Electron spin changes as a general mechanism for general anesthesia?

Aug 11, 2014 by John Hewitt report
Effect of the anesthetic noble gas Xenon on the electronic structure of two short peptides. Top: the highest occupied molecular orbital [HOMO, purple surface ] for two 9-residue helices positioned close to each other. A small fraction of the HOMO extends from one helix to the other. Bottom: when a Xenon atom [gold sphere] is in the gap, the orbital spread increases. Transparent surface is Van der Waals electron density. Credit Luca Turin

(Phys.org) —How does consciousness work? Few questions if any could be more profound. One thing we do know about it, jokes biophysicist Luca Turin, is that it is soluble in chloroform. When you put the brain into chloroform, the lipids that form nerve cell membranes and the myelin that insulates them will dissolve. On the other hand, when you put chloroform into the brain, by inhaling it, consciousness dissolves. It is hard to imagine a satisfying explanation of consciousness that does not also account for how anesthetics like chloroform can abolish it.

Lipid solubility appears to be one key clue to anesthesia. The empirical cornerstone of anesthesiology is a 100 year old rule of thumb known as the Meyer-Overton relationship. It provides that the potency of general anesthetics (GAs), regardless of their size or structure, is approximately proportional to how soluble they are in lipids. Since that time, studies have suggested that GAs can also bind to lipid-like parts of proteins, presumably those near or embedded within cell membranes.

The first real stab at explaining the "how" of anesthetics, as opposed to just the "where", has now been taken by Turin and his colleagues Efthimios Skoulakis and Andrew Horsfield. Their new work, just published in PNAS, suggests that volatile anesthetics operate by perturbing the internal electronic structure of proteins. This would lead to changes in electron currents in those proteins, in cells, and in the organism. They don't just theorize about these effects, they actually measure the electron currents in anesthetized flies using a technique known as electron resonance (often called ).

ESR is similar to nuclear magnetic resonance, the techno-phenomenon at heart of the modern MRI machine. The main difference is that in ESR excited electron spins are measured instead of proton resonance. Typically, microwaves are applied in the presence of a magnetic field to a sample (or whole organism) inside the resonator cavity of an ESR spectrometer. An ESR signal is diagnostic of unpaired electrons, which exist only in certain cellular structures. One particularly strong signal for example, is that of melanin, which can be accounted for in experiments by comparisons with mutants lacking normal melanin content.

What Turin and colleagues have shown is that the total amount of free electron spins in fruit flies increases when they are exposed to general anaesthetics. The amount of free spins generated during anesthesia is independent of melanin content and far larger than any signal previously measured from free radicals which are the other source of spin. These are normally very unstable and undetectable in the absence of "spin traps" to capture them. Furthermore, mutants of Drosophila which have been selected for resistance to certain anesthetics show a reduced, sometimes absent spin signal.

Why did Turin and his musketeers try the experiment in the first place? Some of Turin's most alluring science has been a side effect of his passion for perfume. While not intending to become the fly whisperer that he is today, Turin was able to use these creatures to demonstrate detection of odorants by molecular vibrations. The key mechanism here, and link to anesthetics, is the concept of inelastic electron tunneling, i.e, an electron current that takes place within the receptor proteins in the presence of odorants.

To account for the fact that a very broad class of compounds act as volatile anesthetics the researchers propose a unitary mechanism for their action involving electrons. They note that the smallest among them, Xenon (Xe), presents a puzzle to chemical theories of anesthetic action. Xe is a wonderful (if expensive) anesthetic but it has no biologically relevant chemistry to speak of— it is completely inert. Furthermore, it persists as a perfect sphere of electron density and so is devoid of any possibly interesting shape. However, as Turin and colleagues point out, "Xe has physics". In particular, it can conduct electrons, as the IBM researchers who first used a scanning tunneling microscope to write the company's logo in Xe atoms found out.

