>> 
I'd like to introduce Stuart Hameroff from
the University of Arizona. He is going to
talk about Clarifying the Tubulin bit/qubit,
and then five minutes on Defending the Penrose-Hameroff
Orch OR model.
>> HAMEROFF: Thank you very much. Thank you
all for being here. Thank you Hartmut and
Google for hosting us and you all for coming.
The title of talk is Clarifying the Tubulin
bit/qubit, Defending the Penrose-Hameroff
Orch OR model of quantum computation in microtubules.
Jack--Travis Craddock and Jack Tuszynski are
my co-authors, and Jack is here. Penrose-Hameroff
Orch OR orchestrated objective reduction is
a theory of consciousness, based on quantum
micro--quantum computations in microtubules.
OR is Penrose's mechanism for self-collapse
of the wave function, Orch is orchestration
which is my biological contribution, how this
could happen, and both be isolated and interact
with the environment. But I'm not going to
talk about that specifically. First, I'm going
to give you a little bit of an overview about
microtubules. We've heard quite a bit about
some of the technical aspects, but I want
to kind of backup and give you the big picture
a little bit. Consider a single cell paramecium
which can swim around, avoid obstacles, avoid
predators, find food, learn; if you suck it
into a capillary tube, it escapes. If you
do it again, it escapes more quickly. It can
find a mate and it can have sex. This is actually
a picture of two paramecium having sex. It's
probably the only X-rated picture we'll see
today. And it doesn't have any synapses. It
doesn't have any nervous system per se. How
does it do it? It uses structures called microtubules.
And I often kid my AI friends; they should
be worry about simulating a paramecium before
worrying about a brain. So microtubules seem
to be the nervous system of the cell. And
here's a beautiful immunofluorescence micrograph
of a double-nucleated cell. The yellow is
the microtubules. The red is the actin. And
the microtubules form the kind of cytoskeletal
architecture and bone-like support, but we
also think they're the cells onboard the computer.
In cell division, microtubules are in the
red, the blue--the chromosomes are in the
blue, and the yellow are centrioles which
anchor the mitotic spindles and microtubules
and organize mitosis. And if this goes wrong,
you can get cancer because you get an abnormal
genotype. And the mechanism of this is still
poorly understood. The centrioles are made
up of nine triplets of microtubules so each
of these would be a microtubule or part of
a microtubule and you get nine of these in
forms of mega cylinder. And this is the same
structure also found in cilia, the appendages
that come out at the end of the paramecium.
And we also have them in our body and they're
found in the retina of the eye and they're
found all over the place. And in cell division,
centrioles have two of these barrels in this
odd, perpendicular arrangement. They each
replicate and separate and the mitotic spindles
anchored to them and pull apart the chromosomes.
It's interesting there are also optical--optically-sensitive--Albrecht-Buehler,
who was mentioned earlier, showing that these
centrioles detect photons and orient the cell
in a particular direction towards the light.
And it's interesting that their shape and
their geometry, their dimensions are--could
accommodate photons and they could be some
kind of quantum optical devices or at least
optical resonators of some sort. I just want
to mention that. I'm not going to talk about
it per se. So inside neurons, microtubules
and dendrites are found in this interrupted
type of network, intercorrected--interconnected
by microtubule-associated proteins. So they
form a sort of network and we think a computational
network inside cells, inside neurons of a
neural network. It's kind of a fractal subdimension
inside neurons. Now if you're microtubules
go bad, you get Alzheimer's Disease. There's
actually two lesions in Alzheimer's; amyloid
plaques, which get--for some reason get most
of the money in research. But the real damage
is done by neurofibrillary tangles inside
the neurons which are due to tau proteins
which normally--here, it says stabilize microtubules
but they do other things as well. When they
get all screwed up, the microtubule disintegrates,
that the tau gets hyperphosphorylated and
the microtubule disintegrates literally. You
get the kind of crinkly neuron and you lose
cognitive memory and eventually consciousness.
So Alzheimer's is a disease of microtubules.
Here's a close-up of a disintegrating microtubule.
Now, the tau protein which is thought previously
just kind of hold the microtubule together,
turns out that it does something more. It
acts as a kind of a traffic signal for motor
proteins which transports synaptic materials.
