Archive for the ‘genetics’ Category
epigenetics at the very beginning of life – my explorations
So let me see if I can understand epigenetics through other sources, and through what I’ve read so far. First, it’s essential for the very first cell divisions in human – or shall we say mammalian – life, at least for placental mammals. Their lives begin with a fertilised egg, a sperm cell and an egg cell (both known as gametes), each with its complement of DNA (but the egg cell contains much more, and there’s a difference between an ovum and an oocyte, which I won’t go into, as if I could). This cell, also known as a zygote, is the ultimate totipotent stem cell, potentially able to form every type of somatic (diploid) cell. So what causes this cell to divide and multiply, and become, in a few days, a blastocyst?
A blastocyst is already quite a complex collection of cells, with an outer layer, the trophectoderm, an inner cell mass, and a blastocoel, which is a fluid-filled cavity. So, already quite a jump from a zygote, so I need to know how that happens. But even before that, I need to know how a zygote comes into being. Wikipedia puts it this way:
The formation of a totipotent zygote with the potential to produce a whole organism depends on epigenetic reprogramming. DNA demethylation of the paternal genome in the zygote appears to be an important part of epigenetic reprogramming.
That doesn’t help too much, but I’m guessing that this ‘epigenetic reprogramming’ thing is what creates cell diversity – but this description tells us that the formation of the zygote is itself an epigenetic product. Here’s another description of the first steps:
The four stages of embryonic development include fertilization (zygote formation), cleavage (rapid cell division), blastocyst formation, and finally, implantation into the uterine lining.
Cleavage? The website I filched this from (ferty9.com, listed below) fails to elaborate, and looking up the word an sich just takes me to female breasts, which is pleasant but distracting. AI (never lies) gives more detail, claiming four cleavage stages, 1. the zygote stage, 2. the 2 to 8 cell stage, 3. the morula stage, and 4. blastocyst formation. And presumably epigenetics plays a role in the move from one stage to the next?
So, I’ve tracked down a most sciencey article, from ScienceDirect, entitled ‘Epigenetic regulation of early human embryo development’, which I hope to make sense of. Its opening paragraph is a bit daunting though:
Epigenomes undergo profound change during the first few days of embryonic development. The resetting and establishment of epigenomes are coordinated within and contribute to the wider processes of embryogenesis. As a consequence, faithful epigenetic regulation is required to safeguard development and to establish long-lived epigenetic states that have effects on genome function throughout the life course.
So now we have epigenomes, and here’s a definition:
Epigenome: The epigenome consists of all the chemical modifications of DNA and histones of a cell/organism that contribute to regulate gene expression independently of DNA sequence.
Histone modification involves the post-translational modification of specific amino acids that influence the overall structure of histone proteins. Changes in histone structure may then influence their function, resulting in incomplete DNA unwinding that may also effect transcription activity. Major histone modifications include acetylation, methylation, phosphorylation, ubiquitylation, and, less frequently, ribosylation, sumoylation, and citrullination
References
https://pmc.ncbi.nlm.nih.gov/articles/PMC4783933/
https://www.sciencedirect.com/science/article/pii/S153458072101042
https://embryology.med.unsw.edu.au/embryology/index.php/Blastocyst_Development#Introduction
https://www.sciencedirect.com/science/article/pii/S1934590923003314
could I ever manage to get my head around epigenetics?
Nessa Carey’s book, The epigenetics revolution, was published in 2011, and discusses, and introduces, to many of us, gene methylation, histones, a number of different types of RNA, the names of specific genes, karyotypes, selective serotonin re-uptake inhibitors (SSRIs), phosphorylation, the Waddington epigenetic landscape and much else besides. Wikipedia’s account of epigenetics is no doubt more up-to-date, and is just about book-length (how long does a book have to be?), with over 200 references to scientific papers and such. Although the term was coined in the 1940s, the study of epigenetics is very much a 21st century thing, Our current knowledge of the area, like our knowledge of neurophysiology, has been one of the great developments in modern science. To read about it is exasperating, because there’s just too much to learn, to explore, to get your head around, and yet it’s vital to an understanding of who and what we are. When I think of SETI, for example, the Search for Extra-Terrestrial Intelligence, I wonder – how could such ineffable super-complexity have developed more than once in the universe, even given its incalculably massive extent?
