Jeanne Julie Eleanore de Lespinasse: an open heart, a closed book?
If I were young, pretty, and very charming, I should not fail to see much art in your conduct to me; but as I am nothing of all that, I find a kindness and an honour in it which have won you rights over my soul forever.
Julie de L’Espinasse, to the Comte de Guibert, 1773
Although I managed to spend a bit of time at a university in my thirties, I think I’m largely self-educated, being reluctant to follow any course set down for me, and allergic to too much discipline, and so I’m always fascinated to hear of historical characters of a similar type – Montaigne, Rousseau and Stendhal come to mind (not that I’m comparing my ‘achievements’ to theirs!), and it’s probably not coincidental that they’re all French, though I’ve no idea what this signifies.
So the other day, finishing Aldous Huxley’s strange, well-meaning but unconvincing utopian novel Island, I wondered at the passing mention of Mlle de Lespinasse, a woman I ‘knew’ from my recent rereading of Stendhal’s Love. So here’s a couple of key passages about her from Wikipedia:
Jeanne Julie Éléonore de Lespinasse (9 November 1732 – 23 May 1776) was a French salon holder and letter writer. She held a prominent salon in Paris during the Enlightenment. She is best-known today, however, for her letters, first published in 1809, which offer compelling accounts of two tragic love affairs.
Looked down on for her poverty and illegitimate birth, Mlle de Lespinasse had an unhappy childhood marked by neglect. She acquired a basic education at a convent, but she was largely self-educated, an impressive feat given that she was later able to hold her own among France’s top intellectuals.
This second passage in particular captured my heart, so to speak. I wouldn’t say that I was neglected, or impoverished, growing up, and the term ‘illegitimate’ seems quaint if not grotesque in today’s WEIRD world, but I identify with the thrill, and much of the isolation, of self-education. I feel I’ve spent much of my life talking to myself. As for salons, today’s equivalent, if there is any, would be the meet-ups I’ve occasionally been part of, for humanists, skeptics, ‘literature-lovers’ and the like. Somehow, though, they’ve never quite worked for me. I’m not one for ‘holding forth’, and am pretty easily overwhelmed by others.
But let me focus on Mlle de Lespinasse, a rather formal title, and a rather more tragic figure. She died at 43, probably of tuberculosis, exacerbated, it seems, by an impassioned and immiserated spirit, not to mention liberal quantities of opium. One might say that she died of a broken heart. When I was a kid and first heard the notion of a broken heart, I imagined it snapping like a biscuit, and then you fell down dead. But even then it wasn’t quite so silly, it was awe-inspiring in fact, that the heart could be so brittle, so damaged by a love unrequited or rejected. Now of course, I see this sinking, this despair, this death of a highly intelligent and admired woman, confidante of the likes of d’Alembert and Condorcet, as more of a ‘feminist’ issue. In Saint-Beuve’s introduction to her life and letters, he refers to her emotionality:
But of what use is it to become clear-sighted? Did a woman’s mind, great as it may be, ever check her heart? “The mind of most women serves to strengthen their folly rather than their reason!” La Rochefoucauld says that, and Mlle. de Lespinasse proves the truth of it.
Of course this is just another patronising, patriarchal comment, from a world that largely debarred women from being movers and shakers in any political, scientific and enterprising arenas. Partnership with and encouragement of the males who dominated those arenas was all that could be hoped for. It seems that Julie de Lespinasse, along with Anne Louise Germaine de Staël-Holstein (aka Mme de Staël), her mother Suzanne Churchod (known at the time as Madame Necker), and other salonistes of their time, were all expected to play the purely nurturing role that has been woman’s lot since religio-cultural politics reduced women to vassalage, whenever that might have been – since the rise of agricultural society, at least. The notes to her published letters present a nice example of this nurturing:
In her last hours, already lying on her deathbed, she secured that of La Harpe [to L’Académie française]. “M. de La Harpe”, says Bachaumont in his Memoirs, “was one of her nurslings; by her influence she opened the doors of the Academy to him who is now its secretary. This poet was the last of those whom she enabled to enter them.”
So that would have been in 1776. The novelist Marguerite Yourcenar became the first woman elected to L’Académie française, in 1980.
So I’m currently learning more of Julie de Lespinasse, as she was known, and I’m nervous about my experience of her being filtered through the notes to her letters by “
So I’ve read the first letter in the 1809 collection, addressed to the Comte de Guibert, one of the two men who most occupied her passionate and guilt-ridden thoughts, the other being the Marquis de Mora. Obviously these weren’t your Mellors the gardener types. Guibert was an ambitious army officer, later a General, and Mora was a tubercular semi-invalid. Both were quite a bit younger than Julie (I can’t help thinking of la nouvelle Héloïse), who was forty at the time of the first letter, in 1773. It’s a bit hard to make sense of this letter, being a bit in medias res – she writes a lot of ‘him’ – Mora? – and of ‘you’, and seems almost terrified of her own thoughts – what she thinks and what she should think, as one passion rises and the other falls. Here’s how the letter ends:
But tell me, is this the tone of friendship, the tone of confidence? What is it that is drawing me?Make me know myself; aid me to recover myself in a measure; my soul is convulsed; is it you, is it your departure, what is it that persecutes me? I can no more. At this moment I have confidence in you, even to abandonment, but perhaps I shall never speak to you again of my life. Adieu, I shall see you to-morrow; possibly I shall feel embarrassed by what I have now written to you. Would to heaven that you were my friend, or that I had never known you! Do you believe me? Will you be my friend? Think of it, once only; is that too much?
That is the question – is it too much? I try, and largely fail, to imagine receiving such a convoluted letter, from a person I admired but didn’t love, in the romantic sense. What would a bonobo do? No, that’s not a joke question – I mean of course, what would a ‘bonobo-ised’ human do? I think he would offer comfort, hugs and kisses, but not eternal, undivided devotion. That may not seem enough, but then a bonobo-ised Julie de Lespinasse wouldn’t be placing all her hopes in one individual – especially not a male.
So I may or may not continue reading these letters, and reflecting on what they reveal about human need and pain in an individual surrounded, it seems, by gifted admirers. Sad but uplifting too. It’s a privilege to ride along with someone who feels so much.
References
https://en.wikipedia.org/wiki/Jeanne_Julie_Éléonore_de_Lespinasse
https://babel.hathitrust.org/cgi/pt?id=uc1.c005633001&seq=65
the history of patriarchy in a small room.
The enemy is not men. The enemy is the concept of patriarchy, the concept of patriarchy as the way to run the world or do things.
Toni Morrison
Central Politburo – what if they were all women?
About a month ago I went to a ‘meet-up’ for a group which went under the name ‘philosopher’s corner’. The topic, from memory, was something like ‘Donald Trump and the future of US democracy’. I’ve written a number of posts on and around this topic, so I thought it might be fun, in a perverse way. Unfortunately it wasn’t as much fun as I’d hoped. There were about ten attendees, sitting at tables which more or less faced in each other in a squarish formation, something like a Square Round Table, in an out-of-the way little upstairs room. Again from memory, there were seven men to three women, but in the whole two hours’ non-stop conversation, to which I contributed my fair share, I can only recall one brief comment and one question from the female attendees. So, well over 95% of the conversation was male. I was wearing my bonobo t-shirt, featuring a large photo-portrait of said primate, with underneath the line ‘I’d rather be a bonobo’, which is only occasionally true for me, and this might have been one of those occasions. In any case nobody seemed to notice.
Not that there was any violence or even slight rowdiness in evidence, but a couple of those present did seem to sympathise with Trump’s politics (whatever they thought they were) while deploring his personal behaviour. Fortunately (more or less) the conversation drifted to other political hotspots such as Ukraine-Russia and Israel-Palestine, plus a fair slice of local Aussie politics worth pontificating about. Altogether, I don’t recall much that particularly stimulated me, especially from those who most dominated the conversation (the convenor did quite a good job of giving everyone a fair go), but the bloke immediately to my left made two separate comments that, for hopefully obvious reasons, caught my attention. First, he declared that we need a strong, male leader to deal with the world’s trouble-spots in a firm, no-nonsense way. By ‘we’ he appeared to be speaking for the WEIRD world in general. I did try to respond to this, but others jumped in before me, not to disagree with him specifically, but to turn the conversation in another direction, leaving the notion to fester. But shortly afterward, my left-hand compatriot offered another comment, or rather, a question. What’s wrong with the idea of a first nuclear strike, given the current situation? Again, nobody took up the idea, and I admit to being too stunned to offer a response. Presumably he meant on Russia, on Moscow? I took a closer look at the man – middle-aged, neatly dressed, he looked like a clerk, a public servant. The middle-class ‘man in the street’.