So if a synapse downstream in a dendrite,
say, needs a particular enzyme or precursor
or receptor, it's often synthesized more proximately
and transported by these motor proteins which
carried along as cargo, and they often have
to jump tracks and switch microtubules in
the branching dendrite. And it's been a mystery
how they seem to know where to go. It turns
out that the tau, at specific locations on
the microtubule are kind of traffic signals
and tell particular proteins, like this guy
right here, where to jump off. And so their
placement is critical. Now how do they know
where to--where to be? Is there something--are
they that smart or is there some kind of encoding
in the microtubule itself? So I'm going to
briefly talk about--a little about memory,
some recent evidence about memory that Travis
Craddock, Jack Tuszynski and I have done.
In long-term potentiation, calcium comes in
through the cell and activates CaMKII, calcium/calmodulin
kinase II, which then rapidly--in learning,
rapidly distributes throughout dendrites and
actually throughout many parts of the neuron
or group of neurons quite rapidly and they're
associated with microtubules. And somehow--and
they phosphorylate something in the cell which
stores memory. Now, synapses are created with
memory, but synapse--the proteins of synapses
are very transient. It last hours to days,
but memories can last a lifetime. So the question
is where memories may be stored. And the CaMKII
is a very interesting molecule. It's snowflake-shaped
holoenzyme which when activated and phosphorylated
by calcium coming in, transforms into this
sort of insect-like nano-poodle, we like to
call it, with six legs extending up and six
legs extending down, each of which can phosphorylate
a substrate. So the question is what's the
target for phosphorylation which memory can
be stored? Well being microtubule fanatics,
we thought it might--has something to do with
microtubules. And so here's a microtubule
with two different scales; a microtubule then
a close-up of the tubulin subunit showing
the phosphorylation sites on tubulin with
the C-terminal tails and--so the question
is, how did the CaMKII relate to this microtubule?
And it turns out it matches perfectly. Here's
the CaMKII here with the top set of legs taken
off and overlying the A lattice and B lattice.
And [INDISTINCT] talked about the different
lattices. You can see here that they matched
up perfectly. So each of these legs can either
phosphorylate a substrate or not, therefore,
it conveys a bit of information. And six bits
on a--an ordered array of bits is a bite.
So basically, the idea is that each of these
is--can convey a bite of information onto
the--onto the tubulin lattice. And sure enough
with a little flexibility in these extenders,
the nano-poodle can deposit information on
the microtubule and perhaps move--march along
it by hydrophobic interactions and can convey
synaptic information to the microtubule and,
here, mechanisms at the level of individual
amino acids where the phosphorylation can
occur either through the C-terminal tails
or by a different mechanism. So basically,
we show the possibility for memory storage
in microtubules via calcium-induced phosphorylation
of CaMKII which then deposits the information
for long-term--longer term storage on microtubules.
And depending on a couple of factors; A lattice
versus B lattice, and whether alpha and beta
can be--can be phosphorylated, the number
of bits per bite for CaMKII, in this case,
it's two to the sixth or 64. In this case,
it's about 429. In this case, it's 5,281 just
from one CaMKII. So the amount of information
capacity in the--in the--conveyed through
synaptic interactions, CaMKII on microtubules,
is enormous. And the number of--the amount
of information--storage capacity in a microtubule
even in one neuron is enormous. So that suggest
that microtubules are good information processors
and many of us have thought of this for a
very long time. And on the left, you see a
picture of a microtubule with its sub-unit
proteins tubulin which can switch between
two states and possibly also superposition
on both states, the quantum bit or qubit.
I got interested in microtubules in 1972 when
I was in medical school and worked for about
20 years on the idea that they process information
strictly classically and developed the molecular
[INDISTINCT] models with a number of physicists,
I meet Jack along the way, Steen Rasmussen
of Los Alamos and others, modeling them as
sort of the game of life. This cellular automata
shown here are based on dipolar interactions
between the tubulin and show that, with some
basic assumption using Frohlich oscillations
as a clocking mechanism that microtubules
could process information in principle, based
on a few assumptions, were very efficient
computational devices for both storage and
processing of information. In here, it just
shows a sequence. Initially, we thought the
clocking sequence was Frohlich gigahertz,
but the recent information we're perfectly
happy with eight megahertz clocking that Jirí
Pokorny has discovered and [INDISTINCT] been
talking about. So each of these steps could
be--could be occurring at eight megahertz
and by a--sort of a cellular or molecular
automata type of mechanism, but so far this
is strictly classical. Now in the late '80s,
somebody said to me, "Okay, let's say you're
right, how would that explain consciousness?"
