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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
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
An observer cannot observe a microscopic system
without altering some of its properties (an observer
QUANTIZATION of energy is yet another property of
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)
00 )()( h
The Photoelectric Effect
A Photocell is Used to Study the Photoelectric Effect
Larger frequency, means smaller wavelength, and larger Energy=hf.
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)
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
If 1 and 2 represent two physically-realizable states of the
system, then so is their linear combination
The Second Postulate of Quantum Mechanics
If a system is in a quantum state represented by a wavefunction ,
is the probability that in a position measurement at time t the
particle will be detected in the infinitesimal volume dV.
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)
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
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
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.
Examining the time-dependent SWE, one can also define the following operator for the
Describes well quantum vibrational modes of molecular gases
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?
– superposition of states
– “spooky action at a
distant particles affecting
one another without
Quantum Mechanics and Life
Five Gifts of Quantum Mechanics to
physicists think everything reduces to physics
But interactions matter:
hierarchies of systems form
nucleic acids proteins
(valence is important)
electrons & protons solids
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
No conceivable computer could store a list of
I objects, and even if it could, there would be
no time to inspect it !
Dimensions Matter, too
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
Many discounted QM in biology because…
• Life is big (cells) in comparison to photons/electrons where QM is
• Life is hot (and active) in comparison to where QM works best in
cold isolated environments where it is currently studied [to keep QM
• 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 <
• 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
• 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
• 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
Quantum Mechanics and Life
These states are
keep cold & isolated
too “warm and wet”
Or are they?
Physiological Quantum Effects
• Light detection by the human eye
• Resonant recognition of aromatic
molecules in olfaction (sense of smell)
• Bird navigation
• Mitochondrial Metabolism
• Consciousness (?)
• 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.
• 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
• 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
• 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.
Modern bioelectromagnetic field
• 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.
Anatomy of the Intelligent Cell
Gunther Albrecht-Buehler, NWUniv Chicago
Centriole-Mitochondria Connection (G.
The control center detects objects and
other cells objects by pulsating near
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.
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.
Metabolic activity is localized in the biomembranes
(1.) Plasma membrane Uni-cells
(2.) Thylakoid membrane Chloroplasts in plants
(3.) Inner membrane Mitochondria in animals
Evidence for quantum coherence
•Engel 2007: Quantum Beating: direct evidence of quantum
•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?
Light energy absorbed by light harvesting
LHCs transfer energy to photosynthetic reaction
RCs chemically store some energy (ie. ATP)
Remaining energy removes electrons from water
Electrons used to turn CO2 into organic
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
FMO Complex in C. Tepidum
From a New Zealand
Grow in dense mats
over hot springs that
LHCs made of bacterio
Quantum Search Algorithms
Mohseni et. al.
FMO based on
the Cho et. al.
single-celled algae have a light-harvesting
system where quantum coherence is
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
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
Quantum Beating and Coherence
Superposition states formed during a fast
allows the excitation to reversibly sample relaxation
rates from all component exciton states,
efficiently directs the energy transfer to find the most
The system is essentially performing a single
Analogous to Grover’s algorithm,
Hamiltonian describing both relaxation to the lowest
energy state and coherence transfer
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
Tryptophan path in tubulin and MT
Spacing ~ 20 Ang
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.)
• 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
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 ))
H = emam
am + Vmn (
an + an
Tryptophan excitations in
In collaboration with Travis Craddock
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
Regulation of the Metabolic Pathway
Regulated by several Mechanisms:
A lot of redundancy among pathways
Electron Transport Chain – Oxidative
•Movement of electrons from NADH to terminal electron acceptor through
•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
Energy consumption in
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
Body Size – Metabolism
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
What is the mechanistic basis for these
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)
Metabolic activity has its origin in biochemical
processes which occur within biomembranes.
The theory integrates three classes of
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
iii. The quantization of the energy stored in the
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
among the molecular components
• Energy quantization: After Debye (1912)
Analogies between: coupled oscillations of atoms
crystalline solids and coupled oscillations of
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
L. Demetrius (2003) Quantum statistics and allometric scaling of organisms. Physica
A: Statistical Mechanics and its Applications 322:477-490.
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.
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.
Dendritic spine has microtubules interacting with
Challenge: integration of various levels
in a hierarchy
Building a bridge between
the molecular level (cytoskeleton)
the membrane level (synaptic activity, AP)
is made of a- and b- tubulins
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)
– Absorption/emisison of tryptophan dependent on
– 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)
Quantum link to function
• Mitochondria provide UV source.
• TRP excitations influenced by:
– C-terminal tail positions
– Microtubule associated
• Resulting TRP dipole could affect:
– C-terminal tail position
– MAP attachment
– Ionic currents around MTs
• Quantum computation in TRPs
could couple to MT-MAP
• 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
• How can the brain work with so
low power compared to
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
• 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
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=
BlueGene 1015 flops = 1 Petaflop
Energy limitations on information processing in
• 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)
Fractal organization on time and
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)
Brain has a bandwidth of 1030 Hz
(from 10-15 to 1015 Hz)
Focusing on the Dendrite
MTs and Neurodegenerative
A common feature: a deteriorating cytoskeleton:
Typical sequence of events:
DNA Mutation or PTM ->misfolding->aggregation ->loss of function->
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.
Both the neuronal and cognitive consequences of cytoskeletal
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
Beta amyloid protein accumulates in the ECM
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.
