Quantum Biology of The Eye

Quantum
Biology
of the Eye
Understanding the Essentials
Kambiz Thomas Moazed
123
Quantum Biology of the Eye
Quantum Biology of the Eye

Understanding the Essentials
New York, NY, USA
ISBN 978-3-031-32059-0 ISBN 978-3-031-32060-6 (eBook)

https://doi.org/10.1007/978-3-031-32060-6
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Preface
Entering the quantum era revolutionized our understanding and our concepts of
molecular and atomic particle behavior and their interactions. Applying the rules of
quantum physics to biology was considered impossible at the beginning.
The wet, warm, and noisy environment of biological systems seems hostile to
quantum interactions. Then comes the newer studies that one after another reveal
the existence of quantum effects on biology. This started with the discovery of the
quantum effect of photon energy transfer in plant’s green molecule of chlorophyll in
the photosynthesis process.
This was followed by the discovery of quantum vibration in olfactory receptors
involved in the sense of smell, which was followed by detection of avian magneto-
receptors in the bird’s retina required for their migration flights.
The new studies have now opened the door for understanding the human con-
sciousness and the perception of external senses. In retina, quantum processing has
been observed and plays a major role in vision processing. Visual processing is very
complex and is not limited only to the visual center at the visual cortex in the occipi-
tal lobe, but by simultaneous activation and stimulation of the entire brain.
In this book we start with the orientation to the basics of quantum physics, then
progress to the description of quantum biology and the basics of utilization of light
energy and applied rules of quantum physics on biological systems. Here we start
with the most basic form of light energy utilization which is photosynthesis in
plants, to magnetoreceptors in the retina of the migrating birds, to the more complex
role of retinal phototransduction of energy, and eventually the perception of visual
inputs and the concept of human consciousness.
New York, NY, USA Kambiz Thomas Moazed
v
Acknowledgments
• There were no financial assistance or compensation received from any organiza-

tion or companies towards the preparation of this book.
• All expenses for the preparation of the book were financed by me.
• Many thanks to my graphic designer David Folender who collaborated with me
to create all the images of this book.
• My sincere gratitude and thanks to my brother Hamid R. Moazed for his assis-
tance in preparation and editing of this book.
vii
Contents
1
Introduction to Quantum Physics�� 1
Discussion�� 1
What Is Quantum Physics?�� 2
Classical Physics Versus Quantum Physics �� 2
Characteristics of Quantum Physics�� 3
Specific Behavior of Quantum Physics�� 3
When Did It Start? �� 11
What is Quantum Biology?�� 17
What Are Its Applications?�� 17
References�� 18
2
Introduction to Quantum Biology�� 21
Discussion�� 22
When Did It Start? �� 22
Basic Information for Better Orientation�� 23
The Electron�� 23
Jablonski Diagram �� 28
Quantum Biology Tools �� 32
Nitrogen Vacancy (NV) Centers in Diamond�� 33
The Most Studied Fields of Quantum Biology�� 35
Photosynthesis in Plants�� 36
References�� 41
3
Classic Biology of Human Eye�� 43
The Anatomy Highlights of the Eye�� 44
The Physiology of the Light Absorption in the Retina�� 49
The Visual Cycle�� 52
The Photoreceptors, the Rod Cells, the Cone Cells, and the Ganglion
Cells �� 53
Activation of Rods and Cones�� 54
The Retinal Pigment Epithelium�� 58
The Bipolar Cell’s Function�� 60
ix
x Contents
Activation of Bipolar Cells�� 60

The Amacrine Cells�� 61
The Horizontal Cells�� 61
The Ganglion Cells�� 61
Activation of Ganglion Cells �� 63
Visual Phototransduction Steps�� 63
More Related Interesting Articles�� 64
References�� 64
4 Quantum Retina�� 67
Discussions�� 67
Radiation and Human Eye �� 70
Rhodopsin�� 71
Atomic Orbitals�� 72
Molecular Orbitals �� 74
Binding Orbitals Categories�� 74
Energy Level�� 75
Radiative Decay �� 77
Non-radiative Decay�� 77
Nuclear Response�� 78
Carbon�� 78
Lysine (C6H14N2O2)�� 79
From (E) to (Z) Isomerization�� 80
Isomerization�� 80
Time Fractions in Isomerization of 11-cis Retinal�� 82
Femto Scale�� 83
Femto Chemistry of Rhodopsin �� 84
References�� 85
5 Magnetoreception�� 87
Earth Magnetic Field (EMF)�� 88
References�� 99
6
Quantum Biology of Circadian Rhythms�� 101
Important notes for clarification�� 101
Discussions�� 102
Clock Genes and Signal Transduction Proteins �� 104
Molecular Effect�� 106
List of Neurotransmitters Involved in Circadian Cycles�� 106
List of Hormones Involved in Circadian Cycles�� 107
Light Exposure�� 108
Small Molecules and Drugs �� 109
Transcriptional-Translational Feedback Loops (TTFLs)�� 110
Light Entrainment�� 112
Pupillary Reflexes�� 113
Suprachiasmatic Nucleus (SCN)�� 113
Circadian Clock Networks:�� 113
Contents xi
Cellular Transcription-Translation Feedback Loop (TTFL)�� 114

The Molecular Interplay in Circadian Cycles�� 114
The Brain and Circadian Rhythms�� 115
Conclusion �� 115
References�� 115
7
The Quantum Biology of Consciousness and Visual Perception �� 119
Knowledge and Consciousness�� 120
Neurons�� 121
Synaptic Connections�� 122
Mitochondrion (Mitochondria = Plural)�� 124
Mitochondrial Respiratory Chain Complexes�� 125
Oxygen and Reactive Oxygen Species (ROS) �� 126
Radical Pair Mechanism (RPM)�� 127
Singlet Oxygen: (1O2)�� 127
Triplet Oxygen: (3O2) �� 129
Microtubules�� 130
Functional Architecture of Microtubules in Neurons�� 131
Quantum Biology of Microtubules�� 133
Microtubules Energy Transfer �� 133
Microtubules, Mitochondria ROS and Biophotons Interactions�� 134
Conditions Associated with Microtubule Abnormalities �� 136
Microtubule-Binding Core of the Tau Protein:�� 136
Biophoton or Ultraweak Photon Emission (UPE) �� 137
The Müller Cells�� 139
Retinal Müller Cells as Living Optical Fibers �� 140
Müller Cell Intermediate Filaments (IFs) and Quantum
Mechanism of Light Energy Transfer in the Retina�� 141
Tryptophan �� 142
Properties of Consciousness�� 146
Quantum Phenomena �� 146
Quantum Coherence�� 146
Quantum Superposition �� 147
Quantum Tunnelling�� 147
Quantum Entanglement �� 147
Magnetic Field Effect and Entanglement�� 147
Altered States of Consciousness�� 149
The Quantum Brain�� 152
The Quantum Vision�� 154
Human Perception as a Phenomenon of Quantization�� 155
The Role of Symmetry in Biology and Consciousness �� 155
References�� 157
Addendum�� 161
Index�� 171
Chapter 1
Introduction to Quantum Physics
Abstract
Entering the era of quantum physics opened the door to the emerging new field
of quantum biology. At first, its relevance to living organisms was not recog-
nized, yet as scientific knowledge and experimental studies evolved the new cor-
relation and recognition of quantum entities to the biology is being discovered.
This chapter is to introduce the birth of quantum physics which is the source
of the emergence of quantum biology. Basically, we discuss the birth of quantum
mechanics and its transformation into quantum biology and the main figures that
helped the evolution of quantum biology. In the next chapter, we will discuss the
essential information on what is the role of quantum physics in biology, and how
it affects the physiology of the different cellular structures and organs. As any
biological cellular structure is composed of molecules that are composed of
atoms and subatomic particles, it is expected that the quantum effect would be
applied to them. It is interesting that nature has used quantum biology to its
advantage and has billions of years of head start as we are beginning to learn how
it works today.
Discussion
One important note is that to think and understand the quantum world one should
erase the “normal” way of thinking and enter into the unintuitive, strange, and
spooky world that is called quantum physics.
© The Author(s), under exclusive license to Springer Nature 1

Switzerland AG 2023
K. T. Moazed, Quantum Biology of the Eye,
https://doi.org/10.1007/978-3-031-32060-6_1
2 1 Introduction to Quantum Physics
Also, we cannot discuss the quantum biology without knowing the basic and
fundamental information on quantum physics.
• What is quantum physics?
• When did it start?
• How can it be applied to Biology?
• What is quantum Biology?
What Is Quantum Physics?
The world of modern physics was established, but not started, by English mathema-
tician Isaac Newton in the seventeenth century.
The Newtonian physics, also called classical physics, was based on the three
rules of motion that are essential for calculating the relationship between the motion
of an object and the forces that acting on it. These rules are still applicable to large
objects as a good approximation today. But when the scientist started to work on
very small objects, say smaller than 10−9 m (1 nm), these laws could not be applied.
There was a need for a new set of rules for small objects and that was the birth of
quantum physics. The term quantum physics is the same as quantum mechanics
though the term mechanics emphasizes doing calculations. The birth of quantum
physics was inevitable in order to explain the strange world of small particles and
their effect on all objects.
Classical Physics Versus Quantum Physics
In the late nineteenth century and early twentieth century while physicists were
studying atoms and their components, they noticed that the laws of physics for very
small objects are different from the laws used for ordinary objects which are referred
to as classical mechanics or Newtonian mechanics.
This separated the field of physics into two categories:
• Classical mechanics: which can explain macroscopic phenomena of large objects
even the planets and the Maxwell equation in electromagnetics. However, there
were exceptions that could not be explained by classical physics such as super-
conductors, superfluids, lasers, and crystal dynamics.
• Quantum mechanics: which can explain microscopic phenomena such as pho-
tons and electrons. It has precise mathematical formulations as in Hermitian
operators and Hilbert spaces (Fig. 1.1).
Note that while there may appear to be a dichotomy of rules—one set for the
ultra-small and another for large objects, there actually is only one set of rules—
quantum mechanics—that governs the world of the small and the large. It is just that
Specific Behavior of Quantum Physics 3
Fig. 1.1 Quantum physics applies to small size particles as can be seen in the examples above
the effects of quantum mechanics are so minuscule on large objects that they can in
most parts be ignored, and classical mechanics can be used instead as a very accu-
rate approximation.
Characteristics of Quantum Physics
Multiple interpretations: There are many interpretations on quantum phenomena

and rules and there are still many controversies among the physicists [1].
• Copenhagen
• Multi-world Interpretation (MWI)
• Environmental decoherence
• Others
By the 1920s, key mathematical laws of quantum particles were established and
developed by Erwin Schrödinger (Schrödinger’s Wave equation) and Werner
Heisenberg (Heisenberg matrix mechanics) which established precise calculation
and properties of particles such as electron’s position and speed.
Specific Behavior of Quantum Physics
Here are specific properties of the quantum world that need to be explored and
discussed:
• Heisenberg uncertainty principle: This formula is the foundation of quantum

physics which states that there is a fundamental limit to what one can know about
a quantum system. For example, the more precisely one knows a particle’s posi-
tion, the less one can know about its momentum.
h
x p
4
Δx = Uncertainty in position
Δp =Uncertainty of momentum
h = Planck’s constant
π = pi
• Wave particle duality: In quantum world small particles such as photons or elec-
trons can act as both particles and waves. The observations and experiments
interpretations for this phenomenon are still under controversy 100 years later.
These observations can be narrowed down to two fundamental experiments
which each represents one or the other. The experiment of photoelectric phenom-
ena (The particle characteristic) and the double slit Experiment (The wave
characteristic).
1. Particle Behavior of light (Photoelectric phenomena): Light can eject elec-
trons from material such as metal only if its frequency is above the threshold
frequency. The electrons are dislodged only when the light exceeds a certain
frequency regardless of the light’s intensity [2].
This phenomenon is a clear example of the particle behavior of the light
that cannot be explained by the wave behavior of the light (Fig. 1.2).
The photon energy is directly proportional to its frequency:
E = hc / h
Fig. 1.2 Photons with different electronvolts energy cause the emission of electrons from the
Potassium plate only if its frequency is above the threshold frequency of potassium (2.24 eV)
E (photon energy) (J)

h (Planck’s constant) (6.626 × 10−34)
c (Speed of light) (3.0 × 108)
λ (Frequency) (Hz)
One photon of visible light contains about 10−19 joules of energy (Fig. 1.3).
eV (electron volt): is a common unit of energy and is the amount of kinetic

energy that is gained by a single electron accelerated from a rest state through an
electron potential difference of 1 volt in a vacuum.
Characteristics of photoelectric effect [3]:
• It is instantaneous
• Occurs only when the radiation is above a cut-off frequency (the minimum fre-
quency that is required for the emission of electrons from a metallic surface).
• Does not depend on intensity of the radiation.
• Particle energy only depends on its frequency.
• Each metal has its own characteristic work function.
• Work function is the binding energy of electrons to the metal surface.
• At the surface, the entire energy of an emitting one photon is transferred to one
photoelectron.
List of some metalwork functions:
1. One electron volt (eV) is the kinetic energy acquired by an electron acted upon
by a potential difference of 1 volt.
1 eV 1.6 1019 Joules
“National Institute of Standards and Technology” [4] (Fig. 1.4)
Fig. 1.3 Chart representing photon energy (ev) according to the wavelength of the spectrum
Fig. 1.4 Work function of sample metals in electronvolt
2. Wave behavior of light (Double slit phenomena):

This is one of the most discussed phenomenon in the quantum world and is also
one of the most important experiments which is easy to perform yet is the center of
many interpretations [5] Fig. 1.5.
The experiment is composed of a light source, a barrier with two parallel slits and
a screen to show the image of the projected light from the light source.
The light pattern on the screen behind the double slit creates an interference pat-
tern, producing dark and light bands representing the wave behavior of the light.
Repeating the experiment with single photon emission will produce individual dis-
crete impact points which indicates that it is not a function of the wave behavior.
This pattern of particle accumulation in certain locations that forms the same dark
and light bands is based on probabilistic preference which is the particle behavior of
the light.
The issue here is that the moment the detector is placed to detect which slit the
light particle is traveling through, the striped pattern disappears.
When nobody is looking, no measurement or detection devices are present:
• Systems are described by wave function.
• Wave functions obey Schrödinger’s equation.
• When somebody looking, measurement or detection devices are present.
• Wave function collapses to a measurable particular value.
• Probability of each outcome is equal to the square of the wave function:
2
P x x
P: Probability
Ψ: Wave function
The wave particle duality can also be observed in different circumstances which
can be summarized as follows:
–– Wave function only: Diffraction, Interference, and polarization.
–– Particle function only: Photoelectric phenomenon.
–– Both wave and particle function: Reflection and refraction.

• Probability theory: There is a superposition of a number of possible outcomes of
measurement of physical properties in a quantum state. This was presented by
Schrödinger’s formula.
• Quantization of energy: In physics, quantization is to construct quantum field
theory out of classical field theory, such as basics to particle physics, nuclear
physics, and quantum optics.
Fig. 1.5 Image of Double Slit Experiment: A coherent source of light such as a monochromatic
laser (Top) or electrons from an electron gun (Bottom) passes through two parallel slits on a plane
between the source and screen behind the plate. The interference pattern appears on the screen in
both experiments which mimics the wave nature of the light or even small particles such as
electrons
• Observer Problem (Schrödinger’s cat on the box) [6].

Quantum field alteration or interaction by observing or recording the experi-
ments has produced many controversies and interpretations. Each of these theories
has its shortcomings and yet only the theory of multiverse can reasonably explain
the process and will be briefly discussed. The experiment was presented by
Schrödinger who presented a hypothetical experiment as the destiny of a “cat in the
box” was determined by release of radioactive particles from the source in the box.
The cat would be alive or dead at the same time, due to the release of a poisonous
gas which is attached to a source of radioactive monitor that detects the random
subatomic event that may or may not occur at the same time. When the observer
opens the box only one state (Dead or alive) can be observed. In another word, the
quantum state collapses the moment it is observed. All the interpretations consider
the observer as a classical physics and not as a quantum observer (Fig. 1.6).
When incorporating the fact that the observer is not a part of classic physics and
is made of atoms that obey the rules of quantum physics the interaction of observer.
The event and the object’s destiny which is a cat in this experiment does not col-
lapse, but it simply entangled with the corresponding universe with the specific
status of the cat. All possible outcomes happen in a different universe at the same
time which is very anti-intuitive as many fields of quantum mechanics (Fig. 1.7).
• Quantum Decoherence (Measurement problem).
Fig. 1.6 Copenhagen Interpretation of the Cat in the Box: The moment that the observer opens the
box and looks in it, the quantum state of the cat collapses into one outcome. The cat is either dead
or alive
Fig. 1.7 Many worlds interpretation of the Cat in the Box: The observer is also in a quantum state
in a parallel universe as the cat is, any possible scenario can happen at the same time with the
entanglement of the observer and the cat with highest probability event
The quantum closed system is coherent when there is a definite phase relation
between all its states. According to the Copenhagen interpretation any attempt to
investigate or measure the system causes the collapse of many possibilities of
states into a single state. There are many interpretations on this strange phenom-
enon. According to the Multi-World Interpretation (MWI), all possible states
continue to exist without the “collapse” into a single state. Another general inter-
pretation is that the information interacts with the environment and as the result
it gets lost [7].
The Copenhagen interpretation [8] sets rules of quantum physics regarding the
observer or measurement problem.
1. When there is no observer (detector):
• Wave functions obey the Schrödinger equation.
2. When there is an observer (detector):
• Wave function collapses to a particular value.
• Probability of any outcome is the square of its wave function. Since particles
can have wave particle duality, the behavior of a particle can be described
using a wave function.
• The wave function itself does not represent a physical variable but its square
magnitude does
2
P x x
P: Probability.
Ψ: Wave function.
Entanglement: Small particle can entangle with each other and interact instantly
regardless of their distance. For example, decaying atomic particles can have 2 sub-
particles that can entangle and interact with each other in a way that, for example, if
one spins up the other always spins down (Fig. 1.8).
The Multi-World interpretation (MWI):
• Wave functions obey the Schrödinger equation.
• In MWI entanglement is implied and does not require instantaneous transfer of
information.
In the MWI, the observer is not treated using classical mechanics, instead he or
she is part of the quantum mechanical system and follows the Schrodinger equation
just as the rest of the system. This eliminates the need for the “collapse” of the wave
function and results in a world that appears identical to the one described by
Copenhagen interpretation [9].
W hen Did It Start? 11
Fig. 1.8 The Higgs has

zero spin. When decaying
produces two particles
spinning in opposite
directions
The physical properties of the particles such as position, momentum, spin, and
polarization are perfectly correlated.
In the Copenhagen interpretation the question is how the information in one
entangled particle is accessible to the other instantly which defy the fact that no
information can travel faster than the speed of light. Meanwhile for the MWI inter-
pretation there is no need for transfer of information.
One example is the Higgs Boson that has no spin, which can decay and split into
two particles with opposite spins. Interestingly there is no separate wave function
for each particle. There is only one wave function of the universe (Fig. 1.9) [10].
• Quantum tunnelling: Particles can pass through potential barriers. More pre-
cisely a particle can penetrate a potential energy barrier even though there is
insufficient energy to overcome it. This effect is essential for chemical reac-
tions [11].
• Random world of quantum: The second law of Thermodynamics indicates that
the measure of randomness (entropy) increases in time. The definition of ran-
domness can be used differently in quantum physics and quantum biology which
the randomness is as an essential component of the intrinsic unpredictability of
life. In another word, the biological randomness is required for the structural
stability of a biological system [12].
When Did It Start?
Although the history of modern physics goes back to early 1800s, it was not until
1900 that the revolutionary changes emerged, to the point that the terms pre 1900
physics (classical physics) and post 1900 physics (modern physics) are being
referred to. This was the beginning of the major paradigm shift in physics.
There are numerus scientists that contributed to the development of quantum
physics, we only mention some of the essential figures with the summary of
their work:
• Henri Poincare (April 29, 1854–July 17, 1912) [13]: He elaborated Gravitation
wave theory, Chaos theory, and Special relativity theory. His contributions were
Fig. 1.9 The Table of elementary particles: The Mass Charge and the spin of each particle is indi-
cated on the chart as shown
essential to the origin of special relativity theory, yet he did not get as much
credit as he deserved.
• Max Planck (April 23, 1858–October 4, 1918) [14]: (The first direct quantum
hypothesis).
He was a German scientist who received the Noble Prize in 1918. His work on
blackbody radiation and in 1900 with the hypothetical assumption reached to the
conclusion that electrically charged vibration emitted from blackbody radiation
could only change in a minimal increment and the frequency is proportional to
the frequency of its associated electromagnetic wave.
He was one of the most essential pioneers of quantum physics and best known
for his constant (Planck’s constant) (h) which was formulated as his effort to
produce an accurate mathematical prediction of distribution of thermal radiation
from blackbody radiation. This was fundamental physical constant with a funda-
mental importance in quantum mechanics. His equation was essential and simple:
E hv
(E) energy of a single photon is equal to the (v) incident light frequency and the
(h) Planck’s constant (h = 6.62606957 × 10−34).
• Neils Bohr (October 7, 1885–November 18, 1962) [15]: (Electron orbits).

He was a Danish physicist who made a fundamental contribution to describe
atomic structure and quantum theory. He received a noble prize in physics in
1922. He proposed that the energy levels of electrons are discrete with stable
orbits around the nucleus and can move from one orbit to another.
• Werner Heisenberg (December 5, 1901–February 1, 1976) [16]: (Uncertainty
Principle).
One of the pioneers of quantum physics. He was a German theoretical physicist
and was awarded the 1932 noble prize in physics. His contribution to quantum
physics is his work in the “uncertainty principle” and “subatomic particles.”
Together with Neils Bohr developed the “Copenhagen interpretation” of the
probabilistic nature of wavefunction.
Louis de Broglie (August 15, 1892–March 19, 1987) [17]: (Wave particle
duality).
French physicist that made a major contribution to quantum theory and won the
Noble Prize for physics in 1929. His hypothesis on the wave nature of electrons
and that all matter has wave properties was a major breakthrough in quantum
physics and carries his name.
He suggested that the relation that is derived to relate momentum and wave-
length for light should also be applied to particles.
His formula:
h/ p
λ (Wavelength) = h (Planck constant)/ P (Particle momentum).

Which P (Particle momentum) = m (Mass) v (velocity).
This formula can be used to describe atomic-scale systems.
• Wolfgang Paoli (April 25, 1900–December 15, 1958) [18]: (Spin and quantum
physics)
Austrian physicist who had important role in the field of spin in quantum phys-
ics. He presented his exclusion principle which states that only one fermion* can
occupy a particular quantum state at a given time. If there are more than one, then
their spin should be a different direction. He was the first to propose doubling the
number of available electron states.
*Particles with half-integer spin are fermions (all quarks, leptons, Baryons) asso-
ciate with matter.
*Particles with integer spin are bosons (Electrons, protons) associate with force
carrier particles (Fig. 1.9).
• Erwin Schrödinger (August 12, 1887–January 4, 1961) [19]: (Known for his
book “What is life,” his wave function Formula and the Cat in the box hypotheti-
cal experiment).
One of the most important pioneer figures in quantum physics and quantum
biology.
An Austrian Theoretical physicist who also won the Noble prize in physics for
his contribution to quantum physics in 1933.
His major contributions out of many can be summarized as follows:
–– The application of quantum physics to living organisms. His book publication
“What is Life” [20] for the first time the concept of life is the subject of atomic
particles which expected to follow quantum rules.
–– Schrödinger Equation provides the evolution of wave function over time in a
system. This fundamental and precise calculation of the wave function of a
state is essential in quantum mechanics and is applicable today, 100 years later.
There are different versions of the equation but the most complete is the time-
dependent formula:
Description of Schrödinger formula:
Schrödinger Equation is the most fundamental and essential formula for quantum
physics and it is important to understand it regardless of how complex it looks [21].
The wavefunction is referred to by “Psi” (ψ) and is a complex valued probability
amplitude and is a mathematical description of quantum state of an isolated quan-
tum system.
At a glance the Schrödinger Equation looks intimidating to a non-physicist, yet
when explained and simplified it can be understood by the majority of the readers.
We identify each character and symbol in the equation with a short description.
Schrödinger’s Equation (time dependent):
d x,t
 2 d x ,t
2
i V x x,t
dt 2m dx 2

Total Energy Kinetic Energy Potential Energy
i: Imaginary unit (number) that in combination with real number forms a com-
plex number C and is: −1.
h: Plank’s constant (6.62607004 × 10−34 m2 kg / s).
h
ℏ (h bar): The Plank’s constant over 2 Pi:  .
π: 3.1415926535. 2
Ψ: Wave function.
d: Derivative.
m: Mass of the particle.
x: Position of the particle.
t: time.
V: Potential energy.
Simplification by color tool: (Fig. 1.10.)
Due to the fact that quantum particles do not have the properties of large objects,
it is not possible to directly and accurately measure them. In order to overcome this
problem, the quantum operators are being used.
Fig. 1.10 The most fundamental and essential formula for quantum physics
Quantum operators by manipulating and affecting the system make it possible to

measure the affected system. In another word, quantum operators are associated
with any measurable parameter in the system. These operators are needed to describe
the system.
The list of common quantum operators is as follows:
d
• Energy Operator (time dependent) also called Hamiltonian: H i .
 d
2 2 dt
• Kinetic Operator: KE .
2m dx 2
• Function of x or potential operator: F(x), f(V).

d
Momentum operator (x component): Px = Fig. 1.11.
i dx
Schrödinger’s Cat in the Box
–– The hypothetical experiment of the cat in the box (Discussed earlier) is the most
discussed experiment for many years and it represents the basic example of
quantum theory ambiguity. It is still the subject of many interpretations and dis-
cussions [6] (Figs. 1.6 and 1.7).
–– Paul Dirac (August 8, 1902–October 20, 1984) [22].
–– English theoretical physicist who made a fundamental contribution to Quantum
physics and shared the 1933 Nobel prize in physics with Ervin Schrödinger. His
equation which carries his name is the relativistic counterpart of the Schrödinger
equation. It describes the behavior of subatomic particles with ½ spin-like elec-
trons and predicted the existence of antimatter.
–– Max Born (December 11, 1882–January 5, 1970) [23]: with Werner Heisenberg,
and Pascal Jordan developed “Matrix mechanics” formulation of Quantum
Mechanics:
pq – qp h / 2
i I
P and q are matrices for location and momentum, is the identity matrix.
• Hugh Everett (November 11, 1930–July 19,1982) [24]:
He was the first physicist that proposed the many worlds interpretation (MWI) or
multiverse of quantum physics. Unlike Copenhagen's interpretation, in (MWI)
The Schrodinger equation never collapses and all possibilities of the quantum
Fig. 1.11 Quantum operators are being used and are needed to describe the system
superposition exist at the same time and are objectively real. At first, his idea was
not taken seriously and it took years since its importance was recognized and
became a major contribution to quantum physics.
His proposed theory of multi-world interpretation (MWI) can be summarized as:
–– The Wave function represents reality, entirely and exactly.
–– Wave function never collapses.
–– Wave function always obeys the Schrödinger’s equation.
–– Decoherence splits the wave function into branches representing different mea-
surable outcomes.
–– Distinct outcome branches will never affect each other in any way.
–– The outcomes seem to belong to different and separate worlds.
• Brian David Josephson (January 4, 1940) [25]: (Quantum Tunneling).
• American scientist winner of the Noble Prize in 1973. His work on Quantum
tunneling was essential for this phenomenon in quantum physics. Today there are
many experiments that have confirmed this process and it is considered as one of
the most important phenomena in the quantum world. The most common tunnel-
ing process can be seen in the photosynthesis process.
• Richard Feynman (May 11, 2018–Feb. 15, 1988) [22]: An American theoretical
physicist with his major role in the theory of quantum electrodynamics. The win-
ner of Nobel prize in 1965. His simplification of the description of the behavior
of subatomic particles which carries his name was a major contribution to quan-
tum physics.
• Alain Aspect (June 15, 1947) [26]: (quantum entanglement).
A French scientist verified the process of quantum entanglement.
His work was to establish that when a group of particles is generated, they inter-
act and share spatial proximity with each other regardless of the distance
between them.
W hat is Quantum Biology? 17
What is Quantum Biology? [27]
The majority of organisms are composed of cellular structures and each of their
cells contains approximately 1010 atoms, it is easy to conclude that each of these
atoms will follow the quantum physics laws.
On the other hand, a combination of atoms make formation of molecules and
interaction between the molecules with the formation of DNA will result in cellular
structures and eventually the multiple organs together, the complex life form
evolves.
Even noncellular life forms like viruses are composed of atoms that follow the
quantum world rules.
Schrodinger referred to the application of quantum physics to biology in his
book “What is Life.”
Since then, one by one the relevance of quantum physics to biology is being
unveiled.
The first on the list was the process of photosynthesis. We will discuss that in
other chapters in detail. Then the studies on the sense of smell followed by magne-
toreceptors in the retina of migrating birds and the essence of consciousness could
be explained by quantum physics/biology.
Summary of quantum biology fields that are established and are being studied at
present:
• Enzymes’ super-fast reactions are accelerated by tunneling phenomena.
• Quantum effect on Photosynthesis.
• Protein tunneling and dynamics in enzymatic H-transfer reactions.
• Magnetic field effect on spin-dependent reactions.
• Proton tunneling in DNA.
• Fluorescent proteins as a model.
• Quantum coherence in neuronal Ion channels.
• Magnetoreception (Separate chapter) [28]).
• Neuron responses (Microtubules) (Chap. 10).
• Vision (Separate chapter) (Chap. 2-2a).
• Consciousness.
What Are Its Applications?
There are infinite applications on every field of biology, biochemistry, and genetics
as the main source of origin always points to the atomic structure that follows the
quantum rules.
For instance, we can apply the quantum physics laws to the effect of photons on
the retina, the transformation of energy to neurons, and the process of seeing. The
understanding of the visual input and the concept of the sense of seeing is similar to
the human consciousness as a whole.
We discuss this in detail in the second part of this chapter.