And I had to admit that they were right. I
didn't really know. Fortunately, I read Roger
Penrose's book, 'The Emperor's New Mind',
where he had a mechanism for consciousness
based on quantum computation, but he didn't
have a good qubit in the brain. So I suggested
microtubules were his quantum computers and
tubulin with the quantum bits and he agreed.
He liked the geometry of the microtubules
and we developed the model in the--in the
early mid '90s and it was almost immediately
attacked by a number of people for various
reasons. It--it's threatening to many people
for different reasons. So the basic idea is
that in a microtubule, each tubulin can be
a quant--can be a qubit so it can be in two
states in the superposition of both states.
And consciousness occurs because there's a
superposition that reaches threshold for the
Penrose objective reduction and consciousness
occurs here, involving you know, hundreds
of billions of these. So I'm not going to
really talk about consciousness per se, but
just about fundamentals of how individual
tubulins can switch. And we also suggested
that quantum states can tunnel between neurons
through gap junctions which, it turns out
the gap junctions mediate gamma synchrony
which is a neuronal correlate of consciousness.
So we were attacked, as I said, almost immediately
and--by philosophers, and physicists and so
forth. Nothing too serious. And then in 2000,
Tegmark--Max Tegmark came--tried to prove
the obvious. The brain is too warm and wet
for delicate quantum effects and had this
equation for the decoherence time and published
it in Phys Rev E. And then a year later, Jack,
and Scott Hagan and I published--used his
own decoherence formula, corrected for some
of his errors in terms of how he characterized
our model. In other words--for one example,
he had superposition of a soliton separated
from itself by 24 nanometers where our superposition
separation was the fermi length, the diameter
of an atomic nucleus. So that alone--where
as--so he calculated decoherence time of 10
to minus 13 seconds, that alone saved us seven
orders of magnitude. A couple of other corrections
we got down into reasonable for the Orch OR
model of hundreds of milliseconds. Again,
this is all theory, but we use his--it countered
his theory and more recent findings of quantum
coherence in Biology is supporting this at
least in a general way. Okay. So more recently,
a group of Australian biophysicist, physicists,
chemists, actually a very impressive group
if you look at their credentials, published
a series, at least two so far or maybe more,
attacking us. And in two papers, one in Phys
Rev E and the other one in PNAS; pretty good
journals. And the first one, the one I'll
address first, McKemmish et al. The title
was "Penrose-Hameroff orchestrated objective-reduction
proposal for human consciousness is not biologically
feasible." Well, that's pretty harsh. And
they also said in the abstract that not only
is it--is it not feasible, it couldn't be
fixed by any conceivable modification. So
I don't know if they're psychic or just, you
know, dancing on our grave or what. The other
paper, which actually came first, "Weak, strong,
and coherent regimes of Frohlich condensation
and their applications to terahertz medicine
and quantum consciousness," challenges also
on the basis of the Frohlich condensation
that Jirí Pokorny was talking about. So,
objection number one--I'm going to take the
McKemmish et al paper first. They start up
by saying--which is true--the Orch OR asserts
that tubulin states are regulated by London
force dipoles, the van der Waals-London force
dipoles, in hydrophobic pockets within each
tubulin. So I want to take a minute and explain
about hydrophobic pockets. Luke was talking
about non-polar regions in the GABA receptor,
and Elizabeth was talking about London forces
or van der Waals forces. So when a protein
folds, here's a simple protein. And the non-polar
groups like [INDISTINCT] escaping water coalesce
and they don't have to be all these aromatic
groups. It can be any non-polar group forming
a hydrophobic pocket shielded from water.
So when you--when they say the brain is too
warm, wet, and noisy, it's not really wet
in the hydrophobic pockets because water is
excluded. So, hydrophobic pockets are water
excluding regions inside proteins consisting
of non-polar--of groupa such as aromatic amino
acids, phenylalanine, and tryptophan and so
forth. And if you--if you think about this
non-polar solubility region, it's a very small
portion of the body. Actually, this--you can
think of this triangle as a body ground up
and then distributed in terms of solubility
spaces, different solubility spaces, and you
can see where different solvents will dissolve.
And as an anesthesiologist, I can tell you
that anesthetics binds in this little region
here, aromatics, right down here; very non-polar.
So this is where consciousness is, okay? You
can--the rest of it doesn't really matter
in terms of consciousness. Well, supportive
of course. But this small region of this diagram
is a non-polar region where anesthetics act
and where consciousness resides, but I'm not
going to talk about consciousness. So--well,
I guess I did. Okay, so getting back to the
McKemmish et al attack. They said we assert,
which we do, that tubulin states regulated
by London force dipoles in hydrophobic pockets
within each tubulin. And then attempting to
invalidate our research, and they said that
the electron cloud of a single benzene it
is--suggesting it to be analogous to, and
indicative of, hydrophobic pockets, cannot
be a switch because it's completely delocalized.