I wish I was young and gifted with the opportunity to work in such a field, one which explains us, or tries to. How we manage to replenish all the cells in our bodies throughout our lives – not perfectly, for then we could live forever – but for a period extended enough for us to learn our own history, to fall in love, to learn from our many mistakes, to experience, delight in and suffer through all the stages of life, to observe all its amazing variety – the birds and the bees as they say, and the flowers and the trees, all of which have their genetic blueprints.
To think we had virtually no idea of this only a century ago, and we are 300,000 years old as a species, and DNA-driven creatures have existed for millions, maybe billions of years on this planet. We only worked out the structure of this molecule in the 1950s, and now we know for example that a spruce tree contains about six times more DNA than a human, and that it’s likely that our world was preceded by an RNA world, which still enlivens the viruses that plague us with influenza, hepatitis, polio, COVID-19 and so much else.
And all this epigenetic stuff – which is mainly about DNA methylation and histone modification – has been going on beneath our awareness, and certainly without our permission, since our life began as an embryo. That’s how our cells differentiate into some 200 different types. It has much to do with whether we’re tall or short, sickly or healthy, extroverted or introverted – even before we’ve ever met another soul. All of these goings-on in our growing bodies, as well as the inter-connections, disconnections and reconnections in our growing brains, in the time spent connected to a placenta and the subsequent years being buffeted by parents, relatives, strangers and frenemies, are what shape us for a lifetime.
So where am I going with all this? Those who know me might guess, and be much annoyed, or much heartened.
To return to Carey’s book, which explores, inter alia, how laboratory creatures like rats and mice show specific patterns of behaviour for a lifetime after early deprivation, stress and other conditions, I was struck by this passage:
The human brain possesses sufficient flexibility to generate adult outcomes in response to similar childhood experiences. Our brains contain one hundred billion nerve cells (neurons). Each neuron makes links with ten thousand others to form an incredible three dimensional grid. This grid therefore contains a thousand trillion connections – that’s 1,000,000,000,000,000 (a quadrillion). It’s hard to imagine this, so let’s visualise each connection as a disk that’s 1mm thick. Stack up the quadrillion disks on top of each other and they will reach to the sun (which is 93 million miles from the earth) and back, three times over.
That’s a lot of connections, so it’s perfectly possible to imagine that our brains have a lot of flexibility. But the connections are not random. There are networks of cells within the giant grid which are more likely to link to each other than to anywhere else. It’s this combination of huge flexibility, but constrained within certain groupings, that is compatible with a system that is mechanistic but not entirely deterministic.
Nessa Carey, The epigenetics revolution, pp 235-6
This is, I believe, the only passage in Carey’s 300-page book that refers to determinism, and of course it struck me enough to write one word in the margin.
‘Really?’
I don’t often write in the margins of my books these days. Decades ago I had a girlfriend who expressed shock and great disapproval at finding margin notes in some of my books. She apparently found this behaviour to be sacrilegious in some way. Texts were sacred even if they were reproduced in their thousands. So, though I respectfully disagreed, I’ve reduced my sacrilegious behaviour, maybe to honour her memory. But this time I couldn’t resist.
– ‘mechanistic but not entirely deterministic’? What is the difference between these two terms? Aren’t these mechanisms determined by other mechanistic processes? Isn’t this what the book is all about? Isn’t this how we know about epigenetic processes, because they produce certain changes under certain specific conditions? Aren’t the determining factors precisely what we’re looking for, and what knowledge is all about. And yet there is, I find, a kind of fear or distrust of the word, even amongst those researchers who rely on mapping out the causal chain, often a complex and elusive one, to make good their discoveries. Whether we’re looking at the causes of cancer, or how one or two bees become queens while thousands more become workers, to mention just two topics explored in Carey’s book, we’re always trying to uncover and explain the determining conditions. It’s the sine qua non of all science.