The cell contains approximately 1010 atoms and each will follow the laws of
quantum physics.
There are atomic elements that combine and form molecules and interaction
between the molecules makes the RNA and DNA and by using these blueprints the
resultant cellular structures develop. Multiple cells organize the organs and finally,
multiple organs communicate and the complex life forms emerge.
By looking at this process in reverse all life forms are made of atomic and sub-
atomic particle the all will obey the rules of quantum physics.
We will discuss quantum biology in part 2 of Chap. 1.
References
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https://doi.org/10.4236/jmp.2021.127058.
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3. Publishing, University. 44 Photoelectric Effect. University Phys. n.d.;3 https://opentextbc.ca/
universityphysicsv3openstax/chapter/photoelectric-effect/.
4. Government, US. Fundamental Physical Constants. Phys Measur Lab. 2018; https://www.nist.
gov/pml/fundamental-physical-constants
5. Hui P. Experimental study of mystery of double slit—comprehensive double slit experiments.
Int J Phys. 2021;9(2):114–27. https://doi.org/10.12691/ijp-9-2-6.
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aaf2941.
7. Garcia-Perez G. Decoherence without entanglement and quantum Darwinism. Phys Rev Res.
2020;2 https://doi.org/10.1103/PhysRevResearch.2.012061.
8. Jaeger. Developments in quantum probability and the copenhagen approach. Entropy. 2018;
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9. Maes SH. The Multi-fold theory: a synopsis so far. shmaesphysics.wordpress.com; 2021.
https://vixra.org/pdf/2105.0013v1.pdf.
10. Sirunyan. Evidence for Higgs boson decay to a pair of muons. Exp Phys. 2021; https://doi.
org/10.1007/JHEP01(2021)148.
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Inst Organ Chem. 2020; https://doi.org/10.1016/j.trechm.2020.08.006.
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doi.org/10.1007/s12064-013-0179-2.
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the British Society for the History of Mathemat. 2012; https://doi.org/10.1080/1749843
0.2012.658538.
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2016; https://doi.org/10.1119/1.4955146.
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https://doi.org/10.1515/phys-2017-0086.
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Stochastic Optimal Control Systems in Quantum Mechanics. Symmetries Quantum Mech.
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org/10.12743/quanta.v6i1.60.
20. Schrödinger, E. 1944. What is life. http://herba.msu.ru/shipunov/school/univ_110/papers/
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Chapter 2
Introduction to Quantum Biology
Abstract
Soon after the emergence and development of quantum physics in the early
twentieth century, the possibility of applying these new rules of physics to the
living cell was first suggested by Pascual Jordan and a year later by Erwin
Schrödinger.
This was the beginning of the new field of science called quantum Biology. At
first, there was no interest in this phenomenon due to the general concept that
quantum physics cannot be applied to the crowded, wet, and warm environment
of the living cell. Also, the lack of necessary tools to experiment with these quan-
tum events in the living cell contributed to it.
It was not until a few decades ago that the relevance of quantum physics in
biology was reinvestigated and new tools were invented to verify these processes.
There are many discoveries in quantum biology in recent years and many are in
process at present.
There are many specific mechanisms within living cells that make use of the
non-trivial features of quantum mechanics, such as coherence, superposition,
tunnelling, and entanglement. These rules in the past were considered to be rel-
evant only to subatomic levels and at temperatures near absolute zero.
It should be noted that even today there are many controversies and differing
opinions on quantum biology issues, and it will take time and further studies to
clarify what had been proposed already.
It took 3.5 billion years for living systems to learn and manipulate the quan-
tum systems for their benefit via optimizing evolution, we have only had two
decades to study and learn about these fundamental processes of life.
The entire field of quantum biology has become so vast that will be beyond
the scope of this chapter. We have chosen the best relevant and full access articles
as references.

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-32060-6_2
22 2 Introduction to Quantum Biology
Discussion
Quantum biology is the study of complex and dynamic biological processes to

understand how living systems exploit quantum mechanical effects to enhance their
biological functions.
There is a growing list of quantum biological phenomena that will be summa-
rized and discussed in this chapter.
Due to the fact that all living organisms are made of atoms, it is reasonable to
recognize that biology and life are governed by quantum laws. For example, the
structure of electron orbitals, chemical bonds, and hydrogen transfer in enzymes are
essential in structural biology in living organisms.
There are so many publications on quantum biology in recent years that go
beyond the scope of this introductory chapter. There are especially these review
articles that are very helpful to orient the readers with the recent developments in
quantum biology.
• Quantum effects in Biology [1]
• Quantum biology revisited [2]
• Quantum Biology: An update and perspective [3]
When Did It Start?
Soon after the birth of quantum physics in the early twentieth century, scientists
started to see if they can apply the laws of quantum physics to biology, since the
basis for any biological form is inevitably atoms and subatomic particles.
The origins of quantum Biology have been discussed in more detail in the litera-
ture [4] and here we present a summary.
The list of some of the pioneers in this field is presented below:
• Neils Bohr (October 7, 1885–November 18, 1962) [5]: (Electron orbits)
He was a Danish physicist who made fundamental contribution to describe
atomic structure and quantum theory. He received a Noble prize in physics in
1922. He proposed that the energy levels of electrons are discrete with stable
orbits around the nucleus and can move from one orbit to another. He was the
first scientist who linked quantum theory with biology.
• Pascual Jordan (October 18, 1902–July 31, 1980) [6]: (Pioneer of Quantum
Biology).
He published the first paper on quantum biology in 1932. His book “Physics and
the Secret of Organic Life” was published in 1941 before Schrödinger’s well-
known book “What is Life.” His affiliation with the German Reich made him
unpopular after the WW ll to the point that he was not mentioned as one of the
major pioneers of the quantum biology in many historical papers.
• Erwin Schrödinger (August 12, 1887–January 4, 1961) [7]: (Pioneer of quantum
physics and quantum Biology).
The Electron 23
He is well known for his book “What is Life” [8], his wave function formula, and
the “Cat in the Box” hypothetical experiment.
He was an Austrian Theoretical physicist who also won the Noble prize in phys-
ics for his contribution to quantum physics in 1933. He is considered as one of
the most important pioneering figures in quantum physics and quantum biology.
• Luca Turin (November 20, 1953 [9]: Turin’s Theory of Olfaction was the first
publication on vibration of the molecules on olfaction.
• Francis Crick (June 8,1916–July 28, 2004) and Watson (April 6, 1926) [10]
Discovery of double helix of DNA in 1953 was another step toward understand-
ing the living organism’s Genetic inheritance and mutations.
• Löwden (October 28, 1916–October 6, 2000) ([11]: Proton tunnelling mecha-
nism for a point mutation in DNA.
• De Vault (1915–1990): Electron tunnelling in enzymes [12].
He proposed that the electron transfer in photosynthesis is a temperature-independent
reaction and the electron transport is due to “quantum tunnelling” process.
• Wiltschko [13]: Magnetoreceptor in birds.
His original article on Magnetoreceptors represents the evidence of magnetic
receptors in migrating birds.
Basic Information for Better Orientation
Due to the fact that this book is not written for quantum physicists, there is some
basic information that needs to be reviewed for a better understanding of the essen-
tials of quantum biological phenomenon. This information is very general and can
be reviewed, for instance, in any standard basic science textbook.
We start with the basics of atomic structure and use the hydrogen atom as an
example since it is the simplest (and the most abundant) atom in the universe.
The majority of hydrogen in nature (99.9%) is composed of one proton and one
electron. Other isotopes of hydrogen also have neutrons (deuterium and tritium) as
well and are heavier.
Hydrogen atoms can be found in various states:
• Atomic hydrogen (no charge and not chemically bound).
• Hydrogen can attach to other atoms, for example, oxygen to form water.
• Hydrogen can lose its electron to become a cation (H+) and is called hydron
which is a free proton, which has a major role in many biological processes.
• Hydrogen can gain another electron to become an anion (H−) and is called hydride.
The Electron
Electrons play an essential role in chemistry, magnetism, electricity, and thermal

conductivity and are involved in many applications like electron microscopy lasers
and radiation therapy.
Bohr’s model: Niels Bohr described the electron orbits at the most probable dis-
tances from the nucleus which is approximately 5.29 × 10−11 m in its ground state
and is still being used today as Bohr’s radius constant (Fig. 2.1).
(The electrons travel in defined circular orbits around the nucleus. The orbits are
labeled by the quantum number n. Electrons can jump from one orbit to another by
emitting or absorbing energy.)
In the early 1920s, the intrinsic spin of electrons was confirmed by “Stern-
Gerlach experiment.” In this experiment, silver atoms (neutral particles) were sent
through inhomogeneous magnetic field and their deflection was observed. The
detection screen revealed two separate points of accumulation according to the spin
up or spin down of the particles passed through. This was a historical moment in the
field of quantum physics (Fig. 2.2).
(Inert Silver atoms confined through collimators, travel through an inhomoge-
neous magnetic field. They will be deflected to two separate points according to
their up or down spin) (Fig. 2.3).
Bohr proposed specific characterizations for electrons:
• Electrons can only be in certain discrete orbits or stationary states, n = (1,2,3,…).
• Each first orbital can be occupied by up to two electrons and must have a differ-
ent spin quantum number.
• Electrons do not emit radiation while in these stationary states.
• Electrons can gain or lose energy by jumping between the stationary states.
“Transitional rule” for jumping is limited and is represented by values (n) the
principal quantum number, (ι) the orbital angular momentum, and (m) the mag-
netic angular momentum since the absorption and/or emission of electromag-
netic radiation involves changing in the electromagnetic dipole of the atom.
Fig. 2.1 The electrons travel in defined circular orbits around the nucleus. The orbits are labeled
by the quantum number n. Electrons can jump from one orbit to another by emitting or absorb-
ing energy
The Electron 25
Fig. 2.2 Inert Silver atoms confined through collimators, travel through an inhomogeneous mag-
netic field. They will be deflected to two separate points according to their up or down spin
Fig. 2.3 Schematic presentation of one electron spin, alpha with a spin up vector and beta with a
spin down vector
Energy level: The energy level of electron in an atom has different states. The
“ground state,” which after absorbing energy can jump into the higher state called
“excited state.”
• Singlet state: is when all the systems electrons are paired. The net angular
momentum of the particles is zero and has one line in its spectrum reflecting its
name. Except oxygen almost all molecules exist in a singlet state (S0) (Fig. 2.4).
• Triplet State: is when a system has two unpaired electrons. The angular momen-
tum of the system is 1, so as its quantum number is 1. It will allow three values
Fig. 2.4 Schematic comparison of electron triplet states with S1 and electron singlet state with S0,
using the Z access
Fig. 2.5 Schematic

presentation of the vectors
from + and – canceling
each other so only the X
and Y axes vector exists
of angular momentum as −1, 0 +1. The spectral line also will show three lines
and it is called triplet. Molecular oxygen occurs in triplet state (Figs. 2.5 and 2.6).
• The principal energy level at the orbit of electrons around the nucleus called shell
can be numbered (1–2–3–4...) or alphabetically start from (K -L -M -N…). Each
shell can contain only a certain number of electrons. The first shell can hold only
up to two electrons. The second shell can hold up to 8 electrons (2 + 6). The third
shell can hold up to 18 electrons (2 + 6 + 10) and so on.
• The electron’s angular momentum is quantized and can be calculated as:
L = n
L = angular momentum.
n = Principal quantum number.
ℏ = h (Plank constant) / 2π and is called “h-bar”.
The Electron 27
Fig. 2.6 Schematic presentation of two alpha vectors, combined together forming the larger vec-
tor S1. The beta vectors look similar but in the opposite direction and with a—sign
Later on, Schrödinger described the position of the electron as a wave function
and the probability of its location in his fundamental equation that was described in
part one of this chapter.
Schrödinger’s Equation (time dependent):
d y ( x,t )
- 2 d Y ( x,t )
2
i = + V ( x )y ( x,t )
dt 2m dx 2
¯ ¯ ¯
Total Energy = Kinetic Energy + Potential Energy
There are specific characteristics of electron, that is, the same in the entire uni-
verse and the most essential in the new era of quantum physics and biology.
Electrons characteristics and specification highlights are as follows:
• The electron symbol is (e−).
• It is a subatomic particle belonging to Fermions (see subatomic particle charts).
• It has a negative charge of (−1) and is bound to the nucleus with a positive charge.
• It has an intrinsic angular momentum or Spin of half-integer (1/2) expressed in
units of reduced Planck's constant ℏ which the projection vector axis would be as
shown in Fig. 2.3.
æ  ö
ç + or - ÷
è 2 2ø
• It has a mass of 9.901 × 10−31 kg.

• Electrons can collide with other particles.
• It can have the dual property of wave and particle, the square of the wave func-
tion Ψ gives the probability of the particle location.
• Electrons can be diffracted like light.
• The exchange and sharing the electrons between the atoms is the main cause of
chemical bonding maintained by a pair of electrons shared between two atoms.
• Electrons can radiate or absorb energy in the form of photons. The electrons can
go from ground state to the excited state by absorbing a photon only whose
energy is equal to the energy difference between the levels. On the other hand,
the excited electron can go to the lower level by spontaneously emitting a photon
equal to the energy difference between the levels. The photon energy is equal to
Planck’s constant(h) times the photon frequency (λ).
E = hf
This is the base for spectroscopy which is to analyze the detected frequency or
wavelength of the emitted or absorbed photons.
• Electromagnetic field can affect the motion of electrons.
Jablonski Diagram
Is a schematic arranged electron energy diagram on a vertical axis. Horizontal lines

are representations of the electronic states with multiple vibronic energy states that
may be coupled with the electronic state [14] (Fig. 2.7).
Fig. 2.7 The diagram represents the ground state and excited state of electrons. After excitation,
different pathways of relaxation are shown
Jablonski Diagram 29
The first diagram is usually the “absorbance” of a particular energy by the mol-
ecule of interest. For example, the energy of the photon is absorbed by the electron
and excites it from a lower energy level to a higher energy level. Only certain wave-
lengths of light are possible for absorbance. The energy of the absorbing photon
should correspond to the difference between the two different states of the particular
molecule. The ground state electrons will transition to an excited electronic state as
well as some excited vibrational state.
The second diagram is the “vibration relaxation” and “Internal conversion.”
When the electron is excited, there are many ways that the gained energy can be
dissipated.
–– Vibrational relaxation, is a non-radiative process. It occurs between vibrational
levels and generally electrons do not change their level.
–– Internal conversion can occur when the energy increases which causes the over-
lap of vibrational energy over the electronic levels.
The third diagram is “Fluorescence” in response to the absorbed photon is to
emit a photon. It is a slower process than the previous pathways and can compete
with them only from the first excited electron state and the ground state. The dissi-
pation of energy from higher excited energy states is through the internal conversion
and vibrational relaxation.
The energy of the fluorescence is the same energy as the difference between the
states of the transition, however, the energy of fluorescence is always less than that
of exciting photons.
The last diagram is the “Intersystem crossing” and is another path for energy
dissipation from higher excited levels. In this path, the electron changes spin multi-
plicity from a singlet state to an excited triplet state and is represented by a horizon-
tal curved arrow from one column to another column. It is the slowest path in
Jablonski diagram even slower than fluorescence. Intersystem crossing can lead to
another route from the excited triplet back to the singlet ground state by emitting
Phosphorescence.
There are other non-emitting transitions from excited states to ground state exist
and account for the majority of molecules that are not exhibiting fluorescence or
phosphorescence behavior.
• Two electrons cannot occupy the same quantum space or orbits (Pauli exclusion
principle) and maximum 2 electrons with different spin quantum numbers (bal-
anced spin).
• Double-occupied orbitals are being repelled by an external magnetic field.
• Single-occupied orbits are attracted by the external magnetic field and are
unpaired or unbalanced spins and create a spin magnetic moment in which the
electron behaves like a very small magnet.
• The wave function changes (+ or-) sign when 2 electrons are swapped.
• Electron magnetic moment: caused by an electron’s intrinsic properties of spin
and its electric charge. It is approximately - 9.284764 × 10−24 J/T.
Fig. 2.8 Schematic presentation of the region of probability where the electrons can be found and
the different orbitals and their shapes; s, d, p, and f
• Atomic orbitals are the region of probability where the electron can be found.
There are four orbitals with different shapes s, d, p, and f. Each can hold up to
two electrons (Fig. 2.8).
Spin quantum number: Is one of the four quantum numbers that describe the
quantum state of an electron:
1. (n) the principal quantum number. It represents the energy of an electron. The n
value can be 1–2–3-4 etc. the numbers are increasing as it gets further away from
the nucleus.
n = 1,2,3,4…
2. (ι) The orbital angular momentum. It can have a value from 0 to n-minus one.
This describes the shape of the orbital.
ι = 0, 1, 2…(n−1).
ι = 0 describes s orbital.
ι = 1 describes d orbital.
ι = 2 describes p orbital.
ι = 3 describes f orbital.
3. (mι) The magnetic angular momentum. Describes the number of the types per
energy level.
mι = −ι … to ι.
Example: if ι =2 then mι = −2, −1, 0, 1, 2.
1 1
4. (ms) The spin quantum number. Only in + or - .
2 2
Jablonski Diagram 31
Fig. 2.9 Chart of spin

angular momentum and the
assigned multiplicity
numbers
Spin angular momentum (S) or simply called “Spin” is an intrinsic property of

all elementary particles. All subatomic particles have assigned quantum spin num-
ber (see subatomic particle charts) (Fig. 2.9).
There are very specific rules and characteristics of Spin that are fundamental in
understanding the behavior of particles in nature. Spin implies that the particle’s
phase changes with angle.
• Particles with half-integer spins including electrons are fermions while the ones
with integer spins are Bosons. They obey different rules.
• Fermions (electrons included) cannot have the same spin at the same position,
but bosons can bunch up together.
• Fermions (electrons included) that make up the matter, have a spin of ½.
• Boson particles (photon included) that carry forces, have spin 1.
The spin direction is either up or down on the axis of the electron rotation (Z)
(Fig. 2.3).
Spin vectors are used to be able to easily picture the spin in a classic form.
Phonon: Is a discrete unit or quantum of vibrational motion of uniformly oscilla-
tion of a lattice of atoms or molecules at a single frequency. Similar to photon that
is a quantum of light energy.
There are other specific effects and constants that need to be mentioned such as
g-factor, Zeeman effect, and Bohr magneton:
• g-factor: Dimensionless quantity that characterizes the magnetic momentum and
angular momentum. Three magnetic moments are associated with electron:
1. Spin angular momentum.
2. Orbital angular momentum.
3. Total angular momentum, which is the sum of the two above.
• The electron g-factor (ge) = −2.002319304362 56.
• Zeeman effect: This is the effect of an external static magnetic field on a spectral
line which splits it into several components. It is very important in applications
in nuclear magnetic resonance spectroscopy, magnetic resonance imaging
(MRI), etc.
• Bohr magneton (μB): Is a constant expressing the magnetic moment of an elec-

tron caused by its orbital or spin angular momentum.
e
( mB ) = = 9.274 ´ 10-24
2me
e: The elementary charge
ℏ: The reduced plank constant
me: The electron resting mass
Electron spin resonance (ESR): Is similar to nuclear magnetic resonance (NMR)
but the excited spin is from electrons, not the nucleus. The electron spin quantum
1 1 1
number s = and the magnetic components ms = ms = + or - . By exposure to
2 2 2
an external magnetic field Bo, the electron’s magnetic moment aligns itself parallel
æ 1ö æ 1ö
ç ms = + ÷ or antiparallel ç ms = - ÷ to the field. Each alignment having a specific
è 2 ø è 2ø
energy due to the Zeeman effect with the following formula:
E = ms g e m B Bo
E: Energy
ms: Electron magnetic moment
ge: Electron g-factor
μB: Bohr magneton
Bo: External magnetic field
Therefore, the separation between the unpaired electrons of the upper and lower
state is:
E = g e m B Bo
which implies that the splitting of the energy levels is directly proportional to the
magnetic field’s strength since ge and μB are constant. The unpaired electrons can
change their spin by absorbing or emitting a photon of energy hv (h = Planck’s con-
stant, v = Photon’s frequency) such that the resonance condition, hv = ΔE is obeyed.
This leads to the fundamental equation of electron paramagnetic resonance (EPR)
spectroscopy:
hv = g e m B Bo
Quantum Biology Tools
It was not until recently that the tools for measuring the quantum phenomenon in
biology were discovered and the process of coming up with new tools is in progress
at present.
Here, we discuss only some essential tools that are being used today:
Quantum Biology Tools 33
• Entangled Spectroscopy [15].

• Nonlinear-type spectroscopy of entangled photons [16].
• Nitrogen vacancy centers in Diamond [17].
• Super-resolution Fluorescence microscopy which is the combination of atomic
force microscopy (AFM) with fluorescence-based super-resolution microscopy
modalities [18].
• Fluorescence Fluctuation Spectroscopy [19].
• Ultrafast spectroscopy [20].
One very important factor in biological functions is the very short coherent times
that are critical for the process to happen i [20].
The femtosecond processing has Been discussed in the Chapter on vision [21].
However, for sensing and measuring, a longer coherence time is preferable. That
is why the long coherence time of diamond nitrogen vacancy centers of 2 ms,
becomes very practical for quantum-related experiments.
Nitrogen Vacancy (NV) Centers in Diamond
We will discuss Nitrogen Vacancy (NV) center in diamonds as it has become one of
the most essential and reliable sensing devices in quantum biology. The idea started
30 years ago and yet it has been studied and perfected each year and still is playing
a central role in many scientific research projects being done today.
It is a powerful quantum system with very essential properties such as:
• Long coherence time of up to 2 ms.
• The ability to work on an atomic size system such as individual molecules.
• Single photon source.
• Magnetic field measurement.
• Electric field measurement.
• Does not need near-zero temperatures and can perform under ambient
temperature.
• Can be used as a quantum sensor to optically detect NMR signals from chemi-
cally modified thin film on the surface of the diamond that contains NV cen-
ters [22].
• It is being used in many other fields such as qubits in quantum computers.
The Nitrogen Vacancy (NV) center in diamonds is one of many point defects in
the atomic structure of carbon lattice crystals in diamond. There are two charge
states of this defect:
• NV0 or neutral NV that has one unpaired electron and is paramagnetic, but hard
to detect. It is generally not being used for quantum technology.
• NV−or negative NV that has one extra electron forming the spin S = 1 pair.
The NV0 centers can be converted to NV− by applying an extra voltage to a
doped diamond.
Fig. 2.10 Schematic presentation of nitrogen vacancy center in a diamond crystal
NV centers have a magnetically, electrically, and thermally sensitive electronic

spin at ground state at room temperature at ambient conditions. By changing the
evolution of the spin states and sensing the magnetic field, these changes can be
precisely detected optically. NV− possesses spin-dependent fluorescence which
allows to measure of its quantities.
Carbon atom has 4 valance electrons, Nitrogen has 5 valance electrons which 3
of them covalently bonded to the carbon atoms and the other 2 remain non-bonded
and are called “lone pair.” The vacancy has three unpaired electrons (Fig. 2.10).
The principle of NV center spin detection:
The photoluminescence property of NV centers is used to detect the spin state of
its electrons. External optical absorption of green light (for example, green laser
with a wavelength of 546 nm) can excite the NV electrons to the excited state which
upon decay emits non-radiative and infrared radiation that can then be detected and
measured by optical detection devices “optical read out” using the concept of opti-
cally detected magnetic resonance (ODMR). Pulses or continuous microwave a nd/
or application of external electric field can also excite the electrons to the
excited state.
There is additional splitting due to interaction with surrounding carbon nuclear
spins and the NV’s own spin-orbit interaction that can affect the additional level
splitting into the excited states.
There is an inherent entanglement of the spin-orbit in the molecular structure of
the diamond NV center under a zero magnetic field.
As we mentioned above, the NV centers can be manipulated by external factors:
• Electric fields (DC Current)
• Magnetic fields
• Microwave
Quantum Biology Tools 35
• Light (Laser)
• Temperature and pressure
The above external influences enable applications for imaging with high contrast
and sensitivity.
Detecting the small variations of photons is much easier with optical detectors
than the small magnetic fields. That is why the detection of the emitted fluorescein
plays an important role in sensing the spin status of the electrons.
The quantum spin properties of NV centers in nanodiamonds can be used for
in vitro biosensing, including brightness, low cost, and ability to manipulate their
fluorescent emission [23].
The following are some of the essential applications of NV centers:
Biological sensor: The use of NV centers in nanodiamonds as “quantum sensors”
can detect many essential parameters inside the living cell such as PH, radical spe-
cious, magnetic fields, and rotational movements due to its stability and biocompat-
ibility [24].
Navigation: The NV’s spin’s property can be coherently manipulated by opti-
cally detectable magnetic resonance for sensing and quantifying the precise local
magnetic field and navigation without a need for a satellite [25].
Quantum Diamond Microscope (QDM):
It consists of employing a dense layer of fluorescent NV Centers near the surface
of a transparent diamond chip on which a sample of interest is placed. Microwave-
initialized magnetic field; NV fluorescence is measured across the diamond surface
resulting in a two-dimensional magnetic field image [26].
Magnetic force microscope: The interpretation of images acquired by magnetic
force microscopy with specific near-field magnetostatic interaction between the
probe and sample [27]:
Intracellular Thermometry: Temperature is a fundamental indicator of cell func-
tion. Fluorescent nanodiamonds (FNDs) containing (NV-) centers are good candi-
dates for detecting intracellular temperature due to their inherent biocompatibility,
high photostability, sensitive temperature detection, and suitability for intracellular
use (Wu, Intracellular Thermal Probing Using Aggregated Fluorescent
Nanodiamonds [28]).
The Most Studied Fields of Quantum Biology
The following are the list of the most common quantum biology phenomenon under
study and research at present:
• Quantum effect on Photosynthesis (Wang, Efficient quantum simulation of pho-
tosynthetic light harvesting [29]).
• Enzymes’ super-fast reactions are accelerated by tunnelling phenomena [30].
• Protein tunnelling and dynamics in enzymatic H-transfer reactions [31].
• Magnetic field effect on spin-dependent reactions [32].
• Proton tunnelling in DNA [33].
• Fluorescent proteins as a model [34].

• Quantum coherence in neuronal ion channels [35].
• Magnetoreception (Separate chapter) [36].
• Olfactory sensation [37].
• Neuron responses (Microtubules) (Chap. 10).
• Vision (Separate chapter) (Chapters 2-2a).
• Consciousness [38].
Due to the wide variety of experiments, we will discuss only some of the most
essential fields that the experiments have been very promising:
–– Photosynthesis, which is the process of converting the sun’s energy into chemi-
cal reactions in plants and some bacteria is being discussed in this chapter.
–– The other subjects will be discussed in other chapters:
–– The enzymes’ reaction process which is essential for life.
–– The olfaction processes.
–– The magnetoreceptors [39].
Photosynthesis in Plants
What is photosynthesis?
Photosynthesis is one of the most essential processes for maintaining life on
earth producing oxygen in the atmosphere and converting the sun’s energy into food.
Complete detail of the physical, chemical, and biological principles of photosyn-
thesis is described in a book publication [40].
Here, we summarize the process of photosynthesis with relevant references for
more understandable and simplified details.
In recent years, there has been much interest in discovering the quantum effect
process in light-harvesting pigment chlorophyll. Many researchers are trying to
uncover the role of quantum physics in this process.
The anatomy of the plant harvesting process (Fig. 2.11):
Plant cell
Organelles (Chloroplasts)
Thylakoids
Chlorophyll structure with central Mg
Stacks of thylakoids (sites of photosynthesis)
Thylakoid membrane
Pigment-protein complexes = Light-harvesting antenna complexes
The Thylakoid membrane proteins
Lumen of thylakoid space
Stroma
Ribosomes
Plastidial DNA
Photosynthesis in Plants 37
Fig. 2.11 Schematic presentation of the entire anatomic process of photosynthesis
Fig. 2.12 Schematic comparison of a chlorophyll molecule and a hemoglobin molecule. The pri-
mary difference is that hemoglobin is built around iron (Fe), whereas chlorophyll is built around
magnesium (Mg)
There are many different species that use photosynthesis such as plants some
bacteria and algae but, in this chapter, we only focus on C3 plants.
The general overview process of light harvesting can be summarized in order to
understand the essentials. The entire process of photosynthesis is shown in
Fig. 2.11.
The sunlight hits the plant leaves containing chloroplast organelles. These organ-
elles have multiple disc-like structures stacked on top of each other that are called
Thylakoids that are floating in the fluid inside the chloroplast called stroma.
Thylakoids are the structures that are involved with the light capturing tools such
as chlorophyll molecule as antennae. Their membrane holds the essential proteins
to capture and process electrons and ions necessary to start the process of photosyn-
thesis. The inner space inside the thylakoid space is called the lumen (Fig. 2.12).
Fig. 2.13 The specific wavelength of chlorophyll absorption is shown in the above image. The
green wavelength is reflected out, giving plants their green color
The chlorophyll molecule structure contains MG in its center which has a role in
the H+ flow and concentration in the stroma [41]. As represented in Fig. 2.12.
There is a specific wavelength of the full spectrum that gets absorbed by chloro-
phyll in the blue and red zones. The green zone is just reflecting out that is why the
plants are green (Fig. 2.13).
What happens when photons of light hit the plant leaves:
• The sun’s energy is captured by chlorophyll antenna [42].
• The energy is then transferred to the reaction center.
• The excitation of the electrons forms “electron exciton” and are released from
the reaction centers.
• The transfer of the excited electrons to Photosystem II.
• The electrons will be directed to the stroma via electron transport system
Photosystem I.
• Electrons help the hydrogen ion attaches to NAPD and forms the NADPH
as a fuel.
• At the same time, the generated Oxygen (O2) and Hydrogen (H+) from the split-
ting of the water molecule are being sorted out.
• Oxygen is the waste product and will be sent out to the environment via the small
openings on the plant surface called stomata.
• Hydrogen gets transferred to the lumen and eventually passes through the mem-
brane molecule called ATP Synthase into the stroma. There it will assist phos-
phorylation of ADP to ATP with the use of one inorganic phosphate.
• ADPH and ATP are the necessary fuel to capture CO2 from the environment
through the stomata. The process is called Calvin circle which involves in the
production of carbon containing molecules such as glucose, cellulose, all kinds
of starch and lipids.
Overall formula:
6CO 2 + 12H 2 O + Photons ® C6 H12 O6 + 6O 2 + 6H 2 O

Photosynthesis in Plants 39
Fig. 2.14 Schematic representation of photosynthesis as it occurs in plants. These chemical reac-
tions are shown corresponding to the specific anatomical locations where they occur
Process of photosynthesis:
The process of event in the photosystems II and I in the Thylakoid membrane:
Photosystem II → Excite electron (An Electron-hole pair) + Water photolysis To
O2 and H + ATP synthase → ATP.
Photosystem I → electron transport system → NADP+ H+ + NADP synthase
→ NADPH.
The types of photosynthesis reactions happen:
• Light-dependent reactions → H+ + electron + membrane enzymes →
NADPH + ATP.
Or more in a more complete version (Fig. 2.14.):
(2 H2O + 2 NADP+ + 3 ADP + 3 Pi + light → 2 NADPH +2 H+ + 3 ATP + O2)
• Light independent reactions → NADPH + ATP+ CO2 → Sugar production.
Or in a more complete version:
(3 CO2 + 9 ATP + 6 NADPH +6 H+ → C3H6O3-phosphate +9 ADP + 8 Pi + 6
NADP+ + 3 H2O)
• Calvin Cycle (Stroma) → RUBP + RuBisCo + CO2 → Glucose + Fatty acids+
recycling RUBP.
There are some issues in the process of photosynthesis that cannot be explained
by classic physics and only make sense when quantum theories are applied:
• The biological process of light conversion high efficiency of (84%–95%).
Fig. 2.15 Schematic presentation of various pathways of quantum physics energy transfer theo-
ries, in photosynthesis
• The process of photosynthesis also has a very high efficiency of one photon
being transduced to 1 electron-hole pair.
• The time scale of femtoseconds that the electrons are transferred to the reac-
tion center.
Is extremely short (Femtosecond is a unit of time equal to 10−15 or
1/1,000,000,000,000,000 of a second).
There are also many different theories and controversies in interpretations of
light harvesting process and the role of quantum physics in energy transfer in pho-
tosynthesis, a good argument is discussed in this article [43] (Fig. 2.15).
Ishizaki and Fleming [44] work titled “Photosynthetic Energy Transfer Gained
from Free-Energy Structure: Coherent Transport, Incoherent Hopping, and
Vibrational Assistance”
They discussed the Coherent and incoherent energy transfer and the necessity of
vibrational assistance in a typical photosynthetic system.
Resonant tunnelling in natural photosynthetic systems has been proposed in this
recent article [45].
Another article discusses that photosynthesis tunes the quantum-mechanical
mixing of electronic and vibrational states to steer exciton energy transfer [46].
The vibrational and electronic effects with a review of literature were also dis-
cussed in this article [47].
One very recent publication suggests that the light coherently drains out of nano-
sized photosystems as a unit and its “quantumness” is linked to quantum confine-
ment on the nanoscale [48].
Finally, “Quantum walk” was suggested as an energy dispersion in photosynthe-
sis system [49].
References 41
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Chapter 3
Classic Biology of Human Eye
Abstract
The role of quantum biology in the human eye has been studied in detail and yet
there are many more facts that need to be investigated and discovered.
This chapter is divided into two parts, to better understand the process of visual
systems. Part one will summarize the classic anatomy/physiology of the normal
human eye and in the second part the quantum effect on the visual system will be
discussed. The focus will be on the process of a photon entering the eye and its
absorption by the photoreceptors located in the posterior retinal layer, followed by
the transformation of the photon energy into the neuronal signal to the brain.
Note:
The basic information on anatomy and terminology is standard and accessible
in any information media sources.
Due to the large collection of information in the literature, which is beyond
the scope of this book, the most relevant open-access review articles have been
selected and referenced for further and more detailed information on each
subject.
For light to reach the photoreceptors in the retina it must pass through many bound-
aries. Any defect or abnormality on these barriers will affect this process.
To follow the photons from their sources (sun or projector or reflection), there are
many different media with different indexes of refraction which it must pass to
reach the retina to initiate the phototransduction system. Starting with a photochem-
ical reaction the retina transforms the light energy to electrical signals to reach the
brain. The density differences that the light should travel through are the following:
• Air–cornea boundary.
• Cornea–anterior chamber (Aqueous Humor) boundary.
• Aqueous Humor–lens boundary.
• Lens–Vitreous boundary.