So there's two basic--two ways to look at
a benzene which is basically a phenyl ring
on a phenylalanine, Valence theory that there's
a resonance between two different states for
the--where the double bonds flip back and
forth between two possible locations or you
can just say it's completely delocalized in
molecular orbital theory. They said, "Well,
benzene is, in molecular orbital theory, there's
no switching because it's completely delocalized
therefore the hydrophobic pockets can't be
switches." Well, we agreed that a single benzene
could not be a switch because it takes two
to tango. And in our case we--London forces,
if you have two benzenes together they're
going induce induced dipoles. These are inducible--induce
induced dipoles. So, two clouds come together.
The electrons in one repel the electrons in
the other and then they oscillate back and
forth. So these are the double bonds flipping
back and forth and this is kind of a new schematic
for it. And if you have four, maybe it will
look something like this. And Hartmut borrowed
this for the--for the logo, for this workshop,
but put the Google colors in which I'm quite
proud of actually. So this is what van der
Waals-London forces are. This is shown for
a neon atom, but it works for any neutral--electrically
neutral non-polar, two electrically neutral
non-polar groups where the blue dots are the
electrons and the electrons in one repel the
electrons in the other and this draws in together
the van der Waals-London attractive force.
So they get closer. They actually repel a
100 times stronger. So this very weak but
important force mediates, for example, how
anesthesia works to erase consciousness in
that little piece of the phase diagram. A
hundred--over 100 years ago, Meyer and Overton
showed that the potency of any anesthetic
gas correlates with its van der Waals--well
later, it was appreciated, it was van der
Waals-London force binding in a non-polar
medium akin to olive oil over wide ranges
of molecular structure and concentration.
So getting back to the tubulin bits. So our--one
of our early models show the tubulin switching
between two states due to a hydrophobic pocket
where there's two aromatic rings, where we
only show a piece of each with the electrons
kind of flipping back and forth. And here's
kind of a more recent model and here's the
more current model. But maybe McKemmish et
al didn't realize we were talking about two
different rings because they said we only
had one phenyl or benzene ring in there. Actually,
there's many phenyl and indole rings in a
tubulin. This is some recent work from Travis
Craddock mapping the phenyl--phenylalanine
with the aromatic rings, and indole rings,
and many of these are within three ångström
of each other or less than four ångström,
3.7 is where the van der Waals--van der Waals
forces balance out. So many of these are close
enough to form coalescences of these aromatic
groups to get hydrophobic pockets with a lot
of electron resonance and mobility--electron
mobility which Luke was talking about. And
with a little imagination, you can actually
see pathways for topological qubits that [INDISTINCT]
was talking about. We'll get to that later.
And these aromatic groups can have a particular
orientations for their London forces. And
I think maybe Jack is going to talk about
this so I'm going to skip over it for now.
So conclusion to objection number one; McKemmish
et al missed the boat entirely. The hydrophobic
pockets include minimally two non-polar groups
which utilize van der Waals London forces.
It takes two or more to tango. So they said
while one benzene ring wouldn't do the trick
for you, we agree completely. That's--we never
said that, we're talking about at least two
and actually coalescences of multiple non-polar
group of electron resonance capabilities.
Okay, another aspect of the decoherence as
well into this--we've heard about quantum
coherence in photosynthesis and some in microtubules.
A paper--in 2003 by Ouyang and Awschalom connected
quantum dots by benzene rings, okay? So these
are single benzene rings, but they're just
looking at quantum spin transfer and they
found a very efficient quantum spin transfer
connecting the quantum dots through these
fennel rings basically, benzene rings, the
same--exact same rings found inside the tubulin
and other proteins. And as far as temperature,
they're starting at absolute zero, when they
got to about minus 70, there was a huge jump
up in efficiency which persisted out to bring
temperature by connecting it through this
fennel or benzene ring. This is quantum spin
transfer, not exactly the same as we're talking
about. But it shows that a quantum effect
can be enhanced by temperature and that this
fennel or benzene ring can be utilized in
this way. The same sort of structure--and
I think Hartmut and Luke alluded to this,
are found in psychoactive drugs including
powerful psychedelics, in fact any psycho-active
drug including chocolate. LSD, DMT all have
these non-polar indole-like rings here. And
in the 1970s, we're shown that the--looking
at a series of psychoactive--psychedelic drugs
actually, hallucinogenic drugs, that their
potency was related to their ability to donate
electron resonance energy from the drug to
the receptor. So the potency of the psychedelic
is related to its ability to donate electron
resonance energy, quantum electron energy
to the receptor, to the system and that seems
to push the person into an altered state.
