On plants, bacteria and anaesthetics

Figure 1

Damasio’s short book at reference 1 cover a lot of ground and, of necessity, needs to encapsulate various complicated affairs in very few words. So after observing that plants and bacteria can be anaesthetised using much the same anaesthetics that might be used on humans, he goes on to say on pages 43-44: ‘… I propose that what anaesthetics cause – thanks to a perturbation of the ion channels in the bilayer properties of cell membranes – is a radical and basic disruption of the sensing function we have just described. Anaesthetics do not target minds specifically – minds are no longer possible once sensing is blocked. And anaesthetics do not target consciousness either, because, as we will propose, consciousness is a particular state of mind and it cannot occur in the absence of mind…’.

This against a background of Damasio building consciousness on the dichotomy between sensing the interior self and sensing the exterior other. It is the bringing of these things together as images in a mind which generate feelings in the first instance – and then full blown consciousness. Which might involve drawing interior self up from the brain stem and exterior other down from the cerebral cortex. With more or less anything that is alive doing sensing, but with only larger animals doing mind. And while, at the margins, one might argue about what plants and bacteria get up to, as Baluška and Levin do at reference 3, doing mind mostly means having neurons and usually means having a brain at the top of the heap.

I thought the proposal quoted above worth poking around a bit. Some preliminaries have already been sketched out at reference 2.

I start by observing that both sleeping and general anaesthetics involve reversible loss of consciousness and transitions to and from a conscious state – and that their study should help us to understand the enigma of consciousness.

Anaesthetics

Poking the Internet suggests that we more or less know how local anaesthetics work. They simply block the passing of pain signals up to the brain, whether via the spinal cord or otherwise. Blocked more or less at source.

Contrariwise, the impression that I have got is that while we know a good deal about how general anaesthetics work and about how to make effective use of them, we are some way off a detailed understanding of how they work at a cellular level. How exactly it is, for example, that they turn consciousness off, while leaving basic life support functions like breathing to carry on? The answer presumably being more complicated than saying that the former needs the cerebral cortex up above, while the latter is managed from the brain stem down below. Above and below in both evolution and development, as well as in simple location.

That said, general anaesthetics do appear to act primarily on the cardio-vascular, respiratory and central nervous systems. With something called the triad of anaesthesia being hypnotics (for unconsciousness), analgesic (for pain relief, both in the conscious and unconscious patient) and muscle relaxants. Some anaesthetics are toxic as well as being useful, in which case they are used with particular care.

A lot of general anaesthetics are administered as gas through the lungs. So they have to get across the blood barrier into the blood stream and get carried up to the head where one supposes that they cross the blood barrier in the other direction and go about their business in the brain’s interstitial system  - that is to say the spaces, the gaps between all the neurons and their supporting cells – and presumably they do something of the sort in most other parts of the body too. While some general anaesthetics are injected directly as liquids into the blood stream. With my understanding being that general anaesthesia usually involves a cocktail of chemicals to get everything right during the three stages of induction, maintenance and emergence.

And, as Damasio suggests, they do their business by interfering, from the outside, with the lipid bilayers which envelope all cells. And which all contain the ion channels which are particularly important in the case of those cells which are neurons. Given the assumption that consciousness rests on appropriate firing of neurons in and around the brain, such interference clearly has the potential to make the subject unconscious. But how exactly this is done, without all sorts of unwanted side effects in other parts of the body, is another matter.

Concerning which, there is a suggestive section B in Figure 2 of reference 6, reproduced below

Figure 2

The relevant part of the caption reads: ‘Effect of sevoflurane anaesthesia on functional connectivity. Top: widespread reduction in fMRI thalamocortical connectivity, especially with frontal cortex at all concentrations of sevoflurane. Bottom: changes in directed connectivity as measured by EEG symbolic transfer entropy. Decreases from frontal to parietal, temporal and occipital cortex and from temporal to parietal cortex are evident. Color encodes the direction of information flow (red: rostro-caudal, blue: caudo-rostral)’.

So the top line shows a fairly consistent reduction in connectivity between the thalamus and the cortex with increasing doses of an anaesthetic and the bottom line tells a more complicated story, but certainly involving a weakening of the information flow from front (rostro or face, right) to back (caudo or tail, left).

Figure 3

For the convenience of readers who have trouble, like me, with the names of the lobes of the brain.

Functionality during sleep and under anaesthesia

Figure 4

The figure above being a trace from a long operation in Japan - a robot-assisted laparoscopic prostatectomy – which involved unexpected haemorrhage, some of the consequences of which can be seen in the third quarter. The steady blue line is about blood oxygen levels. Pneumoperitoneum is inflation of the abdominal cavity to make room for the work and was part of the reason why it took a while to notice the haemorrhage. Luckily, the team knew what it was about, and the patient made a complete recovery.

Breathing and the heart clearly carry on under anaesthesia and during sleep, as does the heart – while consciousness is mostly turned off. So what else gets turned off? What are the differences between sleep and anaesthesia? What – if anything – do those differences tell us about the nature of consciousness?