Maybe I’m mis-representing Carey here. Maybe she meant, when she described the ‘huge flexibility’ of our neuronal system, the impossibility of trying to pin things down, cause-and-effect-wise, with absolute certainty. But then, that’s not what she wrote. She wrote ‘not entirely deterministic’, and that was a red flag to me. So what was the part that escaped determinism? It doesn’t actually make sense.
The idea, it seems to me, and the argument that most people try to use against determinism, is that complexity trumps it (sorry to use the word ‘trump’ here). If complexity was infinite, that might be so, but complexity isn’t infinite, it’s just complex.
So, that’s enough for now. Again, I wish I was fifty years younger, and a more disciplined person than I was in my youth, because I’d love to be working in the field of organic chemistry, or molecular biology, or neurophysiology, rather than peering at it over a vast stretch of ignorance, as I am today. But never mind…
References
Nessa Carey, The epigenetics revolution, 2011
on epigenetics and the free will debate, and such…
The free will thing has come to the fore of my head again recently because of an offhand ‘no free will’ remark I made, which of course caused some friendly argy-bargy. When the topic comes up I like to throw ‘the lot’ at it, our early neurological wiring, unwiring and rewiring, our hormonal activity, our genetics, our epigenetics, our position in the womb, our early interactions with parents, siblings and others, our culture, our gender, our first language, the time and place of our birth and so on.
Of all these variables, epigenetics is one that’s likely to catch people off guard. If they ask, I’ll say it’s all about gene expression, hoping that will silence them, and even impress them. But if they inquire further, I’d only be able to say something like ‘environmental factors affect how genes are expressed’ – and that would be the limit of my knowledge, even though, some years ago, I read Nessa Carey’s The epigenetics revolution, published in 2011.
So now I’m reading it again, and it seems for the first time. I’m finding it really hard to understand, and I’m sure it isn’t Carey’s fault. I suspect it’s the kind of topic in which you need to be active in the field to fully understand it, and even then….
But, I’ll have a go. Rett syndrome is a rare but devastating neurological disease which occurs almost exclusively in girls. Apparently, if a male child contracts it, it’s more or less immediately fatal. As AI (never lies) puts it:
Infants typically develop normally for 6 to 18 months before experiencing a severe regression in motor skills, speech, and hand use. While there is no cure, symptoms can be managed with targeted therapies and specific medications.
The development of this syndrome happened to coincide with infants receiving the MMR vaccine, which, as we know, caused much controversy some time ago, but the mechanism was worked out in 1999. It mostly has to do with mutations in a gene called MECP2, which severely affects the production of a functional MECP2 protein. Dysfunction/mutation in other genes have caused the syndrome, or something like it, in a minority of cases. The cells are able to methylate their DNA correctly, which is what much of what epigenetics is all about, but they’re unable to read that section of the epigenetic code properly. So Rett syndrome isn’t a mental/psychological disorder at all, it’s purely genetic, and because the dysfunction is on the X chromosome, and because females have two X chromosomes while males have XY, the male karyotype is more vulnerable to the condition.
I choose this extreme condition (suffered by one in 8500 females) as one among many examples of how our genetics can fail us, and there are many others, much more subtle and hard to pin down, both in terms of our genes themselves and how they are expressed. We – I mean the scientists and researchers among us, and those going along for the ride – have learned especially in recent decades just how complex and beyond our control our brains and bodies are, not just in terms of physical make-up, but genetic and cultural inheritance. A regular awareness of this – a mindfulness, if you like – helps me to cope with the people who damage our world – the war-mongers, the bullies, the intolerant and over-confident – as well as to sympathise with the overwhelmed (like myself).
So, again to epigenetics – I’ll keep trying to comprehend at least some of it, as it’s intrinsically interesting when it’s not completely baffling. Meanwhile, I’ve had a book recommended to me, by two humanists and no-free-will proponents, called Being: why it’s harder to be human than a hamster or a herring, by a daughter and father duo, Rachel and Ross Menzies. Sounds like an antidote to all that epiphenomena…
References
Nessa Carey, The Epigenetics Revolution: How modern biology is rewriting our understanding of genetics, disease and inheritance, 2011.
the language apes – how we differ from bonobos etc
It seems that language is what separates us from every other species, and what has enabled us to dominate our planet. I suppose that’s stating the obvious, but how this language feature of ours evolved isn’t so obvious, as we can’t examine the brains of our more recent hominin ancestors, or listen to them talk, if they could, to connect all the dots. All we have to go on is an increasingly detailed knowledge of the neurological correlates to human language, and similar brain regions in chimps and bonobos. It’s an enormously complicated subject for the brain of a near 70-year-old ignoramus to dive into, so let’s do it.