Okay, so that was the first--the first objection.
The second objection was this. It concern
GTP hydrolysis and tubulin switching. McKemmish
et al say, "Experimentally, the only identified
aspect of the conformation of the tubulin
heterodimer inside a microtubule depends on
whether GTP or GDP is bound to the beta subunit
and is the only process to be ascribed to
the conformational change depicted in the
Orch OR proposal." Well, Jirí talked about
how the Frohlich condensation, the Frohlich
vibrations are fueled or pumped in a cell
by being near mitochondria taking advantage
of mitochondrial energy, but not GTP or ATP
directly. Just being in the field is enough
to drive the coherence. Now, the other point
is this conformational change. And it's true
that in our--in our cartoons, and these are
cartoons admittedly, that there's a significant
conformational change. The tubulin is switching
states by, you know, at least 10% of its volume.
Now, we did that to indicate a change of state,
but actually in reflection, we don't really
need a conformational change to register information.
It can be strictly a dipole state. And although
we showed these cartoons as having conformational
switching, we never really utilized the conformational
change in our model except that for the quantum
state, the superposition separation is of
the diameter of a carbon nucleus, the fermi
length, 10 to the minus 8 centimeters is very,
very small. So that gives you the superposition
separation which gets in the quantum gravity
stuff. But as far as changing the state for
a computer, we don't need a conformational
state. We're perfectly happy with an electronic
state that can be read out by its neighbor.
That's all we need. Now, the GTP business
is also a mistake on their part because when
GTP hydrolyzes on the--from a GTP to GDP,
it does cause a conformational change so that
could be how they got that idea. It releases
the phosphate bond, but it's irreversible.
Once this happen, the microtubule starts to
depolymerize. It may depolymerize at one end
and then repolymerize in the other which gives
rise to treadmilling or may fall apart at
both ends which gives catastrophe or dynamic
instability which is why they rapidly shrink
and grow, shrink and grow. But we point--we
looked primarily for Orch OR in dendrites,
in dendritic microtubules where the microtubules
are capped and don't undergo GTP hydrolysis,
don't undergo treadmilling nor depolymerization-polymerization
cycles. They're quite stable which is why
they would be good for storing information
in dendrites. So they're wrong on this point
also. So the conformational switching greater
than one fermi length, the diameter of one
carbon nucleus, is not required. Electron
dipole state switching is sufficient. So this
is kind of a new model of--for the tubulin
bit or qubit oscillating at eight megahertz
as Jirí was talking about and [INDISTINCT],
between two states. You'll notice there's
no conformational change here. If you didn't
see the electron or couldn't measure the dipoles,
it would look exactly the same just like if
you looked at a computer motherboard, you
might not be able to see all the information
going around because you can't see the electrons.
But we actually have--now have multiple hydrophobic
pockets each consists--each containing a number
of non-polar groups and aromatic rings and
this is perfectly fine for Orch OR. The only
conformational state change we need is down
at the level of--for the qubit function, is
down at the level of the atomic nuclei. So
objection two; conformational switching is
not required, dipole state switching sufficient,
Orch OR applies to dendritic microtubules
which are capped to prevent GTP hydrolysis,
treadmilling and dynamic instability. Orch
OR does not require GTP hydrolysis so they're
wrong on that point also. Now, I want to talk
a little bit about topological qubits. [INDISTINCT]
gave some very elegant results and I'm not
sure my understanding is up to, you know,
from the quantum computing point of view.
So I'll just tell you my interpretation of
topological qubits which may not match--which
may not be right or match what he said. But
historically, how this got started for microtubules
was that Roger Penrose invited me and Jack
Tuszynski to the 1998 meeting at the Royal
Society in London of quantum information to
talk about microtubules. And actually, Jack
was the--was the skeptic and I was the proponent
and since he's kind of come over our side,
thank you. But afterwards, there was a--John
Preskill gave a talk on topological quantum
error correction and topological qubits and
relating to [INDISTINCT] idea and so forth.