To see whether this property would apply to all anesthetics, and not just Xe, Turin used a modeling technique called density functional theory to show that Xe and other anesthetics effect the highest occupied molecular orbit (HOMO) of the alpha helices common to membrane proteins. The HOMO level for organic molecules or semiconductors is analogous to what the valence band maximum is to inorganic semiconductors. Intriguingly, while all the anesthetics were found to extend the alpha helix HOMO level, similar molecules with strong convulsant effects on the brain, but no anesthetic effects, had the smallest HOMO effect.

These results offer a fascinating insight into how anesthetics may be operating and raise many important new questions. Would spin changes be able to explain, for example, the observation that deeply anesthetized tadpoles (a favorite animal model in anesthesia research) can be quickly returned to normal activity just by subjected them to a sobering pressure pulse of 50 bars? Are the cessation of consciousness and the apparent concomitment abolishment of spikes both mere epiphenomena of underlying material reorganizations that result from spin changes? In other words, anesthetics may eliminate the wherewithall for spikes but is that the effect that is really eliminating the conscious state?

Other researchers, in particular those who investigate the solitary acoustic wave nature of spikes, report that the melting point of membranes is lowered by while hydrostatic pressure increases it—ostensibly due to latent volume changes. A rectification of these more global thermodynamic intuitions with lower level physics and chemistry of electron conduction awaits. The work of Turin and his collegues breathes refreshing new life into a field whose increasingly beleaguered explanations of yore (like simplistic effects on ion channels) have now started to crumble under the weight of their own exceptions.

Explore further: Major dopamine system helps restore consciousness after general anesthesia, study finds

More information: Electron spin changes during general anesthesia in Drosophila, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1404387111

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big_hairy_jimbo
not rated yet Aug 11, 2014
This just SOUNDS RIGHT!!! YEah I know what I said isn't science, but considering that next generation electronics will use spin, and various topological effects for efficient logic gating, then perhaps biology has been doing the same all along.
cresta
1 / 5 (2) Aug 11, 2014
I do recognize that I don't read every article included in these mails. I do read only the ones where the heading seems interesting to me. I've been receiving these e-mails with these articles for over a year. For a long time I thought that this newsletter was advertising for Chinese scientific researches. This article about Electron Spin as a anesthesia appears to be the first one I read where a Chinese name is not involved in the research.
George_Rajna
Aug 12, 2014
This comment has been removed by a moderator.
qitana
not rated yet Aug 12, 2014
If the total amount of free electron spins decreases, would it make you feel more conscious?
saccoflame
1 / 5 (2) Aug 12, 2014
"On the other hand, when you put chloroform into the brain, by inhaling it, consciousness dissolves." No, consciousness it's connection to the mind is severed and so it had no content. Consciousness is like space. Space is where matter and energy happens and consciousness is where thoughts, emotions, and perceptions happens.
shavera
5 / 5 (1) Aug 12, 2014
If the total amount of free electron spins decreases, would it make you feel more conscious


The idea is more like... Imagine you short all the circuits in a computer. Current flows about smoothly, but it can't do any processing in the meantime. Then when you remove the shorts and let it go back to normal, it can resume processing.

The proposal is that anesthesia shorts out the proteins in the nerves so currents flow freely, but they can't process any data, so the processes that generate "thoughts" are temporarily muted.
antigoracle
2 / 5 (4) Aug 12, 2014
Why did Turin and his musketeers try the experiment in the first place? Some of Turin's most alluring science has been a side effect of his passion for perfume. While not intending to become the fly whisperer that he is today,...