We need more female leadership, please please please. Above all we need it in Russia, China, North Korea, Israel, Iran, Afghanistan, Syria, Burma, Indonesia, all the places where we have it least. It’s no good saying, as has been said to me, ‘look at this, that or the other female leader, what difference did they make, some were even worse than the men’. These were all odd women out in a patriarchal world, who had to conform, more or less, to the male stereotype. It needs to be a numbers game, a world turned upside-down, with the kind of group leadership in politics, business, the law, science, even the military, that males enjoy today. And the fact is, it’s happening, if too slowly. The academic world isn’t what it was in Virginia Woolf’s time, and that’s only taken a century. Imagine the human world a thousand years from now. If we survive, and I’m sure we will, things will continue along the painfully slow track of incremental empowerment for the sex that gave birth to us all, that nourished and nurtured us in our early years, the ‘without which not’ of all humanity, and more.
That small community of primates south of the Congo River is putting us to shame. How did they manage it? Obviously it wasn’t a conscious development, and it will need to be more conscious for us. We need our patriarchy to be deflated, little by little, puncture by puncture, for the betterment not just of our own humanity, but for the biosphere that we’ve come to dominate so very disturbingly.
no references this time!
what’s on my mind, and in my brain?
The mind is certainly a very mysterious organ, I reflected,.. about which nothing whatever is known, though we depend upon it so completely.
Virginia Woolf, A room of one’s own, 1928
ah yes, it all makes sense now…
So there’s still plenty to learn about the mind, and maybe calling it the brain is only giving us a false sense of the matter (and I’m thinking of ye olde ‘what’s mind, it doesn’t matter, what’s matter, never mind’ jibe), though we’ve made great neurophysiological strides in recent decades. But having just read Virginia Woolf’s thoughts on the position of women almost a century ago, and being old enough to remember texts like ‘Women are from Venus, men are from Mars’, which sought to ‘explain’ and make the best of the pigeonholes the author presumably believed in, I’ve decided to have another quick look at the current expert views on the neurophysiological and hormonal differences between the sexes.
What I’ve found is that it’s still a contested issue. When I last reported on it, I found myself very happy to accept that there are statistical differences between male and female brains, but no categorical differences. That’s to say, both male and female brains vary widely, and it’s reasonable to say that the differences within each gender are as great as the differences between them. Another striking way to think about it is to say that, were you to hand a still living but completely disembodied human brain (just imagine!) to a trained and experienced neurologist, they’d be unable to say categorically that it was M or F.
Well, the first website I’ve come to disputes this claim. It’s from PNAS (often fondly vocalised as ‘penis’, which may or may not be relevant) and it’s a short essay with only one author, Marek Glezerman. My initial sense of it is that he misses the point, and seems disturbingly emphatic. To give an obvious example, the title of the piece is “Yes, there is a female and a male brain: Morphology versus functionality”. In his opening paragraph (but the essay only has two paragraphs), Glezerman summarises the conclusion he disagrees with, a conclusion I based my own essay on years ago:
The authors conclude that brains of women and men are not dimorphic and not categorically different, as are the genital systems of the two genders, but resemble more an overlapping mosaic of specific functional regions and therefore cannot be distinguished as male and female brains.
Reading this made me wonder, and I thought back to the night before – ahhh, the night before – when I spent time at a well-frequented pub full of individuals, male and female, well beyond the first flush of youth. It occurred to me that there wasn’t a single person there whose sex I would feel mistaken about. Many of the men, and none of the women, were balding, bearded and paunchy. Some did have breasts, I admit, that could’ve competed with the females, but I doubt if they’d have managed the same expression, so to speak. And though there was a lot of variety in the voices, it was easy enough to distinguish males from females in that characteristic. Of course there were also differences in dress, mannerisms and choice of drink, but those could be put down to ‘culture’ and dismissed. Even so there might be enough evidence on display to suggest a categorical difference – a morphological difference – traceable to the brain and hormones.
So, what did Glezerman mean, exactly, by ‘morphology versus functionality’? Well, here’s a long, but essential quote from his essay.
Whenever the terms “female brain” and “male brain” are used, the intention should be functional and not morphological, qualitative and not quantitative. Functionally, brains of women and men are indeed different. Not better, not worse, neither more nor less sophisticated, just different. The very brain cells differ chromosomally. The male brain is exposed to a completely different hormonal environment during intrauterine life than the female brain. The available scientific data as to the crucial effect of testosterone on the developing male brain is overwhelming.
Glezerman provides references for his claim about testosterone and its effects, a subject of great interest to me, but I’ll leave that for another essay. But one wonders if this isn’t a storm in a teacup. Going back to my pub reference, of course there were differences within the sexes – some males seemed more ‘feminine’ than others, whatever that may mean, and some women more ‘masculine’. This may again be a matter of hormone expression rather than personal choice, or a complex combination. I find it fascinating that male hormone levels (i.e testosterone) are dropping in the WEIRD world, a matter of concern to some, but not me…. oh, but that’s for that other essay, or did I already write that one?
PNAS has a reply to Glezerman’s essay, which I’ll now focus on. And I should note how polite and civilised these scientific disputes are: far from the world of social media. This response is even shorter that Glezerman’s little essay (I’ll bet that was by design!), so I’ll reflect on it here, passage by passage.
As Marek Glezerman (1) rightly points out, there are differences between females and males in brain and behavior. Glezerman overlooks, however, the fact that such differences may be different and even opposite under different environmental conditions. That is, what is typical under some conditions in a brain composed of cells with an XX chromosomal complement residing in a body with low levels of testosterone, may be typical under other conditions in a brain composed of cells with an XY chromosomal complement residing in a body with high levels of testosterone.
Being a person who spreads himself thinly over a wide variety of intellectual topics (i.e master of none), I had to look up XX and XY (remember mate, two kisses female, one kiss male – which is surely typical). What the response (which has three authors) appears to be saying is that what is typical for a low-testosterone female in some conditions, may also be typical for a high-testosterone male under quite different conditions, in spite of the fact that one set of brain cells carries an XY chromosomal complement, while the other carries XX. Not sure if this carries the day though. But to continue:
Such “reversals” of sex effects have also been reported when the manipulation of environmental conditions was done in utero (by manipulating the dam) and the offspring were tested in adulthood (reviewed in refs. 2 and 3). These observations led to the hypothesis that brains are composed of a “mosaic” of “male” and “female” features rather than of only “male” features or only “female” features, as expected of a “male brain” and a “female brain,” respectively (2, 3)
Wasn’t sure what ‘manipulating the dam’ meant, but a dam is a dam, something that reduces or stops flow, so I suppose this was done in non-human test species? Presumably if you’re able to change hormonal conditions in utero via such methods – or by changing environmental/social conditions, as bonobos appear to have done – you will change the mosaic of behaviour. Bonobos can be quite aggressive, but it appears to be more tilted towards the male of the species. Also, the drop in male testosterone is surely due to changed conditions and expectations for males over a relatively short period – for example in the mere century since A room of one’s own was written, but even more so in the past few decades of mechanisation and anti-machismo, at least in the WEIRD world.
Our study (4) is the first to empirically test whether brains are “male” or “female” by assessing internal consistency in the degree of “maleness-femaleness” of different elements within a single brain. We found that brains with both “female-end” and “male-end” characteristics were more prevalent than brains with only “female-end” or only “male-end” characteristics. This was true for both the volume of brain regions and the strength of connections between regions (assessed in a similar way to ref. 5), in contrast to Glezerman’s assumption that “Other imaging methods might have yielded different results.”
This is claiming evidence for mosaic traits in a majority of the brains under study, both for individual regions in isolation and for brain connectivity. All I can say is that this seems eminently plausible, indeed I would’ve expected such a finding. Not sure, of course, what ‘male-end’ and ‘female-end’ characteristics are exactly. There is a question here, though, about what Glezerman meant by ‘other imaging methods’.
To corroborate our analysis of different aspects of brain structure assessed using MRI, we also analyzed brain function, as revealed in people’s behaviors, personality characteristics, preferences, and attitudes. Also here there were many more people with both “feminine” (i.e., more common in females compared with males) and “masculine” (i.e., more common in males compared with females) characteristics than people with only feminine or only masculine characteristics (4).
Behaviour, over time, can affect brain function and brain regions mightily. An obvious case is language, spoken and written, which is a behaviour that has had considerably impact on the brain, as, for example Maryanne Wolf recounts in Proust and the squid. You’d hardly expect those brain regions that have been adapted/co-opted for language production/reception to have been much affected by gender. The same would go for other skills and practices, such as mathematics. As to the different physical characteristics of males and females (my pub observations), how connected are they to our brains? They certainly have much to do with hormones, of which we have at least fifty types, many of which are connected to/stimulated into action by the pituitary gland, which is in turn stimulated by the hypothalamus, but these regions account for a minuscule proportion of the brain.