And as I understand, that the idea is that
if you have some kind of lattice and the information
can flow through one pathway or another pathway
then the pathway itself can be the bit. So
in the case of microtubules, they have this
Fibonacci geometry, so you can follow this
pathway, or you can follow this pathway, or
this pathway or this pathway, or a number
of other pathways. And if each tubulin was
a bit--if each one of these guys was a superposition
and represented a quantum bit or qubit then
it would be susceptible to decoherence. Each
one--decoherence of any one subunit would
mess up the whole quantum computation. However,
if you make the pathway, the bit or the qubit,
then if one of these guys gets knocked out
or whacked, it's going to get pulled back
in by its neighbors and so it becomes resistant
to decoherence. That's the whole point about
topological qubits and also topological quantum
error correction which is a very similar idea.
And these spiral pathways follow the Fibonacci
geometry; 3, 5, 8, 13, 21 and this was one
of the things that got Roger very interested
in microtubules because he is a geometer at
heart and that's one of the things that captivated
him. And [INDISTINCT] is now shown something
like this, in microtubules, that it actually
occur. So it's also--it might be something
like the Aharonov-Bohm effect where you have
the opposite pathways or alternative pathways,
each of which can be a bit or a qubit. And
if you look at the multiple hydro--non-polar
hydrophobic pockets and line them up, with
a little imagination, you could see how their--states
of each one of them could influence conductivity
of ballistic conductance or quantum coherence
moving through the lattice around--along particular
helical pathways in the microtubule. Okay,
objection number three. This was from the
earlier paper from the same group, same author
group, Reimers et al, about three types of
Frohlich condensation: weak, strong, and coherent.
And Jirí talked about this a little bit.
Based on--and they based their conclusion
on a simulation of a linear chain of tubulins
to represent three dimensional microtubules.
They concluded that only weak Frohlich condensation
at eight megahertz, and they cited Pokorny--so
they essentially validated Jirí's work. And
since they were so negative and skeptic about
everything else, I think it was kind of remarkable
that they--that they, you know, they agreed
to that and they liked it. But they said it
was only weak Frohlich condensation and that
Orch OR requires strong or coherent condensations.
For example, Bose Eins--something like Bose
Einstein condensation. Well, it seems to me
that we don't want Bose Einstein condensation
because in that case all of the--all of the
subunits would be in the exact same state
and you couldn't really do any computing that
way. You need--you need the--you need some--the
possibility for each of the subunits to be
in a different possible state. And so we think
that weak is perfectly fine for us. Orch OR
does not require strong or coherent Bose Einstein
condensate, requiring only synchrony and entanglement.
So we just wanted the Frohlich condensation,
Frohlich excitations to synchronize the operations
like in a cellular automata. In a cellular
automata, you need--you need a clocking frequency.
And a weak condensation is fine as long as
you can have entanglement to mediate the quantum
computation. And also in 1992, Alexei Samsonovich,
Alwyn Scott, who's a Mathematical Physicist,
and myself published--actually Alexei did
this as his thesis--simulated a microtubule
with Frohlich resonance. Now, what Reimers
et al did was they simulated a linear chain
and somehow from a linear chain decided that
you can't have--you can't have significant
Frohlich effects in a three-dimensional microtubule.
Maybe doing a three-dimension was too difficult
for them. But what Alexei did was he took
a two-dimensional sheet of tubulin and wrapped--treated
as a torus, made boundary conditions so that
this would match up with this, and this would
match up with this, so you get a torus. I
was able to run these simulations and he--and
he found maxima and minima for Frohlich resonance
energy at these--at these spots here, the
black ones, which matched experimentally observed
attachment patterns for microtubule-associated
proteins. So, microtubule-associated proteins
bind the microtubules at specific tubulin
locations and their location--locations then
determine the function of the microtubules
in terms of the architecture and regulating
the synapses and doing what microtubules need
to do. So this is a way of representing and
processing information. So in 1992, Alexei
had shown this and they unaware of this paper
which I think refutes their contention also.
It was much more elegant than what they did,
looking at a single tubulin chain. So this
is now what we're thinking that a tubulin
qubit might look like oscillating at 8 megahertz,
as Jirí said or maybe it was [INDISTINCT],
that Frohlich originally said gigahertz, but
microtubules are big so it makes sense to
me perfectly in some sense that they're slower
and 8 megahertz is fine and the number of
operations per second has reduced, but that's
fine. We got plenty of that to play with.