Hmmm.... methinks someone doth sniffeth too much.
MrVibrating
4 / 5 (1) Aug 12, 2014
So if spin currents are forming functional circuits then perhaps this would explain the effects of TMS (transcranial magnetic stimulation) - perhaps TMS experiments could be tailored to test the idea..?
Toiea
1 / 5 (2) Aug 12, 2014
In AWT the maximal complexity of objective reality arises from balancing of longitudinal and transverse waves, when the vacuum behaves like self-focusing metamaterial foam and the massive objects are propagating like the solitons across this foam. Neural network mimics the observable reality with solitons spreading along neuron membranes, so it must balance the longitudinal and transverse waves too with liquid crystal state of neural membranes (and intermediate state between solid state transferring transverse waves and liquid mediating longitudinal wave). When the neuron membrane freezes, it crystallizes and insensitiveness from hypothermia follows. When the neuron membrane gets diluted with lipidic solvents, it dissolves into fluid state and the neural spikes cannot propagate along it at distance as well. Therefore the hypothermia is followed with the same hypnotic state like the anesthesia and it has much to do with the human brain adaptation to geometry of observable reality.
Toiea
1 / 5 (2) Aug 12, 2014
that deeply anesthetized tadpoles ...can be quickly returned to normal activity just by subjected them to a sobering pressure pulse of 50 bars?
The lipid membranes liquefied with dissolved solvent can be forced into crystallization with exposing to pressure (the melting point of membranes is lowered by anesthetics while hydrostatic pressure increases it, as noted above). The xenon dissolves well in the lipids in the same way like for example the nitrous gas, which is used for anesthetics in dentistry and/or artificial whipped cream (it dissolves well in whipping cream). No electron spins are behind it - just a wave mechanics and condensed phase physics.
johnhew
not rated yet Aug 12, 2014
Toiea, from Wiki:

1)Stereoisomers of an anaesthetic drug have very different anaesthetic potency whereas their oil/gas partition coefficients are similar

2)Certain drugs that are highly soluble in lipids, and therefore expected to act as anaesthetics, exert convulsive effect instead (and therefore were called nonimmobilizers).

3)A small increase in body temperature affects membrane density and fluidity as much as general anaesthetics, yet it does not cause anaesthesia.

4)Increasing the chain length in a homologous series of straight-chain alcohols or alkanes increases their lipid solubility, but their anaesthetic potency stops increasing beyond a certain cutoff length.
fabricio_paesdemedeiros
not rated yet Aug 12, 2014
OBS. The fluid membrane becomes more ''static'' because of the Anesthesics; Then the water in the act of pass through the membrane will generate free electron spins!! Simple!
There is no need to be attributed the impossible to (((free electron spins))) When the most responsible is the water electromagnetism, having its hydrostatic pressure increased and generating these (((free electron spins))) because the water is impacting with a membrane more static. less soft!!!
fabricio_paesdemedeiros
not rated yet Aug 12, 2014
The fluid membrane becomes more ''static'' because of the Anesthesics; Then the water in the act of pass through the membrane will generate free electron spins!! Simple!
There is no need to be attributed the impossible to (((free electron spins))) When the most responsible is the water generation of electromagnetism interrupt and having its hydrostatic pressure increased generating these (((free electron spins))) because the water is impacting with a membrane more static. less soft!!! #WaveBiology
Aaron43
5 / 5 (1) Aug 12, 2014
Huping Hu with "Spin-mediated Consciousness theory" was the first to use anasthesia-induced unconsciousness to connect electron spin, biology, physics, and quantum computing.

He should be looked at
TechnoCreed
5 / 5 (1) Aug 13, 2014
Huping Hu with "Spin-mediated Consciousness theory" was the first to use anasthesia-induced unconsciousness to connect electron spin, biology, physics, and quantum computing. He should be looked at
David Bohm proposed that the mind work through some quantum process more than 50 years ago and Roger Penrose followed this path too. Funny that you mentionned Hupping Hu... I had This arXiv paper open before I read your comment: http://arxiv.org/...8068.pdf
lucaturin
not rated yet Aug 13, 2014
@MrVibrating: Good point. This had occurred to us, we're trying to figure out whether there is a way of testing it experimentally.