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-32060-6_3
44 3 Classic Biology of Human Eye
Fig. 3.1 Schematic presentation of light passing through different optical barriers entering the eye
to reach the retina
• Vitreous–retina boundary (Fig. 3.1).

Any physiological or pathological changes in these structures and barriers can
affect the photon reaching the retina and as a result affects the vision.
The visual perception and consciousness will be discussed in another chapter.
The Anatomy Highlights of the Eye
• Cornea [1]
–– Tear film
–– Epithelium
–– Bowman’s membrane
–– Stroma
–– Descemet’s membrane
–– Endothelium
• Lens [2, 3]
–– Index of refraction [4]
–– Anterior capsule
–– Cortex
–– Nucleus
–– Posterior capsule
• Vitreous.
–– Vitreous body ([5])
–– Cloquet canal
The Anatomy Highlights of the Eye 45
• Retina
–– Anterior limiting membrane [6] [7]
–– Nerve fiber layer
–– Ganglion cells [8]
–– Inner plexiform layer
–– Inner nuclear layer
–– Outer plexiform layer
–– Outer nuclear layer
–– Amacrine cells
–– Muller cells
–– Photoreceptor’s structure
–– Photoreceptors: Molecular structure
• RPE [9–11]
• Bruch’s membrane [12]
• Choroid [13]
• Sclera [14] (Figs. 3.2 and 3.3)
The following articles are highly recommended:
Microstructure [15, 16].
Chemical reactions. [17, 18].
Fig. 3.2 Light microscopy (x 40) of the posterior segment of the eye. All retina layers, in addition
to retinal pigment epithelium, choroid, and sclera are identified
Fig. 3.3 Schematic description of the cellular structure of the retina and RPE and their correlation
to the Bruch’s Membrane and Choroid. RPE size is exaggerated in the schematic illustration
Before going any further, we must refer to some basic biological information regard-
ing the physiology of the visual system. The simplified highlights are as follows:
• Photoisomerization:
Isomers are molecules with identical molecular formulas with the same number
of atoms but with different arrangements. The isomers may have different chemi-
cal or physical properties. When the isomerization is the result of photoexcitation
it is called photoisomerization. A relevant example is the photoisomerization of
11-cis retinal to All-trans retinal in the retina.
• Phototransduction:
Phototransduction is the process of converting the detected photon into an elec-
trical signal in the rod and cone cells of the retina.
The process occurs via Opsin (G-protein-coupled receptor) that contains 11-cis
retinal (Chromophore). When a photon hits this complex, 11-cis retinal under-
goes photoisomerization to all-trans retinal which changes the conformation of
opsin leading to the cascade of phototransduction.
• Protein structure and folding:
Proteins are the 3-dimensional chain of averaging 20 different amino acids that
attach to each other by a peptide bond (C=O-N-H). The proteins are made inside
the cytoplasm of the cell by ribosomes that are using messenger RNA as a tem-
plate. The standard protein structure starts with the amino terminal (N) and ends
with a carboxyl terminal (C).
Each protein exists in an unfolded polypeptide after being synthesized by the
ribosomes which then will fold into its characteristic 3-dimensional structure.
The correct folding of amino acids is essential to their function as misfolding is
associated with many pathological and neurodegenerative conditions.
There is a different motif in the secondary structure of proteins such as alpha
helix, beta sheet, and loops. These structures are most commonly presented as
ribbon diagrams. Alpha-helices are presented as thick coiled ribbons, beta sheets
are presented as arrows, and non-repetitive loops are represented as thin lines
(Fig. 3.4).
• Rhodopsin:
The Anatomy Highlights of the Eye 47
Fig. 3.4 Illustration of secondary structure of proteins
Rhodopsin is a G-protein-coupled receptor that is sensitive to light. It is com-

posed of two parts opsin and retinal.
• Retinal:
Retinaldehyde is a derivative of Vitamin A and is bound with opsin in photore-
ceptor cells of the retina and is the first step in the process of vision perception as
light detectors. The retinal transport and cycle involve the absorption of vitamin
A from choriocapillaris. The retinal cycle is involved in co-ordination and inter-
play of retinal pigment epithelium (RPE) and photoreceptors.
• Opsin:
Opsins are a group of proteins that contains retinal, the light-sensitive molecule.
Photons collisions with retinal changes the 11-cis retinal to all-trans retinal which
causes the conformation of opsin, which will start the visual transduction cascade.
• 11 cis retinal and all-trans retinal (Fig. 3.5):
• G-Protein-coupled receptors:
These receptors are located at the cell surface membrane and are usually com-
posed of seven transmembrane domains. They have an extracellular N terminal
that attaches to the ligand to start the intracellular cascade of events as in gluta-
mate receptors or ligands directly binding to transmembrane helices as in
Rhodopsin-like family receptors.
• Cyclic guanosine monophosphate (cGMP):
cGMP is a second messenger that acts as an activation of intracellular protein
kinases in response to extracellular ligand binding. The main function is the con-
trol of the ion channels on the cell membrane. It is degraded by phosphodiester-
ase in the presence of light, which causes the sodium channels to close. This will
lead to hyperpolarization of photoreceptor’s plasma membrane to activate visual
signals.
• Guanosine triphosphate (GTP):
GTP is essential to cellular signal transduction. It converts to guanosine diphos-
phate (GDP) by the enzyme GTPase.
• Phosphodiesterase Guanylate cyclase (GC):
GC is an enzyme that converts GTP to cGMP.
• Cyclic adenosine triphosphate (cAMP):
cAMP is a secondary messenger and is a derivative of ATP and is used for intra-
cellular signal transduction.
• Adenosine triphosphate (ATP):
Fig. 3.5 Schematic

illustration of 11-cis retinal
and all-trans retinal and
their transformation by
light
ATP is composed of a sugar molecule ribose and attached phosphate structure. It

is commonly referred to as the molecular currency of intracellular energy trans-
fer. It constantly converts back and forth to adenosine diphosphate (ADP) and
adenosine monophosphate (AMP).
• Transducin:
This protein is essential for phototransduction in retina rods and cones. Light
activation of rhodopsin that activates Transducin which results in activation of
phosphodiesterase that in turn causes the breakdown of cGMP and closure of
sodium ion channels which starts the visual signaling process.
• Ion channels:
Ion channels are membrane proteins that allow ions to pass through their channel
pore. In general, they have a high rate of ion transport without using metabolic
energy such as ATP.
There are hundreds of types of ion channels and many forms of classifications
according to their specific function. It can be just a pore that permits few ions to
pass, or it may be gated channels that open and close.
Non-gates potassium channels: There is a constant outward potassium current
that tends to hyperpolarize photoreceptors to around −70 mV.
The Physiology of the Light Absorption in the Retina 49
cGMP-gated sodium channels: These channels depolarize photoreceptors to

around −40 mV (dark current).
There are many voltage-gated channels:
1. Voltage-gated sodium channels
2. Voltage-gated potassium channels
3. Voltage-gated calcium channels
4. Voltage-gated proton channels
There are also ligand-gated ion channels such as GABA and Acetylcholine
receptors.
Sodium and potassium pumps: These pumps enable the photoreceptors to main-
tain a steady concentration of intracellular NA+ and K+ (Fig. 3.6).
The Physiology of the Light Absorption in the Retina
The transition of light to neural signal is very complex and requires many steps [19].
This process can be summarized as follows:
• Photon hits the photoreceptors that already have a steady background noise. The
photon energy causes a sudden decrease in the background noise which will be
translated into a biochemical signal.
• A sudden decrease of background noise activates bipolar cells.
• The bipolar cells activate ganglion cells via amacrine cells by negative feedback.
• Ganglion cells transfer the input as an “action potential” to the Brain.
Synaptic connections between the retinal cells [20]:
• Photoreceptors and bipolar cells.
• Bipolar cells to Ganglion cells via amacrine cells.
• Ganglion cells to the lateral geniculate nucleus in the brain [21].
• Muller cells, Horizontal cells, and amacrine synapses.
The processing of visual information is extremely complicated and involves
many steps. Each step has multiple components and interactions. The summary of
the interaction between the retinal cells is well described [22].
One way to simplify the essentials and make it more understandable is to present
the process step by step from the moment that the light reaches the retinal
photoreceptors.
• Photoreceptors are rod cells or cone cells that are light detectors. The Rod cells
are for night vision and have no color perception, the Cone cells are for day
vision and are three different types that can perceive three different colors (blue,
green, and red).
• Retinal Pigment Epithelium (RPE) is a layer of pigmented cells that is in direct
contact and interaction with photoreceptors (Fig. 3.7).
Fig. 3.6 Schematic illustration of various different ion exchange channels and pumps in the pho-
toreceptor cells
The Physiology of the Light Absorption in the Retina 51
Fig. 3.7 Light microscopy (x 100) of retinal pigment epithelium with adjacent structures includ-
ing photoreceptors, Bruch’s membrane, and choriocapillaries
• Bipolar cells (ON and OFF Modifiers) ON bipolar cells are activated by light
stimulation and OFF bipolar cells are activated by absence of light.
• The ganglion cells and their axons that make up the nerve fiber layer and the
optic nerve (long-distance signal transport to the brain).
• Horizontal cells (modulating photoreceptors and bipolar cells).
• Amacrine cells (moderating bipolar and ganglion cells).
• Muller cells (Support system) for entire retina.
Recommended articles for further detail:
The architectures of neuronal circuits [23].
Synaptic specification of retinal cells [24].
The Visual Cycle
Retinoids initiate the process of photochemical reactions that will start the photon
signal transduction to the brain [25].
Retinoids are derivatives of vitamin A and cannot be produced inside the body.
They are absorbed by digesting food containing vitamin A such as fish, dairy prod-
ucts, and meat.
The first step is the chemical reaction that happens when the photon hits the rho-
dopsin molecule in the photoreceptors. There is a constant cycle of chemical
reactions that utilizes and reproduces rhodopsin. That involves close coordination
and cooperation between the photoreceptors and the retinal pigment epithelium.
The chemical process of retinal cycle between the photoreceptors and retinal
pigment epithelium:
1. Isomerization, the light converts 11-cis retinal to all-trans retinal inside the
photoreceptors.
2. All-trans retinal converts to all-trans retinol by the enzyme all-trans retinal dehy-
drogenase (RDH) inside the photoreceptors.
3. All-trans retinol travels to retinal pigment epithelium (RPE).
4. All-trans retinol converts to all-trans retinyl ester by the enzyme lecithin retinol
acyltransferase (LRAT) in RPE cells.
5. All-trans retinyl ester will convert to 11-cis retinol with the enzyme isomerohy-
drolase (RPE65) in RPE cells.
6. 11-cis retinol then converts to 11-cis retinal by the enzyme 11-cis retinal dehy-
drogenase (11-cis RDH) in RPE cells.
7. 11-cis retinal travels back to the photoreceptors to replenish them (Fig. 3.8).
Fig. 3.8 Diagram of the complete cycle of chemical reactions between photoreceptors and Retinal
Pigment Epithelium for constant supply of retinal for use by photoreceptors
The Photoreceptors, the Rod Cells, the Cone Cells, and the Ganglion Cells 53
he Photoreceptors, the Rod Cells, the Cone Cells,

T
and the Ganglion Cells
There are three different types of photoreceptors in the retina. The rods and cones
are located at the outermost layer of the retina and are directly involved with the
vision processing cascade. Another type of photoreceptor is the small population of
ganglion cells in the innermost layer of the retina that carry melanopsin that only
involve with circadian rhythm and pupillary reflexes.
Rods and cone cells are located in-between retinal pigment epithelium and bipo-
lar cells. They produce neurotransmitter glutamate in synapses to bipolar cells and
in direct contact with retinal pigment epithelium for multiple interactions. Rods and
cones have somewhat similar structures with small differences. The inner segment
of rods and cones contains mitochondria which provide ATP for the sodium-
potassium pumps. The outer segments are composed of discs filled with opsin that
reacts to light. The outer segments also contain voltage-gated sodium channels.
Rod cells are specific for low light perception (night vision) and do not perceive
color. The cones are specific for high light perception (day vision) and composed of
three different types (S-cones for blue perception, M-cones for green perception,
and L-cones for red perception) as they are sensitive to specific wavelengths for
color perception (Fig. 3.9).
Activation of Rods and Cones
Activation of rods and cones is the initial step in the phototransduction process of
converting the photon energy to neural signal to be transferred to the brain. Many
steps are involved in this complex process but can be simplified and separated into
phototransduction in the dark and phototransduction in light.
These processes are as follows:
Phototransduction in Dark: There is a high level of cGMP which keeps the
sodium channels open (dark current) and keep photoreceptors depolarized leading
to release of glutamate to inhibit the excitation of neurons.
Phototransduction in light: Decrease level of cGMP closes the sodium channels
that switch off the (dark current) causes hyperpolarization of photoreceptors that
reduces the release of glutamate that reduces the inhibition of neurons (Double
negative feedback) (Figs. 3.10, 3.11, 3.12, and 3.13).
Fig. 3.9 Schematic illustrated comparison of rods and cones photoreceptors

Activation of Rods and Cones 55
Rod Cell Outer Rod Cell Outer

Membrane Membrane
Rhodopsin Transducin Phosphodiesterase
Disc Membrane
cGMP
Na+
Extra Open
Cellular Cytosol cGMP
Fluid Gated
cGMP Channel
cyclase
Closed
α α α α
γ γ
β αβ
GTP
Light GMP cGDP
GTP
GDP
Step 1 Step 2 Step 3-4 Step 5
Fig. 3.10 Illustration of early steps of phototransduction in photoreceptor disc
Fig. 3.11 Light microscopy image (x100) of cone cell of the retina with superimposed illustra-
tions of schematic structures
Fig. 3.12 Light microscopy image (x100) of three color cone cells of the retina with superim-
posed illustrations of schematic structures
Activation of Rods and Cones 57
Fig. 3.13 Light microscopy image (x 100) of rod cell of the retina with a superimposed illustra-
tion of schematic structures
The Retinal Pigment Epithelium
Retinal Pigment Epithelium (RPE) is the outer pigmented layer of the retina as the
result of the invagination of the embryonic optic cup which the inner layer develops
into retina and the outer layer develops into retinal pigment epithelium. It is located
in between the retina and the choroid and can communicate and interact with pho-
toreceptors and the choriocapillaris. It plays an important role in the maintenance
and storage of visual systems. Multiple physiological functions can be summarized
as follows (Fig. 3.14):
• Darkroom function by absorbing scattered light entering the eye by its melanin
contents.
• Controlling and diminishing the high photo-oxidative stress by melanosomes.
• Blood–retinal barrier due to its tight junctions, which isolates the inner retina
from systemic influences.
• Preserve immune privilege of the retina.
• Supply nutrients to photoreceptors.
• Controls ion homeostasis.
• Eliminates water and metabolites.
• Participation in the constant processing and replenishing of 11-cis retinol for
photoreceptors.
• Storage of the “retinal” and adaptation of reaction speed.
• Phagocytosis of photoreceptors’ outer segments.
• Secretion of multiple varieties of factors and signaling molecules: ATP, FGF,
PDGF, VEGF, PEDF, etc (Figs. 3.15 and 3.16).
Fig. 3.14 Illustration of the entire phototransduction steps with RPE participation in the
visual cycle
The Retinal Pigment Epithelium 59
Fig. 3.15 Illustration of RPE function with exaggeration of size proportion in order to emphasize
the importance of RPE collaboration with photoreceptors
Rod Photoreceptor Discs
RPE
Disc Fragments
Lysosome
Bruch’s Membrane
Choriocapillaries
Fig. 3.16 Light microscopy (x 100) highlighted the microscopic image of phagocytosis of photo-
receptor (rod cell) discs
Ganglion Cells
Inner Plexiform
Layer
Muller Cell
Biopolar Cells
Outer Plexiform
Layer
Nucleus of Rods
& Cones
External Limiting
Membrane
Fig. 3.17 Light microscopy (x 100) of retinal bipolar cells with adjacent structures including
ganglion cells and the nucleus of rods and cones
The Bipolar Cell’s Function
• The bipolar cells connect photoreceptors to the ganglion cells.

• There are different types of bipolar cells, metabotropic (ON) bipolar cells that
terminate in the inner of the inner plexiform layer and ionotropic (OFF) bipolar
cells synapse in the outer layer of the inner plexiform layer of the retina with
their specific properties.
• Bipolar cells also connect to other surrounding cells via receptors or secondary
messengers.
• Multiple different inputs from photoreceptors and from amacrine cells and hori-
zontal cells (Fig. 3.17).
Activation of Bipolar Cells
Bipolar cells receive synaptic input from both rods and cones. There are multiple
forms of cone bipolar but only one type of rod bipolar cell.
In the presence of light, rods and cones stop the production of glutamate. “ON”
bipolar loses its inhibition and “OFF” bipolar cells lose their excitation.
In the dark, rods and cones will release glutamate. This inhibits the “ON” bipolar
cells and excites the “OFF” bipolar cells.
Rod bipolar cells synapse onto amacrine cells and not directly to ganglion cells. The
amacrine cells via gap junctions excite “ON” cone bipolar cells and inhibit the con
The Ganglion Cells 61
“OFF” bipolar cells which enables it to send signals to ganglion cells in a dim (scoto-
pic) light.
The Amacrine Cells
Amacrine cells interact with bipolar cells and ganglion cells. They operate in the
inner plexiform layer of the retina. They induce lateral inhibition to the axon termi-
nals with efficiency on signal transduction with high “signal-to-noise” ratio. Their
mosaic arrangement ensures that all parts or retina have access to the full set of
processing elements.
There are different types of amacrine cells in the retina. GABAergic with subtypes of
dopaminergic, glycinergic, and neither. These neurotransmitters contribute to many prac-
tical functions such as detection of directional motion, modulation of light adaptation,
circadian rhythm, and control of high sensitivity in dark via connection with bipolar cells.
The Horizontal Cells
The horizontal cells are located in the inner nuclear layer of the retina. The main
function is the integration and regulation of the input from multiple photoreceptor
cells. They induce lateral inhibition and adjust to bright and dim conditions. They
have inhibitory or negative feedback to rods and cones.
The Ganglion Cells
Ganglion cells are responsible to transfer the visual signals that are collected by reti-
nal sensory cells to the brain via their long axons which form the nerve fiber layer
of the retina and the optic nerve. Ganglion cells represent less than 1% of all retinal
cells. At least around 30–40 subtypes have been identified. Each of these subtypes
are differing in morphology, location, function, susceptibility to degeneration, and
regenerative capability [26].
Some subsets of ganglion cells are intrinsically photosensitive and contain mela-
nopsin that activates by light directly [27].
There is another uncommon signal transfer to Ganglion cells [28].
These melanopsin-expressing retinal ganglion cells play a major role in non-
visual responses to light such as:
• Regulation of sleep-wake cycles
• Pupillary reflexes
• Modulation of mood
• Some aspects of vision (Fig. 3.18)
62
3
Fig. 3.18 Schematic description of the cellular structure of the retina and RPE and their correlation to the Bruch’s membrane and choroid
Classic Biology of Human Eye
The Ganglion Cells 63
Activation of Ganglion Cells
Multiple neurotransmitters are involved in transferring signals between ganglion

cells and bipolar cells and amacrine cells. Glutamate is the primary source of excita-
tion; however, Acetylcholine is an excitatory neurotransmitter that often acts as a
modulator of glutamate receptors [29].
• The N-methyl-D-aspartate (NMDA receptor) is a glutamate receptor and ion
channel found in neurons. NMDA receptor activity regulates synaptic connec-
tions between retinal ganglion cells and bipolar cells [30].
• The gamma-aminobutyric acid (GABA) receptors are the chief inhibitory recep-
tors and are divided to GABAA that are ligand-gated ion channels or GABAB are
G-protein-coupled receptors. The binary activation and suppression of these
receptors are complex and have been studied and reported [31].
• Dopamine is a crucial neuromodulator for light adaptation. Dopamine receptors
are expressed by horizontal cells and some bipolar cells, amacrine cells and gan-
glion cells [32].
• Retinal ganglion cells are strictly postsynaptic neurons. They feedback into the
inner retina and participate in a recurrent circuit, not being a mere collector of
retinal signals but actively involved in visual computation [33].
Visual Phototransduction Steps
As complicated as the visual transduction seems to be, it can be simplified to the

following steps which make it much easier to understand.
1. Photon hits 11-cis retinal inside the opsin molecule and converts it to all-trans
retinal inside the rhodopsin molecule.
2. Opsin undergoes conformation and changes to metarhodopsin II.
3. Metarhodopsin activates Transducin which causes two events to happen;
Transducin separates from its attached GDP and binds to cytoplasmic GTP, and
its alpha subunit separates from its beta and gamma subunits while it is still
attached to GTP.
4. Alpha subunit + GTP complex activates phosphodiesterase (PDE6).
5. PDE6 hydrolyzes cGMP to GMP cause the sodium channels to close.
6. Closure of sodium channels causes hyperpolarization of the photoreceptor cells
due to constant potassium ion efflux.
7. Hyperpolarization causes voltage-gated calcium channels to close.
8. As calcium level drops neurotransmitter glutamate level drops as calcium is
required for fusion of glutamate vesicles to cell membrane for release.
9. A decrease in glutamate level in photoreceptors causes the depolarization of
ON bipolar cells and hyperpolarization of OFF bipolar cells.
10. Bipolar cells with interaction with amacrine cells and horizontal cells transfer
the signal to ganglion cells which initiate action potential to take a long journey
to the brain (Fig. 3.14).
More Related Interesting Articles
Pan [34] metabolism.

Xu [35] Metformin.
Ramachandra [36] Pic + physiology.
Tsin [37] Visual Sycle.
The interaction of rods and cones Gordon [38].
Retinal cell summary Muthuswamy [39].
References
1. Patel. Cornea: A review; 2019. https://doi.org/10.1016/j.clae.2019.04.018.

2. Borchman. Lipid conformational order and the etiology of cataract and dry eye. J Lipid Res.
2021a;62(January 1):100039. https://doi.org/10.1194/jlr.TR120000874.
3. Borchman. Lipid conformational order and the etiology of cataract and dry eye. J Lipids.
2021b;62:100039. https://doi.org/10.1194/jlr.TR120000874.
4. Khan. Change in human lens dimensions, lens refractive index distribution and ciliary
body ring diameter with accommodation. Biomed Opt Exp. 2018;9(3):1272–82. https://doi.
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5. Schultz A. Novel vitreous substitutes: the next frontier in vitreoretinal surgery. Curr Opin
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segment disk architecture and photoreceptor viability. PNAS. 2020;117:4400. https://doi.
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7. Kakakhel. Syntaxin 3 is essential for photoreceptor outer segment protein trafficking and sur-
vival. PNAS. 2020;117:20615. https://doi.org/10.1073/pnas.2010751117.
8. Sethuramanujam S, Awatramani GB, Slaughter MM. Cholinergic excitation complements
glutamate in coding visual information in retinal ganglion cells. J Physiol. 2018; https://doi.
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9. Fu. Fatty acid oxidation and photoreceptor metabolic needs. J Lipid Res. 2021a;62:100035.
https://doi.org/10.1194/jlr.TR120000618.
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TR120000618.
11. Comitato. Pigment epithelium-derived factor hinders photoreceptor cell death by reducing
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s41419-018-0613-y.
12. Meng. Lipid accumulation and protein modifications of Bruch’s membrane in age-related
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https://doi.org/10.1038/s41467-018-03507-2.
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Biomed Opt Express. 2018;9:157. https://doi.org/10.1364/BOE.9.000157.
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org/10.1177/0192623320976375.
Chapter 4
Quantum Retina
Abstract
The new era of quantum physics and its application to quantum biology has revo-
lutionized all fields of science and its applications, especially to the sense of
smell and vision.
Studying the fast chemical reactions in biological processes seemed impos-
sible since some of these reactions happen in a very short time such as in femto-
seconds. With the introduction of femtosecond laser spectroscopy and
development of NV-diamond sensing (discussed in the previous chapter) and
electron echo detection, these obstacles have been removed and a new era of sci-
ence of the very small and very fast has begun.
In this chapter, the initial process of phototransduction in the retina which can
only be explained by means of quantum physics is simplified and explained.
Discussions
The process of visual perception starts with the collision of a photon with the rho-
dopsin molecule in the photoreceptors of the retina. As discussed in the first part of
this chapter, the isomerization of the retinal portion of the rhodopsin molecule initi-
ates the phototransduction process. Retinal is what gives chromophore rhodopsin
sensitivity to light (Figs. 4.1 and 4.2).
Retinal is a derivative of vitamin A. It attaches to the opsin molecule via a cova-
lent link to its lysine residue of opsin molecule by a Schiff base (–C=N–) bond.
Recently, the most focus in vision has been on the quantum efficiency of rhodop-
sin which is almost 70%. The ultrafast excited state double bond isomerization of
rhodopsin happens in a few femtoseconds, which leads to its distinct contribution to
its quantum efficiency.
Due to the small size of molecules, direct observation and evaluation is limited,
however, by exciting the molecule with electromagnetic (EM) radiation and
Switzerland AG 2023
https://doi.org/10.1007/978-3-031-32060-6_4
68 4 Quantum Retina
Fig. 4.1 Schematic

illustrations of 11-cis
“Retinal” molecules with
their atomic carbon
numbers
Fig. 4.2 Schematic

illustration of all-trans
“Retinal” molecules with
their atomic carbon
numbers
recording and analysis of the emitted, absorbed, or scatted waves more detailed
information can be obtained. The process of interaction of electromagnetic radia-
tion with matter can be studied by spectroscopy.
The electrons fill orbitals to stay at the lowest energy level possible, called the
ground state. By exposure to EM radiation, the electron absorbs energy from the
incoming photon and moves to the excited states. Eventually, it will return to its
ground state by different relaxation pathways, these can be either radiating relax-
ation with emission of a photon as fluoresceine or phosphorescence, or non-radiating
relaxation such as vibrational decay or rotational energy level decay, or heat. The
process of absorption and emission is an essential factor in spectroscopy.
The initiation of the phototransduction is a quantum phenomenon, that starts
with the excitation of chromophore rhodopsin by light. The retinal segment of rho-
dopsin then becomes excited and is isomerized by rotation of its segment between
carbon numbers 11 and 12 (it also affects 10 and 13), which separates it from opsin
molecule and triggers the photoreceptor cells of the retina toward neural response.
As the result, the hyperpolarization of the photoreceptor’s membrane occurs and
causes the transmission of signals to ganglion cells of the retina via bipolar cells,
which produce the action potential nerve response. The signals are then transmitted
to the visual cortex where it is translated into a visual response with communication
with multiple regions of the brain for conscious orientation and understanding of
the source.
Standard Jablonski excitation diagram and vibrational Jablonski diagram are shown
below. Vibrational Spectroscopy [1] and Vibrational coherence rhodopsin [2]
have been discussed thoroughly (Figs. 4.3 and 4.4).
Discussions 69
Fig. 4.3 The diagram represents the ground state S0 energy level and the excited state S1 energy
state. After excitation, which is called absorption, the electron will return to its stable ground state
via different pathways which is called relaxation. In radiative pathway, the electron releases pho-
tons in the form of fluoresceine of phosphorescence. In non-radiative pathway, the relaxation is via
vibrational or intersystemic crossing or as heat dissipation
Fig. 4.4 The diagram represents the ground state S0 energy level and the excited state S1 and S2
energy states. After excitation/absorption, the different pathways of relaxation have been shown.
There are multiple vibrational levels that are presented as V1, V2, V3, etc. The radiative and non-
radiative pathways have been shown. S refers to singlet and T refers to triplet states
70 4 Quantum Retina
Fig. 4.5 Schematic presentation of regions of light spectrum used in spectroscopy to evaluate dif-
ferent properties of molecular and atomic structures
There are a wide range of spectroscopy techniques according to the molecule of

interest and the type of information to be studied.
Different wavelengths are assigned to evaluate different properties of the molec-
ular behavior, for example:
• Short wavelengths such as X-ray are used for bond breaking and ionization
process.
• UV wavelengths are used to evaluate electron excitation properties.
• Infrared wavelengths are used to evaluate vibrational properties.
• Microwave is used to evaluate the rotational properties (Fig. 4.5).
Radiation and Human Eye
To have a physiological effect the energy of the radiation must be absorbed. Consider
the full range of EM radiation from Gamma rays to Radio waves, which all have a
different effect on the eye. These conditions will not be discussed in this chapter and
only listed with their relevant references.
• Gamma rays: [3, 4].
• X-rays: [5].
• Ultraviolet: [6].
• Visible light: [7].
• Infrared light: [8].
• Microwave: [9].
• Radio waves: [10].
Since this book is for understanding the essentials for non-physicists, some basic
quantum information must be explained and simplified for the reader to be able to
follow the concepts of quantum biology of the retina.
R hodopsin 71
Rhodopsin
Rhodopsin is a light-sensitive receptor protein that is composed of the chromophore reti-

nal and a G-protein-coupled receptor Opsin which is located in the rod cells of the ret-
ina. Rhodopsin is extremely light sensitive and enables vision in the low-light conditions.
Rhodopsin is embedded in the bilayer cell membrane of retinal photoreceptors
(rods) with molecular weight of 40 kD. Rhodopsin is composed of two segments,
Retinal molecule in the form of 11-cis Retinal a Vitamin A derivative and Opsin
protein (Part of G-protein-coupled receptor family) which has 7 transmembrane
alpha helix folds and contains 348 amino acids. Opsin attaches to Retinal via its
lysine residue located on the seventh helix by covalently bonding to the protonated
Schiff base (−NH+ = CH−). After activation with light, 11-cis Retinal will isomerize
to all-trans (metarhodopsin II) which separates from opsin molecule by hydrolyzing
the Schiff base, to start the phototransduction process.
Eventually, the excited molecule all-trans retinal will terminally relax back to
11-cis retinal and will attach to opsin again in its docking pocket containing the
docking site for the ring element and for the C19 methyl group, which is located next
to the lysine residue [11].
Retinals have an extended conjugated chain (alternating single (C−C) and dou-
ble (C=C) bonds) which reduces the excitation energy of the retinal molecule by
light. Also, the protonated Schiff base with lysine residue, generated upon covalent
binding of retinal with opsin, will further reduce the excited state of the retinal caus-
ing the red shifting of the absorbed frequency detection of 440 nm [12].
The N terminal of rhodopsin is in the extracellular space and the C terminal is
located in the cytoplasm.
The entire circle of rhodopsin isomerization and participation of retinal pigment
epithelium (RPE) in the process has been described in the first part of this chapter
[13, 14]
Rhodopsin is categorized into 2 types:
Rhodopsin Type I (microbial φ = 0.81).
Rhodopsin Type II (animal φ = 0.15) (Fig. 4.6).
Other good reviews that are recommended are as follows:
–– Shedding new light on the generation of the visual chromophore [15].
–– Rhodopsin Activation in Lipid Membranes Based on Solid-State NMR
Spectroscopy [16].
–– Opn5L1 is a retinal receptor that behaves as a reverse and self-regenerating pho-
toreceptor [17].
–– Isorhodopsin: An undervalued visual pigment analog [11].
Quantum Yield ( j ) = number of photos emitted / number of photos absorbed
Quantum efficiency ( QE ) = number of incident photon / number of converted electrons.