There is no doubt that sex affects the structure and function of brain cells. However, the fact that sex can affect brain cells does not necessarily entail that the form and function of brain cells are either “male” or “female” nor that the brains comprised of these cells can be divided into two distinct categories. For such claims to be true it is necessary that the effects of sex are dimorphic, resulting in the formation of distinct “male” and “female” types, as well as internally consistent (2, 3, 6).
I think what’s being said here is that just because our brain cells, indeed all our somatic cells, have either an XX or XY chromosomal complement in their nuclei, this doesn’t dictate essential expressed traits – our intelligence, our humour, our physical skills, our bodily needs, and so forth. As this essay suggests, ‘manipulating the dam’ in utero is likely to have a far greater effect on human development than gender does, unless of course you’re born into a culture in which one gender is significantly undervalued. But let’s not go too near that hornet’s nest.
So to the last lines of the reply to Glezerman:
Hopefully, future studies looking at the relations between sex and other systems in which sex differences have been documented (e.g., the immune system, the cardiovascular system) will assess both internal consistency and degree of overlap, to reveal whether the relations between sex and other systems are more similar to the relations between sex and the brain (mosaicism) or to the relations between sex and the genitalia (dimorphism).
And no doubt there will be differences, especially in relation to hormonal levels associated with the reproductive system, but also in those associated with diabetes, the heart and the circulatory system and so forth, but these are not easily predictable based solely on gender. And there’s another problem with fixating on sex differences in a hard and fast way. It’s not exactly coincidental that male supremacists are all for favouring such differences. That’s why the bonobo example needs to be known and promoted far more than is currently the case.
References
https://www.pnas.org/doi/10.1073/pnas.1600791113#core-r2
What do we currently know about the differences between male and female brains in humans?
the male and female brain, revisited
on the lymphatic system and its clever cells, mostly
Activation of macrophage or B cell by T helper cell
Jacinta: So we’re focussing now on the lymphatic system, ‘clear water’ remember. A most misleading definition. So there’s this network of vessels, nodes and ducts….
Canto: What’s a node?
Jacinta: It’s a point of connection, or connections. In plants, a node is a point of branching, like with leaves.
Canto: Yeah I knew that. What’s a duct?
Jacinta: Don’t kid kid. It’s like a vessel, only, somehow different. Maybe bigger? Anyway, nodes go with lymph. There are over 500 of these lymph nodes throughout our bodies. The system does a lot of clean-up work, preserving fluid balance. It’s also much implicated in the immune system of course, and it’s involved in other stuff that’s quite hard to summarise, as you know.
Canto: Something from a reliable enough website:
The lymphatic system plays a key role in intestinal function. It assists in transporting fat, fighting infections, and removing excess fluid. Part of the gut membrane in the small intestine contains tiny finger-like protrusions called villi. Each villus contains tiny lymph capillaries, known as lacteals. These absorb fats and fat-soluble vitamins to form a milky white fluid called chyle. This fluid contains lymph and emulsified fats, or free fatty acids. It delivers nutrients indirectly when it reaches the venous blood circulation. Blood capillaries take up other nutrients directly.
Jacinta: Never heard of lacteals. Have heard of chyle, but don’t know much about it. So chyle contains lymph. But what’s lymph?
Canto: It’s a not-so-clear beige-coloured milky fluid containing lots of WBCs, especially lymphocytes, of course, and fatty stuff. Well, actually, that’s not lymph, that’s chyle. Or both… So there’s this lacteal system of the small intestine, capillaries for absorbing fats – well, actually transporting them… but we need to know what bile is, and emulsification, and lipase, and glycerides and esters, and no doubt much much more.
Jacinta: Well we’ve committed ourselves to learning about the immune system and associated processes for some ineffable effing reason, so let’s soldier on.
Canto: Okay, so bile has nothing to do with Trump, at least not in this context. Bile ducts are this network of tubes inside the liver – well actually there are intrahepatic and extrahepatic bile ducts. Bile itself is a fluid made and released by the liver, for breaking fat down into fatty acids. For ‘digesting’ fat, sort of. Not particularly relevant to the immune system, but it’s all interesting en it? And it can cause problems, such as chronic bile reflux. I suspect I’ve experienced bile reflux, though not chronically. I think it’s also called acid reflux, suggesting bile is a kind of acid.
Jacinta: Or maybe not. Here’s another one of those websites that know more than us:
Bile is composed of ingredients designed to digest fat. While it isn’t an acidic formula, it’s harsh on the sensitive linings of your stomach and esophagus. Chronic bile reflux can erode these protective linings, causing painful inflammation and, eventually, tissue damage (esophagitis).
Anyway, I’m not sure how we got from chyle to bile.
Canto: Right, back to chyle and lymph. Have you heard of lymphoedema? That’s a blockage of the lymphatic system, which causes tissue swelling, mostly in the arms and legs but possibly just about everywhere.
Jacinta: Yes, and things fall apart, the centre doesn’t hold. So let’s get back to lymph nodes and the cells they contain. Within lymph nodes there are germinal centres containing a lot of B cells, or B lymphocytes. These have receptors (B cell receptors) on their membranes which are IgD antibodies, all of which have different binding domains, due to genetic recombination, which allows them to deal with differently structured antigens. Once binding occurs, signals are sent to the lymphocyte’s nucleus, resulting in what’s called receptor-mediated endocytosis. The signalling response creates pseudopods and/or clathrins which pull the membrane inside.
Canto: Ok, sorry to be boringly predicable, what are clathrins?
Jacinta: They’re proteins, very ‘clever’ proteins, as so many of them are. They mediate endocytosis, which is essentially the surrounding and cutting off of extracellular material within the cell, creating a vesicle, called an endosome I think, which might be transported to further action sites. So this is happening within the B lymphocyte. We have this B cell receptor bound to a foreign antigen, and chromosome 6 of this cell then can produce a molecule (MHC2) to ‘fit’ the antigen and fuse it to the cell membrane. This has the effect of activating the B cell, carrying an MHC2 antigen-carrying molecule on its surface, and IgD antibodies. Of course I haven’t explained how the clathrins actually carry out this transformation, because I can’t but I believe it’s all been worked out.
Canto: Yes of course, and now our lymphocyte is an antigen-presenting cell. There are three types of such cells – B lymphocytes, macrophages and dendritic cells. However, the lymphocytes still need to proliferate to be effective, and this requires a stimulus. And so enter the macrophages. These have MHC2 molecules on their surface, bound to a specific foreign antigen, and they also have MHC1 surface molecules bound to a self antigen (as do all nucleated cells). The macrophage presents this MHC2 molecule with its antigen to a type of T cell, described as a’naive’ (i.e. non-specific) T helper cell. These helper cells will have, somewhere on their surface, specific protein molecules, called CD4, that ‘fit’ with the MHC2 molecules, and other specific molecules (T cell receptors) that fit with the foreign antigen. Specific TCRs fit with specific antigens. It’s all a matter of geometry, sort of.
Jacinta: These different types of TCRs are a product of genetic recombination, which involves RAG1 and RAG2 genes, and I can only guess that the R stands for recombination… Now these helper cells have CD3 signalling molecules inside (they send signals to the nucleus), and a molecule called CD28 on their surface. The macrophage has a protein, B7, which interacts with the CD28, and this protein interaction, called a co-stimulation reaction, sends a secondary signal to the nucleus – as opposed to the first, primary signal. This is known as co-stimulation.
Canto: So next, the macrophage starts secreting a molecule called interleukin-1, which binds to a specific receptor on the T helper cell, which results in a third signal to the nucleus, and activation of the T cell. The cell’s genes now produce interleukin-2, which can be secreted and will then bind to a receptor, as an ‘autocrine’, resulting in genes secreting another cytocrine, interleukin-4, and then interleukin-5. With all this, the T helper cell moves to another stage, becoming either a T helper 1 cell (stimulated by interleukin 12) or a T helper 2 cell (stimulated by interleukin 4). So, focussing on the T helper 2, it has activated interleukins 2,4 and 5, the latter two of which are especially important, after these cells have started dividing. That’s when those cytokines are produced.
Jacinta: We might be learning something. Now to the proliferation of the B lymphocyte. Interleukin 4 activates the B lymphocyte to start turning on genes for its proliferation – called clonal expansion. And they will have receptors (BCRs) specific to the foreign antigen. They’ll also have MHC2 surface molecules with exposed foreign antigens. They’re now ‘immuno-competent’ cells, and then, through the medium of interleukin 5, they will start differentiating. Some of these new types of cells are called plasma cells, which have a very prominent rough endoplasmic reticulum (RER), others are called memory B cells. Interleukin 5 and 6 stimulate plasma cells to produce and secrete antibodies specific to particular foreign antigens – or, rather, having variable regions that can adapt to and bind to those antigens.
