and Disease Quantum coherence= a healthy state Decoherence=transition to disease Location of decoherence determines “disconnection” from the rest of the organism; canonical example: cancer 141
  128. 128. • Already doing this with EKG, EEG for diagnostic purposes Body: Bioelectric medicine 142
  129. 129. • Is this an avenue for non-invasive signals? – Yes • Able to deliver quality information on the health of the body? – Yes • Able to detect disease at an early stage? – That’s what we’re working on Bioelectric medicine 143
  130. 130. • Bioelectric signals • Morphogenesis • Cell membrane (cancer depolarized) Michael Levin 144
  131. 131. Morphogenesis and cancer Levin, BioSystems 109:243-261, 2012 145
  132. 132. • Hypothesized by Dr. James Oschman • High-speed electric communication system made up of biological wires in the body: networks of: – Microtubules – Actin – Collagen The Living Matrix Friesen et al. BioSystems 127:14-27, 2015 146
  133. 133. Microtubule conductivity Friesen et al. BioSystems 127:14-27, 2015 Coherent Energy Transfer 147
  134. 134. • Flexible, transient electronics Nanotechnology advances John A. Rogers Group University of Illinois 148
  135. 135. • NanoFET (Nano Field Effect Transistor) • Intracellular electrical recordings • Charles M. Lieber group (Harvard) Nanotechnology advances Tian and Lieber, Annu. Reb. Anal. Chem 6:31-51, 2013 149
  136. 136. • Nanosensors to measure health of body, in terms of communication within cells and between cells and between organs and tissues (pictures of nanosensors) • Possible explanation of acupuncture meridian system, and 24 hour monitoring of this system • Further understanding of microtubule to understand possible quantum computation and access to holographic information • Better models to understand why processes like NLP work Bioelectronic future 150

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