So--but the 8 megahertz is interesting for
another reason. So I'm going to digress a
minute. And here's [INDISTINCT] picture which
I like very much. And so the 8 megahertz would
be--and another megahertz would be in the--in
the microtubule wall itself; not in the water,
not in the C-terminal, but the microtubule
itself and, interestingly, that's in the--that's
in the RF for electromagnetic, but it's also
in the ultrasound if you took--look--just
think of mechanical vibration, mechanical
oscillations. And recently there's been a
movement looking at--effects on the brain
on cognition and consciousness of transcranial
therapies, transcranial magnetic stimulation
for depression, for all kinds of things, transcranial
electrical stimulation to enhance memory,
and transcranial ultrasound using vibrational
energy into the head through the skull showing
effects in the brain. Now this was shown--behavioral
effects was shown, but nobody was sure whether
the--whether it was actually getting into
the brain and having none thermal effects.
And this guy William J. Tyler at ASU, Arizona
State University, did a very good study with
rats or mice, I guess, where they put electrodes
in the mice, let them recover, they're walking
around, they can record from the electrodes.
They then did transcranial ultrasound. And
in addition to behavioral effects saw interesting
electrophysiological effects so proving that
the ultrasound is having physiological effects
in the brain. And they've got a grant from
the government for some kind of mind control
in--I'm not sure what they're trying to do
actually, but it's--I think they have good
intentions. But in their--I hope. And also
they've spun off a company. And if you look
at their prospectus, they're promising beneficial
effects of transcranial ultrasound on about
any psychiatric diagnosis you can think of,
including from depression to memory problems
to what have you. So anyway, we at the University
of Arizona, including my colleague Chris Duffield
who's here, have started our own studies.
So I'm an Anesthesiologist, we skipped the
rat business and we're going right to humans.
And we've tried it on ourselves actually.
It's a very interesting effect on your consciousness.
Let's just put it that way. And so we think--we
think people will like it. And we've got a
proposal in for--we've got a proposal in for
effects on chronic pain. And after that, we're
going to put it--that's almost through, it
looks pretty good for chronic pain patients.
And after that we're going to try memory,
effects on memory because as [INDISTINCT]
showed, stimulating at 8 megahertz causes
microtubules to polymerize and grow so you
could enhance synaptic plasticity, you could
enhance turn over, and enhance learning, and
it could be a treatment for Alzheimer's disease.
So I think this is a very, very promising
new technology. And we're going to have a
session on this as Hartmut mentioned, I co-organize
a conference every year--every other year,
it's in Tucson, and in the odd number years
it's elsewhere in the world. So next May it'll
be in Stockholm, Sweden, "Toward a Science
of Consciousness: Brain, Mind, and Reality."
And one of the sessions will be on transcranial
therapies. We have Allan Snyder talking about--well,
he's done a lot of transcranial magnetic,
but he's going to talk about transcranial
electrical. Tyler's going to talk about transcranial
ultrasound and Wasserman from NIH will talk
about transcranial magnetic stimulation. We're
also going to have a session on Quantum Biology
and several other interesting sessions. And
I've left some flyers over there for you to
take if you're interested. So conclusions;
the objections to Orch OR by McKemmish et
al and Reimers et al are invalid as far as
I can tell. They didn't lay a glove on us
as far as I can tell. Maybe I missed something,
but they whiffed. There's nothing in there
that's threatening in any way. Of course I'm
biased, but you know. So Orch OR remains viable
and finally it is far better to be criticized
than ignored. Thank you very much.
>> Okay, we have time for some questions.
Could you use the microphone, please?
>> Only a comment. Only a comment. The mistake
of Dr. Reimers and Dr. McKemmish was the following
two mistakes: First was, that they neglected
to [INDISTINCT] linearity. And if you neglect
[INDISTINCT] linearity, you must strongly
[INDISTINCT] linearity. System can only be
described linearly. You must have no mistake.
And the second mistake, they neglected the
fact that oscillators maybe normal, this--than
[INDISTINCT] more than [INDISTINCT]. Oscillators
critically damped, and oscillators over damped
and then if you have over damped oscillators
then the coherent time of which I spoke here
about one microsecond, decreases to ten times
[INDISTINCT] for instance or something like
this. This is two mistakes in their work.
The second point, I would like to say something
that--concerning schizophrenia which is somehow
is connected to this--to this--your work.
A physician in our country measured immunoreactions
by some special antigen and found that in
illnesses that have disturbed, somehow, mitochondria
function, there is a special reaction. And
the reaction is the same in cancer for instance,
in heart failures, in schizophrenia, and in
predetermined [INDISTINCT] on the--very, very
and so on predetermined. And in all these
cases very likely, also in schizophrenia,
is disturbed function of mitochondria therefore
somehow that system that supply energy to
oscillating system in the--in the cells which
belong to biological activity. Thank you.