Canto: And these antigens might be on the surface of bacteria, or not as the case may be. If they can bind to all the antigens on the bacterial (or viral) surface they can render it ineffective (neutralisation). Binding to freely circulating antigens can, however, cause problems. Such binding creates a precipitation reaction and this can be deposited in tissue resulting in a type 3 hypersensitivity. Don’t ask.
Jacinta: This is what United Staters call getting into the weeds, maybe. So that’s surely enough for now.
do bonobos have families – and should humans have them?
‘We all belong… to an MAC – a Mutual Adoption Club. Every MAC consists of anything from 15 to 25 assorted couples. Newly elected brides and bridegrooms, old timers with growing children, grandparents and great-grandparents – everybody in the club adopts everyone else. Besides our own blood relations, we have our quota of deputy mothers, deputy fathers, deputy aunts and uncles, deputy brothers and sisters, deputy babies and toddlers and teenagers’.
Susila, in Island, by Aldous Huxley, 1962
Bonobo mum with adopted child
I’ve mentioned how, in childhood, I perused a book called Children of the Dream, which looked at a different way of rearing children, in which they had a variety of adults and older kids to learn from, and they could gravitate towards some and away from others according to their inclinations. I was hungry for ideas like this as I felt trapped in an embattled family situation and yearned for both freedom and some kind of instruction or sponsorship that would promote my development in the most positive way. I was five when our smallish nuclear family (2 adults, 3 kids) moved from Scotland to the other side of the globe, so I had no experience of an extended family. And we lived together within a brick construction divided into compartments for eating, watching TV, sleeping and reading, washing our clothes, washing ourselves and defecating, surrounded by some land on which we could grow grass, various plants, or nothing much.
Twenty-five or so years later, I learned about bonobos, our closest living relatives, equally with chimpanzees. The lifestyles of these two other types of ape provided a fascinating contrast, while both types provided an equally fascinating contrast with H sapiens.
Returning to my childhood, I gradually learned that, outside of my family, which was female-dominant, the human world was dominated by the males. They were the headmasters, the bosses, the political leaders and so forth. We kids were, rather suddenly, sent to Sunday school where we were taught about our Father who was in heaven, but also everywhere else, who made us and made the world and loved us and watched over us constantly, and whose son died for our sins on a wooden cross long ago. None of this made any sense to me, and it seemed of a part with Santa Claus and the tooth fairy, only the adults who told us these stories took it all so seriously that I felt no inclination to question them. I was a timid child, but also skeptical before I knew the word.
Much later, I came to wonder more about this religious double act of the Father and Son, and about the Church as it existed before the Protestant Reformation, with its history of male Popes, and its male Cardinals, male Archbishops, male Bishops and male Priests. And of course I learned about the history of male political leaders, generals, dictators, monarchs and emperors, and the tiny sprinkling of females among them, and it all stuck me as very odd and sad. And a bit stupid. And then, again, bonobos.
We are, of course, the only mammals who build our own structures for our nuclear families to live in. In doing so we have in a sense, ‘naturalised’ the nuclear family. And this happened not so long ago in the history of H Sapiens, which goes back to around 315,000 years ago according to the findings from Jebel Irhoud in present-day Morocco.
The term ‘housing’ isn’t so easy to define. If we think of purpose-built structures for living in, what about termite mounds or bee-hives? And before these human structures we imagine cave dwelling, but just how many caves are there dotted about the place? It’s likely that our first domiciles combined natural shelter and human ingenuity, using wood, bones, skins and such. Fireplaces would probably have featured. But it surely wasn’t just families in the modern sense that built or used these sites. Think again of bonobos:
Bonobos live in fission-fusion social groups where a large community of individuals separate into smaller groups, or parties, of variable size and composition. These “unit-groups” range from lone individuals to groups of 20 or more bonobos (Badrian et al. 1984; White 1988, 1996).
The size of human groups would have evolved over time – not too big, not too small, and quite likely having flexible fission-fusion lifestyles for much of human history. This also reduces inbreeding, as even chimps/bonobos have come to realise (unlike the Habsburgs).
What I’m really getting at, though, is when did we, as kids, come to recognise and acknowledge that we had one father, one mother, and the odd sibling? And that we belonged to this grouping, were in effect ‘owned’ by it? In spite of the great service the internet has provided for us over the past few decades, I can’t find any clear answer to this question – unsurprisingly, I suppose. Neither chimps nor bonobos are monogamous, but of course they live in ‘troops’, with the mother as principal care-giver, but with plenty of other adults or adolescents to help out, siblings or no. This is especially the case in bonobo society, which can, at a stretch, be seen as one big Mutual Adoption Club. The difference of course is that the bonobo way developed naturally, it simply evolved, whereas the ways of the Kibbutzim and Huxley’s MAC have a seemingly top-down artificiality about them. Interestingly, we’re having the same problem with our own gender issues, with a ‘natural’ understanding, based on neurology and the study of history, not to mention a multitude of writings such as Woolf’s A room of one’s own and Beauvoir’s The second sex, that women have been intellectually undervalued for millennia, together with a more artificial quota system for women/girls in STEM, or women in government. In any case, with the gradual receding of patriarchal religious systems (very gradual in some places), and obvious successes of women in science, business and politics, as well as the much more publicised behaviour of men behaving badly, re warfare, political machinations, capitalist exploitation and the like, it seems inevitable, to me at least, that we will gradually, in a two steps forward, one step back fashion, evolve into a female-dominant human culture (remembering that that there’s no gender equality among any of the social mammals – gender inequality isn’t just the norm, it’s universal). It seems to me unproblematic that the gender that brings humans into the world should be the ones in charge – with a little help from their friends.
As for the compartmented nuclear family thing – who knows? Change is a constant, and we now accept same-sex marriages, no-fault divorce, single parentage and the like, all in the last few decades. Our society has also become more child-focussed, just as we’ve reduced family sizes. No more corporal punishment in schools (too late for me, sadly), no more ‘bastards’, and more government assistance in terms of subsidies, childcare centres, maternity leave and so on. The concept of family itself has been altered and extended, and evolution is a never-ending story…
References
Aldous Huxley, Island, 1962
https://en.wikipedia.org/wiki/Kibbutz (note especially the subsections ‘children’ and ‘child rearing’)
https://phys.org/news/2021-03-female-wild-bonobos-infants-social.html
more baffling immune system stuff
1RH2 Recombinant Human Interferon Alpha 2b – evidemment
Jacinta: We’ve been mostly educating ourselves via the NinjaNerd YouTube series on immunology, which seems very comprehensive and yet comprehensible, for beginners, and then going to other websites for details. Now getting back to cluster differentiation (CD), a commonly used immunological term. Here’s a useful definition:
The cluster of differentiation (CD) is a protocol used for the identification and investigation of cell surface molecules present on leukocytes. CD molecules often act as receptors or ligands important to the function of immune cells.
Canto: That’s useful indeed. Each CD – 4 or 8 or 25 – represents a cluster of differentiation. Differentiated from other clusters. So back to T regulatory cells, which would be differentiated into those cells that predominantly have CD4 or CD8 molecules, as well as TCRs. All to help suppress auto-immune diseases in particular.
Jacinta: So we have these T regulatory cells, as well as helper and cytotoxic T cells, all created in the thymus essentially, and then they’re distributed to the lymphoid organs – the lymph node locations include ‘the groin, armpit, behind the ears, back of the head, sides of the neck and under the jaw and chin‘. There’s also the spleen and its sinusoidal capillaries, where T cells form a surrounding layer known as the ‘periarteriolar lymphoid sheath’ (PALS), more commonly known as white pulp. A large number of T regulatory cells however remain in a thymus region known as the thymic (Hassal’s) corpuscles. They’re also distributed throughout the body – the tonsils, the respiratory tract and so on. All originating from the red bone marrow.
Canto: Well I’m still a little confused about the difference between the innate and adaptive immune systems and whether there really is any clear distinction between them (I suspect not). My own distinction so far is that the innate system is quick and not very specific and well-attuned, and the adaptive is – everything else.
Jacinta: Well, a bacterial antigen releases endotoxins which causes a massive release of inflammatory cytokines, got that?
Canto: Not particularly. Get this:
Endotoxins (lipopolysaccharides, LPS) are agents of pathogenicity of Gram-negative bacteria, implicated in the development of Gram-negative shock. Endotoxin reacts with lipopolysaccharide-sensitive cells producing endogenous mediators such as tumour necrosis factor alpha (TNFα).