72 4 Quantum Retina
Fig. 4.6 Schematic presentation of Rhodopsin molecule. The seven transmembrane components
of opsin molecule are presented in green. The docking site of Retinal is located on the seventh
alpha helix fold as shown. The isomerization rotation site of the molecule Retinal is located at the
double bond between carbon 11 and 12. The rotation outcomes in this region are presented in dif-
ferent colors orange and yellow. The 11-cis retinal segment is in orange color and the rotated seg-
ment that makes All-trans molecule is presented in yellow color. The position of neighboring two
CH3 residues is also changing position as a result of isomerization. The protonated Schiff base and
its attachment to opsin molecule via its lysine component through its sidechain is also presented
in orange
Atomic Orbitals
As it was described in previous chapters it is crucial to discuss the basics again to

better understand the quantum biology concepts.
Electrons according to quantum mechanics description are confined to certain
discrete energy levels around the nucleus. There is an interaction between the posi-
tive protons of the atomic nucleus and the negative electrons which makes the com-
position of an atom. Neutrons carry no charge.
The electron is not orbiting the nucleus like planets orbiting the stars. It only can
be described as a cloud around the nucleus and can behave like a wave which will
follow the Schrödinger equation as described in previous chapters. An electron does
not really exist in one place but the probability of being in a certain position at cer-
tain time can be predicted and calculated.
Atomic Orbitals 73
Fig. 4.7 Schematic 2-dimensional presentation of atomic orbitals (shells), each in different colors
and presented on the right side of the image. Each shell’s suborbital is presented on the left side of
the image. Each subshell has a different number of suborbitals. Each suborbital s, p, d, and f can
only occupy a certain number of electrons. The suborbital’s 3D images are illustrated on the lower
part of the image. The s orbital can only have up to 2 electrons. The orbital p can have up to 6
electrons. The orbital d can have up to 10 electrons and orbital f can have only up to 14 electrons.
Please notice that each shell except K shell is composed of suborbitals and the total number of
electrons in each shell is the sum of the electrons located in the suborbital of that shell
The atomic orbitals are characterized for simplification and presented in a two-
dimensional image.
It is important to mention that the electrons cannot exist between these orbits,
they can only jump up and down to the next orbit via excitation and relaxation events.
There are a number of orbits (n) that are around the nucleus and start from n1 and
increase to n2, n3, and so on. They are also called as shells K, L, M, N, and so on.
Except n1, which is the K shell and contains only one s orbital, every other shell
contains subshells.
Subshells include s orbitals, p orbitals, d orbitals, and f orbitals (Fig. 4.7).
Each suborbital contains a certain number of electrons:
74 4 Quantum Retina
s orbitals can take 2 electrons, one spin up one spin down.

p orbitals can take 6 electrons, each pair one spin up and one spin down.
d orbitals can take 10 electrons, each pair one spin up and one spin down.
f orbitals can take 14 electrons, each pair one spin up and one spin down.
The order of the suborbitals is in a specific arrangement as follows:
1s, 2s, 2p, 3s, 3p, 4s, 3d, 4p, 5s, 4d, 5p, 6s, 4f, 5d, 6p, 7s, 5f, 6d, 7p.
For example, the carbon atom has 6 electrons, the first orbit, 1 s, contains 2 elec-
trons (shell K or n−1), and in the second orbit or shell (shell L or n−2) 2 electrons
in 2 s suborbital, and 2 electrons in 2p suborbital. The atomic configuration of car-
bon atom is then 1s2 2s2 2p2 and atomic configuration of Iron is 1s2 2s2 2p63s2 3p6 4s2
3d6 since it has 26 protons and 26 electrons.
The first numbers are the number of the orbitals, the letters are the suborbitals
and the superscripts are the number of electrons in that suborbital.
Molecular Orbitals
Molecular orbitals describe the location and wave-like behavior of an electron in a

molecule. Since the molecule is a combination of atoms, its orbitals are the combi-
nation of atomic orbitals to form the molecular orbital. They also follow the
Schrödinger equation for the electron in the field of the molecule’s atomic nuclei.
Molecular orbitals are usually constructed by combining atomic orbitals, or hybrid
orbitals from the same or another molecule.
There are three types of molecular orbitals:
Bonding orbitals: Promote chemical bonding and are in phase and have less
energy than the atomic orbitals that formed them.
Antibonding orbitals: The interaction is out of phase and forms nodal planes in
which the wave function between the interacting atoms becomes zero. The anti-
bonding orbitals are higher energy than the atomic orbitals that formed them.
Non-bonding orbitals: This is due to no interaction between atomic orbitals
because of lack of compatible symmetries.
The energy level is the same level as the atomic orbitals that form them.
Binding Orbitals Categories
Molecular orbitals can be categorized according to bonding in their symmetry:

Sigma bond: Strongest chemical bond with head on overlapping between atomic
orbitals. A single bond is typically a Sigma bond, double bonds are usually one
Sigma bond and one Pi bond, triple bonds are one Sigma and two Pi bonds
(Fig. 4.8).
Energy Level 75
Fig. 4.8 Schematic presentation of s orbital bondings with each other in two different formats;
antibonding and bonding
Fig. 4.9 Schematic

presentation of p orbital
bondings with each other
in two different formats
Pi bond: covalent chemical bonds. Two lobes of an orbital on one atom overlap
the two lobes of another atom’s orbital. They are weaker than Sigma bonds. This
type of bonding is the most common form of p orbitals (Fig. 4.9).
Delta bond: Covalent chemical bonds. Four lobes of one atomic orbital overlap
with four lobes of the other involved atomic orbital. It is the usual form of bond-
ing in d orbitals (Fig. 4.10).
Phi bond: Covalent chemical bonds. Six lobes of one atomic orbital overlap with
six lobes of another involved atomic orbital. It is the common form of bonding in
f orbitals Fig. 4.11.
Energy Level
In a Quantum mechanical system, electrons can only exist in certain discreet energy
levels bound by positive electric charge of the nucleus. As described above, each
electron shell and subshell represent a particular level of energy.
76 4 Quantum Retina
Fig. 4.10 Schematic

presentation of d orbital
Fig. 4.11 Schematic

presentation of f orbital
When not excited, the electrons always occupy the lowest possible energy level
called ground state. When electrons absorb energy and are excited, they move up
to higher energy levels, and the molecule or atom moves to an excited state.
Excited states are unstable, and the electron will soon return to its ground states
via different modes called relaxation.
There are different modes of relaxation such as radiating decay which emits
photons or non-radiating decay (relaxation) which does not emit photons. There are
many forms of radiating decay, which is the release of photons during relaxation
process such as fluorescence and phosphorescence. There are also many non-
radiative relaxations such as vibrational decay, photochemical transformation,
and heat.
The excitation as was mentioned above can be induced with many different elec-
tromagnetic rays such as X-rays, Infrared, monochromatic lasers, UV, and micro-
waves. This stage is called absorption.
Non-radiative Decay 77
Radiative Decay
When a ground state molecule interacts with light of the appropriate energy, an
electron in the molecule moves to a higher electronic state called excited state. This
excitation is dependent on the energy of the incident radiation. The excited state is
very unstable and if the electron is excited to a high-energy state, then it will return
to the lowest vibrational level of the lowest electronic state. At this point some
energy will be lost as heat during the decent to the lower energy state. From the low-
est excited state, the electron can return to the ground state via different pathways:
1. Fluorescence: Because the electron returns from a lower vibration state than
from the one that was originally excited, the emitted fluorescent light will have
less energy which will appear as in a longer wavelength.
2. Phosphorescence: If the electron is transferred to the lowest triplet state via
intersystem crossing. This requires a reversal of the electron spin. The electron
then returns to its ground state with the emission of light in a relatively long
interval.
3. Energy transfer: The energy of the excited molecule is transferred to another
molecule.
4. Internal conversion: The excited electron returns to the ground state with its
energy dissipated as heat.
Non-radiative Decay
Also called vibrational relaxation, is when an electron relaxes from a higher vibra-
tional level to the lower vibrational level of the excited electronic state, as there are
multiple vibrational states in each excited state. This process is much faster than the
radiative decay and can be referred to as the quenching of luminescence. The relax-
ation in non-radiative decay to the ground state can happen via different pathways:
1. Vibrational relaxation: As mentioned above occurs between the different vibra-
tional states of the same excited state.
2. Intersystem crossing: Relaxation proceeds between two different excited states
with different spin multiplicity such as between S1 and T1.
3. Internal conversion: The excited energy dissipates as heat.
4. Crystal vibrations in solid state.
In the case of Rhodopsin molecule, the process is non-radiative relaxation in
which no light is emitted. Similar process happens in nuclear position when the
excitation is associated with emission of a photon as fluoresceine which is a radia-
tive relaxation process (Fig. 4.12).
78 4 Quantum Retina
Fig. 4.12 Schematic presentation of nuclear influence on destination of 11-cis isomerization

toward either back to ground state in the intersection space with unsuccessful outcome or All-trans
configuration by in-phase interaction with nucleus and a successful outcome
Nuclear Response
Electron excitation is so fast that there is a delay in the nuclear response to the pro-
cess. The nuclear response and position can be discussed as follows:
1. In the ground state S0, the nuclear fluctuation is near the lowest energy level S0.
2. After the excitation to S1, the nucleus response is to move from a higher excited
state to the lowest energy level of the excited state S1.
3. The nucleus fluctuates at the lowest excited state of S1.
4. Eventually after the relaxation, the nucleus returns to its original lowest energy
level of the ground state S0, Fig. 4.13.
Carbon
Before we get to Isomerization, which is a fundamental step in phototransduction,

we must have a quick review of the properties of a carbon atom which has a major
role in the initiation of this process:
Carbon symbol is C and has an atomic number 6 which means it contains 6 pro-
tons and 6 electrons. The outer shell contains 4 electrons (2 from 2s suborbital and
2 from 2p suborbital) which is why Carbon has 4 valence electrons in its outer shell.
Carbon-to-carbon bonding can be single C-C (one Sigma bond) or double bond
C=C (one Sigma bond and one Pi bond), or triple bond (one Sigma bond and two
Pi bonds).
Lysine (C6H14N2O2) 79
Fig. 4.13 Schematic presentation of radiative photoisomerization and emission of fluores-

cent photon
When carbon atoms only attach to other carbon atoms, they form a diamond
crystal. The use of diamond and its nitrogen vacancy space as a sensing device is a
major forward step in quantum physics tools for experiments as was discussed in
the earlier chapter. Carbon is the second most abundant element in the human body
(about 18.5%) after oxygen.
Carbon is the common element of all known life forms due to its unique diversity
of forming organic compounds and polymers at ambient temperature. In a mole-
cule, the carbon atoms are numbered, and this can be done by finding the longest
carbon chain in the molecule and starting from the side that has the shortest sub-
stituent attached. For example, carbon numbering in a retinal molecule (C20H28O) is
shown in Figs. 4.1 and 4.2.
Lysine (C6H14N2O2)
Lysine is an amino acid that is a precursor to many proteins. It contains protonated

amino group (-NH3+) and Carboxylic acid (-COOH) and a side chain ((CH2)4NH2) + H
as protonated.
Lysine’s most important functions are as follows:
• Proteinogenesis
• Crosslinking of collagen Polypeptides
• Uptake of mineral nutrients
• Fatty acid metabolism
• Production of Carnitine
80 4 Quantum Retina
• Histone modification
• Participation in the phototransduction process.
Lysine role in phototransduction: Ammonium group (NH3+) forms a Schiff
base (–C=N–) with the conserved lysine residue and extra H+ (protonated) which
is involved in its interaction with light.
Protonated Schiff Base (PSB): The carbon double bond with nitrogen (-C=N-)
forms the Schiff base on a general formula RN=CR’R”. For example, Retinal
forms a Schiff base with opsin as shown above.
From (E) to (Z) Isomerization
“From E to Z” is just another fraze for 11-cis to all-trance retinal isomerization. The
primary event occurring during the E-Z photoisomerization of the protonated Schiff
base is single-to-double bond conversion causing the unlocking of the C=C double
bond. This “unlocking” process is the primary event during the rhodopsin photoi-
somerization [18].
There are several studies that discuss the E to Z isomerization with detailed
descriptions. The reader can refer to the following article for a more in-depth
review ([13]):
(E) = German “entgegen” opposite for example, 11-cis Retinal (E)
(Z) = German “zusammen” together for example, all-trans-Retinal (Z)
Isomerization
Photoisomerization or photon-induced isomerization starts in the S1 excited state

which is unstable and will decay to S0 ground state via non-radiative decay. The
decay can cause the molecule to go back to the initial isomer or forward to the isom-
erized configuration. The initial step of this reaction proceeds via a coherent evolu-
tion primarily along the torsional and HOOP modes which both exhibit 90 degrees
of rotation. At this point, the outcome depends on their relative phasing of HOOP
and torsion. When in-phase rotation continues another 90 degrees to a total of 180
degrees to form “all-trans retinal” (Fig. 4.14).
When out of phase, the rotation goes backward 90 degrees to 0 degree, which
becomes “11-cis retinal,” back to its original isomer [2].
The isomerization is caused by the following changes in the rhodopsin molecule:
1. Bond Length Alteration (BLA).
2. Twisting of the dihedral angle (C10−C11 = C12−C13) which happens at Intersection
Space (IS) between S1 and S0, which at first is 90 degrees, then another rotation
Isomerization 81
Fig. 4.14 The effect of intersection space known as Conical intersection (CI) which is under the
influence of the nucleus vibrations. The destination of the isomerization is decided in CI with in-
phase or out-of-phase interaction with the nucleus. In-phase becomes a successful reaction toward
All-trans initiating the phototransduction and out of phase becomes unsuccessful and moves back
to its original ground state
of 90 degrees either pro or con to original rotation, depends on “in phase” or “out
of phase” in their vibrational relative phasing.
Dihedral angle is the angle between the two planes, but which pass through
the same bond.
3. Twisting of hydrogen out of a plane (C11−H+ C12−H) or (HOOP) [19].
4. Hydrogen out of plane motion (HOOP) and molecular vibrational phase-
dependent torsion dictates the outcome of the initial step of isomerization.
5. The splitting into subpopulations at the Intersection Space (IS), also called coni-
cal intersection (CI). The excited retinal splits into two destinations, either back
to its original position as 11-cis or transforming into its isoform all-trans
depending on if it is “in phase” or “out of phase” with nuclear motion of the
molecule.
6. Potential energy surface (PES) induced by coherent motion with nucleus at the
excited state imposes the specific mode relationship toward the outcome of the
splitting process [20].
7. Overall, the outcome of isomerization is governed by opsin electrostatics
(Fig. 4.15).
Immediately after “in phase” splitting, the first product is photorhodopsin with its
transition within picoseconds to bathorhodopsin as the intermediate stage. The sub-
sequent intermediates lumirhodopsin and metarhodopsin I maintain their reddish
color due to their Schiff’s base linkage to all-trans retinal, as long as it remains proton-
ated. The final conversion of metarhodopsin I to metarhodopsin II is associated with
deprotonation of the Schiff’s base and as a result the color changes from red to yellow.
Dual photoisomerization on distinct potential energy surfaces in a UV-absorbing
Rhodopsin has been reported and can be reviewed in this article [21].
82 4 Quantum Retina
Fig. 4.15 The diagram illustrates isomerization of 11-cis retinal to all-trans retinal with hydrogen
out-of-plane (HOOP) presented in green and protonated Schiff base in orange
Time Fractions in Isomerization of 11-cis Retinal
From (E) to (Z The primary isomerization reaction) is completed in less than 150
femtoseconds [13].
The excitation process is extremely fast which is around 1 fs.
Bond length alteration (BLA) begins at 15 fs.
Femto Scale 83
Fig. 4.16 The diagram represents the time scale of the events after excitation of electrons. After
excitation, different pathways of relaxation are shown as seen in the schematic above
The splitting happens 30 fs to form subpopulations.

Subpopulation decays at different times. The fastest decay is between 35 and
80 fs and the slowest decay happens between 170 and 200 fs (Fig. 4.16).
Femto Scale
In recent years, there has been a lot of attention to femto scale since the creation of
femtosecond lasers (Fig. 4.17).
84 4 Quantum Retina
Fig. 4.17 International System of Units with femto highlighted in red as being referred to in
the text
Femto Chemistry of Rhodopsin
Femtosecond laser spectroscopy is used to interpret the transition of rhodopsin

through a conical intersection (CI) with retention of the coherence of the vibrational
wave pockets generated during excitation [22]. The femtolaser pump-probe spec-
troscopy is performed by using an intense short laser wave to excite the molecule
referred to as “pump.” To measure the ultrafast behavior of the molecule the second
pulse is sent shortly after the first one which is referred to as “probe.” By changing
the delay between the pump and probe multiple snapshots will be recorded. It is
then possible to reconstruct the ultrafast motion of the molecule frame by frame.
This allows a time resolution down to the femtosecond (1 × 10−15) [23] (Fig. 4.18).
There is a basic article from 2014 that describes the fundamentals of “quantum
retina” [24], since then multiple advances and more recent publications and new
studies have been performed.
The recent articles on quantum biology and vision are highly recommended to
update the readers’ knowledge of quantum effects on the eye [25, 26].
References 85
Fig. 4.18 The diagram represents the ground state and excited states of electrons after excitation
with the pump laser pulse, followed by femtosecond laser probes which effects the vibrational states
References
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Commun. 2018;9:313. https://doi.org/10.1038/s41467-017-02668-w.
2. Schenedermann. Mode-specificity of vibrationally coherent internal conversion in rhodopsin
during the primary visual event. J Am Chem Soc. 2015;137:2886. https://doi.org/10.1021/
ja508941k.
3. Muranov. Biochemistry of eye lens in the norm and in cataractogenesis. Biochem Mosc.
2022;87(February 11):106. https://doi.org/10.1134/S0006297922020031.
4. Akagunduz. Radiation-induced ocular surface disorders and retinopathy: ocular structures
and radiation dose-volume effect. Cancer Res Treat. 2022;54:417. https://doi.org/10.4143/
crt.2021.575.
5. Ke Q. Multinucleated retinal pigment epithelial cells adapt to vision and exhibit increased
DNA damage response. cells. 2022;11 https://doi.org/10.3390/cells11091552.
6. Marro. Assessing human eye exposure to UV light: a narrative review. Front Public Health.
2022;10 https://doi.org/10.3389/fpubh.2022.900979.
7. Fan. The molecular mechanism of retina light injury focusing on damage from short wave-
length light. Oxidat Med Cell Longevity. 2022;2022 https://doi.org/10.1155/2022/8482149.
8. Praveena. Prevalence and pattern of ocular disorders due to chronic exposure to arc welding
among occupational welders in Western Rajasthan. J Family Med Primary Care. 2022;11:2620.
https://doi.org/10.4103/jfmpc.jfmpc_1880_21.
9. Bijlard. Direct microwave burns in an infant: description of burn characteristics, management
and outcome. Burns Open. 2022; https://doi.org/10.1016/j.burnso.2022.07.001.
10. Moon. Health effects of electromagnetic fields on children. Clin Exp Pediatr. 2020;63:422.
https://doi.org/10.3345/cep.2019.01494.
86 4 Quantum Retina
11. de Grip. isorhodopsin: an undervalued visual pigment analog. Colorants. 2022; https://doi.
org/10.3390/colorants1030016.
12. Wenging. The photochemical determinants of color vision. BioEssays. 2013;36:65. https://doi.
org/10.1002/bies.201300094.
13. Metternich. Photocatalytic E → Z Isomerization of Polarized Alkenes Inspired by the Visual
Cycle: Mechanistic Dichotomy and Origin of Selectivity. Am Chem Soc. 2017; https://doi.
org/10.1021/acs.joc.7b01281.
14. Broser. Far-red absorbing rhodopsins, insights from heterodimeric rhodopsin-cyclases.
Frontiers in Molecular Biosciences. 2022; https://doi.org/10.3389/fmolb.2021.806922.
15. Palczewski. Shedding new light on the generation of the visual chromophore.
PNAS. 2020;117:19629. https://doi.org/10.1073/pnas.2008211117.
16. Perera. Rhodopsin activation in lipid membranes based on solid- state NMR spectroscopy.
Encyclopedia Biophysics. 2020; https://par.nsf.gov/servlets/purl/10264174
17. Sato. Opn5L1 is a retinal receptor that behaves as a reverse and self-regenerating photorecep-
tor. Nat Commun. 2018;9:1255. https://doi.org/10.1038/s41467-018-03603-3.
18. Olivucci. Unlocking the double bond in protonated Schiff bases by Coherent superposition of
S1 and S2. J Phys Chem Lett. 2021; https://doi.org/10.1021/acs.jpclett.1c01379.
19. Clarivate. Acylhydrazone switches: E/Z stability reversed by introduction of hydrogen bonds.
Eur J Organ Chem. 2018; https://doi.org/10.1002/ejoc.201801466.
20. Xuchun. 2022. https://www.readcube.com/articles/10.1038/s41557-022-00892-6?no_
publisher_access=1. Nat Chem March 3. https://www.readcube.com/articles/10.1038/
s41557-022-00892-6?no_publisher_access=1.
21. Hontani. Dual Photoisomerization on distinct potential energy surfaces in a UV-absorbing
rhodopsin. J Am Chem Soc. 2020;142:11464. https://doi.org/10.1021/jacs.0c03229.
22. Ostrovsky. Femtochemistry of rhodopsins. Russian J Phys Chem B. 2020;15:344. https://doi.
org/10.1134/S1990793121020226.
23. Kiefer. Intrinsic photoisomerization dynamics of protonated Schiff-base retinal. Nat Commun.
2019; https://doi.org/10.1038/s41467-019-09225-7.
24. Sia. Quantum biology of the retina. Clin Exp Ophthalmol. 2014;42:582. https://doi.
org/10.1111/ceo.12373.
25. Mazzoccoli. Chronobiology Meets Quantum Biology: A New Paradigm Overlooking the
Horizon? Front. Physiol. 2022; https://doi.org/10.3389/fphys.2022.892582.
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org/10.1038/s41557-022-00892-6.
Chapter 5
Magnetoreception
Abstract
As we reviewed, the effect of quantum mechanics on biological phenomenon
such as photosynthesis and visual phototransduction in the previous chapters, we
hope that the quantum concepts and effects on cellular structures have become
more familiar and understandable for the reader. Another field of biology that has
been the center of attention in the past 40 years is the role of quantum physics in
the process of magnetoreception in migrating birds. There have been multiple
theories and experiments on the subject that we will summarize in this chapter,
and we will discuss the latest info available in the literature at the present time.
The ability of sensing the earth’s magnetic field has been reported in many living
organisms, from plants to insects such as fruit flies and honeybees, fish such as
salmon and migrating birds. Recently, the existence of human magnetic sense has
been reported and is suggested that it is mediated by a light and magnetic field
resonance-dependent mechanism [1, 2]. The main use of magnetoreception is for
navigation.
Even though the exact mechanism of the effects of magnetic fields on biological
systems is not completely understood, there are many researchers who have nar-
rowed it down to specific mechanisms that will be discussed here [3].
The birds can sense the inclination of the magnetic field by a process that involves
the absorbance of the blue light, indicating the involvement of photoreceptor pro-
teins in their retina.
The discovery of the chromophore proteins Cryptochromes and their ability to
produce radical-pair mechanism seemed to match all the requirements for a magn-
etosensor. Recent studies also have provided strong evidence that European robin
cryptochrome 4a (ErCry4a) and alpha subunit of a cone-specific G-protein interact
in vivo, and this interaction could be the first trigger step of biochemical signaling
in radical-pair-based magnetoreception Görtemaker [4, 5]).

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-32060-6_5
88 5 Magnetoreception
The light-dependent magnetic perception of night migratory songbirds can be

disrupted by weak radiofrequency fields. This confirms that at least one of the com-
ponents of the radical pair was involved in the magnetoreception which was a result
of the existence of a substantial number of strong hyperfine interactions as would be
in the case of flavin-tryptophan radical pair as a magnetic sensor [6].
The quantum nature of avian compass has been established recently and again is
inspired by the cryptochrome protein qualifications for magnetoreceptor sensing [7].
The following review article is highly recommended which covers the basics of
magnetic field effects from the perspective of the radical pair mechanism [8]
At present, there are different theories regarding magnetoreception, but it is
believed that the main source of magnetic field detection is the protein “Cryptochrome”
in the eye and relies on the quantum radical pair mechanism to function.
Again, we must review some biochemistry essentials to understand the
magnetoreceptor process.
Earth Magnetic Field (EMF)
Earth’s magnetic field is generated by electric currents produced by the motion of

the molten iron and nickel in the Earth’s outer core convection currents. These cur-
rents are caused by heat escaping from the core. At the surface, the Earth’s magnetic
field is very weak and ranges from 0.25 to 0.65 G (The international unit of
magnetic-B field is Tesla which is equal 10,000 Gauss).
The interaction of Earth’s magnetic field with cryptochrome molecules causes
interconversion between the singlet and triplet states of the radical pair.
It should be realized that the electrons in atoms and molecules except for oxygen
are at singlet state which is referred to as a system in which all electrons are paired
and are in a stable mode. Their net angular momentum is zero and overall spin quan-
tum number s = zero.
The excitation with electromagnetic waves can cause a transit to a singlet excited
and/or to a triplet state.
Paired electrons are two electrons that occupy the same molecular orbit but
have opposite spins.
Because the spin of paired electrons is opposite the magnetic moment of electrons
cancels each other and the magnetic property is generally diamagnetic which is
repelled by magnetic field and has no dipole moment.
Unpaired electrons on the other hand have an electron that occupies an orbital
singly. Unpaired electrons also occur briefly during reactions and radical formation.
The unpaired electron has a magnetic dipole moment. Only elements with unpair
electrons exhibit paramagnetic which attract by a magnetic field.
Hyperfine Structure: Small shift and splitting of energy level of atoms,
molecules, and ions due to electromagnetic multipole interaction between the
nucleus and the electron cloud.
Pauli exclusion principle: Two electrons with the same value occupying the same
orbit must have opposite spins, if one has +1/2 spin the other must have −1/2 spin.
Earth Magnetic Field (EMF) 89
Free Radicals are atoms, molecules, or ions that have at least one unpaired
valence electron. Free radicals have a major role in living organisms, for example,
superoxide and nitric oxide and their reaction products regulate many processes
such as controlling the vascular tone or as a messenger in redox signaling.
Redox (reduction-Oxidation) is a chemical reaction in which the oxidation
states of atoms are changed. Reduction is the gain of electrons or decrease in the
oxidation state of atoms. Oxidation is the loss of electrons or increase in the oxida-
tion states of atoms.
Electron Transfer is when an electron relocates from one atom or molecule to
another. It is the foundation of photo redox catalysis.
Cryptochromes are 70–80 KDa proteins and are evolutionary proteins belonging
to the flavoproteins superfamily found in plants, insects, and animals that are
sensitive to blue light. The molecule contains two chromophores: Flavin in the form
of Flavin Adenine dinucleotide (FAD) and Petrin (MHFR) [9, 10].
Immunohistochemical staining in migrating birds has located the cryptochrome
in many locations in the retina such as ganglion cells’ inner nuclear layer and in
both outer and inner segments of the photoreceptors [11].
The cryptochrome molecule has different segments and attachments that have
non-covalent bonding.
• The N-terminal, when activated with blue light undergoes dimerization.
• The conserved body of around 500 amino acids which is called photolyase
Homology Region (PHR), with non-covalently attached to two molecules, Pterin
and FAD.
• Pterin is the antenna that detects the blue light and transfers it to FAD.
• Flavin adenine dinucleotide (FAD) is a coenzyme that interacts with many
enzymes.
• The central pocket for Flavin adenine dinucleotide (FAD) attachment.
• The C-terminal “Cryptochrome carboxyl terminal (CCT) has a variable number
of amino acids from 25 to 150 or more and is the (output domain). It involves
phosphorylation and signal transduction to the nucleus.
Cryptochromes work as a dimer when activated via their N-terminal. They are
blue light sensing and their production increases at dark (night).
Their formula is very similar to Photolyases except they do not have the ability
to repair DNA (Fig. 5.1).
Pterin-MTHF FAD
380 nm 450 nm
N Terminal Photolyase Homology Region (PHR) Carboxy-terminal Domain

~ 25-150 Amino Acids C Terminal
500 Amino Acids
Dimerization α/β Domain Interdomain Helical Domain

Loop
Photolyase Homology Region (PHR) Carboxy-terminal Domain

N Terminal C Terminal
500 Amino Acids ~ 25-150 Amino Acids
Pterin-MTHF FAD
380 nm 450 nm
Fig. 5.1 Schematic representation of two cryptochrome molecules dimerized by blue light. The
dimerization, as shown by the red circular oval, which is through the N-Terminals causes the acti-
vation of the molecules
Multiple functions of cryptochromes are as follows:

• Circadian rhythm [12].
• Phototropism determines the direction of plant growth toward the light
source [13].
• Photomorphogenesis in plants is responsible for switching from the vegetative
stage to the flowering stage [14].
• Photoreceptor and phototransduction in Drosophila [15].
• Magnetoreception in birds (Görtemaker, Direct Interaction of Avian
Cryptochrome 4 with a Cone-Specific G-Protein [4, 5]).
The molecules that are essential and are involved in magnetoreception is being
individually discussed and presented in the following:
• Petrin captures the energy and transforms it into flavin (Fig. 5.2).
• Flavin is an organic compound that is required by most life forms to provide
specific catalytic tasks. Humans obtain flavin as vitamin B2 in their diet. Flavin
is usually found in the form of flavin mononucleotide or in the form of flavin
adenine dinucleotide (FAD) which then is reduced to FADH which mediated
phosphorylation of certain domains in Cryptochrome which then triggers the
signal transduction chain of events (Fig. 5.3).
• Flavin adenine dinucleotide (FAD) is a coenzyme associated with many
enzymatic proteins. It can exist in different forms by accepting or donating
electrons. FAD is the fully oxidized form (quinone), and when it accepts 2
electrons and 2 protons it becomes FADH2 (hydroquinone). FADH (semiquinone)
can be formed either from reduction of FAD or from oxidation of FADH2
(Fig. 5.4).
• Cofactor FAD exists in three interconvertible redox forms, FAD, FADH,
and FADH.
FAD = Non-signaling (Inactive)
Fig. 5.2 Structural O

representation of Petrin
N
molecule
HN
H2H N N

representation of Flavin
H3C N
molecule
NH
H3C N N O
R
Fig. 5.4 Color NH2

presentation of the
different molecular N
substructures of FAD. The Adenine N
top lavender square is the
Adenine molecule, the rose N N
square represents the
Ribose molecules, the
green rectangle represents O
Diphosphate and the O OH Ribose
bottom lavender rectangle
contains Flavin molecule O P
OH
O
O
Diphosphate
O P
O O
OH
HO Ribose
HO
N N O
NH
N
O
Flavin
FADH = Signaling (active)