What is ‘theory of mind’? It’s the ability to attribute mental states to others. We can do this with dogs and cats and other creatures we’re familiar with, in a vague way, but our fellow humans communicate this – not always accurately or honestly of course – with language. Certainly language is a tool that gives us an incalculably enormous advantage over other species, and we have created many thousands of them – languages, that is. It helps that we have brains some three times the size of our closest living relatives, but size isn’t everything, as we know, for example, from corvids and other smart species.
So we’ve been studying certain areas of the brain, such as Broca’s area, involved in language production, and Wernicke’s area (language reception) for many decades, and have found similar regions in other primates, though there are important differences. The human Broca’s area is larger in the left than in the right hemisphere, and there are similar but different enlargements for the left Wernicke’s area. The same asymmetry exists for their smaller, less developed analogues in other primates. Interestingly, left-handed types, like myself, have less asymmetry (or I’d prefer to say, more symmetry) than right-handers.
Sadly, we can’t study the brains of Neanderthals or any other extinct hominid in close relation to H sapiens to determine whether they had anything like our language skills, or indeed whether the first members of our species had them. According to AI (never lies), gathering info from such sources as the Australian Museum, Reddit, Wikipedia, Science Daily and Discover Magazine, ‘complex’ language (as opposed to complex language) was in operation among humans from 200,000 to 50,000 years ago, so it’s all a bit vague.
Exploring the issue by way of brain processes is more than problematic because I can’t see how we’ll ever have evidence outside of modern H sapiens, but what about the physical structures required to produce speech? There’s a difference, at least in my mind, between speech and language in that speech doesn’t necessarily involve grammar, it just starts with vocalisations representing objects, states (fear, pleasure, anger, warning etc). To produce these requires particular ‘hardware’. Here’s AI again:
The ability to speak required specialized “hardware” that differs significantly from other primates:
- Lowered Larynx: In humans, the larynx (voice box) is positioned lower in the throat, creating a larger space (the pharynx) that allows for a wider range of resonant sounds.
- Tongue and Mouth: Unlike other mammals, the human tongue is thick, muscular, and almost circular, allowing it to move vertically and horizontally to shape complex sounds like vowels.
- Breath Control: Humans evolved finer control over the muscles used for breathing, which is necessary to sustain the long exhalations needed for sentences.
The third item mixes hardware with neural developments, no doubt, but our current and perhaps permanent inability to trace these developments back in time is teasingly frustrating.
One interesting finding has to do with the FOXP2 gene, aka ‘the speech gene’, which we share with Neanderthals. It’s so named because it encodes the FOXP2 protein (Foxhead box protein P2), which is found in many vertebrates, and is associated with vocalisation, including birdsong and echo-location.
References
https://med.stanford.edu/news/insights/2025/09/speech-gene-foxp2-huntingtons-wysocka.html
genetics for the faint-hearted
get it got it good
What’s a haplotype? It’s a bunch of alleles, so I have to be clear first about alleles. A haplotype, also known as a haploid genotype, is a set of alleles inherited (as a set) from a single parent.
Alleles are pretty complex, at least to me. I think of Mendel and his peas, but it’s vague. Looking up a definition hasn’t helped much. It might, or might not, be better to start with DNA and/or RNA, and of course I know something about these macromolecules and their structure. They’re made up of nucleotides, and an allele is described as ‘a variant of the sequence of nucleotides at a particular location, or locus, on a DNA molecule’. This doesn’t help much. Do I repeat myself?
I’ll keep trying. There are haploid cells and diploid cells. In humans they’re called gametes – the sperm and the eggs, and they each have 23 chromosomes. Fertilisation of eggs by sperm creates zygotes which are paired – 23 chromosomes from each gamete type. Twenty-three pairs of haplotype make a genotype.