That was my first stop in trying to find out what endotoxins are. Needless to say, it’s meaningless to me. Though I know that ‘endo’ means ‘from within’ as opposed to ‘exo’… I think.
Jacinta; If you look that up you’ll find it’s horribly complex. Okay the bacteria release toxins which release cytokines in reaction. There are many different kinds of cytokines, including histamines, prostaglandins and leukotrienes. Amongst other things these cytokines will impact smooth muscle cells causing vasodilation, increasing blood flow causing heat and redness. Cytokines will also contract endothelial cells, causing fluid leakage and permeability, affecting pain receptors. Bradykinins are also involved in vasodilation and increased blood flow. All this induces swelling and pain. Broadly, the four signs of inflammation are: swelling, pain, heat and redness. That answers a basic exam question. Joint immobility is a fifth sign in some extreme cases.
Canto: I’m looking at a different video, “introduction to the immune system”, because I think we need to stay on the ground floor for a while. I also think looking at language might help. For example, ‘cytokines’ feature heavily, and I was thinking that they were like some kinds of proteins or enzymes, something sub-cellular that could whizz about the body, but then I noticed that white blood cells were called leukocytes, and there were lymphocytes and phagocytes… cells! Like, complex organisms. And ‘kine’, apart from being about cattle, is where our word ‘kind’ came from, as in Kinds of Minds. So ‘cytokines’, methinks, are just the vast array of cells relating to the immune system.
Jacinta: Yes, this is good – a phagocyte is an ‘eating cell’. A lymphocyte is a type of WBC that’s involved in the immune system. T cells are lymphocytes, as are B cells. So, yes, they’re complex, gene-containing thingumies, all of them, and lymphocytes are so called because the lymph system is full of them. But note that ‘cyte’ just means ‘cell’, not necessarily of the white or immune kind.
Canto: So starting again at the beginning, with the innate and adaptive systems. So the innate system is what often causes pains and fevers, that redness and itchiness and raised temperature mentioned before – inflammation. Because of the release of cytokines, as you’ve explained.
Jacinta: Ah but here’s where it becomes confusing and unhelpful. On a website designed, I think, for high school biology students I found this:
Cytokines…. are a broad category of small proteins that are important in cell signaling. They are released by cells and affect the behavior of other cells. Cytokines include interferons, interleukins, lymphokines, and tumor necrosis factor.
So it looks like you were right in the first place. It is confusing though. Interferons are proteins, as are interleukins, and ScienceDirect, which is generally reliable, says this:
Cytokines, chemokines, and lymphokines are multifunctional immunoregulatory proteins secreted by cells of the immune system.
So we’ve both been confused, and maybe looking at language origins might confuse us more. Best just to accept what the biochemists say.
Canto: So, are we starting again, again? Let’s look at some of the cytokine types. Interferons are as mentioned, signalling proteins. But what, exactly, is meant by signalling, and what exactly is a protein? A chain of amino acids, je crois. So, signalling – that’s about sending and receiving and responding to signs of change:
Individual cells often receive many signals simultaneously, and they then integrate the information they receive into a unified action plan. But cells aren’t just targets. They also send out messages to other cells both near and far.
So far, so obvious. These signals are essentially chemical. Even neurotransmission reduces down to the chemical level. But we’ll stick with pathogens and immunity. Receivers of signals are generally called receptors, and immune-system cells often, but not always, have receptors within or sticking out of the cell membrane.
Jacinta: Interferons are so-called because they interfere with viruses and such. We’ve actually been able to create them in the lab since the 80s for treating some cancers:
Interferons are the frontline defenders in your body. A variety of cells, including white blood cells, produce interferons in response to infection and other stimuli, like cancer cells. They initiate signaling cascades by stimulating the infected cells and those nearby to produce cytokines.
Canto: But are they the frontline defenders? And they’re cytokines themselves, as aforementioned. Cytokine seems a pretty broad term.
Jacinta: Our refined or not-so-refined new definition – cytokines are types of stuff created by a variety of cells as an immune response to pathogens. As to interferons, don’t worry about it.
Canto: Too late, I’m worried. Here’s another quote:
More than twenty distinct IFN [interferon] genes and proteins have been identified in animals, including humans. They are typically divided among three classes: Type I IFN, Type II IFN, and Type III IFN. IFNs belonging to all three classes are important for fighting viral infections and for the regulation of the immune system.
Should we just devote the rest of our lives to interferons and forget the rest?
Jacinta: Everything’s connected to everything else. And we shouldn’t despair – we’ve learned much about the lymphatic system, for example, that we didn’t know before.
Canto: We didn’t know anything before. But yes I’m encouraged. And getting back to language, lymph is apparently Latin for ‘clear water’, which is a good start for thinking about lymphatic fluid, even if it’s anything but clear.
Jacinta: Like sea or river water I suppose. The more you look… Blame all those pesky microscopes and such. Anyway, one video describes the lymphatic system as having three main functions: 1) returning fluid to the heart: 2) helping large molecules (hormones and lipids) enter the blood: 3) immune surveillance.
Canto: Okay let’s look at all that in a bit more detail next time.
stuff on the immune system 2: T cells, mostly
It’s still early days, but gene-therapy modifications of bone marrow stem cells may be the solution to many haematological malignancies
Peter Doherty, An insider’s plague year
something like…
Canto: So we’re going to try and educate ourselves with the help of all these videos out there on the immune system, with hopefully occasional references to the SARS-Cov2 coronavirus. And we’re not going to reference all these videos and websites because it’s just too time consuming and nobody else is going to read this stuff, it’s just for ourselves, mostly much.
Jacinta So in a vid about T-cell development (and they’re a product of the adaptive immune system) we hear that T-cells are produced in the red bone marrow. Why red?
Canto: Bone marrow comes in 2 types:
Red bone marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow bone marrow is made mostly of fat and contains stem cells that can become cartilage, fat, or bone cells.
Jacinta: So it’s not about red bones. So stem cells are like stems, green shoots that can develop into all sorts of different plants?
Canto: Yes and so you can imagine the potential, if we can induce them to specialise in ways that we want. Homo deus and all that. My brief research tells me that they’re found all around the body, not just the marrow. But it doesn’t tell me how they came into being. And there are apparently different types, as in ‘blood stem cells’. So these particular cells are pushed out into the world via sinusoidal capillaries…
Jacinta: Capillaries are the narrowest of blood vessels, I know that much…
Sinusoid capillaries allow for the exchange of large molecules, even cells. They’re able to do this because they have many larger gaps in their capillary wall, in addition to pores and small gaps. The surrounding basement membrane is also incomplete with openings in many places.
Canto: I must say that the number of high-quality, comprehensive videos on immunology, e.g. on YouTube, is such a boon. The comments say it all, ‘if only I had this info available when I was doing my PhD’ etc etc. So back to T cells. They move, I think as precursor T cells, to the thymus, via those capillaries. The thymus is a small gland near the top of the lungs (in the thoracic cavity) which is an essential component of the lymphatic system, itself a part of our general immune system.
Jacinta: It’s described as a primary lymphoid organ – at last I’m going to find out more about lymph! I hope. So the thymus is where T cells develop, and the red bone marrow, another primary lymphoid organ, is where B cells develop.
Canto: And B cells are a ‘type of white blood cell that makes infection-fighting proteins called antibodies’. Whereas T cells fight infections more directly as well as doing a lot of signalling…
Jacinta: Interesting thing about the thymus – it functions mostly through early childhood and adolescence, after which it atrophies, its tissues becoming fibrous and non-functional. So its role in T cell maturation occurs in our early years.
Canto: The thymus secretes different types of chemokines, or chemotactic agents (thymosin, thymotaxin, thymopoetin and thymic factors) which are somehow able to pull these undeveloped T cells in the right direction. This process is called chemotaxis.
Jacinta: A chemical taxi system, how cute. So we mentioned the two primary lymphoid organs, and there are secondary lymphoid organs – the lymph nodes (found in a number of bodily locations) and the spleen (on your left side, just around the bottom of your rib-cage). Just on chemokines – we’ve heard of cytokines, and the worrisome ‘cytokine storm’ that was oft-mentioned during the Covid period. Chemokines are a subset of these cytokines, which are –
‘an exceptionally large and diverse group of pro- or anti-inflammatory factors that are grouped into families based upon their structural homology or that of their receptors. Chemokines are a group of secreted proteins within the cytokine family whose generic function is to induce cell migration’.