Figure 5

According to the sleep foundation: ‘muscles gradually relax during each stage of non-REM sleep, and the body’s total energy expenditure drops. During the REM stage, most muscles are paralyzed in a condition known as atonia. This keeps the legs and arms from flailing in response to dream content. Respiratory and eye muscles stay active, though, and the darting of the eyes behind closed eyelids is the inspiration for the name rapid eye movement sleep’.

Thermoregulation changes during sleep, but changes appearing to amount to something more complicated than just turning it off, the fairly widespread instinct to nest during sleep notwithstanding. In small animals, in places which can get cold, this may be more to do with energy conservation than anything else.

Thermoregulation is weakened during anaesthesia, and changes in subject temperature during and after anaesthesia can be a problem.

Digestion carries on during sleep. The liver and kidneys carry on.

A sleeping person can take some pain without waking up, although chronic pain is associated with difficulty sleeping properly.

Particularly but not only during REM sleep, a sleeping person often dreams, with triggers for such dreams sometimes including sensations from the body or beyond, dreams which may be remembered afterwards. While an anaesthetised person is sometimes aware, possibly of pain, possibly of chatter in the operating theatre, and sometimes remembers either or both afterwards. Matters touched on, last year, at reference 9.

Very much work in progress.

Lipid bilayers

Figure 6

I have learned that lipid bilayers are what envelopes more or less all cells and what controls what goes in and what comes out, at least to the extent of opening and shutting the necessary gates, one of which is shown left in the figure above and a lot of which are called ion channels. With neurons being a particular kind of cell and which have lots of ion – and other – kinds of channels. 

A lot of these ion channels, closed by default, are opened for a short while by binding the right molecule to them – with the choice running, I think, to hundreds, and locked shut by binding some other molecule to them. The agonists and the antagonists. The ligands. Which makes getting the right molecule to the right place at the right time important – something that can be helped with medicines and hindered with toxins. And I dare say the process will also be affected by temperature and pressure.

Watching these goings on in-vivo can be difficult, in part because they happen very quickly, but it seems that computer simulations have got to the point where they can do it in-silico. One might use something like the CHARMM computer package, already mentioned at reference 2. 

Figure 7

An appealing story as all this seems to be more or less universal, but it is not the whole story, not least because at the next level up, in larger plants and animals anyway, the cells are built up into larger structures, like veins, kidneys and intestines, which might have boundary layers of their own, something rather grander than a lipid layer.

The snap above, turned up by Bing but originating, I think, from reference 4, shows a boundary layer of the intestine of a fish, mainly made up of a single layer of cells, mostly tightly bound together, but with some gaps. Suggesting traffic both through the epithelial cells, that is to say through their lipid bilayers, and past them.

Oddments

Regarding vegetables and managing without neurons, from reference 3 I got to reference 8, from which I learn that chemical soups, properly constituted and considered, are Turing complete, that is to say that can be made to perform all kinds of computations, although such computation is likely to be slow and to be constrained by the lack of suitable chemicals to function as memory. Vegetables are not as dumb as they might look.

As it happened reference 5 turned up while all this was going on, citing Damasio and his work on a Mr Eliot and a Mr Gage, two men who, for different reasons, lost the ability to feel much, if anything, in the way of emotions. Which meant that they were unable to get on with anything and otherwise lead a normal life. But there is no suggestion that either of these men was anything other than fully conscious. Which seems to be something by way of a counter example to the proposal introduced above.

And reference 6, where I read that: ‘… similarly, the fact that general anaesthetics do not seem to grossly impair primary sensory networks … supports the earlier proposition of Crick and Koch that primary sensory processing is not sufficient for consciousness…’. Which does not seem to support the first part of the proposal.

Conclusions

While it is reasonable to draw attention to the emerging facts that life manages lots of computing without neurons and that ion channels are to be found in lipid bilayers in most cellular life – animal, plant and bacterial – and while it is true that anaesthetics do what they do by interfering with the ion channels in lipid bilayers, I do not find the Damasio proposal that consciousness is turned off by turning off sensory input convincing: ion channels do a lot more than look after sensory input and I am not convinced that messing about with certain ion channels in plants is very comparable to messing about with some other ion channels in animals. But I shall carry on with my second reading of his book notwithstanding.

References

Reference 1: Feeling and knowing: Making minds conscious – Antonio Damasio – 2021.

Reference 2: https://psmv5.blogspot.com/2022/02/on-doors.html. 

Reference 3: On having no head: Cognition throughout biological systems – František Baluška and Michael Levin – 2016. 

Reference 4: Transcriptomic responses in the fish intestine – Samuel Martin, Carola Dehler, Elzbieta Krol – 2016.

Reference 5: What We Owe Our Fellow Animals: Can we develop a theory of justice that encompasses nonhuman animals? – Martha C. Nussbaum, NYRB – 2021.

Reference 6: Neural Correlates of Unconsciousness in Large-Scale Brain Networks - Mashour GA and Hudetz AG – 2018. 

Reference 7: An introduction to anaesthesia – Ciara Donohue, Ben Hobson, Robert Stephens – 2013. A study aid from UCL, turned up by Bing. The source for Figure 1.

Reference 8: Evolution of associative learning in chemical networks - McGregor S, Vasas V, Husbands P, Fernando C – 2012.

Reference 9: https://psmv5.blogspot.com/2021/11/bayne-and-howhy-revisited.html.