FADH- = fully reduced Non-signaling (Inactive)
Blue light activates FAD to FADH.
Green light deactivates FADH to FADH.
The activation and deactivation of FAD and FADH involve radicals and are affected
by the magnetic field. The radical pair is formed between flavin and an oxygen mol-
ecule, or between flavin and tryptophan side chins in a Cryptochrome molecule.
Flavin Adenine Dinucleotide (FAD) consists of two portions (dinucleotide) the
adenine nucleotide and the flavin nucleotide.
• Adenine nucleotide (A) is one of the four nucleobases in nucleic acid of DNA. It
participates in the formation of FAD and many other essential molecules like
ATP and Coenzyme A (Fig. 5.5).
• Flavin nucleotide is often attached to adenosine diphosphate to form Flavin
adenine dinucleotide (FAD). It is also found as flavin mononucleotide (FMN), a
phosphorylated form of riboflavin. Flavin group is capable of undergoing
oxidation-reduction reactions and can accept either one electron in a two-step
Fig. 5.5 Structural NH2

representation of Adenine
N
molecule
N
N N
H

representation of
CH3 N
Riboflavin molecule
NH
CH3 N N O
OH
OH
HO
OH
Fig. 5.7 Structural CH2OH OH

representation of Ribose
molecule O
OH OH

representation of
Tryptophan molecule
OH
HN NH2
process or two electrons at once. Reduction is made by addition of hydrogen

atoms to the specific nitrogen atoms on the molecule (Fig. 5.6).
• Ribose, a simple sugar with molecular formula C5H10O5. It is an important
addition to other molecules such as RNA, and is a necessary compound for
coding, decoding, regulation, and expression of genes. Ribose in adenosine
triphosphate (ATP), with three phosphate groups and an adenine base is a product
of cellular respiration and is an essential currency for energy that involve in
cellular metabolism, signaling pathways, and nucleotide biosynthesis (Fig. 5.7).
• Tryptophan (TRP) is an essential amino acid for humans which means the body
cannot synthesize it and it must be obtained from diet. It is a polar molecule and
a precursor to the neurotransmitter serotonin and the hormone melatonin. The
tryptophan molecule has a critical role in electron transfer to flavin in crypto-

representation of Tyrosine
molecule
OH
NH2
HO
chrome molecule and formation of unpaired radicals in the process of magneto-

receptor perception in migratory birds (Fig. 5.8).
• Tyrosine (Tyr) is one of 20 standard amino acids that is used by cells to
synthesize proteins. Tyrosine residues play an important role in photosynthesis
and magnetoreception. It can be tagged to a phosphate group and its
phosphorylated form is one of the key steps in many signal-transduction
processes. The tyrosine side chain location in the cryptochrome molecule is at a
close distance to Tryptamine D which is close enough to be able to be oxidized
by it and this will extend the electron transfer chain. Also, its interaction with
Flavin causes the conformation of C-Terminal delays the relaxation to the
favorite lifetime for ability of cryptochrome to start the signaling process
(Fig. 5.9).
• HOMO, Highest occupied molecular orbital.
• LUMO, lowest unoccupied molecular orbital.
• SOMO, singly occupied molecular orbital such as in radicals.
Asterisk symbol * on top of any atom or molecule refers to its excited state.
A chain of four tryptophan residues in animal cryptochrome molecules are
involved in photoreduction of FAD cofactor. Radical pairs are formed between
FADH and each of the tryptophan residues during the electron transfer process after
blue light exposure which causes the singlet excited state which permits a magnetic
field effect in cryptochrome molecule.
In the cryptochrome molecule, the “Flavin adenine dinucleotide “FAD and four
tryptophan amino acid side chains are positioned in a chain from center of the mol-
ecule toward the surface in around 1.9 nm. In the resting or ground state the combi-
nation of FAD and Tryptophan is in the fully oxidized state. This distance between
the molecules is essential for electron transfer and interconversions between singlet
and triplet states. Very small, or much longer distances prevent these processes to
happen [16] (Fig. 5.10).
When Flavin absorbs the blue light it triggers electron transfer from terminal
tryptophan to the Flavin, which is from HOMO of terminal tryptophan to the LUMO
of Flavin. This produces the radical state and formation of triplet states by oscilla-
tions due to an external magnetic field. It is the fast interconversion change of sin-
glet to triplet back and forth which make the system susceptible to the EMF, in other
words, The created radical pairs of flavin and tryptophan which their singlet-triplet
interconversion rate, make them susceptible to and become modulated by earth’s
magnetic field. From here, there are different pathways of non-radiative relaxation
back to the ground state with different speeds:
Fig. 5.10 Schematic representation of electron transfer in the cryptochrome molecule. The
sequence of electron transfer from Tryptophan D to Tryptophan C and Tryptophan B to Tryptophan
A and then to the Flavin molecule. The sequence of events behaves like a wire for the transfer of
electrons. The Tyrosine interaction affects the C-Terminal of the cryptochrome molecule and
causes its conformation
• The excited radical flavin and Tryptophan can return directly to the ground state
in about 1 microsecond. This process is too short for interaction with the earth’s
magnetic field.
• The excited radical flavin individually can gain a proton and become neutral in 1
microsecond and then return to the ground state in about 100 microseconds. This
is enough time for interaction with the Earth’s magnetic field.
• The excited radical Tryptophan individually can lose a proton and become
neutral in 1 microsecond and then return to the ground state in about 100
microseconds. This is enough time for interaction with the earth’s magnetic field.
• In vivo the Flavin C-Terminal can undergo conformation and interact with nearby
tyrosine molecules which delayed lifetime of the relaxation to the ground state to
about 1 second. This long lifetime will allow the 1.4-megahertz oscillation to
happen and have a significant effect on the efficiency of FAD for signaling pro-
cess and as a magnetoreceptor (Fig. 5.11).
The latter is the most productive pathway and is when individually the flavin
radical conformation occurs in its C-Terminal domain, causing the involvement of
nearby tyrosine residue which slows down the reaction lifetime. This process in vivo
Fig. 5.11 The diagram represents excitation of the Cryptochrome molecule with blue light.
Electron transfer from four Tryptophan side chains causes radical pair formation which makes the
molecules susceptible to the Earth’s Magnetic Field. From there will be multiple pathways from an
excited state to the ground state. There could be a fast (~1 μs) and immediate return to the ground
state directly as shown or it can transform to the neutral state as Stabilized Radicals which can
return to the ground state directly at a slower pace (~100 μs). Flavin can individually interact with
Tyrosine which will slow down the process of relaxation to as long as about 1 second
could increase the lifetime to up to a second, allowing enough time for integration
averaging signaling.
As mentioned before, a reaction less than 100 microseconds cannot affect the
phototransduction process [17].
Cryptochrome molecule also has a molecular pocket for oxygen radical
trafficking. The molecular oxygen radical (superoxide) O2- enters the Cryptochrome
pocket at a constant rate forming a radical pair (FADH+O2-) with 25% in a singlet
state and 75% in a triplet state [18].
If the radical pair is in singlet state it forms (FADH- + O2-) which has lower
energy state than (FADH+O2-) which separates the O2- radical which escapes from
the molecular pocket. EMF effect in activation of cryptochrome (signaling state)
happens via photoreduction process. However, cryptochrome can revert to its non-
active state if the unpaired electron on FDAH back transfers to one of the three
tryptophan molecules.
The EMF interaction affects the interconversion between the singlet and the
triplet states of the radical pair and depends on the orientation of the earth’s magnetic
field. Once the FAD cofactor is reduced to the FADH state, Cryptochrome stops
signaling. If the radical pair separates before signaling stops, the radical O2 escapes
from the pocket and leaves the cryptochrome to stay in its signaling state. This state
stays until another O2- radical arrives [19].
The separation and re-encounter of radical O2- delay the magnetic field-dependent
reaction, shifting it into the millisecond time scale relevant to biological signaling.
Now that we reviewed the ingredients of the magnetoreceptors let us start with
the recipe.
What is necessary for humans to use Earth’s magnetic field for navigation:
• Earth magnetic field.
• Small dipole magnet to align itself with the magnetic field (a compass).
This was done for hundreds of years by humans, is very simple and is still being
used today.
Magnetoreception has been reported in plants, insects, fish, and turtles and even
in humans.
In animals, the process of magnetoreceptors is much more complex, yet has been
used for millions of years. Since animals cannot use technology, the process should
have very specific criteria to be able to be accomplished. So, let us see what the
requirements are for using magnetoreceptors for navigation in migrating birds since
there is a vast body of studies done successfully.
The requirements for migrating birds to use the earth’s magnetic field are:
• Blue light to start activation of specific light-sensitive molecules.
• Biological compass in the eyes and perhaps in the beak.
• Specific genes to manufacture the light-sensitive proteins.
• Photosensitive protein molecules.
• Unpaired electrons.
• Electron transfer.
• Spin selective chemistry.
• Photoreceptors.
• Photo signaling process.
• Ion channels.
• Transferring to the specific brain region to process the transferred information.
There has been lots of research to find the molecule that fits all the above criteria,
and the only molecule that was qualified was finally identified as Cryptochrome.
In vertebrates, cryptochromes are the only class of molecules known which form
radical pairs upon activation with blue light. Cryptochrome molecules are capable
of all the above requirements to be magnetic field sensors in animals (Fig. 5.12).
The cryptochrome has been in the cone photoreceptors of the migrating bird’s
retina. During the day, the cones are active with color perception in bright daylight.
It is during the night that the cryptochromes get activated in the cones. So, from
engagement of the blue light with the cryptochrome molecule in the cone
Fig. 5.12 Schematic representation of two cryptochrome molecules dimerized by blue light. The
dimerization, as shown by the red circular oval, which is through the N terminals causes the activa-
tion of the molecules. The molecular structures of Pterin and FAD have been included
photoreceptor cells of the bird’s retina to the perception of magnetic field there is a
long process and yet very fast, which can be summarized as follows (Fig. 5.13):
The entire process of magnetoreception can be summarized in an image with all
the required steps from exposure to blue light to perception of the magnetic field
(Fig. 5.14).
Blue light to the eye →
• Cryptochrome excitation →
• Light-induced excited singlet formation →
• Singlet state of FAD + Tryptophan →
• HOMO of tryptophan→
• LUMO of Flavin →
Fig. 5.13 Schematic representation of cryptochrome molecule and its location on the photoreceptor
disc. Influence of blue light and the earth’s magnetic field on the molecule and its activation is
shown above
• electron transfer →
• Unstable formation of radicals flavin and tryptophan →
• Magnetic field interaction →
• Neutral radical formation →
• C-Terminal conformation →
• Interaction of cryptochrome with tyrosine →
• Slowing down reaction time→
• Ion channel response →
• phototransduction →
• Signaling to the brain →
• Magnetoreception.
We should keep in mind that many of the above steps can be reversible or
bifurcate to different pathways as the process is very complicated.
In conclusion, the process of magnetoreception can only be explained by
quantum physics/Biology and the development of new tools in recent years has
References 99
Fig. 5.14 Blue light to the eye →Cryptochrome excitation →Light-induced excited singlet
formation →Singlet state of FAD + Tryptophan →HOMO of tryptophan →LUMO of
Flavin→Electron transfer→Unstable formation of radicals Flavin and tryptophan→Magnetic field
interaction→Neutral radical formation→C-Terminal conformation→Interaction of cryptochrome
with tyrosine→Slowing down reaction time→Ion channel response→Phototransduction→Signal
ing to the brain→Magnetoreception
helped experimenting and confirming different steps of this process. Each step has
been shown in the image above and has been simplified to make it tangible for the
non-physicist and non-quantum scientist readers.
References
1. Chae. Human magnetic sense is mediated by a light and magnetic field resonance-dependent
mechanism. Sci Rep. 2022; https://doi.org/10.1038/s41598-022-12,460-6.
2. Kwon. Human magnetic sense is mediated by a light and magnetic field resonance-dependent
mechanism. Sci Rep. 2022; https://doi.org/10.1038/s41598-022-12460-6.
3. Binhi. Theoretical concepts in magnetobiology after 40 years of research. Cells. 2022; https://
doi.org/10.3390/cells11020274.
4. Görtemaker. Direct Interaction of Avian Cryptochrome 4 with a Cone Specific G-Protein.
Cells. 2022a; https://doi.org/10.3390/cells11132043.
5. Görtemaker. Direct Interaction of Avian Cryptochrome 4 with a Cone Specific G-Protein.

Cells. 2022b; https://doi.org/10.3390/cells11132043.
6. Leberecht. Broadband 75-85 MHz radiofrequency fields disrupt magnetic compass orientation
in night-migratory songbirds consistent with a flavin-based radical pair magnetoreceptor. J
Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2022; https://doi.org/10.1007/
s00359-021-01537-8. Epub 2022 Jan 12.
7. Smith. Observations about utilitarian coherence in the avian compass. Sci Rep. 2022; https://
doi.org/10.1038/s41598-022-09901-7.
8. Zadeh. Magnetic field effects in biology from the perspective of the radical pair mechanism. J
Royal Soc Interface. 2022; https://doi.org/10.1098/rsif.2022.0325.
9. Kavet. Cryptochromes in mammals and birds: clock or magnetic compass? J Am Physiol Soc.
2021; https://doi.org/10.1152/physiol.00040.2020.
10. Liedvogel. Cryptochromes—a potential magnetoreceptor: what do we know and what do we
want to know? J Royal Soc Interface. 2009; https://doi.org/10.1098/rsif.2009.0411.focus.
11. Ahlers. Integration and evaluation of magnetic stimulation in physiology setups. PLoS One.
2022; https://doi.org/10.1371/journal.pone.0271765.
12. Smylie. Cryptochrome proteins regulate the circadian intracellular behavior and localization
of PER2 in mouse suprachiasmatic nucleus neurons. PNAS. 2022; https://doi.org/10.1073/
pnas.2113845119.
13. Rai. Perception of solar UV radiation by plants: photoreceptors and mechanisms. Plant
Physiol. 2021; https://doi.org/10.1093/plphys/kiab162.
14. Trojak. Effects of partial replacement of red by green light in the growth spectrum on
photomorphogenesis and photosynthesis in tomato plants. Photosynthesis Res. 2021; https://
doi.org/10.1007/s11120-021-00879-3.
15. Au. Mosquito cryptochromes expressed in Drosophila confer species-specific behavioral light
responses. Curr Biol. 2022; https://doi.org/10.1016/j.cub.2022.07.021.
16. Xie. Searching for unity in diversity of animal magnetoreception: From biology to quantum
mechanics and back. Innovation(Camb). 2022; https://doi.org/10.1016/j.xinn.2022.100229.
17. Wong. Cryptochrome magnetoreception: four tryptophans could be better than three. J Royal
Society Interface. 2021; https://doi.org/10.1098/rsif.2021.0601.
18. Solovyov. Radical pair formation in cryptochromes. Quantbiolab.com; 2021. https://
quantbiolab.com/research/radical-pair-formation-in-cryptochromes
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articlelanding/2019/CP/C9CP00782B
Chapter 6
Quantum Biology of Circadian Rhythms
Abstract
The 2017 Noble Prize in physiology or medicine was awarded to three scientists
for their discoveries of molecular mechanisms that control circadian rhythms. The
internal biological clock anticipates day/night cycles due to the rotation of the earth
to optimize the physiology and behavior of organisms. The discovery of the genes
involved such as Period (PER) and its partner TIMELESS (TIM) led to the discov-
ery of a Transcription-Translation Feedback Loop (TTFL). Multiple regulations
and modifications of TTFL generate autonomous oscillations in a period of 24 h.
The central clock of mammalian circadian system is located in the
suprachiasmatic nucleus (SCN) of the hypothalamus, functioning as a pacemaker.
The circadian oscillation within individual cells responds differently to
external signals and controls many physiological outputs, such as sleep patterns,
body temperature, hormone release, blood pressure, and metabolism.
Important notes for clarification
Oscillation: Repetitive or periodic variation in time of some measures from the

central point of equilibrium between the two states.
Vibration: The term is used to precisely describe a mechanical oscillation.
Ubiquitination: Small protein “ubiquitin” that attaches to the protein substrates
of a protein for degradation.
Proteasome: Complex intracellular process that regulates the degradation of
cellular proteins.
Transcription: The process of copying a segment of DNA to RNA.
Translation: The information from mRNA is used to create amino acids during
protein synthesis.
Enhancer box (E-box): Regulatory proteins that bind to a single strand of DNA
to promote a wide range of gene expression.
Switzerland AG 2023
https://doi.org/10.1007/978-3-031-32060-6_6
102 6 Quantum Biology of Circadian Rhythms
Entrainment: The synchronization of different rhythmic cycles that interact

with each other.
Ganglion cells: The cells that are located on the innermost layer of the retina and
are transferring the visual signals from photoreceptors via their axons through the
optic nerve to the brain.
Discussions
The two closely related superfamilies of cryptochromes and photolyases are blue
light receptors. The former, cryptochromes, are involved in magnetoreception as
was discussed in the previous chapter and are also involved in the process of circa-
dian cycles. The latter, photolyases, are involved in the repair of damaged DNA.
All the recurring chemical processes that sustain life (by repositioning and exchange
of atoms, molecules, and ions in response to external interactions) obey the rules of quan-
tum mechanics. The effects of quantum mechanics on biological processes such as quan-
tum entanglement, quantum superpositions, quantum coherence, and quantum tunneling
have been used by all life forms for millions of years. The recognition of this phenome-
non which is called “quantum biology” has only begun in the twentieth century.
In previous chapters, we reviewed the effects of quantum mechanics on
photosynthesis, vision, and magnetoreception. In this chapter, we will explore the
effects of quantum mechanics on the circadian biological clock. The active
involvement of cryptochrome molecule and the role of radical pair states and
electron transfer via tryptophan molecules to FAD have been discussed in detail in
the previous chapter and are as relevant as in this chapter. The quantum biology of
the cryptochromes and the role of radical pairs will not be repeated in this chapter,
and instead, we will discuss the molecular interactions to better understand the
process of this ancient biological response to the earth’s rotation.
Cryptochromes are flavin-containing blue light sensors that play a key role in the
circadian clock and entrain the circadian clock to light. Photoexcitation of crypto-
chrome molecules causes reduction of an oxidized flavin cofactor by a chain of
tryptophan residues as discussed in the previous chapter. The photoinduced electron
transfer process along the chain of conserved tryptophan residues reduces the
excited state of the FAD cofactor [1].
The radical pair mechanism (RPM) is one of the most well-established models in
quantum biology. Superoxide radicals O2-, and the formation of “FADH- O2-” can be
an alternative partner for flavin as discussed in the previous chapter. The effect of
Lithium on FADH-O2- formation on CRY molecule in the SCN directly affects the
circadian cycle. It was suggested that Lithium’s nuclear spin modulates the dynam-
ics of singlet-triplet interconversion in FADH-O2- radical pair complex. This also
explains the different therapeutic effect of each Lithium isotope. This effect has
been reported on avian magnetoreception and Xenon-induced anesthesia [2].
The cryptochrome genes (Cry1 and Cry2) are essential to circadian rhythms and
are directly involved in circadian cycles by binding to the two master regulatory
genes, CLOCK/BMAL1 genes (Circadian clock genes), and affect their regulation
and the outcome [1, 3].
Discussions 103
Although the molecules involved in the circadian clock exist in all branches of
the evolutional tree such as plants, insects, and animals, in this chapter we will con-
centrate on mammalian circadian systems [4].
The central clock of mammalian circadian system is located in the suprachiasmatic
nucleus (SCN) of the hypothalamus, functioning as a pacemaker. The light signals
are transferred to SCN via the Retinohypothalamic tract (RHT) which is regulating
the peripheral clocks throughout the body. At the cellular level, each cell in the body
is governed by its own independent clock, yet their oscillations are coupled with the
central oscillator at SCN. The oscillatory coupling between the central and regional
oscillators is critical for the functioning circadian clock which provides a wide
range of adaptability for the organism.
Cellular circadian clock exhibits intrinsic, self-sustaining cycles, close to 24 h
and is called “free-running rhythms” which are independent of external signals and
involve sleep–wakefulness behavior, body temperature, blood pressure, fluctuations
of gene/protein expressions, and release of hormones such as testosterone, melato-
nin, and neurotransmitters (Fig. 6.1).
Regardless, the circadian clock is also under the influence of cyclic changes in
the environment such as day–night cycles, seasonal changes, and temperature
changes. The circadian clock plays a critical role in the survival of species as a
whole [5].
Fig. 6.1 Schematic representation of important events during 24 h time period influenced by
circadian rhythms
The sleep cycle is also controlled by a balance between the SCN and the reticular
activating system (RAS) in the brain stem. The activation of SCN will inhibit RAS
from inducing sleep [6].
The alignment of the circadian clock to such environmental influence is referred to
as “Zeitgebers” (Time givers in German), and for all organisms light is the strongest
Zeitgeber, others including temperature, feeding time, and social interactions. These
zeitgebers can influence the circadian clock by phase shifting it forward or backward.
The mechanism of circadian rhythm depends on so many internal and external
factors.
Masking is the mechanism that is more prominent in nocturnal mammals. This
effect of light can directly conceal the control from the circadian clock. Positive
masking happens during the dim light conditions due to confidence based on visual
input. The suppressive effect of bright light is called negative masking.
Clock Genes and Signal Transduction Proteins
Multiple genes are involved in circadian rhythm regulations which are called clock
genes, and new genes are being discovered as time goes by. The molecular mecha-
nism of circadian rhythm depends on a negative feedback system by clock genes.
The two important products CLOCK and BMAL1 bind to E-Boxes in the promoters
of DEC1, DEC2, PER1 and CRY1 which produce the relevant proteins DEC1,
DEC2, PER1 and CRY1, and CRY2. These proteins will be degraded by ubiquitina-
tion or phosphorylation, or by dimerizing and suppressing the CLOCK/BMAL1
transactivation. This negative feedback plays a crucial role in circadian cycle regu-
lations in the central suprachiasmatic nucleus (SCN) and peripheral cells (Fig. 6.2).
Here, we only refer to the most essential circadian genes:
• Circadian Locomotor Output Cycles Kaput (CLOCK) is a transcription factor.
CLOCK is synthesized in the cytoplasm and enters the nucleus which then
dimerizes with BMAL1. This dimer then recruits coactivator CREB-binding
protein and binds to the E-box of promoters of (PER) and (TIM), causing the
production of proteins “per” and “Tim,” which in a negative feedback fashion
stops their gene translation.
• Brain & Muscle ARNT-Like 1 (BMAL1) is a transcription factor. It forms
heterodimer with the protein “CLOCK.” This complex drives transcription from
E-box elements to regulate the circadian rhythm of a spectrum of gene expressions [7].
• PERIOD (Per) 1,2, and 3, encoding PAS protein.
Fig. 6.2 Structural H3 C

representation of O
Melatonin molecule
N HN
H CH3
O
Clock Genes and Signal Transduction Proteins 105
• Cryptochrome (CRY) genes 1 and 2 binds to Clock/BMAL1.

• TIMELESS (TIM) its effect on circadian clock in insects are established but not
in mammals yet.
• Jetlag (JET) ubiquitin ligase is responsible for TIM ubiquitination.
• Immediate Early Genes (IEGs) part of the transcription network controlling Per
1 and 2 transcription.
• cAMP response element binding (CREB) protein. Influences the target genes.
• Cocaine and Amphetamine-Regulated Transcription (CART) genes, which
modulate dopamine system and are linked to eating disorders, Obesity, drug
addiction and circadian clock shift.
• Extracellular signal-regulated kinase (ERK) 1 and 2, blocking light-induced
response by SCN during the day.
• Vasoactive Intestinal Peptide (VIP), its signaling is necessary for the maintenance
the synchronization of the circadian oscillations in SCN.
• Activator protein 1 (AP-1) is a family of transcription factors involved in cell
proliferation and survival, apoptosis, transformation, and oncogenesis. They
contain a basic leucine zipper (bZIP) domain. There are three subfamilies, Jun,
Fos, and ATF. To bind to DNA these subfamilies need to form dimers [8].
• Mitogen-activated Protein Kinase (MAPK) is a cellular signaling pathway or
cascade, which regulates both the expression and posttranslational modifications
of AP-1. Many different ligands such as growth factors and cytokines, can trigger
the MAPK cascade which activates transcription of target genes [8].
• Differentiated embryonic chondrocyte 1 and 2 (DEC1 and DEC2) play an
important role in circadian system, cell proliferation, apoptosis, hypoxia
response, and have opposite effects in regulating tumor progression [9].
• Retinoic acid-related orphan receptor elements (ROREs) alpha, beta, and gamma
are subfamily of nuclear receptors that function as ligand-dependent transcrip-
tion factors. ROR genes produce several isoforms, and most isoforms exhibit a
distinct tissue-specific pattern of expression and regulate different biological
processes and target genes.
• RORs genes can regulate gene transcription by binding to ROR response element
(ROREs). By competing for RORE binding, these receptors can antagonize each
other’s effects on transcription. The cross talk between RORs and Rev-Erbs, for
example, regulates transcription of clock genes.
• (Rev-erb) is nuclear receptor subfamily “alpha” and “beta” that are Key regulators
of clock gene expression via transcription repression of BMAL1.
• Nicotinamide phosphoribosyltransferase (NAMPT), which is part of a separate
feedback loop which creates metabolic oscillators. This plays a positive role in
Clock-BMAL1 loop.
• Salt inducible kinase 1 (SIK1) with CRTC1 is involved in a resetting of the clock
by deactivating the CRTC1.
• CREB-regulated transcription coactivator 1 (CRTC1), when activated by
phototransduction stimulates activation of CREB, inducing the expression of
Per1 and Sik1.
• (SIRT1) gene encodes the protein “Sirtuin1” which is a NAD-dependent histone
deacetylase.
Molecular Effect
The “core” molecular feedback loop of the circadian clock consists of: CLOCK and
BMAL1, PER1, PER2, CRY1, and CRY2 [10].
The molecular bases of circadian clock are self-sustaining molecular oscillators
that constitute the transcriptional–translational feedback loop. Due to the fact that
the circadian clock rhythm is not exactly 24 h, these oscillators must constantly
readjust to remain in alignment with the external world through the process called
“entrainment” which accomplishes the adjustment to SCN. In mammals, the pri-
mary time adjustor or zeitgeber of SCN is light.
The SCN, in turn, entrains with the peripheral clock through the entire body.
Within the SCN, light information is integrated with signals from other zeitgebers
such as food, external temperature, and sleep to make a precise tuning with the
environment.
There are also other extra-SCN hypothalamic nuclei monitoring the fluctuation
of nutrients and hormonal signals which function semi-autonomously or indepen-
dent of SCN innervation.
The extra-SCN in the brain participates in the control of the circadian cycles via
the neural connections and rhythmic function of the autonomous systems, sympa-
thetic, and parasympathetic.
The endocrine system also participates in this complex interactive process via
many hormones and neurotransmitters.
The hormonal and neurotransmitter regulation of circadian cycles also involves
communication between many centers, including hypothalamus, pituitary gland,
and adrenal cortex [11].
List of Neurotransmitters Involved in Circadian Cycles
The major neurotransmitters that are involved in communication system of circadian

rhythms are:
• Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter. Inducing
sleep by affecting the neurons in the posterior hypothalamus that contribute to
wakefulness.
• Hypocretin is produced by hypothalamus and interacts with dopamine,
histamine, norepinephrine, acetylcholine, regulating the sleep/wakefulness cycle.
• Glutamate is the most common inhibitory neurotransmitter in the brain that
regulates the sleep duration and regulation of REM and wakefulness.
• Acetylcholine is a cholinergic neurotransmitter with inhibitory action. It is
involved with initiation of REM sleep.
• Norepinephrine acts both as neurotransmitter and a hormone. It plays an
important role in sleep/wake cycle and is Involved in arousal from sleep.
• Dopamine regulates initiation of sleep/wake cycles and can also downregulate
melatonin synthesis which contributes toward waking up from sleep.
List of Hormones Involved in Circadian Cycles 107
• Serotonin is a neurotransmitter with a similar action as norepinephrine. Lack of

serotonin is commonly associated with depression. It helps to maintain arousal
and cortical responsiveness, as well as inhibiting REM.
• Adenosine is an inhibitory neurotransmitter involved in promoting sleep. Its
build up in the brain during the day promote sleepiness at night. Caffeine is an
adenosine antagonist.
List of Hormones Involved in Circadian Cycles
• Melatonin:
Melatonin is a hormone that is released by pineal gland in the brain during the
night. It is involved in synchronizing the circadian rhythms.
It affects the sleep/wake cycle and also is involved in seasonal rhythmicity and
other functions such as reproduction, molting, and hibernation. Melatonin level
secretion changes and shifts during the aging process as delayed release in teen-
agers and decreased release in elderly.
Melatonin secretion is regulated by norepinephrine which is released from the
sympathetic nerve fibers [12] (Fig. 6.3).
Fig. 6.3 Schematic representation of circadian molecular transductions. The neurotransmitters

released by ipRGCs Terminal activate the surface receptors of SCN which in turn activates CREB
inside the nucleus to initiate the process of circadian gene transcription
Melatonin acts in the following ways:

1. As an agonist of melatonin receptors 1 and 2, which belong to G-Protein-
Coupled Receptors (GPCRs).
2. As a free radical scavenger within mitochondria it also promotes the expression
of antioxidant enzymes.
3. Increases the expression of clock genes Per1 and Per2.
• The corticotropin-releasing hormone (CRH) also a stress hormone, it
stimulates the anterior pituitary gland to produce adrenocorticotropin hormone
(ACTH). It affects the REM sleep and promotes wakefulness.
• Adrenocorticotropic hormone (ACTH) is a stress hormone that is released
by the pituitary gland. regulates production of “cortisol” by adrenal cortex
and androgens.
• Cortisol is a stress steroid hormone and is released by the adrenal gland. It
helps the body maintain hemostasis and the disruption of regular production
can affect the sleep pattern. Cortisol has a strong effect on synchronizing the
circadian clock. Cortisol has many other important roles:
–– Metabolism of fat, proteins, and carbohydrates
–– Suppressing inflammation
–– Regulating blood pressure
–– Regulating blood sugar
–– Release of sex hormones
• Growth hormone-releasing hormone (GHRH) promotes the release of
growth hormone from anterior pituitary gland. Its contribution to interleu-
kin-1 is involved in endogenous sleep promotion substances.
• Norepinephrine, also as a hormone is a stress hormone, and one of the main
components of fight-or-flight response. Its increased levels can decrease the
REM sleep.
Light Exposure
Exposure to light provides the primary cue to the SCN and suppresses melatonin
synthesis by the pineal gland.
• Norepinephrine release via adrenergic fibers from SCN to pineal gland causes
synthesis of melatonin.
• Melatonin feeds back to master circadian clock.
Small Molecules and Drugs 109
Small Molecules and Drugs
Examples of some small molecules and drugs that can affect the circadian clock:
• Dexamethasone can synchronize and amplify circadian clock which suggests
that glucocorticoids are time signals for peripheral clocks.
• Sildenafil, the words most used erectile dysfunction drug, inhibits cGMP-specific
phosphodiesterase 5, and enhances photoactivated phase advancement.
• Caffeine, the world’s most widely consumed psychoactive drug, has antagonist
effect on SCN receptors, enhancing the photic response and counteracting the
effect of sleep deprivation. It causes the release of norepinephrine, dopamine,
and serotonin in the brain and blocks adenosine receptors.
• Amphetamine and cocaine, the world’s most popular recreational drugs, affect
the (Cocaine- and Amphetamine-Regulated Transcript) System “CART” [13].
• Metformin, the world’s most popular anti-diabetic drug, affecting the circadian
cycle by partial activation of AMPK [14].
• Lithium, which is used in bipolar disorders, affects the dynamics of radical pair
in cryptochrome on FAD with superoxide radical oxygen pair [2].
The Phase shifting of circadian clock can happen in many ways. Even the effect
of light, the powerful zeitgeber depends on the time of light exposure. The light
detected during early morning causes “phase advance” to start activity. On the
opposite side, the light exposure during the dusk causes “phase delay” or signal that
it is time to retire.
As we mentioned earlier, the main zeitgeber in mammals is light. The light input
to the SCN is primarily provided by the retina. The primary photoreceptors respon-
sible for photoentrainment are a small class of photosensitive ganglion cells (rod
and cone cells of the retina are not primarily involved, however, they may contribute
when ganglion cells are not present). These small groups of ganglion cells carry the
photoreceptor “melanopsin” and are involved in transferring the light input to SCN
via Retinohypothalamic Tract (RHT).
The photosensitive ganglion cells are called “pRGCs” or The Intrinsically
Photosensitive Retinal Ganglion Cells “ipRCGs” are the major source of light
detection for circadian clock adjustment and are approximately 1–2% of ganglion
cell population that contains the photosensitive molecule “melanopsin.” Melanopsins
are encoded by the gene “Opn4” and absorb blue light of around 420–440 nm and
are playing major role in non-image-forming signals to SCN.
Melanopsin is a photopigment belonging to the large family of photosensitive
proteins called opsins. It is activated most efficiently by blue light between 420 and
440 nm [15]. Its structure is similar to rhodopsin in retinal rod cells and photopsin
in retinal cone cells. Melanopsins located in the ipRCGs are involved in signal
transfer for circadian cycles.
Melanopsin have been located in many locations in the brain [16].

The Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) consist of
six subtypes (M1–M6) according to their anatomical and morphological differ-
ences. They also exhibit distinct electrophysiological properties and mediate differ-
ent light responses:
• Photoentrainment
• Pupillary response
• Sleep induction
• Masking
• Alertness
• Mood
Some studies have shown ultraviolet light could signal SCN via detection by rod
and cone cells of the retina, although their contributions are limited [17, 18].
Transcriptional-Translational Feedback Loops (TTFLs)
The connection of retinal ganglion cells “ipRGCs” to the SCN is via monosynaptic
pathway of RHT, the process of molecular photoentrainment of SCN autoregulatory
Transcriptional-Translational Feedback Loop (TTFL). Many feedback loops are
involved in circadian rhythms. We will just mention the essential feedback loops.
The summary is as follows:
1. Clock-BMAL1 and PER and CRY negative feedback:
The clock and BMAL1 attach to each other and form a heterodimer. This will
activate PER and CRY genes by directly interacting with the E-box element. The
accumulation of resulting PER and CRY proteins inhibit the expression of
BMAL1/Clock.
2. Clock-BMAL1 and Rev-erb and RORE:
The clock and BMAL1 attach to each other and form a heterodimer. Their
transcription is regulated by positive and negative feedbacks. The positive
feedback is activated by RORs (alpha, beta, and gamma) and the negative loop is
activated by REV-ERBs (alpha and beta).
Clock and BMAL1 in turn regulate the expression of RORs and REV-Erbs
(Fig. 6.4).
3. Clock-BMAL1 and NAMPT-SIRT1:
Another feedback loop involves the rate-limiting enzymes synthesis nicotinamide
phosphorybosyltransferase (NAMPT) regulating the level of nicotinamide
adenine dinucleotide (NAD+). The inhibition of NAMPT promotes activation of
PER2 by releasing CLOCK/BMAL1 from suppression by SIRT1. In turn, Clock
binds to NAMPT completing the loop [19] (Fig. 6.5).
Transcriptional-Translational Feedback Loops (TTFLs) 111
Fig. 6.4 Schematic representation of Transcriptional-Translational Feedback Loop (TTFL). Two

of the core feedback systems are represented here. On the top right is the BMAL1 and REV-ERB
and ROR systems, and on the bottom right is the BMAL1 and PER & CRY feedback system
Fig. 6.5 Schematic representation of NAMPT feedback system in circadian rhythm. SIRT1 is
required for the NAMPT PROMOTER and contributes to the synthesis of NAD+ which is impor-
tant for its deacetylation activity
Fig. 6.6 Schematic representation of the most simplified core negative loops of the circadian system
4. CRTC1-SIK1 pathway:
This feedback involves the activation of CREB-regulated transcription cofactor
1 (CRTC1) by light which induces the expression of Per1 and Sik1. Sik1 deacti-
vates CRTC1 by phosphorylation and acts as a break on Per1 [20] (Fig. 6.6).
The process of the feedback mechanism:
• The activation of the primary neurotransmitters glutamate and Pituitary Adenylate
Cyclase-Activating Polypeptide (PACAP) by light.
• Release of Ca2+ and cAMP.
• Activation of Kinase-based signaling cascade (PKA, PKC, PKG, MAPK, and
CaMKll).
• Activation of transcription factor “cAMP Response Element-Binding”
Protein (CREB).
• Modulation and transcription of clock genes PER1 and Per2.
• Upregulation of PER1 (Dawn) and Per2 (Dusk) adjusts the TTFL which shifts
the phase of the clock into alignment with the external light/dark cycles [21].
Light Entrainment
The process of light “entrainment” on circadian clock and resetting of the circadian
clock SCN is as follows:
1. The photons are detected mainly by melanopsin in retinal ganglion cells called
Photosensitive Retinal Ganglion Cells (ipRGCs).
2. The signals are then transferred via Retinohypothalamic tract (RHT) to
suprachiasmatic nucleus (SCN) in the brain.
Circadian Clock Networks: 113
3. The signals are transferred by neurotransmitters Glutamate and PACAP from the
RHT nerve terminals.
4. The pathway between the ipRGCs and SCN is via a monosynaptic connection.
5. The result is an increase in intracellular Ca2+ and cAMP levels in the SCN.
6. This initiates the cascade of kinase-based signaling pathways such as Protein
kinase A (PKA), Protein kinase C (PKC), Protein kinase G (PKG), Mitogen-
activated protein kinase (MAPK), and Ca2+/calmodulin-dependent protein kinase
ll (CaMKll).
7. Phosphorylation of Calcium-cAMP Response Element Binding (CREB) protein
in the nucleus.
8. Transcription of Key clock genes PER1 and PER 2 (Fig. 6.4).
Pupillary Reflexes
The ipRGCs are also involved in light-induced pupil reflex by connecting axons to
the olivary pretectal nucleus of the pretectum.
Suprachiasmatic Nucleus (SCN)
In Mammals, the SCN is a pair of oval nuclei in the anterior hypothalamus, located
just above the optic chiasm. It is composed of two regions, the core and the shell [10].
• The core receives input from the retina via Retinohypothalamic tract (RHT) and
its neurotransmitters and glutamate. Also, receives serotonergic input from the
thalamic intergeniculate leaflet.
• The shell plays an important role in rhythmic output and has communicating
neurons to the core.
• Almost all neurons in SCN are GABAergic neurons.
Circadian Clock Networks:
There are three oscillators that have been identified in SCN:

1. M-oscillators, located in the posterior tip.
2. E-oscillators, located in the anterior part.
3. The cells in the central part, responding to light-on and light-off circumstances.
4. Intracellular Ca mediates input signals to the molecular clock of the cell such as
phase-resetting stimuli to the SCN and output signals from the molecular clock
via neurotransmitter release.
Cellular Transcription-Translation Feedback Loop (TTFL)
The circadian clock is ultimately depending on 24-h rhythms at the cellular level.
The detail of cellular transcription-translation feedback loop (TTFL) can be simpli-
fied and described as follows:
1. TTFL at cellular level promotes the key transcription factors and central
transcriptional activators of the core clock mechanisms Clock and BMAL1.
2. Production of CLOCK and BMAL1 heterodimer promotes rhythmic expression
of E-Box-containing output genes.
3. The promoted genes, Period (Per 1-3) and Cryptochrome (Cry 1-2) function as
direct repressors of CLOCK: BMAL1 heterodimer.
4. Resumption of CLOCK: BMAL1 activity occurs by degradation of the above
suppressors (Per 1-3 and Cry 1-2) in different pathways.
(Per 1-2) are degraded by phosphorylation by Serin/Threonine casein kinases
via ubiquitination.
(Cry 1-2) is tagged by (AMPK) for proteasome degradation by direct
phosphorylation.
5. Additional loops transactivate or repress the BMAL1 via retinoic acid receptor-
related Orphan Receptors (RORs) and Nuclear subfamily 1 D member 1
(NR1D1).
6. Non-Circadian loops involved with nicotinamide adenine dinucleotide (NAD+)
regulate CLOCK and BMAL1 transcription.
Note: BMAL1 gene is the only single gene that when knocked out will result
in the full loss of rhythmically at cellular and behavioral levels in a normal light-
dark cycle.
The Molecular Interplay in Circadian Cycles
Here are multiple molecular interplays between circadian clock and other molecular
regulatory pathways with their relevant references for further information:
• Cell growth and cancer [22]
• DNA repair [23]
• Angiogenesis and Hypoxia [24]
• Apoptosis [25]
• Metabolism [26, 27]
• Redox state [28]
• Immune process [29, 30]
• Inflammatory process [31]
• Aging [32] :
References 115
The Brain and Circadian Rhythms
Many brain functions, such as sleep/wake, food intake, emotions, motivations, and
other cognitive processes are controlled by various regions, and are affected by the
circadian rhythms.
These centers are under direct or indirect communication with the SCN and their
own internal molecular clockwork.
The complex system of brain regions is beyond the scope of this chapter and can
be accessed by this review article [33].
Conclusion
In conclusion, the biological clock in a nutshell is based on quantum effect of

Phototransduction, the main contributor to the complex process of circadian
rhythms. This process, as was discussed, involves many interactions between the
environment and the biological systems in almost all organisms. The study of circa-
dian cycles involves combining many different fields of science, from quantum
physics to molecular biology, genetics, organic chemistry, and in mammals the
review of anatomy and physiology, to be able to understand the essentials.
• Activation of cryptochrome by light.
• Phototransduction and membrane depolarization.
• Intracellular calcium flux.
• cAMP activation.
• Transcription of circadian genes.
• Tunning of the circadian rhythms process by interaction between multiple central
and cellular responses via direct neural connection or neurotransmitters and
hormones.
Suprachiasmatic nucleus; a responsive clock regulating homeostasis by daily

changing the setpoints of physiological parameters.
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Chapter 7
The Quantum Biology of Consciousness
and Visual Perception
There would be no such thing as science without

conscious minds
Abstract
Recently, there has been a lot of interest in the subject of consciousness and its
quantum biology properties. Here, we discuss the role of the eye as an important
source and participant, in the process of consciousness, and the quantum biology
of consciousness. We have discussed the quantum biology of the retina in a pro-
cess of phototransduction and transfer of information to the brain in the previous
chapters. However, we will discuss the role of Müller cells in retina as it partici-
pates and facilitates the photon transfer in the inverted retinal thickness. The
input of visual information has been recognized as the first step or first “wave” of
initiation of the 3-wave processing of consciousness.
The possible link between biology and quantum mechanics as first suggested
by Schrödinger in his book “What is Life” has revolutionized the world and cre-
ated the new field of quantum biology. Quantum biology could explain the pro-
cess of photon harvesting and electron transfer, different states of excitation and
relaxation of electrons, emission of photons, and the generation of ultraweak
photon emission (UPE) in the neurons. Also, generation of biophotons, and pos-
sibly the process of complex neuronal activity and ultimately the
consciousness.
What brings all the chapters of this book together is the suggestion that the
quantum effects may underlie the magnetic field effects on the microtubule
dynamics. It is the similar mechanism behind magnetoreception in animals, the
circadian clocks, Xenon-induced general anesthesia, and the Lithium effect on
mania. So here, the old expression “All roads lead to Rome” can be replaced by

Switzerland AG 2023
https://doi.org/10.1007/978-3-031-32060-6_7
120 7 The Quantum Biology of Consciousness and Visual Perception
“All roads to “neuron quantum Biology” lead to “Tryptophan” since it is the

Tryptophan molecules that works like an antenna and transfer the electrons and
biophotons for a quantum biological task. Due to the fact that all anesthesia-
inducing molecules and psychedelic drugs affect tryptophan molecules embed-
ded in tubulin proteins, which are the building blocks of microtubules in neurons,
points to the crucial role of this protein in consciousness.
Quantum entanglement may also play a crucial role in brain function and
consciousness, particularly the photoemission of singlet oxygen that serves as a
quantum messenger to establish long-distance connections that might be essen-
tial for consciousness. The role of radical pairs in reorganization of microtubules
and generation of biophotons are well recognized, and is an important part in
neuronal function, and as the result, the brain function and consciousness.
The fundamental task of the brain as consciousness, is to orchestrate the
multiple parallel external events via sensory inputs, combined with the internal
cognitive processing to obtain a stable perception of the environment. This is
mainly dependent on the perception of conscious sensory experience based on
rhythmic sampling of information most effectively by visual input. The process
of quantum vision will be discussed with special focus on major components of
quantum energy generation in the eye and its transportation to the brain.
It is very interesting to note that nature was able to utilize both classical
physics and quantum physics side by side without competition, to combine in
order to obtain maximum benefits. It seems that, from photon transfer in retina to
neuronal transfer to the brain and interactions in different centers in brain, there
are both classic physics, which describe the chemical and electrical modes of
communication, and there is quantum mechanical energy transfer via biophotons
and vibrational energy transfer, which works hand in hand for optimal results.
Recent studies on primates suggests that various visual cognitive functions
exhibit slow rhythmic effects on task performance, which would be supported by
low-frequency brain oscillations mainly in the 4–8 Hz frequency range. Alpha
brain oscillations (8–12 Hz) play a role in many cognitive functions including
visual perception. Alpha oscillation’s amplitude and phase, seem to predict corti-
cal excitability. This will emphasize the significant role of visual input in the
process of consciousness since about one-third of the cortical surface in primates
brain is involved in visual processing tasks, however, in case of visually impaired
or the blind, the plasticity of the brain compensates with rewiring the other sen-
sory inputs instead of optical input to the process of consciousness Kienitz (Eur
J Neurosci, 2021).Knowledge and Consciousness
Consciousness is the individual awareness of thoughts, memories, senses, the

environment, and even the sense of awareness itself [2].
Knowledge and consciousness are closely related since both are associated with
the awareness of a physical object or phenomenon.
We cannot claim knowledge of anything unless we are aware of the phenomenon
of knowing, so at the core of the phenomenon of knowledge lies consciousness, as
Neurons 121
the sense of understanding is also closely related. Meanings, symbols, semantics,

thinking, reasoning, and understanding are all associated with the conscious mind.
As the current state of awareness, consciousness consists of things that we are
currently experiencing either via our five senses, or mentally via thinking, or emo-
tionally via feeling. We become conscious of anything that we direct our attention
toward, since the active knowledge involves attention.
Memory serves as repository of personal information in one’s mind, which in
combination with consciousness creates knowledge.
Also, the level of knowledge is proportional to the level of interest and attention
of the learner, and thus the level of consciousness it involves [1].
Note
In order to understand and comprehend this chapter, relevant components have been
explained and discussed and references provided on each subject for further in-
depth information if desired. We will step by step explain the essential factors
involved, and that are fundamental to brain and its neurons to communicate. We also
discuss the effect of quantum biology on these processes based on the information
available in the literature at present time.
• Brain anatomy (basics):
• The basic anatomy of the brain is beyond the scope of this chapter and can be
reviewed at: University [2].
• Cellular structures of the brain:
• The brief review of the histology can be reviewed at: Tartu [3]
• Neuron anatomy:
• A well-presented structure of neurons can be reviewed at: Waymire [4]
The major players on visual participants in the process of consciousness will be
discussed individually and then the entire concepts as a whole will be discussed:
1. Neurons
2. Synaptic connections
3. Mitochondria
4. Oxygen radical species (ROS)
5. Radical pair mechanism (RPM)
6. Microtubules
7. Biophotons
8. Müller cells
9. Tryptophan
Neurons
There are about 100 billion neurons in human brain [5].

Fig. 7.1 Schematic

representation of a
simplified neuron structure
Neurons are the main components of nervous system with the ability to transport
and transfer energy with communication via synaptic spaces. Typical neurons con-
sist of a cell body (Soma) with branch-like dendrites usually for the inflow of
impulses and the axons for outflow. The axons are covered with a lipid-rich material
called myelin. There are spaces along the myelinated section that are called nodes
of Ranvier.
The structure of a neuron is shown in Fig. 7.1 as a reference for its basic functional
properties.
Synaptic Connections
The communication between the individual neurons is fundamental for any

neurological task including consciousness. This communication between the
neurons has many modes of “information transport system.” This transfer of
information can be via:
Synaptic Connections 123
• Chemical, as in synaptic spaces.

• Electrical, by ion transport as action potential.
• Optical, by biophotons via microtubules.
• Vibrational, by generated electric fields along the profilaments of microtubules
Each of these systems have their own specific properties and speed.
One common classical mode of neuron communication is via synaptic spaces.
That is usually when an axon of one neuron transfers the information to the dendrite
of the next neuron. Many other types of synapses can also exist, but here we are
referring to neuron-to-neuron synopses at central nervous system.
Chemical synapse is when the electrical activity of the presynaptic neuron
causes the release of neurotransmitters at its axonal terminals. This is via release of
calcium at the voltage-gated calcium channels. The neurotransmitters will bind to
the receptors located in the plasma membrane of the postsynaptic neuron which
initiates a positive or negative response, and as the result, action potential.
Chemical synapses usually classified according to the type of neurotransmitter
that they carry such as (Fig. 7.2):
1. Glutamatergic (often excitatory)
2. GABAergic (often inhibitory)
3. Cholinergic (Neuromuscular junctions)
4. Adrenergic (Epinephrin release)
Fig. 7.2 Synapsis cleft showing the release of neurotransmitters by flux of calcium ions inside the
axon terminal. The neurotransmitter receptors of the dendrites detect the neurotransmitters and
initiate the transport of the information to the receiving neuron
Electrical synapses have much faster signal transfer due to the connection of
presynaptic and postsynaptic neurons via a gap junction. This permits the passing of
the electric current causing voltage changes passing through the junction and pass-
ing the signals to the next neuron.
Optical and vibrational synapses are by generated biophotons, and the elastic
vibrations of the tubulins around their equilibrium position within the microtubules
which is called phonons.
Mitochondrion (Mitochondria = Plural)
Mitochondria are double-membraned organelle inside the cells that use aerobic
respiration to generate ATP (Adenosine Triphosphate) the energy currency of the
cell and its referred to as the powerhouse of the cell. Mitochondria have a dynamic
and transitional form depend on its activity of fusion or fission machinery [6].
–– Fusion causes longer mitochondria and produces more energy.
–– Fission causes shorter mitochondria and more likely will go under degradations [7].
In mammalian cells, mitochondria are transported by motor protein Kinesin-1
and Dynein along microtubule tracks (Fig. 7.3).
Structure of mitochondrion: [8]
• The outer membrane is similar to cell membrane. Contained a large number of
integral membrane proteins.
• Intermembrane space, freely permeable to small molecules.
• The inner membrane contains, ATP Synthase, Electron transport, and Protein
transport.
• The Cristae space, enhance expanded surface.
• The matrix (Space within the inner membrane) production of ATP and contains
many essential enzymes.
Fig. 7.3 Schematic presentation of mitochondrion. The outer membrane and inner membrane are
creating space between them called intermembrane space. The most inner section is called the
matrix of mitochondrial DNA and ribosomes
Mitochondrial Respiratory Chain Complexes 125
Mitochondrial Respiratory Chain Complexes (Fig. 7.4)
Mitochondria has many functions in the cell:

• Cellular energy supply adenosine triphosphate (ATP)
• Generating reactive oxygen species (ROS)
• Production of Biophotons
• Signaling, specially calcium signaling
• Cellular differentiation
• Apoptosis
• Cell growth
• Cell cycle (Fig. 7.5)
Energy releasing reaction and production of adenosine triphosphate (ATP):
1. Glycolysis, when glucose is converted to pyruvate, which enters the mitochondria
and is converted into acetyl-CoA and then into citrate.
2. Citric acid cycle (Krebs cycle), series of chemical reactions that occur in the
matrix of the mitochondrion. It releases the stored energy through the oxidation
of acetyl-CoA. The cycle consumes acetate from acetyl-CoA plus a water mol-
ecule, reduces NAD+ to NADH, releasing carbon dioxide (CO2).
3. Beta-oxidation: Catabolic process by which fatty acid molecules are broken in
the mitochondria generating acetyl-CoA which enters citric acid cycle, and
NADH and FADH2 in the electron transport chain.
Fig. 7.4 Magnified section of mitochondrion membranes and membrane proteins in charge of its
respiratory processes. The respiratory chain complexes are numbered from left to right. Complex I,
ubiquinone oxidoreductase transforms NADH to NAD+ and O2 and transfer electron to
CoQ. Complex II, Succinate dehydrogenase transforms FADH2 to FADH. Complex III, Cytochrome
c reductase releases O2 to SOD 1 and SOD 2 to generate H2O2. Complex IV, Cytochrome c oxi-
dase transforms O2 to H2O. Complex V, ATP synthase Transform ADP to ATP. Complex I, III, and
IV pump protons (H+) across inner membrane, creating a proton gradient that is utilized by com-
plex V to produce ATP. SOD1, Superoxide dismutase 2 located in the matrix convert O2 to
Hydrogen peroxide. GPX, Glutathione peroxidase reduces hydrogen peroxide to water
Fig. 7.5 Chemical structure of adenosine triphosphate (ATP), the energy currency of the cell. By
donating the phosphate to other molecules, it will transform into adenosine diphosphate (ADP) or
adenosine monophosphate (AMP)
Oxygen and Reactive Oxygen Species (ROS)
WE can start with Oxygen atom, the essential gas to living organisms with the
atomic number 8 on the periodic table of elements. It is on nonmetal group 6 of the
periodic tables of elements, which means it has 6 outer orbit electrons.
Its electron configurations are: 1S22S22p4 (Discussed in previous chapters) which
means it has 2 electrons on its first atomic orbital 1S (N1 orbital), 2 electrons on the
second subatomic orbital 2S, and 4 electrons on the third subatomic orbit 2d (N2
orbital) makes total of 6 electron at its outer orbit and 8 electrons as a whole.
Octet rule: As a very general rule (with many exceptions), there need to be 8
electrons on the outer orbit of each atom with the exception of Hydrogen that has 2
outer electron orbits. For molecular bonding, the 2 electrons of the first orbital “1S”
is not counted and only covalent bonds are mentioned (2S, 2p, and higher energy
orbitals) which makes a total of 8 electrons on the outer orbit.
Lewis Diagram or dot structures: A network of covalent bonds is shown as
number of dots around the atomic symbols. It refers to the number of the electron at
the outer most orbital which has the highest energy level. Double dots represent
paired electrons and single dots represent unpaired electron. The covalent bond
between two atoms is shown as a short line and the double bond as double line and
triple bond as three lines. Each covalent bond contains 2 electrons (Fig. 7.6).
Oxygen forms compounds by reaction to many elements and particularly with
hydrogen to form water molecule essential for life on earth.
Oxygen has many different forms such as diatomic (O2) or triatomic (O3) as
ozone, or in radical oxygen species with singlet or triplet configurations [9].
Reactive oxygen species (ROS) are numbers of reactive molecules and free
radicals derived from oxygen molecule during aerobic respiration. These molecules
are produced in mitochondria as a byproduct of electron transport, or by
oxidoreductase enzymes, and by metal catalyzed oxidation.
1. ROS are generated from the transfer of electrons (e−) from molecular oxygen to
form superoxide (O2−) at the mitochondrial electron transport chain complexes I
and III.
Radical Pair Mechanism (RPM) 127
Fig. 7.6 Lewis diagram of triplet oxygen. Double dots represent paired electrons and single dots
represent unpaired electrons. The covalent bond between two atoms contains two electrons in
each bond
2. Superoxide is decomposed enzymatically by superoxide dismutase 1 (SOD1) in

the intermembrane space and by superoxide dismutase 2 (SOD2) in the matrix
to form hydrogen peroxide.
3. Hydrogen peroxide is then catabolized to water by the action of enzyme such as
glutathione peroxidases (GPx), to avoid possible buildup of oxidative stress.
4. Hydrogen peroxide in the presence of Fe2 can form highly reactive hydroxyl
radical (*OH).
5. Superoxide may react with nitric oxide to form the potent oxidant and nitrating
agent peroxynitrite (ONOO−).
ROS are involved in many essential metabolic processes:
1. Production of ATP
2. Pathogen response
3. Cellular hemostasis
4. Cellular signaling
5. Biophoton production
Radical Pair Mechanism (RPM)
Radical pair electrons are the unpaired electrons that spin coherently at the outer
orbitals of the molecule and are created simultaneously. Radical pairs are usually
created in either singlet or triplet states. Interaction of radical pairs with the nucleus
happens via hyperfine (HF) reactions. Interaction of radical pairs can also happen
with external magnetic field via Zeeman effect (splitting of spectral line into several
components influenced by magnetic field). Altering external magnetic field or sub-
stituting isotopes with different spin can change the extent and timing of the sin-
glet–triplet interconversion, resulting in altered yields of products [10].
Singlet Oxygen: (1O2)
• A reactive oxygen species is generated by the excitation of ground state

(triplet) oxygen.
• It is an inorganic gas with the formula (O=O) which is in a quantum state that all
electrons are spin paired.
• Unlike many other reactive oxygen species (ROS), it is not radical; instead, it is
strongly “electrophilic” due to its low-lying lowest unoccupied molecular
orbital (LUMO).
• It is more reactive toward organic compounds.
• Its intracellular lifetime is around (3 x 10-6) seconds.
• Trace amount of singlet oxygen are found in upper atmosphere and in the polluted
urban areas.
• It has only one possible arrangement of electron spin with a total quantum
spin of 0.
• It has different chemical properties than triplet oxygen, including absorbing and
emitting light at different wavelengths.
• It is most commonly generated via transfer of energy from excited photosensitizer
to ground state (triplet) oxygen.
There is a need for three harmless components to interact with each other and
generate the potent singlet oxygen:
1. Photosensitizer (PS) such as methylene blue or red Bengal.
2. Light, usually within the visible spectrum.
3. Molecular oxygen.
The excitation of ground state photosensitizer (PS) results in formation of excites
singlet (PS), which undergoes intersystem crossing to long living “triplet excited
state,” which then will collide with an O2 molecule and form singlet oxygen (1O2)
(Fig. 7.7).
• Singlet oxygen: Intracellularly it is generated by neutrophils using NADPH
oxidase and myeloperoxidase.
• It can react with intracellular fatty acids, amino acids, and DNA base guanine.
• It has an essential role in intracellular signaling transduction [11].
• In solutions, Singlet oxygen can be excited to its “singlet excited state” by the
use of photosensitizer. Then by internal conversion (Intersystem crossing) trans-
forms to “triplet excited state” [12].
00 Spin Inversion
00
( 0)
3
2 (0)
1
2
Triplet Oxygen Singlet Oxygen