@Aaron43, TechnoCreed Thanks for the pointers, I did not know abt this work.
Aaron43
5 / 5 (1) Aug 13, 2014
@ technocreed yup very true, I knew Bohm, Penrose, and Hameroff were prior, but thought Hu was an original when using anesthesia to support his thesis. Didn't realize he had citations when he began discussing such elements. Ha.

For fun: I think a very interesting connection can be made with Huping's "spin-mediated consciousness theory" and Gerald T'Hooft 's proposal on quantum mechanics with his deterministic 'cogwheel' model (pg. 21 & 41 - figure 2 & 6) http://arxiv.org/...48v2.pdf

I see it as 2 sides of the same coin of observable reality. Should fit nicely together.
And getting philosophical: If a single spin-controlled mind-pixel dependent on choice has a diluting influence over the rest of the pixels that create an individual's consciousness - following with the cogwheel model - could maybe, just for fun, create and explain a possible quantum framework threshold for the existence of morals. Just gonna throw that one out there. :)

Aaron43
not rated yet Aug 13, 2014
@Aaron43, TechnoCreed Thanks for the pointers, I did not know abt this work.


Ah woops didn't mean to disclude you on the last response, all of this stuff is incredible. Thanks for the feed back
TechnoCreed
not rated yet Aug 13, 2014
@Aaron43
After a few hours of reading, I would say that this Huping Hu is too esoteric for me. But this article brought me to two interesting TED talks. The first one about consciousness from Stuart Hameroff https://www.youtu...RetvkkuQ the second one about the sense of smell from Luca Turin https://www.youtu...cvINn8Iw
TechnoCreed
not rated yet Aug 13, 2014
@lucaturin
@MrVibrating: Good point. This had occurred to us, we're trying to figure out whether there is a way of testing it experimentally.