>> Okay, thank you. Any more questions?
>> HAMEROFF: Let me just say that Jirí's
work is a huge help to us, number one, showing
the eight megahertz coherence and also showing
where the energy comes for the--for the excitations
from the mitochondria without requiring GTP
because that's--that was a critical issue
as what's--I mean, Frohlich's [INDISTINCT]
the heat bath, but that's a little bit vague.
But showing that it's coming from mitochondria
is very, very helpful and I think a great
discovery.
>> Thanks. It's always nice to hear it tour
de force and that was really well done. And
I had a question. If you think--I like to
think of a cell as a four bit microprocessor
or eight bit because it's hard to do much
more unless you quantum it. And if you're
a cell and somehow something signals you that
you have to now be differentiated to a certain
task, there's a complex set of subroutines.
You have to know somehow how to extract if
you're going to deliver work for example.
So for a long time, I wondered, well if I'm
going to discover, I have to do a subroutine,
I need a bit to store to know that I'm now--I
need something that works with the rest of
the complex informatics which what you've
shown with the CaMKII sounds like the perfect
kind of a cellular memory.
>> HAMEROFF: Yeah.
>> I remember in 1999, you and Jack and Porter
published a paper that also suggested, with
some fascinating diagrams, that the microtubules
of a cell can form electrical circuits also.
And I just--I'm thinking, in addition to all
the quantum discovery, if you're not showing
us how there is a--almost a perfect microprocessor
memory state in cells.
>> HAMEROFF: Yeah. Well thank you. Yeah. As
I said, I worked 20--for 20 years on the idea
of microtubules as classical computers. I
don't even think about quantum. And I only
went to the quantum business when somebody
stymied me with a question, "Okay, wise guy,
how's that going to explain," you know, "how
we have feelings and feel joy and redness
and, you know, the heart—what's now known
as the heart problem in consciousness research?"
And at that time I read Roger's book, "The
Emperors New Mind," which was beautiful for
many reasons and he had a mechanism, but he
didn't have a structure. I had a structure,
but didn't have a mechanism. So I--you know,
I wrote to him and he immediately got it.
He immediately saw that microtubules could
be, you know, what he needed and, you know,
we teamed up. And we're kind of an odd couple.
We're very different in almost every way,
but he's a wonderful guy and, you know, he's
still very interested. He's gone off to worry
about, you know, the origin of the universe
and stuff like that, but he's still very keen
on this stuff and we stay in touch and he'll
be doubling back into this. But microtubule
is classical information processing, mediating
differentiation and memory. And I don't know--maybe
Jack knows whether CaMKII is found widely
in other cells other than neurons--I think
it is--and can mediate all kinds of things
in terms of memory. There's got to be a memory
site within. And it's not just a bit, each
tubulin can be more than just two states.
It can--it can be--it can be post-translationally
modified. It can be tyrosinated. There's--the
potential for information processing in microtubules
is vast even in one cell.
>> Any idea how fast?
>> HAMEROFF: How fast what?
>> A memory can be stored and retrieved?
>> HAMEROFF: Well, within seconds the CaMKII
is distributed widely throughout the dendrites
of one neuron and then--and neighboring neurons.
And if you stimulate simultaneously, it can
go widely throughout the brain, so within
seconds. Now, whether that's--you know, I
think of it as probably a short term memory,
not immediate consciousness because I think
the--that's a little bit different. But the
storage is seconds to minutes at the most.
So--and then the retrieval can be--can be
pretty fast.
>> So one more question. Just guessing, is
it possible the short-term memory can be stored
one way and then we go to sleep and it goes
to long term and...
>> HAMEROFF: Yeah. Well there's a lot about
that in terms of--when you go to sleep, the
consolidated memory. And it involves, you
know, hippocampal gamma oscillations and stuff
like that. So that may involve some kind of
hardwiring. Maybe it's transferred from the
microtubules to the neurofilaments which are
way more stable than even microtubules or
maybe there is--there is a posttranslational
modification, you know, enzymatic or non-enzymatic
changes in the tubulin so it becomes more
hardwired and that could be what memory consolidation
is.
>> Well, for what it's worth, keep it up.
>> HAMEROFF: Thank you.
>> Okay. Well, thank you. I'd like to thank
Stuart and...
>> HAMEROFF: Thank you.