Canto: So now we’re looking at these precursor T cells arriving at the thymus. So the thymus has a heap of thymic, epithelial cells which secrete the above-mentioned chemokines, which stimulate certain genes within the T cells to produce two enzymes (proteins), RAG1 and RAG2 (RAG stands for recombination activating gene – the genes encode the proteins). These are types of recombinase…
Jacinta: Think of genetic recombination, or mixing:
Recombinases are a family of enzymes having functional roles in homologous and site-specific recombination. It’s an event in organisms that involves DNA breakage, strand exchange between homologous segments, and ligation of DNA segments using DNA ligase.
Canto: So in this T cell context the gene ‘shuffling’, as it might be called, produces different protein types to deal with different antigen types. For example they produce T cell receptors (TCRs) designed to recognise and ‘receive’ differently-shaped antigens.
Jacinta: So getting back to those chemokines, they’re inducing other genetic activity to produce CD (cluster differentiation) proteins, of which there are various conformations, such as CD4 and CD8. These proteins form on the outside of the T cells, where they, hopefully, bind to MHC (major histocompatibility complex) proteins on the thymic cells. And of course there’s always more complexity – ‘a human typically expresses six different MHC class I molecules and eight different MHC class II molecules on his or her cells’. For now just think MHC-1 and MHC-2. Recognition of the appropriate MHC molecules by the CD4 and 8 proteins is called ‘positive selection’. If positive selection doesn’t happen the T cells will die (apoptosis).
Canto: The next step, assuming T cell survival, has to do with the previously-mentioned TCRs. The MHC molecules on the thymic cells carry a ‘self peptide’, and just to show how complex and relatively recent our immunological knowledge is, here’s a quote from a Pub-Med abstract from late 2001:
Twenty years ago, antigenic and self peptides presented by MHC molecules were absent from the immunological scene. While foreign peptides could be assayed by immune reactions, self peptides, as elusive and invisible as they were at the time, were bound to have an immunological role. How self peptides are selected and presented by MHC molecules, and how self MHC-peptide complexes are seen or not seen by T cells raised multiple questions particularly related to MHC restriction, alloreactivity, positive and negative selection, the nature of tumor antigens and tolerance.
So, if we could imagine ourselves as upper-class kids who entered university in the late 70s, (instead of working in factories or bludging off the dole as we were doing), none of this would’ve been known to anyone and we could’ve helped make the breakthrough…
Jacinta: Woulda-coulda-shoulda. Back again to those T cell receptors (TCRs), which apparently are not supposed to recognise or connect with the thymic cells’ self or antigenic peptides, as that would lead to auto-immune complications. So they’re ‘designed’ for that purpose, so that they don’t recognise those peptides, and don’t connect with them. This is called negative selection. If for some reason recognition does occur, apoptosis will result. That process occurs by the release of FAS (aka APO-1 or CD95 – don’t ask) from the thymic cell to a receptor in the T cell.
Canto: So, up to this point, if the T cell has come through alive, it’s TCR-positive, CD4 positive and CD8 positive. Its CD4 molecule may interact fortuitously with the thymic cell’s MHC2 (but the CD8 doesn’t interact with MHC1). In that case, there will be gene up-regulation of the cell’s CD4 molecules and down-regulation of CD8. That’s to say, CD4s will increase and CD8s will reduce, and it will present other TCRs. This turns it into a ‘T helper cell’. On the other hand, if the cell’s CD8s connect with the MHC1, there will be up-regulation of CD8, down-regulation of CD4, converting it into a cytotoxic T cell. Some of these helper and cytotoxic T cells can further develop into T regulatory cells, aka T suppressor cells, important for auto-immune disease suppression. This is promoted by molecules such as CD25 and interleukin 2.
Jacinta: Ok that’s enough head-spinning for one post, except perhaps just to say that interleukin 2 is ‘a protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity’. And we might find out more about what ‘cluster differentiation’ actually means….
Reference
This almost all comes from one video:
stuff on the immune system and that recent pandemic: 1 – how to get lost in a single cell
got that?
Canto: So, looking way back to the Covid-19 year or two, which we survived (and I’m wondering if the virus has too), have we retained what we’ve learned from all those Medcram videos we watched, and from the various ‘vaccine hesitant’ characters we encountered…
Jacinta: One of whom was a nurse as I recall, but I must say, mind like a sieve, I don’t feel I’ve retained much, so we’re reading Nobel Prize-winning immunologist Peter Doherty’s An insider’s plague year, to help us set down some info and promote our lifelong learning.
Canto: So what’s the difference between a drug and a vaccine, Doherty asks, noting that even experienced journalists confuse the two. Drug of course is a broad term, for anything chemical used to treat people, by pill, injection, bottle, patch or suppository. At the beginning of his ‘plague journal’ Doherty mentions two drugs I recall from our Medcram viewings, hydroxychloraquine, an anti-malarial, and remdesivir, ‘an experimental anti-Ebola drug’.
Jacinta: Yes, hydroxychloraquine was touted early on in the year (2020) as being of some use. A USA site, Drugbank online, said this:
Chloroquine and hydroxychloroquine are both being investigated for the treatment of SARS-CoV-2
followed by this:
The FDA emergency use authorization for hydroxychloroquine and chloroquine in the treatment of COVID-19 was revoked on 15 June 2020.
Remdesivir seems to have been somewhat more effective in reducing symptoms, as was seen earlier in treating MERS-CoV sufferers. It received the FDA’s authorisation just a few weeks before the other drug’s authorisation was revoked.
Canto: The word drug features in the USA’s FDA (Food and Drug Administration), while in Australia we have the TGA (Therapeutic Goods Administration), and therapeutic is simply medicalese for drug. The first of these tended to be natural remedies such as quinine, a useful anti-malarial extracted from Cinchona tree bark. Tonic water has quinine in it, hence the name. Another natural anti-malarial is artemisinin, from sweet wormwood. These ingredients, extracted and purified, have been extremely important in combatting the biggest killer disease in the global south.
Jacinta: In treating SARS-CoV2, remdesivir was the only effective antiviral in the first 12 months, apart from – monoclonal antibodies. I’ve heard of them, now I’m going to try and explain them. I’ll start with this quote from the Mayo Clinic:
Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance, modify or mimic the immune system’s attack on cells that aren’t wanted, such as cancer cells.
Antibodies (aka immunoglobulin, of which there are 5 types) are Y-shaped proteins that can bind to specific antigens (the foreign nasties) via a lock-and-key mechanism. Monoclonal antibodies, as mentioned above, have been particularly effective in some cancer treatments.
Canto: Well, only this month our TGA has posted an update on the decreased effectiveness of monoclonal antibodies against emerging SARS-CoV2 variants:
emerging data show that anti-spike protein monoclonal antibodies demonstrate a significant decrease in their in-vitro neutralising activities against many newer circulating SARS-CoV-2 variants, particularly Omicron and its subvariants.
Jacinta: Mmm. So let’s go on with our very basic training in immunology. So it’s the organs of the lymphatic system – the lymph nodes, the thymus, the spleen and the bone marrow – that produce or harbour and further develop our immune cells. Now, these immune cells come in different types with different names, such as phagocytes, which are a type of white blood cell (WBC)…
Canto: Yes, this immune system stuff might require dozens or hundreds of posts. Phagocytes can be ‘professional’ or non-professional’ depending on effectiveness. The professionals include neutrophils, macrophages, mast cells, dendritic cells and monocytes – all WBCs. They’re all more or less good at detecting antigens. And I believe these WBCs form what’s called the innate, rather than adaptive, immune system.
Jacinta: So getting back to the SARS-CoV2 Betacoronavirus – we’ll be jumping around a lot in these posts, methinks – it has this thing called a spike protein on its outer coat, and this protein has a receptor-binding domain (RBD) with binds to the angiotensin-converting enzyme (ACE) receptor, or ACE2 receptor. ACE2 receptors exist throughout the body but the principal pathway for this virus involves the epithelial cells at the base of the lungs and in the blood vessels. So I’m reading a Nature article, referenced below, entitled ‘Mechanisms of SARS-CoV-2 entry into cells’, and I want to frame this stuff in my own words to understand it. Apparently ACE2 is the receptor for other Betacoronaviruses and Alphacoronaviruses, so immunologists and virologists are pretty familiar with it.
Canto: Yes, and there’s all this terminology – for example a virion is the whole viral particle – not just the DNA or RNA core and its proteins but the external envelope – everything that allows it to exist extra-cellularly. So a coronavirus virion is made up of nucleocapsid and other proteins, including the spike proteins that facilitate entry into potential host cells via the ACE2 receptors.
Jacinta: So let’s focus for now on the nucleocapsid (N) protein. Another Nature article, with multiple authors, has this title: ‘The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA’, which sounds ominous. And the article starts with a problem:
The SARS-CoV-2 nucleocapsid (N) protein is an abundant RNA-binding protein critical for viral genome packaging, yet the molecular details that underlie this process are poorly understood.