MT’s in Parkinson’s and
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
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
Stroke and traumatic brain injury – The cytoskeleton is
disrupted following ischemia due to blood hemorrhage, occlusion, or
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
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.
What is Memory?
Ability to encode, store and
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
What is the underlying substrate?
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
• Is memory localized? Persistence of long-term
memory after head regeneration
Shomrat & Levin, Journal of Experimental Biology 216:3799-3810, 2013
• 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
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
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
Cytoskeletal Involvement in
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
Dysfunction affects learning/memory.
MT disrupting agents affect memory.
Calmodulin kinase complex CaMKII as memory
• Phosphorylation conveys
• Each CaMKII – MT event
conveys 64 - 5218 bits.
• Each kinase event releases
• Robust encoding
Long-term Potentiation (LTP):
“Cytoskeletal Signaling: Is Memory Encoded in Microtubule Lattices
by CaMKII Phosphorylation?” by Craddock, Tuszynski, Hameroff
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.
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.
models of CaMKII and
•Kinase regions found to
closely match MT
lattice geometry with
• Field lines convergent
• ~10 kT/e (6 kcal/mol at
310 K) attraction for single
• Considerable binding
• Phosphorylation conveys
• Each CaMKII – MT event
conveys 64 - 5218 bits.
• Each kinase event releases
• Robust encoding
How does this affect neural function?
• PTMs may serve as tags
for MAPs to bind.
• Neural structure
• Synapse structure
• TRP excitation
Potential base for Universal Logic
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
This is consistent with the Hameroff hypothesis of the quantum
states of tubulin being involved (if not responsible) for mental
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
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
• Could anesthetics inhibit this
Hypothesis: The microtubule (MT)
network in dendrites is related to
memory, and interaction with
anesthetics can influence
consciousness and alter memory
Anesthetics natural probe for
functional sites of consciousness
Memory formation and learning rely
on normal MT cytoskeleton
Postoperative Cognitive Dysfunction
Exacerbation of diseases (Alzheimer’s,
FTD, Schizophrenia) following
GAs Possess Dissimilar Structure
What about anesthetics?
• Anesthetics provide analgesia, hypnosis, paralysis
• 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
• 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
• 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
Anesthetics and Tryptophan Excitation
• Anesthetics possess a large dipole moment.
• Putative anesthetic sites lie as close as 7 Å to tryptophan
• Anesthetic dipole can influence tryptophan transition dipoles.
• Plausible that anesthetics interfere with potential energy transfer.
The Development of a New Formalism: Second Quantization:
Transitions between Normal States of Mind (Maslow’s hierarchy of
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
• The Development of a New Formalism: Q-Deformed Algebras and the
Distorted States of Mind in Mental Diseases
• q-bosons and q-fermions
• 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;
Connection to clinical psychiatry
• multidimensional classification systems taking account of quantum
• 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
• 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.
The Problem with Embryology
Kneeling Male Nude (Self-
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
1,000,000 µm = 1 meter
Staging of Axolotl Development
T.A. Dettlaff, S.T.
Duhon & G.M.
series of axolotl
Armstrong, J.B. &
Biology of the Axolotl,
New York: Oxford
University Press, p.
Staging of Axolotl Development
Timing, at 20oC:
2- 0 Synchronous
2 0.6 2 cells
3 2 4 cells
8 16 Blastulation,
10 26 Gastrulation
14 36 Neurulation
19 69 Neural tube,
44 340 =
Stages 36-44 of Axolotl Development
No increase in dry weight
since it was an egg!
The Cell State
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.
waves. Int. Rev.
Cytol. 150, 373-
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
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
1. What launches these
waves at specific times
2. What confines their
3. What stops them?
The Differentiation Tree is the Physical Embodiment
of Conrad Waddington’s Epigenetic Landscape
Held Jr., L.I. (1992). Models for Embryonic Periodicity, Basel: Karger.
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,
in collaboration with:
Institute of Mathematics & Computing
University of Groningen
• 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
When an egg is inverted:
• 1. The egg will not develop at all.
• 2. It will develop but with colors of dorsal and vegetal .
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),
• Cortical rotation aligns microtubules attached
to the inner surface of the cortex via global
• 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
ComFlo Computational Fluid
Symmetric sloshing of the heavier liquid (yolk) in the inverted egg. This particular case has too
low a viscosity.
• Memory depends on the neuronal cytoskeleton.
• This basis yields:
– A molecular mechanism of synaptic plasticity and memory
– 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
Implications for Health and
Quantum coherence= a healthy state
Decoherence=transition to disease
Location of decoherence determines
“disconnection” from the rest of the organism;
canonical example: cancer
• Already doing this with EKG, EEG for
Body: Bioelectric medicine
• Is this an avenue for non-invasive signals?
• Able to deliver quality information on the
health of the body?
• Able to detect disease at an early stage?
– That’s what we’re working on
Morphogenesis and cancer
Levin, BioSystems 109:243-261, 2012
• Hypothesized by Dr. James Oschman
• High-speed electric communication system
made up of biological wires in the body:
The Living Matrix
Friesen et al. BioSystems 127:14-27, 2015
Friesen et al. BioSystems 127:14-27, 2015
• Flexible, transient electronics
John A. Rogers Group
University of Illinois
• NanoFET (Nano Field Effect
• Intracellular electrical
• Charles M. Lieber group
Tian and Lieber, Annu. Reb. Anal. Chem 6:31-51, 2013
• 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