Why am I bothering with this? I can’t remember now, but I think it was about alleles. There is a problem in my mind about a haplotype, say inherited from Mum, and this ‘bunch of alleles’ thing. I mean, what’s the difference between an allele and a gene?
So I plug this into the machine. It seems that genes are things that code for things. In the phenotype. Your phenotype is the expression of your genes. Hair colour, penis size, intelligence maybe. Also I suppose your species. Bonobos have 24 pairs, but so do chimps. So…
Whales, since I’ve been focussing on them a bit lately, have mostly 44 chromosomes (22 pairs), but some species have 42.
Anyway this all began with talk on social media about XY and XX chromosomes, male and female humans and longevity. XY is male (for humans and some other mammals, and some fish, snakes and even plants). These are the ‘sex chromosomes’, at least in these species. That’s to say, the sex-determining chromosomes.
So a karyotype is, for my information, ‘the general appearance of the complete set of chromosomes in the cells of a species or in an individual, mainly including their sizes, numbers and shapes’. The sex chromosomes, obviously, are part of that karyotype, and they’re not always named XY or XX. Bird sex chromosomes, very interestingly, are ZW for females and ZZ for males. And what researchers are finding, in this doubling up (ZZ for male birds, XX for female humans) has some effect on their longevity – male birds, on average, and somewhat dependent on species – live longer than females, while female humans, and other mammals with XX chromosomes, live longer, on average, than males. Correlation or causation?
But all of this stuff on haplotypes, and full genotypes, is intrinsically interesting, and I could do a complete free online course on it, maybe…?
So if you know the genotypes of both your parents, could you work out their particular contribution to your phenotype? ‘I got my braininess from mum and my good looks from dad’ type thing? I should listen to the Sapolsky videos online maybe…?
If only I was 40 years younger. Still my genotype, and some luck, has kept me alive thus far…
bonobos – how did they do it, and how should we?
Science is always at its most thrilling when unsettled: it is the process of tackling mysteries, not the habit of accumulating facts.
Matt Ridley
bonobo matriarchy – still a mystery
So let’s switch from the ridiculous to the sublime and get back to bonobos. A recent bonobo video I’ve watched, together with my current reading of Carl Safina’s Beyond Words, which, so far, deals mostly with elephants, has made me wonder about the survival of these fascinatingly intelligent creatures in the wild. The human story of the DRC, where all wild bonobos live, has, since the arrival of white men, been one of horrific slaughter and suffering. The whites have mostly left, with their treasure, having created the boundaries of this new nation, where over 200 indigenous languages are spoken. Its official language, though, is French. It’s the second largest country in Africa, and has ten other mostly white-invented countries on its borders, along with a wee bit of the southern Atlantic. The land is very heavily forested, with bonobos being unevenly spread over an area of half a million square kilometres, bounded by the Congo, Kasai and Lualaba rivers.
The estimated minimum number of bonobos in the wild is between 15 and 2o thousand. Obviously it is hard to ascertain very precise numbers due to the dense terrain. The human population of the DRC is over 110 million. Habitat loss has been a problem, as has the bushmeat trade, hunting for medico-magical cures, and selling as novelty pets. Human depredations, enfin. Safina estimates the effects of such depredations on elephants:
Since Roman times, humans have reduced Africa’s elephant population by perhaps 99 percent. African elephants are gone from 90 percent of the lands they roamed as recently as 1800, when, despite earlier losses, an estimated 26 million elephants still trod the continent. Now they number perhaps 400 thousand (the diminishment of Asian elephants over historic times is far worse).
Bonobos were separated from chimps by the creation of the Congo River, said to be the deepest river in the world. The river is estimated to have formed between 1.5 and 2 million years ago, and this is supposed to have created the separate species. It sounds plausible, but I wouldn’t know.