@Aaron43, TechnoCreed Thanks for the pointers, I did not know abt this work.
Qu'un chercheur reconnu recherche l'approbation d'inconnus sur le web, n'est-ce pas là le monde à l'envers M. Turin?
Toiea
not rated yet Aug 13, 2014
Stereoisomers of an anaesthetic drug have very different anesthetic potency whereas their oil/gas partition coefficients are similar
Such a drugs aren't lipophillic after then and their anesthetic effect is very specific instead. Are we talking about general mechanism of anesthesia after then?
Certain drugs that are highly soluble in lipids, and therefore expected to act as anaesthetics, exert convulsive effect instead
It just means, they can dissolve in neuron membrane. Such a solution may increase or decrease its melting point after then, depending on their molecular weight and structure.
A small increase in body temperature affects membrane density and fluidity as much as general anaesthetics, yet it does not cause anaesthesia
I just remember, how I attempted to swim in the water at the temperature of 16 degrees of centrigrade. I'm pretty sure, the temperature of my body didn't decrease bellow 35 °C, but I felt completely immobilized after few seconds inside of it.
Toiea
not rated yet Aug 13, 2014
Increasing the chain length in a homologous series of straight-chain alcohols or alkanes increases their lipid solubility, but their anesthetic potency stops increasing beyond a certain cutoff length
It's difficult to say without knowledge of conditions of particular experiment. The general solubility and ability of anesthetics to penetrate the tissue decreases with increasing of molecular weight as well. This is the reason, why the eating of polyethylene foil doesn't act as an instant hypnotic killer for us, despite its chains have very high length. The schematic thinking doesn't help here very much.
lucaturin
5 / 5 (1) Aug 13, 2014
@techno creed
Simple politesse envers ceux qui expriment un intérêt. Pourquoi un chercheur "reconnu" devrait il éviter un dialogue fructueux? Ce serait plutôt enfin le monde à l'endroit!
TechnoCreed
5 / 5 (1) Aug 13, 2014
@techno creed
Simple politesse envers ceux qui expriment un intérêt. Pourquoi un chercheur "reconnu" devrait il éviter un dialogue fructueux? Ce serait plutôt enfin le monde à l'endroit!
Luca Turin is a little less than a decade older than me and should have the wiseness to understand my skepticism. This being said, this kind of outreach is unusual but not impossible. The tangible effect it had on me is to learn more about M. Turin and his work. Thank you for that...TC
johnhew
not rated yet Aug 13, 2014
Whoa there horses! While I congratulate Luca for being one of the few, if not the ONLY researcher to actually care enough about his or her work to field questions from the larger populace who actually care about it without getting paid for it, I have to caution against all the foreign code being used on an English speaking site. We have found that the only language able to express things with more nuance and compactness than our mother tongue is Python
lucaturin
not rated yet Aug 13, 2014
Excuse my French... But wasn't COBOL the original language spoken by humans before Babel?
johnhew
not rated yet Aug 13, 2014
I am a fan of Grace Hopper, but it appears she was rejected for early admission to Vassar College since her test scores in Latin were too low, so she invented Cobol. French is fine I suppose for art forums and discussing bagellettes, but for here we require one must have a Facebook Appreciation Society page (like S. Hameroff) to use it: https://www.faceb...9043398/
TechnoCreed
not rated yet Aug 14, 2014
@johnhew
I have to caution against all the foreign code being used on an English speaking site. We have found that the only language able to express things with more nuance and compactness than our mother tongue is Python
Even if your comment has humorous undertones, I am not sure of its intention. Writers on physorg tolerate a lot of nonsensical comments under their articles and although foreign language is challenging for many, it should not be seen as nonsense. Anyway, if you want an evaluation of this 'test' I assure you that the answer had the proper formulation and came from somebody who is comfortable with French. Maybe not you, but somebody who proudly qualifies himself as 'xerolas' can appreciate that.
lucaturin
not rated yet Aug 14, 2014
@TechnoCreed Undertones and overtones too. @johnhew is the most fluent speaker of Neptunian I have ever encountered, and a Knight of the August Order of Xerolas.
johnhew
not rated yet Aug 14, 2014
Have a beer on me @techno, just send me your email/paypal, but remind, the learned men such as yourself should never have left the books where gargoyles like me can find them, for like small bureaucrats stuck in menial existence, we are wont to use what little powers we are afforded
TechnoCreed
not rated yet Aug 15, 2014
@johnhew
I should know better than accepting ethylic beverages from neuroscientists or biophysicists for there are more chances that I end up being a test subject than being accepted in their fraternity, so I sneaked to your beer blog and helped myself with the Leffe.
TechnoCreed
not rated yet Aug 15, 2014
@lucaturin
The subtlety of your reply leaves very few doubts. Without the help of johnhew I would have failed to notice that I bumped into someone who might someday get a Nobel for his work on olfaction or the mechanism of GA. My advice, if you care enough to interact with people who are interested by your work but do not have the time to take care of a blog, is to submit an article to Aeon Magazine; there Joe Public will not be so surprised to interact with you. It has been an honour to exchange a few words with you sir.
johnhew
5 / 5 (1) Aug 15, 2014
@techno Leffe is a lightweight, barely increases spin content, I put the real beers here: https://plus.goog...38916846
phorbin
not rated yet Aug 16, 2014
"is that of melanin, which can be accounted for in experiments by comparisons with mutants lacking normal melanin content"

Since this is about anaesthesia, is the use of the word 'melanin' an error and would 'melatonin' be the intended word?
johnhew
not rated yet Aug 16, 2014
melanin is to melatonin as glycogen is to glucose, only 100 times less similar
fabricio_paesdemedeiros
not rated yet Aug 18, 2014
Membranes-Water interactions are amplified when the membrane is more mobile, under the influence of anesthesia they harden which decreases this good interaction with the water, so I believe that in this case the water impacts on the static membrane instead of being moved by her. .. Which increases the (((hydrostatic pressure))) and gendered (((free electron spins)))! The consistency of the membrane influence the ''depolarization''