(Ground State) (Excited State)
Fig. 7.7 Lewis diagram of triplet to singlet oxygen spin inversion. Double dots represent paired
electrons and single dots represent unpaired electrons. The covalent bond between two atoms
contains two electrons in each bond
Radical Pair Mechanism (RPM) 129
Triplet Oxygen: (3O2) [13]
• Unusually oxygen molecule is in triplet state in its ground state with formula (.
O – O.).
• Most other molecules are, except for oxygen, at singlet state while in the
ground state.
• It is the most stable and common form of oxygen.
• It has three possible arrangements of electron spin with a total quantum
number of 1.
• It contains two unpaired electrons at its outer orbital.
• It can get excited to singlet excited state and also the triplet excited state.
• It has a non-zero spin magnetic moment makes it a paramagnetic molecule.
• It does not directly interact with other molecules, which are often in the
singlet state.
• It reacts with molecules in a doublet states, such as radicals to form new radicals.
(Fig. 7.8)
Fig. 7.8 Jablonski diagram of generation of radical oxygen species by activation of photosensitizers
and energy transfer to produce different products via different pathways. Different relaxation
pathways after the excitation produce different wavelength photons
Excitation of photosensitizer (P) with light causes the absorption of that energy and transfers it
from its Ground state S0 to its excited state S1. Direct relaxation back to the ground state releases
fluorescence photons with a wavelength of around 500 nm. Intersystem crossing by conversion
into excited triplet (P) T1. Relaxation from Excited Triplet (P) T1 to the ground state (P) S0 will
release Phosphorescence photons with a wavelength of around 280 nm. The triplet (P) T1 can
interact with oxygen in two different pathways. First pathway of interaction of triplet (P) T1 by
transferring energy to the oxygen from the surrounding tissues to form reactive oxygen species
(ROS). Second pathway of interaction of triplet (P) T1 is by transferring energy to the triplet 3O2
ground state T0, by spin inversion to form the excited singlet oxygen 1O2 state S1, which releases
photons with a wavelength of around 1270 nm. It is a special property of oxygen that exists in a
triplet state at the found state, most other elements are at singlet state in the ground state
Microtubules
Microtubules are cylindrical structures that form the cytoskeleton of eukaryotic

cells with many essential key functions. Recently, microtubules have been the cen-
ter of attention due to their role in the quantum biology of neurons and the brain
function.
Microtubules are composed of polymerization of a dimer of two subunit proteins,
alpha and beta tubulins. Their main role in the cell is in cell division and intracellular
trafficking.
Microtubules are formed by assembly from 13 protofilaments of alpha and beta
tubulin dimers to form a hallow cylinders. The interior of the cylinder is filled with
water molecules, which implies the existence of electric dipole and electric fields.
They rapidly grow and shrink in length via GTP regulated process [14].
They can get as long as 50 micrometers and are around 25 nm wide, the inner
hallow diameter is around 12 nm.
The closest structure to nanotubules in nanotechnology is the carbon nanotube.
Carbon nanotubes can display a striking similarity in size and morphology to micro-
tubule biometric properties. This resemblance suggests that tubulin and microtu-
bules could possibly serve as units for optoelectronic and quantum information
devices in cells such as axons and dendrites of the neurons [15, 16].
Microtubules have a distinct polarity with (−) and (+) ends. The end with exposed
beta-tubulin is (+) and the end with exposed alpha-tubulin in (−).
Microtubule Assembly (Fig. 7.9):
Each tubulin molecule contains four tryptophan molecules and when they form
a dimer (alpha- and beta-tubulin) as the result they carry eight molecules of tubulin
[17] (Fig. 7.10).
Microtubule Cargo Transport (Fig. 7.11):
The potential energy transfer in microtubules is mediated by aromatic amino
acids and tryptophan specifically, which behave as an optical metamaterial and may
serve as a template for bioinspired technologies [14].
Microtubule organizing centers like centrosomes are where the microtubules
emerge for cell division process, which separates the DNA for the formation of
daughter cells during mitosis.
Summary of the main functions of microtubules are:
• Formation of cytoskeleton for the cell
• Cell division
• Cargo transport
• Cellular motility
• Electron transfer
• Biophoton transfer
• Phonon transfer
Microtubules 131
Fig. 7.9 The assembly of microtubules starts with dimerization of alpha-tubulin molecule with a
beta-tubulin molecule. The dimers then attach together to form a filament called protofilament.
These filaments attach together side by side to form microtubule sheets. When 13 filaments attach
together, they form a hollow tube which is called a microtubule. There is always a positive end
which is the beta-tubulin end and the negative end which is the alpha-tubulin molecules. Most of
the growth happens at the positive end
Functional Architecture of Microtubules in Neurons
Microtubules are essential structures for functioning neurons. There are differences
in microtubule organization and their microtubule-associated proteins in axons and
dendrites of the neurons. These differences have been identified in acetylation and
their mechanisms of organization that regulate motor activity and cargo delivery. A
neuron’s morphology and function depend on the underlying microtubule cytoskel-
eton. Another essential function of the microtubules which sustains neural function
is the transport of RNAs, mitochondria, and other vesicles, proteins, and other
organelles [18].
Fig. 7.10 Tubulin molecules alpha and beta contain four tryptophan residues. The dimer of an
alpha-tubulin and beta-tubulin contains 8 tryptophan residues which participate in electron transfer
and biophoton production in microtubules
Fig. 7.11 Microtubules play as a highway for transport of different cargo across the cell cytosol.
The transport of mitochondria along the microtubules is by the transport proteins dynein and kine-
sin, each in different directions. Dynein direction of movement is towards the negative end of the
microtubule and kinesin direction of the movement is toward the positive end of the microtubule
Microtubules 133
Quantum Biology of Microtubules
At first, it was believed that biological systems are far too “warm and wet” to support
quantum phenomena mainly due to thermal effects disrupting quantum coherence.
Later studies proved that thermal energy may assist, rather than disrupt, quantum
coherence transport. This can happen in the dry hydrophobic interiors of
biomolecules. We discussed the arrangements of chromophores for coherent energy
transfer in photosynthetic complexes in previous chapters. The tubulin subunits of
microtubules contain tryptophan molecules with geometry and dipolar properties of
their aromatic chains. These are similar to those found in photosynthesis units indi-
cating that tubulin can support coherent energy transfer.
The role of quantum biology in utilizing photon energy, as was discussed in
previous chapters, refers to the biological networks of photoactive antenna molecules
such as chlorophyl, FAD, and tryptophan, which are able to absorb sunlight and
transport the excited states to specific molecule aggregates. The coherent wave
behavior which is the property of quantum mechanics is responsible for the high
efficiency of these processes due to superabsorption and supertransfer of excited
states by these molecules.
These light-harvesting molecules delocalize the excited state of the other
photoactive molecules, which can be in toward an external molecule, or between
different parts of the same system. The velocity of photoexcitation spreading is
enhanced by the supertransfer effect between nearest-neighbor coupling between
tryptophan molecules in the microtubules [19].
Microtubules Energy Transfer
The tryptophan residues spatial distribution and orientation in tubulin molecule (4

tryptophan per tubulin) is about 11.4 and 41.6 Å. Which is comparable to the dis-
tances between chromophores in cryptophyte marine algae. This has been shown to
support quantum-coherent transfer of electronic excitation [20].
The excited energy travels from one tryptophan molecule to the next, covering
the length of the tubulin dimer. The interdimer spacing of tryptophan is uninter-
rupted which efficiently transfers the energy along the stack of tubulin dimers called
protofilaments. The protofilaments form a hollow tube, which is the microtubule.
The energy transfers along the protofilament length via a combination of coherent
tunnelling and incoherent relaxation/excitation.
The unique cylindrical lattice symmetries in tubulin lattices of microtubules can
effectively serve to enhance transfer rates and distances, and potentially enable
Fig. 7.12 Schematic presentation of microtubules in the neuronal axon and dendrites. These
microtubules are connected with microtubule-associated proteins (MAP). The MAP has a major
role in the stabilization, orientation, and function of microtubules
energy transfer along helical arrangement of tubulin and its chromophores in micro-
tubules pathways [21].
A closely packed group of molecules interacting under certain symmetry can
collectively donate an excitation state with a rate much faster than each individual
molecule. This will result in the excitation becoming highly delocalized, leading to
a large dipole moment associated with the entire group. The resulting enhanced
oscillator strength can lead to “Supertransfer” of excitation energy transfer [22]
(Fig. 7.12).
Microtubules, Mitochondria ROS and Biophotons Interactions
There is a close relationship and functional interaction between the generated

biophotons and microtubules. It seems like interaction of biophotons generated by
mitochondria in the neuron, causes transitions/fluctuations of microtubules between
coherent and incoherent states [23].
The generated biophotons in the neuron cells, and their profound effect on
microtubules, is partly due to their alteration in the microtubule orientation. The
majority of generated biophotons have a wavelength of around 280 nm, which
happens to be the peak absorption wavelength of tryptophan.
Radical pairs also play a role in microtubule reorganization [24].
There is a delicate balance and correlation between the generation of radical
oxygen species and generation of biophotons with normal brain function, since
decrease or increase production of biophotons is associated with neural pathol-
ogy [25].
Microtubules 135
Another interesting information is that the index of refraction of mitochondria

and microtubules are much higher than the surrounding tissues which can act like
optical waveguide or fiberoptic to transfer information [26] (Fig. 7.13).
The role of Phonons in microtubules: The elastic vibrations of the tubulins
around their equilibrium position within the microtubules are called phonons. The
velocity of vibrational modes of microtubules are between 200 and 600 m/s as
was mentioned above, the tubulins are made of dimers of tubulin alpha with a
negative charge and tubulin beta with a positive charge with dipolar water mole-
cules in the hollow space. Each monomer profilaments contains alpha and beta
wells and their vibrations generate electric fields along the profilaments. By quan-
tum tunnelling phenomenon, an electron may go from one well to another, thus
depends on the situation of the mobile electron, the tubulin dimer can have the two
basic states [27]. The quantum field theory of microtubules are fully discussed in
the literature and can be reviewed at [28].
Fig. 7.13 Microtubules play as a highway for transport of different cargo across the cell cytosol.
The transport of mitochondria along the microtubules are by the transport proteins dynein and
kinesin. Photons generated in mitochondrion are absorbed by FAD (Flavin adenine dinucleotide)
and tryptophan. The absorption causes the excitation from ground state S0 to excited state S1.
Non-radiative intersystem crossing causes conversion from S1 to excited triplet state T1. Radical
pair is formed between the flavin of FAD, tryptophan singlet, and triplet states. Relaxation at dif-
ferent stages causes the release of photons as fluorescence or phosphorescence. The generated
photons are then transported via microtubules in the neuron axon
Conditions Associated with Microtubule Abnormalities
Abnormalities in microtubules have been associated with many neurological

conditions, such as:
• Cognitions abnormality
• Memory problems
• Intellectual impairment
• Autism
• Alzheimer’s
• Parkinson’s
• Huntington’s chorea
Microtubule-Binding Core of the Tau Protein:
Tubulin Associated Unit (Tau): The group of six highly soluble protein isoforms
that are primarily in charge of maintaining the stability of microtubules in axons of
the neurons of central nervous system [29].
The other functions of tau proteins are:
• Regulation of long-term memory
• Cellular signaling
• Neuronal development
• Neuroprotection
• Apoptosis
Alteration in microtubule-associated protein (MAP) that is the key protein in
stabilizing microtubule architecture that regulates neuron morphology and synaptic
strength, is associated with neurodegenerative disorders such as Alzheimer’s dis-
ease, Parkinson’s, and dementia.
The production of reactive oxygen species (ROS) by mitochondria results in the
ultraweak photon emission (UPE) or biophotons within the cell. These biophotons
gets absorbed by aromatic amino acids such as tryptophan in the microtubules of the
neurons. Functional microtubule networks utilize and traffic these ROS-generated
endogenous biophoton energy for cellular signaling or channeling out or dissipa-
tion, and as the result protecting the cell from ROS toxic effects (Rahnama2011).
Targeting microtubules and microtubule-associated proteins (MAPs) is the focus
of many efforts to produce therapeutic intervention agents and drugs to treat neuro-
degenerative diseases. This includes factors such as microtubule modifying enzymes
which modulate tubulin post-transitional modifications (PTM) that modulate micro-
tubule stability or targeting tubulin PTMs, such as tubulin acetylation [30].
Due to the fact that microtubules are essential for both cellular mitosis and
meiosis, tubulin has become a major target of chemotherapy drugs. The role of
microtubules in neural function and cognitive process in the brain is well established.
Biophoton or Ultraweak Photon Emission (UPE) 137
The cognitive impairment in patients receiving chemotherapy (Chemo brain) have

been related to damage to tubulin within microtubules [31].
Biophoton or Ultraweak Photon Emission (UPE)
A very good review article on the subject of biophotons is by Wijk et al. [32].
There is a continuous release of photons in all living life forms tissues, such as
plants and animals, involving radical oxygen species (ROS) and are called biopho-
tons, or ultraweak photon emission (UPE). The process of biophoton emission is
due to the generation of excited ROS (Singlet excited oxygen) from the mitochon-
dria, and its return to its ground state (triplet oxygen). These biophotons are ranging
from ultraviolet and visible light (100–800 nm) to infrared (800–1270 nm). These
biophotons are absorbed by different chromophores and molecules, for example,
flavins, collagen, NADH, and tryptophan, and emit different wavelengths accord-
ingly. Tryptophan has an essential role in the transport of biophotons via
microtubules.
This generation of background biophotons is via aerobic metabolism in
mitochondria. Glutamate is the most abundant excitatory neurotransmitter in the
nervous system that can produce neural activities such as long-term potentiation,
can also generate glutamate-induced biophoton activities. The glutamate-induced
biophotons play a role in biophotonic transmission in neural cells and neural
circuits [33].
The relation between the level of intelligence (problem solving and analytical
properties) in different species have been shown by measuring the glutamate-
induced biophotonic activities and transmission in the brain. There was a presence
of increased spectral redshift from animals (bullfrog, mouse, chicken, pigs, and
monkeys) to humans, which can explain the higher level of intelligence in humans
[15, 16].
While a physiological level of mitochondrial ROS and normal biophoton release
correlates with normal neural and brain function, increased or decreased biophoton
production is associated with neural pathology. It is suggested that increased bio-
photon can alter the orientation of the microtubules. There is a significant release of
biophotons that occurs at 280 nm, which corresponds to the peak absorption wave-
length of tryptophan. Increased mitochondrial activity and biophoton release result
in abnormal tryptophan metabolism and excess production of neurotoxic kynuren-
ines, which in turn, damage microtubules [31].
Transsynaptic transfer of biophotons in mouse hippocampal slices opens the
perspective for clarifying the information transmission and processing mechanism
of the brain. The conventional chemical synaptic exchange of information from
action potential at synaptic terminal and release of neurotransmitters to be detected
by the receptors to transfer the information is too slow. For fast and simultaneous
interaction between multiple neurons involved in complex brain tasks, that is why
there is a need for a fast relay of information via biophotons. Even the ionic action
potential firing is too slow for fast processing tasks in the brain. filaments and
nanotubules in neurons can fire a thousand times faster via their electromagnetic
and vibrational transfer properties [34].
This non-delayed propagation of information in neural circuits becomes possible
also via biophotons through quantum effects of entanglement, coherence, and
superposition [35] (Fig. 7.14).
The photons emitted from singlet oxygen in neurons are infrared and have a
wavelength of [15, 16] nm. It is very close to the wavelength of infrared being used
in fiberoptics for higher speed, longer distance multimode applications, for instance,
LED with a wavelength of 1300 nm. The myelin coating of the nerve fibers not only
act as an insulator that increases the signaling speed, but also its axon’s index of
refraction profile plays an essential role in transmitting light as a waveguide. This
process of optical waveguide behavior also happens in the presence of both axon
and myelin with bends, myelin sheet variation of thickness, and the node of
Ranvier [36].
Opsin molecules are well known for their ability to detect light in skin, retina,
and the brain of mammals. The existence of opsin in deep brain suggests that they
possibly serve as biophoton detectors and also suppress thermogenesis in the tissue.
The photo detection response which causes opsin-mediated suppression of thermo-
genesis, could lead to more production of ATP by mitochondria, which results in
more biophoton production. Thus, it could constitute a relay across the neuron in the
photonic backpropagation channel. Mitochondria always balances ATP production
versus thermogenesis [37].
Fig. 7.14 General overview of biophoton production by mitochondria. Step one is the generation
of ATP and singlet-excited oxygen by mitochondrion. Step two is the electron transfer by trypto-
phan. Step three is radical pair formation. Step four is biophoton generation
The Müller Cells 139
The Müller Cells
Müller cells are the support cells (glial cells) for the retinal neurons. They are the
only retinal glial cells that share a common lineage with retinal neurons.
While their cell bodies are located in the inner nuclear layer of the retina, they
span across the entire retinal thickness, from the inner limiting membrane to the
outer limiting membrane. The Müller cells exhibit radial morphology and cover the
entire retina parallel to the photoreceptors. There are three main types of glial cells
that maintain homeostasis in the retina: microglia, astrocytes, and Müller cells.
Optical waveguide in the neurons via a quantum property of light has also been
identified in Müller cells, the glial supportive cells in the retina that has the same
origin lineage as neurons and has been shown that have a significant role in the
perception of sharp images in the brain. We will discuss how the Müller cells as
their participation in quantum visual perception have become more evident in its
initiation of the process of information transport to the brain (Fig. 7.15).
The main role of the Müller cells is to maintain the structural and functional
stability of retinal cells, which includes [38]:
• Uptake of neurotransmitters.
• Removal of debris by phagocytosis.
• Regulation of K+ levels.
• Storage of glycogen.
• Electrical insulation.
• Mechanical support of retina
• Photon transport through the retinal thickness.
• Cell-mediated neuroprotection and neuron regeneration via progenitors.
• Blue light perception.
Fig. 7.15 Schematic description of the cellular structure of the retina and RPE and their correlation
to the Bruch’s Membrane and Choroid. RPE size is exaggerated in the schematic illustration
There is a special focus on Müller cells in recent years, due to its multiple roles
in vision as a whole and many essential functions that it carries.
The complex cellular morphology of Müller cells makes it possible that they
contact with many other cells such as photoreceptors, neurons, synaptic spaces, and
blood vessels. Müller cells can respond to retinal damage by differentiation and
proliferation and produce neuron progenitor cells that migrate to the injured retinal
regions and differentiate into lost neuronal types, and eventually repair the damaged
retina [39]. They also share many features with astroglia located throughout the
brain including maintenance of homeostasis, modulation of neurotransmitters, and
response to injury [40].
The use of zebrafish has become a valuable model for studying retinal cellular
reprograming and regeneration due to its spontaneous reprograming of its Müller
cells [41]. Unlike in mammals, that after injury, the retina enters the state of gliosis
(scar formation) which damages the vision processing, Zebrafish reprogram its
Müller cells to divide asymmetrically to maintain the glia and to produce a neural
progenitor cell (NPC). This will continue to proliferate to produce a cluster of mul-
tipotent progenitors that differentiates into all retinal cell types, with a bias toward
the cells lost to damage [42].
Retinal Müller Cells as Living Optical Fibers
In order to understand the role of the Müller cells one should understand the
structure of the retina. The retina is an upside-down structure. That is the photo
sensors are located in the back and all the cellular structures and glial tissue are in
front, as light approaches the retina (Fig. 7.15).
In order for a photon to reach the photosensor discs of photoreceptors, they have
to pass through many retinal layers such as internal limiting membrane, nerve fiber
layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform
layer, and outer limiting membrane. The Müller cell is participating by many mech-
anisms to prevent light scattering and distortion, in transferring light through the
inverted retina [43].
• The Müller cells extend the entire thickness of the retina and bypass the
retinal layers.
• Higher index of refraction compared to surrounding tissues.
• Cylindrical form as a light wave guide.
• Bypass the light from scattering by nerve fiber layer and both plexiform layers.
• Rare mitochondria in their cytoplasm decrease light scattering.
• The existence of intermediate filaments along its axis.
• The end feet projection of the müller cells cover the entire inner retinal surface,
with low index of refraction permits light transfer from vitreous to the Müller
cells as light collector.
The Müller Cells 141
• Parallel coupling with one cone for sharp daytime vision(photopic) preserve
initial image resolution by guiding the light directly to their respective cone,
minimizing image distortion.
• Improve image contrast by increasing signal-to-noise ratio.
• Work as an optical system on the inverted retina.
Recent studies have confirmed the photosensitivity of the Müller cells and
intrinsically respond to blue light. They also confirmed the interaction with all the
neural elements within the retina. In addition, Müller cells express non-visual opsins
and photoisomerases [44].
üller Cell Intermediate Filaments (IFs) and Quantum

M
Mechanism of Light Energy Transfer in the Retina
Intermediate filaments are components of cytoskeletal structure of vertebrate cells.

They are composed of a family of proteins with an average diameter of 10 nm.
Most are cytoplasmic except type V that is nuclear. The type lll intermediate
protein called Vimentin functions against mechanical and other forms of stress.
Mutated vimentin induces upregulation of Heat Shock Protein 70 (Hsp70) and
leads to extensive cytoplasmic aggregation of proteasomes that causes posterior
age-dependent cataract [45].
The quantum mechanism of light energy transfer from inner limiting membrane
to the photoreceptors is proposed to be via the intermediate filaments of the Müller
cells. This mechanism involves electronic excitation energy transfer in excited inter-
mediate filaments by photons as the donor to the visual pigments in the photorecep-
tor cells as energy acceptor. It was shown that intermediate filaments with a diameter
of 10 nm demonstrate properties of light energy guide, where excitation propagates
along the filaments from Müller cell end feet area to photoreceptor area. The trans-
fer is via contact exchange quantum mechanism.
The estimated energy transfer efficiencies in such systems may exceed 80–90%.
This quantum mechanism of light energy transfer in the inverted retina explains the
high image contrast achieved in photopic conditions (daytime vision) [46].
Another study proposed two different modes of energy transfer by Müller cells.
The high contrast and visual resolution in the daylight are provided by the quantum
mechanism of energy transfer by intermediate filaments in the form of an excited
state, whereas the retinal sensitivity of the night vision is provided by the classical
mechanism of photon transmission by the Müller cell light guide [47].
Tryptophan
Tryptophan is one of the 20 standard essential amino acids. It cannot be synthesized

by primates and is produced by diet. It contains an alpha-amino group (R-NH2) an
alpha-carboxylic acid group (R-COOH) and a side chain Indole (C8H7N).
Tryptophan biosynthesis proceeds from chorismite, the common precursor of
several aromatic metabolites in many single-cell organisms and plants.
It is under the category of aromatic amino acids with tyrosine and phenylalanine.
They carry an aromatic ring which is formed by ring shape carbon atoms, for exam-
ple, like benzene molecule with 6 carbon cycle with hydrogen attached to
each carbon.
Tryptophan is synthesized in the chloroplast under correlated genes ASA1 and
ASA2. Tryptophan is used to produce many indole-containing substances in plants,
but animals cannot produce tryptophan and their intake is through diet [48]
(Fig. 7.16).
Tryptophan not only has a fundamental role in light absorption and electron
transfer and biophoton absorption, production, and transport, but it is the precursor
of many important metabolic products with direct effects on the central nervus sys-
tem and other organs.
The tryptophan function as a biochemical precursor can have a positive or
negative effect depending on the pathway and the end product (Fig. 7.17).
The following compounds are listed below:
1. Serotonin (Neurotransmitter)
2. Melatonin (Neurohormone)
3. Kynurenine (Catabolic metabolites)
4. Niacin (Vitamin B3)
There are different pathways of tryptophan metabolism:
Fig. 7.16 Structural representation of Tryptophan molecule which is composed of an amino group
(blue), a carboxylic group (orange), and a side chain of indole (green)
Tryptophan 143
Fig. 7.17 Tryptophan has a fundamental role in light absorption, electron transfer, biophoton
absorption, production, and transport. It is also the precursor of many important metabolic prod-
ucts with a direct effect on the central nervous system and other organs
• Serotonin pathway: Serotonin is synthesized by the enzyme Tryptophan

hydroxylase. Serotonin also synthesizes Melatonin via N-acetyltransferase and
5-hydroxyindole-O-methyltransferase enzymes.
• Kynurenine pathway: Kynurenine is synthesized by enzymes Indoleamine2,3-
dioxygenase (IDO) in the immune system and the brain, and by tryptophan
2,3-dioxygenase (TDO) in the liver.
• Indole pathway: Indole is synthesized from tryptophan by the gastrointestinal
microbiota in humans. The end product can vary due to bacteria involved.
• The 3-indole propionic acid (IPA) is a highly potent neuroprotective antioxidant.
Also, Indole-3-aldehyde (13A) increases the inflammatory responses (Fig. 7.18).
The exposure of tryptophan to ultraviolet light (UV) will result in its metabolism
along the kynurenine pathway. These metabolites are major ultraviolet-
photooxidation products of tryptophan and oxygen has a key role in this process.
The ultraviolet light stimulates the generation of superoxide anion and hydrogen
peroxide. The process of UV exposure, generation of oxygen reactive species
(ROS), and production of tryptophan toxic products have many consequences in
humans, including [31]:
• Skin damage due to sun exposure.
• Damage to the lens of the eye due to modifying lens proteins and cataract
formation.
• Release of cytokines, interferon-gamma, and tumor necrosis factor (TNF-alpha)
in the brain results in greater release of biophotons from mitochondria and as a
result, many neurological disorders.
• Toxicity to neurons can cause axonal degeneration and cell death.
• Phosphorylation of microtubule-associated proteins (MAPs) causes disassembly
of microtubules and development of many neurological diseases, including,
Parkinson’s disease, Huntington’s chorea, amyotrophic lateral sclerosis (ALS),
Alzheimer’s, dementia, multiple sclerosis (MS), AID’s dementia, Schizophrenia,
and cognitive decline of aging.
Tryptophan Role in Light Energy Harvesting and Electron Transfer. “All brain
‘quantum Biology’ lead to Tryptophan”
In previous chapters, we discussed the essential role of tryptophan in quantum
biology, from photosynthesis to magnetoreception and circadian rhythms, due to its
specific molecular structure as light harvesting and ability to transfer electrons in
microtubules.
Sun energy as photons was the key to the origin of life on earth. The earliest life
forms such as “cyanobacteria” captured the photons from sunlight to generate
energy through photosynthesis. This was done by converting the photon energy to
biological energy by tryptophan amino acid and the subsequent production of oxy-
gen as a waste product, which eventually changed the earth’s atmosphere, and as a
result, changed the living organisms.
Early life on earth evolved in accordance with the earth’s rotation and as a result
the circadian rhythm is tied to the sensitivity to sunlight patterns. Light absorption
Tryptophan 145
Fig. 7.18 Tryptophan metabolic pathways with the production of essential molecules with
different functions. Serotonin pathway synthesizes serotonin by the enzyme tryptophan
hydroxylase. Serotonin also synthesizes melatonin via N-acetyltransferase and 5-Hydroxyindole-
O-methyltransferase enzymes. Kynurenine pathway synthesizes serotonin to kynurenine by
enzymes indoleamine2,3-dioxygenase (IDO) in the immune system and the brain, and by
tryptophan 2,3-dioxygenase (TDO) in the liver. Indole pathway synthesizes tryptophan by the
gastrointestinal microbiota in humans. The end product can vary due to bacteria involved. The
3-indole propionic acid (IPA) is a highly potent neuroprotective antioxidant. Also, Indole-3-
aldehyde (13A) increases inflammatory responses
of tryptophan is the property of its indole ring, which was carried through the evolu-
tion of all branches of plants and animals. Combining tryptophan with molecular
oxygen and production of serotonin probably first started in photosynthetic single
organisms such as blue algae. Tryptophan and its product serotonin play an essential
role in the physiology of plants, animals, and humans (mood, sleep, cognition). It is
very interesting to note that all photon-sensing molecules throughout evolution
utilize the aromatic amino acid tryptophan, residing at the center of their light-
harvesting active sites.
The unique capacity of electron transfer during photosynthesis due to tryptophan
aromaticity in the earlier life forms was evolved in more complex functions, in the
more complex organisms, and was carried out to allow the generation of the build-
ing blocks of neuronal energy transfer to fabricate “complex systems” in higher life
forms. This proposed concept defines the role of tryptophan in the emergence of life
and conciseness [49].
Properties of Consciousness
A Dual utilization of classic physics and quantum physics by brain cells after
millions of years of evolution.
Understanding the biological basis of consciousness has been very challenging
and has been investigated for many years via multiple fields of science including
neuroscience, medicine, phycology, quantum physics, philosophy, and artificial
intelligence.
It seems that nature has learned to utilize all available tools in order to climb the
ladder of evolution and harness the classic and quantum physics properties.
Quantum Phenomena
In quantum biology, the quantum effects of coherence-decoherence, superposition,

tunnelling, and entanglement play an important role. Before we get to quantum
brain, we briefly refresh the basic concepts of quantum physics.
Quantum Coherence
Quantum coherence is based on the idea that all objects have wave-like properties.
It is the physical condition of two or more particles or systems being in the same
quantum state or phase, for example, the state of photons is coherent in a laser
beam. Quantum coherence refers to the ability of a quantum state to maintain its
entanglement and superposition in the face of other interactions and the effects of
thermalization. To maintain coherence, one should overcome noise, leakage, and
decay channels that constitutes the main source of decoherence. Coherence and
entanglement are two landmark features of quantum physics and are considered to
be “operationally equivalent.” Decoherence is when the quantum states become out
of phase.
Quantum Phenomena 147
Quantum Superposition
The superpositioning concept allows a physical system to exist in two or more

quantum states, until a measurement is made on it. The non-intuitive phenomenon
prompted Erwin Schrödinger his famous “cat in the box” thought experiment. This
allows the theoretical construction of a system built on qubits, which can have an
array of values, either 1, or 0, or an indeterminate value.
Quantum Tunnelling
Quantum tunnelling is the ability of a particle to pass through an energy barrier,

lacking the energy required to overcome the barrier by classical physics. This phe-
nomenon has been used in many technologies such as scanning tunnelling micros-
copy and flash memories.
Quantum Entanglement
Quantum entanglement is a phenomenon that occurs when two particles are

generated, interact, or share spatial proximity in a way that quantum state of each
particle cannot be described independently of the state of the other, including when
they are separated.
Measurement of physical properties of particles such as position, momentum,
spin, and polarization can be found to be perfectly correlated. For example, if a pair
of entangled particles is generated such as their total spin of zero, and one particle
has a clockwise spin on the first axis, the second particle will have a counter clock
spin on the same axis.
Entanglement is a primary feature of quantum mechanics and does not present in
classical mechanics.
Magnetic Field Effect and Entanglement
Magnetic field effect and its effect on initiated singlet states entangled oxygen has
been shown to affect neurogenesis on adult hippocampus. It is interesting to note
that triplet oxygen is not entangled, while the singlet state is entangled. This empha-
sizes the important role of entanglement in biology. As we discussed before the
singlet oxygen generates biophotons which serve as quantum messengers to estab-
lish long-distance connections via microtubules [10].
All different states of human conscious, from conscious and subconscious states,
sleep and awake states to coma and vegetative states or under anesthesia or influ-
ence of psychogenic drugs, have been studied in order to decipher the properties of
human consciousness. With all the progress that have been made in the field of
consciousness, there are still not complete explanation or universally agreed on
theory exist as of today.
Here, we discuss the present theories on human conscious state and its major
component, the visual conscious state.
The common list of the brain’s cognitive functions is summarized as follows:
• Generation of subjective experience.
• Memory formation, long term, and short term.
• Learning process.
• Computational properties.
• Cognition and Consciousness.
Due to the fact that visual input contains the majority of influx of information to
the brain, two-third of the brain and 30% of cortical gray matter involved in visual
information processing, many of the research is done using the visual system as a
base to study human consciousness (Figure 7.19).
The recent understanding of the role of quantum physics in biology, for example,
in photosynthesis, magnetoreception, and circadian rhythms, opened the door to
investigate other biological events. Another field that is becoming the center of
attention is to convey the quantum process of energy transfer in the brain, which
Fig. 7.19 Schematic representation of an overall view of consciousness as the function of neurons
in the brain. A complex interaction between the subatomic (electrons and photons), atomic (oxy-
gen), and molecules (tryptophan). Many important players are involved and have important roles
in this process, such as mitochondrion generating ATP and excited singlet oxygen, forming radical
pairs, and electron transfer by tryptophan, to produce biophotons in microtubules
seems to have an essential role in many brain functions including neurogenesis and
consciousness.
So far, we have reviewed all the ingredients necessary for understanding the
process of consciousness, yet it is not that easy. There are still many controversial
theories regarding the cognitive properties of the brain. We try to summarize what
is known today, and yet, there will be many more additions to explain such a com-
plex phenomenon.
Altered States of Consciousness
One way to understand consciousness is to see how it can be affected and manipulated
by other small molecules and anesthetics. This includes understanding the effect of
antidepressants and psychogenic chemicals as they induce altered states of
consciousness.
There are many levels in brain function, from a network of neurons to the
molecular and atomic particles involved in neurons, and with the utilization of
classic physics and quantum physics that combined together making the process of
a complex mind.
Even though many of the chemicals work on the synaptic neurotransmitters and
many mental illnesses are associated with abnormality in neurotransmitters, it could
not explain the complex functions of the brain. Many years of studies on the brain
and its properties have narrowed its mechanism of function down to the essential
work of microtubules inside the neurons.
There are many new theories that explain the involvement of microtubules on
brain function Hameroff [50].
According to these theories, the conductive resonances in microtubules, originate
in terahertz quantum dipole oscillations, and optical interactions among pi electron
resonance clouds of aromatic amino acid rings of tryptophan (also tyrosine and
phenylalanine), initiate within each tubulin. The frequency starts in dendritic and
somatic microtubules as gigahertz and megahertz and then it transfers to the distal
axonal branches and synaptic spaces. In summary, the cognition in the brain
originates in microtubules inside neurons.
Vibrational Effect
The classic theory of olfaction (the sense of smell) was based on the action of
neurotransmitters as lock and key by the receptors at the synaptic spaces. The
studies with different isotopes disqualified this theory, as using the isotopes had
different effects due to their mass and spin difference without changing the shape of
the isotope.
Alternative theory suggests that olfaction may use principles of vibration-assisted
quantum tunnelling. This theory is now has been applied to the action of other
neurotransmitters as well. Vibration-assisted tunnelling is when the energy of one

molecule’s movement matches the energy necessary for an electron to tunnel
through a potential barrier. This means the vibration of a particular neurotransmitter
would be recognized by its specific receptor.
Neurons are unique as they are non-dividing cells, therefore, their microtubules
are not required to repeatedly disassemble and assemble to form mitotic spindles,
which causes the neuron to stay in a stable state. This stability is crucial for neuron
function as it maintains neuron morphology and prevents cell division. Many phar-
maceutical products are based on their function on microtubules, as anesthetic
agents are weak destabilizers of microtubules, and antimetabolite medications pre-
vent microtubule polymerization.
The Three-Wave Processing
On a larger scale, the cellular layers of gray matter of the brain and their bidirectional
functions are involved in sorting and transferring the neural signals. This would
initiate the three steps or “waves” toward the processing of the information
throughout the entire brain. It starts with the sensory inputs carrying impulses from
all senses, for example, the retina (the main source) to lateral geniculate nucleus in
the thalamus (wave1), then the impulses are relayed to visual cortex via optic radia-
tion (wave2) and then the impulses will feedback through associative cortex in the
frontal lobe (wave3) which initiates a global broadcast from frontal and pre-frontal
cortex to all regions of the brain.
In the gray matter, the input activity also conveys in 3 waves. Input arrives in
layer IV (wave1), then to layers l, ll, lll, and Vl (wave2) and finally to layer V the
giant pyramidal neurons (wave 3). The most likely site for the perception-action in
psychology is layer V cortical pyramid neurons (Fig. 7.20).
Anesthetic Action and Quantum Consciousness
Anesthetic agents block the consciousness selectively, sparing nonconscious brain