Yes, especially by me. I get that these N proteins bind and ‘package’ the RNA, but I don’t get ‘phase separation’…
Canto: Phase separation is a key biological concept, it seems, but complex, and probably something that requires lab work to fully comprehend. Here’s a quote from ScienceDirect that might help:
Many biological macromolecules, such as proteins and nucleic acids, exert their biological functions by forming phase-separated condensates, and phase separation is closely related to various human diseases. Gene transcriptional regulation is an indispensable part of gene expression and normal function in cells. Its abnormal regulation often causes the occurrence of different diseases. In recent years, the occurrence of phase separation during transcriptional regulation has become an area of intense research.
It sounds like problems with phase separation may lead to irregular transcription, or vice versa, resulting in variants, mutations and such, but I’m guessing.
Jacinta: So reading further into the ScienceDirect article, you’re right, it’s near impossible to understand this stuff just through reading – you surely need to see it happening in cells. And cells, such as our own, are effing complex. Here’s another (long) quote to prove it:
In cells, which are the basic unit of the structure and function of organisms, the need for various components to perform their corresponding functions at the correct time and space is a problem that cells continuously need to solve. To this end, cells have evolved a set of organelles, including membrane-encapsulated organelles (such as mitochondria, nuclei, lysosomes, the Golgi apparatus, and endoplasmic reticulum) and membrane-less organelles (such as nucleoli, Cajal bodies, stress granules, P bodies, U bodies, and signaling bodies) …. Membrane-encapsulated organelles enclose specific proteins, nucleic acids and other substances to perform their functions within a particular space. Still, how other types of membrane-less organelles form and exert their biological functions has eluded investigators for many years. In recent years, it has been discovered that different intracellular biological macromolecules assemble and separate from each other to form liquid-like structures called “biomolecular condensates”….
and it goes on. It’s dauntingly complex, but I must say I wish I was 40 years younger and working in this fascinating field. To work out more precisely the processes involved and then to be able to manipulate them…
Canto: Homo deus indeed.
Jacinta: Femo deus if you don’t mind, and that’s not even a recognised term. I just can’t wait for the 31st century.
Canto: Well let’s just stay in the shallows and say a few words about these membraned and unmembraned intracellular organelles. Mitochondria we know a bit about, the ATP-yielding (making?) organelles that existed separately eons ago as prokaryotes…
Jacinta: Thank the indefatigable iconoclast Lynn Margulis for presenting this argument, and endosymbiosis in general, against vociferous mostly male opposition…
Canto: Lysosomes are the ‘digestive system’ of the cell, containing enzymes that break down the polymeric structures of proteins, lipids, nucleic acids and carbohydrates. They vary greatly in size depending on the digestive tasks they work on. The Golgi apparatus or complex is, unsurprisingly, a complex organelle that packages proteins to be sent out into the intracellular or intercellular world – nuff said. The endoplasmic reticulum has two sub-units, rough and smooth. They’re kind of attached to the nuclear membrane of the cell, the smooth further out than the rough. It’s involved in transportation and protein folding, let’s say no more.
Jacinta: So now to the membrane-less organelles – but it looks like phase transition as a subject for analysis is about how these organelles transition from dormant to active states or how they transition from one task to another. Anyway, just a few words to introduce these organelles. Nucleoli are defined briefly as ‘small dense spherical structures in the nucleus of a cell during interphase’. They also appear to segregate in unexpected ways as cells divide – again something about phase transition. Cajal bodies are often associated with nucleoli and are involved in the processing of some RNA molecules. They appear to have other roles that aren’t yet fully understood. Stress granules are these changeable, dynamic, liquid-solid entities made from RNP (ribonucleoprotein). P bodies are somewhat similar, as are U bodies, named for being ‘uridine-rich’, whatever that may mean. In any case P and U bodies appear to act co-operatively. Signalling bodies, according to Khan Academy:
A signaling molecule is released by one cell, then travels through the bloodstream to bind to receptors on a distant target cell elsewhere in the body.
Canto: Okay, that’s enough terminology, and we won’t do all the references as nobody reads this stuff anyway.
Jacinta: Fine, we’re having fun, though it may take till doomsday to get our heads around this stuff. Wish I could afford a lab, and all its equipment….
References
Peter Doherty, An insider’s plague year, 2021
https://go.drugbank.com/drugs/DB01611
https://www.nejm.org/doi/full/10.1056/nejmoa2007764
https://www.tga.gov.au/news/news/update-effectiveness-monoclonal-antibodies-against-covid-variants
touching on women, the principal carriers of bonobo humanity
that book again…
So I feel I’ve been skating around the edge of the bonobo world lately, not getting the message across, and not even quite sure what the message is. Clearly their sexual openness is sort of intimidating to many humans, but it’s also clear that this openness is profoundly connected to their culture of greater caring and sharing than exists in chimp culture, or our own. It slightly annoys me when commentators suggest we should look past the sexual activity to the bonding and helping and mutuality that goes on, as if we (very literally) buttoned-up humans can have one without the other, but having said that, I too am nervous about focussing on frottage, outside of Max Ernst.
So now I’m going to focus a bit more on the sexual side, and not just in reference to bonobos. Some years ago I read Jared Diamond’s little book Why is sex fun? (though I was pretty sure I knew the answer). Erogenous zones are hypersensitive, even more so when stimulated by another – like tickling, only different somehow. And with concealed ovulation, adult humans, like bonobos and dolphins, are sexually receptive for most of the time. This isn’t the case with chimps, so for bonobos this is an intriguing case of relatively recent evolution. Diamond’s book didn’t speculate too much, but looked at two extant theories:
“Many-fathers” theory says that concealed ovulation allows women to have sex with many men and create paternity confusion, which then decreases the chances of infanticide. “Daddy-at-home” theory says that women entice men to be around, provide and protect, by allowing them to have sex regularly. By combining both, we reach the conclusion that concealed ovulation arose at a time when our ancestors were promiscuous to avoid infanticide (“many fathers theory”) but once concealed ovulation evolved, the women chose monogamous relationships with more dependable cave-men (“daddy-at-home theory”).
Much of this is less than relevant to today’s WEIRD human world with its contraceptives and prophylactics, but ‘permissive’ sex has still to overcome the barriers of religion, and, for women, discrimination.
In any case Diamond completely missed the possible role of sex in bringing people together, in creating alliances, and the kind of overall cultural harmony that appears to subsist in bonobo society. This cultural harmony, which transcends the mother-child bond or the supposedly ideal development known as the nuclear family, has been the main attractant for me vis-a-vis bonobos, because I was brought up in what is called, by cliché, a ‘toxic family situation’, bearing in mind Tolstoy’s clever dictum that every unhappy family is unhappy in its own way. This situation was most salient for me in the late sixties and early seventies, the ‘hippy era’, when free love was touted, along with the death of the nuclear family. The hope that this idea gave me in my teen years was almost unbearably painful, but it all fizzled out. I didn’t learn about the bonobo lifestyle until more than a decade later, in the mid to late 80s, but that was rather too late, and a whole species out of reach…
But that’s just my personal situation. Bonobos still offer an example for our species in general, as we socially evolve, very slowly and in piecemeal fashion, out of patriarchy. But what exactly is this example, if it isn’t sexually modulated empathy, which is so far from a species that is so compartmentalised, un-neighbourly, sexually repressed, competitive, materialistic and personally hubristic as ours?
Of course, the hope surely lies with the greater empowerment of the human female, who, by and large, hasn’t quite the intensity of the above-mentioned traits than the male. Or am I just pissing in the wind? Of course, there are outrageous and apparently obnoxious females on the political scene, especially in the USA, when a lot of reportage focuses on the outrageous and obnoxious. But I believe, and fervently hope, that women are better at operating co-operatively and below the radar. For example, I’ve written before about Arab and Israeli women getting together to lobby against injustice and to promote sexual freedom, amongst other things (okay, sexual freedom is probably low on their list of priorities right now), a particularly difficult task considering the status of women in Moslem cultures, and their apparently feverish fear of homosexuality, especially among the lower classes. The Haifa Women’s Coalition, for example, based in that coastal northern Israeli city, suffers from the sorts of cultural tensions no bonobo would ever have to deal with, such as a concern about being dominated by Ashkenazi Jews, and a fear of backlash re ‘abnormal’ sexual preferences. Sigh, if we could only just give in to and celebrate sharing our basic primate primacy.
I could go on about the backlash against female empowerment in China, Russia, Burma, the Middle East, etc etc, the product of power politics that I like to hope are ultimately ephemeral – given a 1000+ year time-line for a bonobo humanity – which reminds me, I need to save my pennies to be cryopreserved – I really really want to see that future.
Meanwhile, I’ve noted, rather belatedly, that others have been discovering and basing some writings on bonobos, one way or another. Two recent examples, The bonobo gene: why men can be so dumb, is apparently a light-hearted account by an Aussie TV sports producer, Steve Marshall, of toxic masculinity and the male appendage. It’s clearly not about science (what could this bonobo gene be?), but anything that mocks the jocks can’t be a bad thing. More intriguing to me, though, is The bonobo sisterhood: revolution through female alliance, by Diane Rosenfeld, which sounds like it’s tactfully avoiding the sexual stuff. We’ll see – I’m definitely going to grab myself a copy.
Taking the long view on a future bonobo humanity is of course the only way to stay hopeful. In spite of the situation in Israel-Palestine, in Ukraine-Russia, in Afghanistan, Syria, South Sudan, Burundi and so on, the human world is far less overtly violent than it was centuries and millennia ago. Reading Simon Sebag Montefiore’s rather too whirlwind a world history (The World: a family history), amongst countless others, will tell you that. Even with a nuclear holocaust currently hanging over us (I recently encountered someone who fervently favours a nuclear strike – and strong male leadership – to stop Putin), and our slowness in handling the global warming crisis, I can’t seriously envisage a future human wipeout. The fact is, it often takes shocks at our own cruelty and stupidity to bring about anything like bonoboesque reform. It took two World Wars and all the barbarity they entailed to get us to become more global in our concerns, to take more seriously the concept of universal human rights and united nations, though these are still not taken seriously enough. Worse before it gets better? I can only hope not.
Meanwhile, I must get hold of that book…
References
on the French political system, and maybe bonobos
I’ve always had an interest in France, its history and its literature, having done a BA in French language and literature, decades ago, for some reason. Stendhal and Beauvoir are a couple of my heroes. I even stayed in Paris for a week a few years back – bien exotique pour moi. But whenever I read about French politics, I just felt confused. They have a President and a Prime Minister, but which, if any has seniority? Have any of them been female? I knew that, in spite of a prominent female intelligentsia, France has had a reputation as a rather chauvinist nation, but I’ve never made much effort to dig deeper.
So, as I’m just finishing off Cecil Jenkins’ A brief history of France, which, being brief, hasn’t managed to unconfuse me, I’m going to use this post to educate myself a bit more, while keeping bonobos – that’s to say dominant women – in mind, wherever I can find them.
France is currently experiencing its Fifth Republic, constituted in 1958 under then President Charles de Gaulle. The Constitution of 1958 still operates, apparently. From Wikipedia,
The constitution provides for a separation of powers and proclaims France’s “attachment to the Rights of Man [sic] and the principles of National Sovereignty as defined by the Declaration of 1789”.
Whenever I think of the ‘Rights of Man’ and 1789 I think of honorary bonobo, Olympe de Gouges, playwright, political activist, humanist and author of the Declaration of the Rights of Woman and the Female Citizen, whose moderate opposition to Robespierre and the radicals led to her execution during the Reign of Terror.
The first thing I should say about the current French political system is that it seems brain-befuddlingly complex to me. Cutting to the chase, the President has, these days, a considerably more powerful position than the Prime Minister, whom he’s responsible for appointing. There has of course never been a female President, hardly surprising for a nation that didn’t even allow women to vote until after the Second World War. At least there have been a couple of female Prime Ministers, Edith Cresson (1991-2) and Elisabeth Borne (2023-Jan 2024), neither of whom managed to last a year.
French state politics seems based on a key, controversial concept – dirigisme. Often associated with de Gaulle’s post-war government, and the ‘Trente Glorieuses’, a thirty-year period of largely state-managed growth following WW2, dirigisme is an odd amalgam of authoritarianism and something like socialism, which has seen France benefit from some of the most generous health and welfare benefits in the world. I can well remember my shock when riots broke out last year because of a proposed raising of the pensionable age by the Macron/Borne government, from 62 to 64 (the original plan was to raise it to 65). I found it hard to believe that any wealthy, healthy nation could maintain such a low pension age. In Australia, the age is now 67, and rising. It should also be noted that, according to the New York Times:
Macron sought to gradually raise the legal age when workers can start collecting a pension by three months every year until it reaches 64 in 2030 (!).
Such generosity seems scarcely credible to other WEIRD world countries, surely, remembering that increased longevity means many pension payouts for upwards of 30 years. They do have some kind of pay-as-you-earn scheme, but it doesn’t seem to be as comprehensive as Australia’s superannuation system.
So, Presidential elections are held every five years (reduced from seven in 2000!), and Emmanuel Macron won the last election in 2022, defeating the less than bonoboesque Marine Le Pen in a run-off second vote. So Macron will have been Prez for ten years at the end of his term, which seems a bit much.
So the run-off system clicks in when no candidate gets a majority – 50%+ – in the first round, which will be commonplace when there’s a large field and a diversity of public views/ideologies out there. My own personal view is that the two or three candidates with the most votes should get together and form a collaborative governmental team, but that’s no doubt way too idealistic. However, bonobos come close to managing it, according to Wikipedia:
At the top of the hierarchy is a coalition of high-ranking females and males typically headed by an old, experienced matriarch who acts as the decision-maker and leader of the group.
Ah, if we could only achieve the emotional maturity of bonobos, what a wonderful world it would be.
So the Presidential elections in France don’t involve anything so pesky as an Electoral College, and they don’t pit one I-alone-can-fix-it guy against another, instead they have any number of I-alone-can-fix-it guys, but someone has to get that 50%. And then there’s the legislative election, the last of which was held in June 2022, shortly after the Presidential election, and that’s the way it has been since 2000 – in other words they’re also held every five years, and candidates are elected as députés to the National Assembly, the Parliament’s lower house. There are no less than 577 of them, including eleven who represent, surely rather vaguely, the ‘French overseas’. This presumably multi-party crowd makes for interesting decision-making, or not. And finally there’s the upper house, the Senate (at least it’s not the House of Lords, which should’ve been killed off by now – how many female lords are there?), which consists of 377 six-year term senators. I would say ‘don’t ask’, but I suppose these long terms at least reduce the cost of more regular elections. I just wonder how this rabble of almost a thousand politicians ever gets things done. Then again I’m in favour of more collaborative government, with lots of involvement, so I should be careful what I ask for…
So who/what are the main French parties? Australia has the Liberals (actually conservatives), the Nationals (rather more conservative, and in coalition, sometimes fractious, with the Libs), the Labor party (generally centre-left, and currently in government), the Greens (further left), and a semi-connected group of independents, with a large proportion of women. Currently, 44.5% of Australian federal parliamentarians are women. In France, the percentage as at 2017 – I can’t find more recent figures – was 38.8%.
The French parties are a little more numerous – on the more or less extreme right is Marine le Pen’s National Rally (Rassemblement National), then there’s the more centre-right Les Republicains, and in the centre is Macron’s party, Renaissance (formerly La Republique en Marche!). On the centre left is the Parti Socialist, with La France Insoumise (rebellious France) on the radical and greener side. In the last elections, the ‘old guard’ leftist and rightist parties, i.e the Republicans and the Socialists, performed very poorly,
Pretty straightforward, but I’m trying to work out how it all comes together, particularly relating to the President (currently Macron), the Prime Minister (Gabriel Attal) and the president of the National Assembly (Yaël Braun-Pivet, the first woman to hold the position) and their respective powers. In Australia, there’s no President, and the Prime Minister leads the lower house as the head of government, though there’s a Speaker, chosen from among the governing party MPs, who keeps order in the house (and maybe that’s the role of the National Assembly prez). Anyway, the role of the French PM is nothing like that of our PM, in that he (Gabriel is male) is appointed by the President and ‘is the person who controls the government of France day-to-day’ (Wikipedia), presumably leaving the President to hob-nob with other world leaders and promote the country overseas.
So it sounds like the French President, like the US President, doesn’t have to lower himself by sitting in the parliament, suffering the slings and arrows of outrageous opposition members and back-benchers. And he gets to dump his PM, it seems, whereas our PM can only be dumped by a full party vote.
Anyway, that’s enough of this sujet for now – I’m sure I haven’t fully worked it out but it’s been fun trying… and I’ve note an occasional ‘first female’ along the way. Vive les bonobos en humaine – it may take a thousand years, but it will happen.
References
Cecil Jenkins, A brief history of France, 2011
https://en.wikipedia.org/wiki/Olympe_de_Gouges
https://en.wikipedia.org/wiki/Politics_of_France
https://en.wikipedia.org/wiki/Dirigisme
https://en.wikipedia.org/wiki/2022_French_presidential_election