activities, and thus their specific action could unravel how the brain generates con-
sciousness. One example is xenon gas that used to be used for general anesthesia.
Xenon is an element with the symbol Xe and atomic number 54 and has many iso-
topes. The isotope of anesthetic xenon (129Xe) with the quantum property of nuclear
spin ½ has a very different effect than their isotopes without the spin. ½ spin is
optimal for entanglement since it has the longest coherence time.
As we discussed before, the spin is a particular property of quantum physics and
is related to angular momentum with a magnetic moment at discrete, quantized
levels. Atoms with imbalance of protons and neutrons can have nuclear spin. It
seems extraordinary, that changing something as small as the spin of a nucleus
Fig. 7.20 Schematic presentation of cellular layers of gray matter of the brain and their
bidirectional functions. In the gray matter, the input activity also conveys in three waves. Input
arrives in layer IV (wave1), then to layers I, II, III, and VI (wave2) and finally to layer V the giant
pyramidal neurons (wave 3). The arrows represent the movement of signals between different layers
might result in a macroscopic change on the level of something as complex as con-

sciousness [51].
These spin states can entangle by being intimately connected with other spin
states. This implies that the consciousness involves quantum brain processes which
supports the theory of quantum consciousness. The complexity of consciousness
involves entanglement, coherence, and quantum computing via microtubules, in the
brain that binds and integrates multiple sources of information from multiple regions
of the brain into a unified conscious moment.
In addition to nuclear spin entanglement, Quantum dipole oscillations among Pi
electrons resonance clouds in the membrane proteins or cytoskeletal proteins have
been implicated to be involved in the process of consciousness.
Perhaps the rotational force of nuclear spin magnetic moments tunes quantum
electromechanical activity in neuron membrane and/or microtubule proteins to
increase their vibrational frequency, the opposite of anesthetic damping, and thus pro-
mote consciousness. Rather than a computer, the brain may be more like an orchestra;
rather than a computational output, consciousness may be more like a music.
Microtubules and “Orch OR”
“Orch OR” is the most complete, and most easily falsifiable theory of
consciousness [50].
In 1996, Penrose and Hameroff proposed microtubules orchestrated quantum

superpositions, encoding inputs, and memory as entangled qubits of collective
quantum dipole oscillations, which then compute and terminate by collapse of
quantum wavefunction due to an (“objective reduction,” “OR”) in the fine-scale
structure of the universe. This is referred to as Orchestrated Objective Reduction or
“Orch OR” theory.
Roger Penrose shared the Nobel prize in physics in 2020 for his work on black
holes and Stuart Hameroff is an anesthesiologist and professor at the university of
Arizona and is known for his studies on theories of consciousness.
The summary of the concepts is as follows:
1. Photosynthesis proteins utilize superpositioned “Pi resonance” electrons.
2. Quantum electron states resonate in microtubules at terahertz, gigahertz,
megahertz, and 10-kilohertz frequencies.
3. Anesthetics may selectively erase consciousness by quantum interactions inside
microtubules.
Computer modeling shows collective terahertz oscillations among tubulin’s 86
“Pi electron” resonance rings are specifically dampened by anesthetics Hameroff [52].
The “Orch OR” qubit inside tubulin “Pi electron” resonance forms quantum-
friendly regions which extend to neighboring tubulins along helical lattice pathways
to support collective “giant dipole oscillation” qubits [53].
The Quantum Brain
Quantum Effects in the Brain
Biological systems, such as brain, operate at physiological temperatures and is in

direct contact with their environments. There are multiple tasks being performed
instantaneously that require multiple modes of communication between the neurons
of the brain.
Different tasks require different modes with different speeds. Here the dual role
of classic physics and quantum physics are being utilized hand in hand, through
millions of years of evolution, which can provide a wide range of possibilities for
the neurons to communicate.
A variety of experimental techniques benign used to investigate the relationship
between brain activity and the state of perceptual consciousness. The most common
techniques are electroencephalography (EEG), magnetoencephalography (MEG),
and functional magnetic resonance imaging (fMRI).
The slower neuronal transmissions are the property of classical physics, this
process is composed of a signal being received via dendrites be transferred through
the axon to the next neuron via the synaptic cleft by neurotransmitters. The effect of
neurotransmitters that binds to the receptors causing the openning of the ion chan-
nels and altering the next neurons action potential, passing along the signal.
The faster communications, that is, required for complex tasks, such as
consciousness, requires high-speed communications. This was described by the
generation of biophotons and involvement of microtubules which is a property of
quantum physics and is 1000 times faster than classical neural ionic and chemical
conduction. This system also exempts neurons from quantum effect of the
surrounding environment, as standard quantum systems require isolation from
quantum destructive forces of environment and near zero temperatures.
Nuclear Spin and the Brain
The Posner Molecule
The possibility of quantum processing with nuclear spins has been suggested to
operate in the brain information processing function. Phosphorus is identified as the
unique biological element with a nuclear spin that can serve as qubit, whereas phos-
phate ion is the qubit transporter. “Posner molecule” is presented as the unique
molecule that can protect the neural qubits for very a long time period and serve as
a quantum memory utilizing quantum entanglement.
When ATP beaks down it releases phosphates, the released pyrophosphate ion
breaks down into two phosphate ions, they become quantum entangled pair of
qubits. Posner molecule, formed by binding the phosphate pair with extracellular
calcium ions, will inherit the nuclear spin entanglement. When two Posner mole-
cules bind and subsequently melt, they release a shower of intracellular calcium
ions that can further ignite postsynaptic firing [54].
rain Wide Web Collective Excitation of Neurons (World Wide

B
Web Concept)
In all major areas of physics, a collective excitation has gained as much physical
reality as a particle itself. The similarity of world wide web to the network of neu-
rons in the brain represents similarities in regard to information distribution and
transfer.
The brainwide web extends into those neural networks where processed
information is received from the senses, memories, and it unifies those regions via
vast complexity of neuronal interactions with the multiple other regions in the
brain [55].
Good review article is recommended, titled “From quantum chemistry to
quantum biology: a path toward consciousness [56].
The Quantum Vision
Human visual consciousness involves large-scale cortical and subcortical networks

independent of task report and eye movement activity [57].
As we mentioned earlier, conscious vision is the key to unraveling the mysteries
of the human consciousness. It represents the process that the information is being
detected, processed, and interacts with multiple areas of the brain including the
memories to achieve the sense of visual cognition.
After the visual information is detected by retina, as was discussed earlier, the
information will be transferred to the lateral geniculate nucleus via the optic nerve.
Then to the visual cortex in the occipital lobe via optic radiation. The perceptual
information for an object’s shape, color, motion, and meaning is processed at differ-
ent times in different areas of the visual cortex (V1, V2, V3, and so forth). Yet some-
how, the disparate contents are bound together in unified scenes.
Entanglement may quite literally bind and integrate disparate brain contents into
a unified conscious moment. The post-perceptual processing of the neural mecha-
nisms of conscious perception are widely distributed across cortical and subcortical
sites. These rich and complex overlapping systems can provide a satisfactory expla-
nation for consciousness.
The visual perception process to form conscious experience are summarized as
follows [58]:
1. Early signal detection and activation of signal detection centers such as V1 in
visual cortex.
2. Dynamic transient pulse of arousal and attention.
3. Limbic signal amplification.
4. Network switching off of the networks that interfere.
5. Wave of processing to many cortical regions to form consciousness.
Manipulation of visual conscious is an ideal way to study the consciousness.
This has been done by studying the difference between the consciously visible and
consciously invisible perceptions. A human subject is presented with two different
images to each eye at the same time, making one of them the dynamic image domi-
nant and the other completely suppressed. This offers a controllable and reliable
means to manipulate and study the subconscious and conscious perceptions, thus
making it an ideal paradigm for studying consciousness [59].
As we mentioned, EEG has been used to study visual cognition. Many studies
have associated the different EEG waves and their association with visual process-
ing which is shown in the following:
EEG (Electroencephalography):
Noninvasive method of recording the spontaneous electrical activity of the brain by
placing the electrodes along the scalp. The first human EEG was documented by
German psychiatrist Hans Berger in 1924. EEG is a standard diagnosis proce-
dure to confirm epilepsy.
The Role of Symmetry in Biology and Consciousness 155
Description of EEG waves:

Delta waves: Frequency range up to 4 Hz. In adults reflects slow-wave sleep.
Theta waves: Frequency range 4–7 Hz. Drowsiness or arousal and in meditation.
Alpha waves: Frequency range 8–12 Hz. Relaxation or closing the eyes.
Beta waves: Frequency range 13–30 Hz. Motor behavior and active thinking.
Gamma waves: Frequency range 30–100 Hz. During cognitive or motor function.
Mu waves: Frequency 8–13 Hz. Partly overlap other frequencies reflects resting state.
Tuning alpha rhythms to shape conscious visual perception has been studied to
further understanding the relationship between the waves and visual perception.
The alpha wave amplitude and frequency have been linked to sampling sources and
interpretation of sensory events, respectively [60].
Spontaneous alpha oscillations have been associated with various cognitive
functions, including perception. Their phase and amplitude independently predict
cortical excitability and subsequent perceptual performances [61].
Human Perception as a Phenomenon of Quantization
Quantum mechanics has been used successfully in recent years to describe the
human cognition process. The phenomenon of “Categorical perception” has been
proposed to better understand the presence of the quantum structure in human
cognition.
According to this process, the human perception consists of two compartments.
The reconciliation of a bottom-up stimulus and the cognitive expectation with a top-
down pattern. The typical warping of categorical perception is when groups of stim-
uli clump together to form quanta, which move away from each other and lead to
transfer the dynamic information. The individual concepts, which are these quanta,
can be modeled by a quantum prototype theory by Schrödinger’s wave function.
The super position of two such wave functions accounts for the interference pattern
that occurs when these concepts are combined. Using a simple quantum measure-
ment model, the human perception can be quantized [62].
The Role of Symmetry in Biology and Consciousness
We cannot close this chapter without mentioning the role of symmetry and chirality
in biology and consciousness. So, lets breifly review what is symmetry and bio-
molecular chirality and why its relevant to us.
Symmetry: There are many interpretations of this fundamental entity according
to the different fields of science.
• In Physics: It refers to “Invariance” which is lack of change under any kind of

transformation. This concept has become one of the most powerful tools of theo-
retical physics. Apparently, all laws of nature originate in symmetry, on the other
hand, the symmetries of the laws of physics determine the properties of all the
particles found in nature.
• In Mathematics: It occurs not only in geometry but in other branches of
mathematics. In general, every kind of structure in mathematics will have its own
kind of symmetry. For example, calculus, algebra, statistics, also as symmetric
probability distributions.
• In Chemistry: It essentially involves all specific interactions between molecules
in nature. Understanding the symmetry explains fundamental observations in
quantum chemistry, and in the applied areas of spectroscopy and
crystallography.
• In Biology: It is used mostly to describe body shapes. But the notion of symmetry
is also used in physics. A remarkable property of biological evolution is the
changes in symmetry corresponding to the appearance of new parts and dynamics.
Chirality: This is the property of asymmetry and also is important in several
branches of science. An object or system that is distinguishable from its mirror
image, on the other hand it cannot be superimposed. Human hands are perhaps the
most recognized example of chirality. They are non-superimposable mirror images
of each other.
• In Physics: It is found in particle spin, where the handedness of the object
determined by the direction of the particle’s spin.
• In Chemistry: Most often the cause of chirality in molecules is the presence of
an asymmetric carbon atom. It has many applications in organic chemistry and
stereochemistry.
The question of the origin of life may be resolved assuming that non-biological
and biological entities obey nature’s universal laws grounded on space-time sym-
metry. This symmetry governing the behavior of the elementary particles and gal-
axy structures, imposes its fundamental laws on all hierarchical levels of the
biological world. All objects across spatial scales may be classified as chiral or
achiral concerning a specific space-related symmetry transformation [63].
Chirality is the critical structural feature of natural systems, including subatomic
particles and living matter. According to the Standard Model (SM) Theory and
String Theory (StrT), elementary particles associated with the four fundamental
forces of nature determine the existence of micro (atomic) and the macro (galaxies)
scales of nature. The inheritance of molecular symmetry from the symmetry of
elementary particles indicates a bidirectional causal pathway of biochirality. It is
assumed that the laws of the physical world impact the biological matter’s appear-
ance through both extremities and spatial dimensions. The chain of chirality transfer
References 157
links ribosomal protein synthesis, cell morphology, and neural signaling with the
laterality of cognitive functions.
The fundamental significance of biochirality at the molecular and cellular levels
is grounded on the basic principle of spatial organization and function which
includes brain morphology, behavior, cognition, and consciousness. The biochiral-
ity concept is closely associated with all vital events of the organism, including
fertilization, asymmetric cell division, organism development, and aging [64].
The introduction of a new kind of symmetry ushered in a golden era for theoretical
physics. The marriage of this theory with quantum field theory reached the highest
point in the standard model of particle physics. The unification of all three non-
gravitation forces of the universe (strong nuclear force, weak nuclear force, and
electromagnetism) was the momentous milestone in human knowledge. Inspired by
this success, physicists hope for a “theory of everything” uniting the standard model
with general relativity and the theory of gravity [65].
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Addendum
Quantum Biology Awareness Survey
To understand the subjective response of random diverse population responses on

quantum biology in the United States, we prepared a specific questionnaire and used
a commercial survey company to collect the responses.
Material and Methods
We used 10 survey questionnaires that were conducted as three responses to each

question (yes, No, and I don’t know) in October of 2022.
There were 520 responses from 520 participants.
The age of participants was categorized into four groups:
• 18–29 years old
• 60 years old
Gender was categorized into three groups:
• Male
• Female
• Other
US regions used for the study
• New England
• Middle Atlantic
• East North Central
• West North Central
© The Editor(s) (if applicable) and The Author(s), under exclusive license to 161
Springer Nature Switzerland AG 2023
https://doi.org/10.1007/978-3-031-32060-6
162 Addendum
• South Atlantic
• East South Central
• West South Central
• Mountain
• Pacific
Survey device type
• IOS phone/ tablet
• Android phone/ tablet
• Other phone/ table
• Windows desktop/ laptop
• Mac OS desktop/ laptop
O
hsret
Addendum 163
164 Addendum
Addendum 165
166 Addendum
Addendum 167
168 Addendum
Addendum 169
170 Addendum
Index
A Bohr’s model, 23
Absorption, 76 Bond length alteration (BLA), 82
Acetylcholine, 106 Bonding orbitals, 74
Activator protein1, 105 Born, Max, 15
Adenine nucleotide (A), 91 Boson particles, 31
Adenosine, 107
Adenosine diphosphate (ADP), 48
Adenosine monophosphate (AMP), 48 C
Adenosine triphosphate (ATP), 47, 125 Caffeine, 109
Adrenocorticotropic hormone (ACTH), 108 Calcium-cAMP Response Element Binding
Altered states of consciousness (CREB) protein, 113
anesthetic action and quantum Carbon, 78, 79
consciousness, 150 Carbon atom, 33
microtubules and ‘Orch OR, 152 Carbon bonding, 78
three-wave processing, 150 Cellular circadian clock, 103
vibrational effect, 150 Central clock, 102
Amacrine cells, 51, 61 cGMP-gated sodium channels, 49
Amphetamine, 109 Chemical synapse, 122
Antibonding orbitals, 74 Chirality, 156
Aspect, Alain, 16 Chloroplast organelles, 37
Asterisk symbol *, 93 Circadian clock networks, 113–114
Atomic hydrogen, 23 Circadian Locomotor Output Cycles
Atomic orbitals, 29, 72–74 Kaput, 104
Circadian rhythms, 89
brain and, 115
B cellular transcription-translation feedback
Bathorhodopsin, 81 loop (TTFL), 114
Beta-oxidation, 125 circadian clock networks, 113–114
Biochirality, 157 clock genes and signal transduction
Biophotons, 137 proteins, 104
Bipolar cells, 51, 61, 65 light entrainment, 112
BMAL1, 104 molecular effect, 106
Bohr magneton (μB), 31 molecular interplay in, 114, 115
Bohr, Niels, 12, 22, 23 neurotransmitters, in circadian cycles, 106
© The Editor(s) (if applicable) and The Author(s), under exclusive license to 171
Springer Nature Switzerland AG 2023
https://doi.org/10.1007/978-3-031-32060-6
172 Index
Citric acid cycle (Krebs Cycle), 125 Entrainment, 101

Classical mechanics, 2 Enzymes super-fast reactions, 35
Classical physics, 1 European robin cryptochrome 4a
Cocaine, 109 (ErCry4a), 87
Cocaine and Amphetamine-Regulated Everett, Hugh, 16
Transcription genes, 105 Excited radical flavin, 93, 94
Computer modeling, 152 Excited radical tryptophan, 94
Cone cells, 53, 56 Excited state, 76
Conical intersection (CI), 84
Consciousness, 35, 119
Copenhagen interpretation, 8, 10, 11 F
Corticotropin-releasing hormone (CRH), 108 Faster communications, 153
Cortisol, 108 Femto scale, 83
Crick, Francis, 22 Femtosecond laser spectroscopy, 84
Cryptochrome, 88, 89, 95, 96, 102 Femtosecond processing, 32
Cryptochrome genes, 102 Fermions, 27, 31
Cryptochrome molecule, 95, 102 Feynman, Richard, 16
Cryptochrome protein qualifications, 87 Flavin, 90
Crystal vibrations, 77 Flavin adenine dinucleotide (FAD), 90, 91
C-Terminal domain, 94 Flavin C-Terminal, 94
Cyclic adenosine triphosphate (cAMP), 47 Flavin nucleotide, 91
Cyclic guanosine monophosphate (cGMP), 47 Flavin-tryptophan radical pair, 87
Fluorescence, 28, 77
Fluorescence fluctuation spectroscopy, 32
D Fluorescent nanodiamonds (FNDs) containing
de Broglie, Louis, 13 (NV-) centers, 35
Delta bond, 75 Fluorescent proteins, 35
Dexamethasone, 109 Free radicals, 88
Differentiated embryonic chondrocyte, 105 Functional magnetic resonance imaging
Dopamine, 63, 106 (fMRI), 152
Dot structures, 126
Double occupied orbitals, 29
Double slit phenomena, 6 G
GABAergic, 61
Gamma-aminobutyric acid (GABA), 63, 106
E Ganglion cells, 51, 61, 101
Earth’s magnetic field, 88 g-factor, 31
Electrical synapses, 123 Glutamate, 63, 106, 137
Electroencephalography (EEG), 152, 154 Glycolysis, 125
Electromagnetic (EM) radiation, 67 G Proteins-coupled receptors, 47
Electron magnetic moment, 29 Growth hormone releasing hormone
Electron microscopy lasers, 23 (GHRH), 108
Electron paramagnetic resonance (EPR) Guanosine triphosphate (GTP), 47
spectroscopy, 32
Electron spin resonance (ESR), 31
Electron transfer, 89 H
Electron’s angular momentum, 26 Heat Shock Protein 70 (Hsp70), 141
Electrons fill orbitals, 67 Heisenberg matrix mechanics, 3
11-cis retinal, 52 Heisenberg uncertainty principle, 3
11-cis retinol, 52 Heisenberg, Werner, 3, 12
Energy level, 24 Horizontal cells, 51, 61
Energy transfer, 77 Human eye, quantum biology in
Enhancer box (E-box), 101 activation of rods and cones, 53
Entangled spectroscopy, 32 amacrine cells, 61
Entanglement, 154 ganglion cells, 61, 63
Index 173
horizontal cells, 61 M
photoreceptor, rod cells, cone cells, and Magnetic field effect, 35
ganglion cells, 53 Magnetic force microscope, 35
retinal pigment epithelium (RPE), 58 Magnetoencephalography (MEG), 152
visual cycle, 51–58 Magnetoreception, 35, 87, 90, 96, 98
visual transduction, 63 Magnetosensor, 87
Human perception, 155 Melanopsins, 109
Hydrogen, 23, 38 Melatonin, 107
Hydrogen atoms, 23 Memory, 119
Hydrogen peroxide, 126 Metabotropic (ON) bipolar cells, 60
Hyperfine structure, 88 Metarhodopsin I, 81
Hyperpolarization, 63 Metarhodopsin II, 81
Hypocretin, 106 Metformin, 109
Microtubule-associated proteins (MAPs),
136, 144
I Microtubules, 129, 130, 149
Immunohistochemical staining, 89 Microwave, 68
Indole pathway, 144 Mitochondria, 123
Infrared wavelengths, 68 Mitochondrial respiratory chain
Inner plexiform layer and ionotropic (OFF) complexes, 124–125
bipolar cells, 60 Mitogen-activated Protein Kinase, 105
Internal conversion, 28, 77 Molecular orbitals, 74
Intersystem crossing, 29, 77 Molecular oxygen radical, 95
Intracellular thermometry, 35 Müller cells, 51, 139
Intrinsically Photosensitive Retinal Ganglion Multi World Interpretation (MWI), 8, 10
Cells (ipRGCs), 110
Ion channels, 48
Isomerization, 52, 80, 82 N
Net angular momentum, 24
Neuron responses, 35
J Newton, Isaac, 1
Jablonski diagram, 28–32 Nicotinamide phosphorybosyltransferase, 105
Jordan, Pascual, 22 Nitrogen-Vacancy (NV) center, 32, 33
Josephson, Brian David, 16 N-methyl-D-aspartate, 63
Non-bonding orbitals, 74
Non-gates potassium channels, 48
K Nonlinear-type spectroscopy, 32
Knowledge and consciousness, 119 Non-radiative decay, 77, 78
Kynurenine pathway, 144 Norepinephrine, 106, 108
Norepinephrine release, 108
Nuclear magnetic resonance (NMR), 31
L Nuclear response, 78
Lecithin retinol acyltransferase (LRAT), 52
Lewis diagram, 126
Light absorption, in retina, 49 O
Light dependent reactions, 38 Octet rule, 125
Light entrainment, 112 Olfactory sensation, 35
Light harvesting, 37 Opsin molecules, 138
Light independent reactions, 39 Opsins, 47
Lithium, 109 Optically detected magnetic resonance
Löwden, 22 (ODMR), 33
Lumirhodopsin, 81 Optical synapses, 123
LUMO, 93 Oscillation, 101
Lysine, 79, 80 Oscillatory coupling, 102
174 Index
P classical physics vs, 2

Paired electrons, 88 specific behavior of, 3, 4, 7, 8, 10–15
Paoli, Wolfgang, 13 Quantum retina
Pauli exclusion principle, 88 binding orbitals categories, 74
Petrin, 90 carbon, 78, 79
Phi bond, 75 energy level, 75
Phonon, 31 Femto chemistry of rhodopsin, 84
Phosphodiesterase Guanylate cyclase (GC), 47 isomerization, 80, 82
Phosphorescence, 29, 77 lysine, 79, 80
Photoelectric effect, characteristics of, 4 molecular orbitals, 74
Photoelectric phenomenon, 4, 7 non-radiative decay, 77, 78
Photoisomerization, 46 nuclear response, 78
Photomorphogenesis, 90 radiation and human eye, 70
Photon energy, 4 radiative decay, 77
Photoreceptors, 47, 51, 52, 54, 90 rhodopsin, 70, 71
Photorhodpsin, 81 Quantum superposition, 147
Photosensitive ganglion cells, 109 Quantum theories, 39
Photosynthesis, 35, 36, 38 Quantum tunnelling, 11, 147
Phototransduction, 46, 55, 90 Quantum vision, 154
Phototropism, 89 Quantum walk, 40
Pi bond, 75
Pituitary Adenylate Cyclase-Activating
Polypeptide (PACAP), 112 R
Planck, Max, 12 Radiation therapy, 23
Planck’s constant, 12, 14 Radiative decay, 77
Plant harvesting process, 36 Radical oxygen species (ROS), 137
Poincare, Henri, 12 Radical pair, 87, 135
Potential energy surface (PES), 81 Radical-pair-based magnetoreception, 87
Probability theory, 7 Radical pair mechanism (RPM), 87,
Proteasome, 101 102, 127–129
Protein structure and folding, 46 Random world of quantum, 11
Protofilaments, 133 Reactive oxygen species (ROS), 125, 126,
Proton tunneling, 35 136
Protonated Schiff Base (PSB), 80 Redox (reduction-oxidation), 88
Pupillary reflexes, 113 Reflection, 7
Refraction, 7
Relaxation, 76
Q Relaxation pathways, 67
Quantization of energy, 7 Resonant tunneling, 40
Quantum biology, 16, 17, 102 Reticular activating system (RAS), 103
Quantum brain Retinaldehyde, 47
nuclear spin and brain, 153 Retinal ganglion cells, 63, 64
quantum effects, 152, 153 Retinal Müller cells, 140, 141
World Wide Web concept, 153, 154 Retinal pigment epithelium
Quantum coherence, 35, 146 (RPE), 47, 58, 71
Quantum decoherence, 8 Retinals, 71
Quantum diamond microscope (QDM), 35 Retinohypothalamic tract (RHT), 102,
Quantum dipole oscillations, 151 112, 113
Quantum entanglement, 147 Retinoic acid-related orphan receptor
Quantum field alteration, 7 elements, 105
Quantum mechanics, 2, 155 Retinoids, 51
Quantum operators, 15 Rhodopsin, 46, 70, 71
Quantum phenomenon, 67 Ribose, 91
Quantum physics Rod bipolar cells, 60
characteristics of, 3 Rod cells, 49–53
Index 175
S V
Schrödinger, Erwin, 3, 13, 22 Vasoactive intestinal peptide, 105
Schrödinger’s equation, 14, 27, 74 Vibration, 101
Schrödinger’s wave equation, 3 Vibrational Jablonski diagram, 68
Serotonin, 107 Vibrational synapses, 123
Serotonin pathway, 144 Vibration relaxation, 28, 77
Short wavelengths, 68 Vision, 35
Sigma bond, 74 Visual participants, consciousness
“Signal-to-noise” ratio, 61 light energy transfer, in retina, 141
Sildenafil, 109 magnetic field effect and entanglement,
Single occupied orbits, 29 147, 148
Singlet oxygen, 127–128 microtubules, 129, 130
Singlet state, 24 abnormalities in, 136
Slower neuronal transmissions, 153 energy transfer, 133, 134
Small dipole magnet, 96 functional architecture of, 130
Spectroscopy techniques, 68 mitochondria ROS and biophotons
Spin angular momentum, 30 interactions, 134, 135
Spin-dependent reactions, 35 quantum biology of, 132, 133
Spin-orbit interaction, 33 role of Phonon, 135
Spin quantum number, 29 tau protein, 136
Spin vectors, 31 mitochondrion, 123, 125
Standard Jablonski excitation diagram, 68 Müller cell intermediate filaments
Stern-Gerlach experiment, 24 (IFs), 141
Superoxide radicals O2, 102 Müller cells, 139, 140
Super-resolution Fluorescence microscopy, 32 neurons, 120, 121
Suprachiasmatic nucleus (SCN), 102, 113 oxygen and reactive oxygen species
Symmetry, 155 (ROS), 125, 126
quantum coherence, 146
quantum entanglement, 147
T quantum superposition, 147
Three-wave processing, 150 quantum tunnelling, 147
Thylakoids, 37 radical pair mechanism (RPM),
Transcription, 101 127–129
Transcriptional-Translational Feedback Loops retinal Müller cells, 140, 141
(TTFLs), 110–112 synaptic connections, 121, 123
Transducin, 48 tryptophan, 142, 144
Transitional rule, 24 Voltage-gated channels, 49
Translation, 101
Triplet oxygen, 128–129
Triplet State, 25 W
Tryptophan (TRP), 92, 93, 142 Wave particle duality, 3
Turin, Luca, 22 Wiltschko, 22
Tyrosine (Tyr), 92
X
U Xenon, 150
Ubiquitination, 101
Ultrafast spectroscopy, 32
Ultraweak photon emission (UPE), 136 Z
Unfolded polypeptide, 46 Zebrafish reprogram, 140
Unpaired electrons, 32, 88 Zeeman effect, 31
UV wavelengths, 68 Zeitgeber, 103

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New York, NY, USA Kambiz Thomas Moazed

• There were no financial assistance or compensation received from any organiza-

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© The Author(s), under exclusive license to Springer Nature 1

What Is Quantum Physics?

Classical Physics Versus Quantum Physics

Characteristics of Quantum Physics

Multiple interpretations: There are many interpretations on quantum phenomena

Specific Behavior of Quantum Physics

• Heisenberg uncertainty principle: This formula is the foundation of quantum

E (photon energy) (J)

eV (electron volt): is a common unit of energy and is the amount of kinetic

1 eV  1.6  1019 Joules

“National Institute of Standards and Technology” [4] (Fig. 1.4)

Fig. 1.4 Work function of sample metals in electronvolt

2. Wave behavior of light (Double slit phenomena):

–– Both wave and particle function: Reflection and refraction.

• Observer Problem (Schrödinger’s cat on the box) [6].

Fig. 1.8 The Higgs has

When Did It Start?

• Neils Bohr (October 7, 1885–November 18, 1962) [15]: (Electron orbits).

λ (Wavelength) = h (Planck constant)/ P (Particle momentum).

Quantum operators by manipulating and affecting the system make it possible to

• Function of x or potential operator: F(x), f(V).

What is Quantum Biology? [27]

What Are Its Applications?

We discuss this in detail in the second part of this chapter.

1. Strumia A. A “Potency-Act” interpretation of quantum physics. J Modern Phys. 2021;12(7)

© The Author(s), under exclusive license to Springer Nature 21

Quantum biology is the study of complex and dynamic biological processes to

When Did It Start?

Basic Information for Better Orientation

Electrons play an essential role in chemistry, magnetism, electricity, and thermal

Fig. 2.5 Schematic

• It has a mass of 9.901 × 10−31 kg.

Is a schematic arranged electron energy diagram on a vertical axis. Horizontal lines

Fig. 2.9 Chart of spin

Spin angular momentum (S) or simply called “Spin” is an intrinsic property of

• Bohr magneton (μB): Is a constant expressing the magnetic moment of an elec-

Quantum Biology Tools

• Entangled Spectroscopy [15].

Nitrogen Vacancy (NV) Centers in Diamond

Fig. 2.10 Schematic presentation of nitrogen vacancy center in a diamond crystal

NV centers have a magnetically, electrically, and thermally sensitive electronic

The Most Studied Fields of Quantum Biology

• Fluorescent proteins as a model [34].

Fig. 2.11 Schematic presentation of the entire anatomic process of photosynthesis

6CO 2 + 12H 2 O + Photons ® C6 H12 O6 + 6O 2 + 6H 2 O

© The Author(s), under exclusive license to Springer Nature 43

• Vitreous–retina boundary (Fig. 3.1).

The Anatomy Highlights of the Eye

Fig. 3.4 Illustration of secondary structure of proteins

Rhodopsin is a G-protein-coupled receptor that is sensitive to light. It is com-

Fig. 3.5 Schematic

ATP is composed of a sugar molecule ribose and attached phosphate structure. It

cGMP-gated sodium channels: These channels depolarize photoreceptors to

The Physiology of the Light Absorption in the Retina

The Visual Cycle

 he Photoreceptors, the Rod Cells, the Cone Cells,

New York, NY, USA Kambiz Thomas Moazed

Activation of Bipolar Cells�� 60

Cellular Transcription-Translation Feedback Loop (TTFL)�� 114

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The Anatomy Highlights of the Eye

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