Bonobos have been described as the hippy apes – probably by hippies. They’ve also been lauded for their vegetarianism, but they’re not vegetarian. Their lush environment has promoted a largely frugivorous and nutatarian diet, but the odd small monkey or large rodent-like creature, savagely ripped apart, doesn’t go amiss. What’s most interesting about them, for me, is their matriarchy, developed over those couple of million years, despite a slight, and apparently diminishing, size difference in favour of males. Bonobos are generally more gracile than chimps, and weigh less, on average (they used to be called pygmy chimpanzees). Their lips are more pink and kissable – well, maybe not, their faces are darker at birth, but lighten up with age, though their ears remain much darker than those of chimps. They have longer legs, and are more bipedal, and finally they generally have more high-pitched vocalisations than the guys north of the Congo. But does any of this offer a clue to their matriarchy? And are they really matriarchal? I’ve read articles that have claimed that there have never been any human matriarchies, though this seems to depend on the definition. After all, we can say that we, e.g. in Australia, live in a patriarchy, though it is less patriarchal than it was, a mere two hundred years ago. The change in that time has been social rather than physiological or genetic. Bonobos and chimps have, however, undergone physiological changes, as aforementioned – with respect to each other, and we have no way of knowing which of them has changed most. Interestingly there are four subspecies of chimps, with the possibility of a fifth. What’s the basis of these differences? Presumably they can interbreed, since bonobos and chimps can do so (they’ve done it in captivity and ‘genetic studies show that they have exchanged genes at least twice in the past 550,000 years [in the wild]’ – thanks, AI). And here’s what AI, which I presume is in this case a combination of primatologists, geneticists and such, has to say about the establishment of these subspecies:
Primatologists distinguish chimpanzee subspecies (or populations) based on a combination of genetic differences and geographic distribution. Genetic studies, including genome-wide analysis, reveal distinct populations with unique genetic markers. These genetic differences are often correlated with geographic separation, suggesting that physical barriers like rivers or mountain ranges have historically limited gene flow and led to the evolution of distinct subspecies.
References
Carl Safina, Beyond words: what animals think and feel, 2015
https://en.wikipedia.org/wiki/Democratic_Republic_of_the_Congo
https://www.bonobos.org/blog/whats-the-difference-between-a-bonobo-and-a-chimp/
Christopher Tyerman, God’s war: a new history of the crusades, 2006
more on the complexities of breeding behaviour – how do we know?
The Hapsburg, and sickly, Charles II of Spain (1665-1700). All in the family.
Here’s a simple thought experiment, if perhaps an unlikely scenario. Imagine two children born to the same parents, a male and a female. For some reason they’re both separated from those parents at a very early age, before they know each other as siblings. For the next twenty years or so they’re brought up in separate households, unaware of each others’ existence.
Guess what happens next – they meet, they ‘fall in love’, because after all they’re each as good-looking as the other, and they share interests, politics and ambitions, and they each want to start a family. What could go wrong?
Or more to the point of these explorations, how would these two individuals have any sense that they might be entering into dodgy territory? Of course they might start comparing backgrounds and entertaining suspicions, but what if they both share a tendency to bullshit about their past? Obviously this is a ridiculously rare scenario, but hopefully it makes a point.
So, when I try to learn about inbreeding I’m quickly taken into the inherent dangers, and the complexities of autosomal inheritance, whether dominant or recessive – all of which is fascinating in itself, but of little interest to bonobos, bats or budgerigars – or bodgies and widgies – when mating season arrives. Inbreeding avoidance is all very well if you know who to avoid. But a lot of the info I’m gathering tells me that we do know who to avoid, and I don’t just mean we humans. According to Wikipedia’s article on inbreeding avoidance, ‘there have been numerous documented examples of instances in which individuals are shown to find closely related conspecifics unattractive’. But this bald statement strikes me as totally unconvincing. I’m sure we could find plenty of ‘documented examples’ of the exact opposite too.
However there does seem to be something, beyond choice or preference or awareness, that promotes inbreeding avoidance, whether it’s pheromones, MHC (major histocompatibility complex) genes, or other evolved mechanisms. We generally manage it – and by ‘we’ I mean just about all breeding entities – but not in a foolproof way, it seems. What interests me is the kind of set process for inbreeding avoidance that we find in chimps, bonobos, Tiwi Islanders and other human societies, which rises to the point of incest taboos in humans. With humans there is knowledge. We know that breeding with siblings and other close kin is problematic, yet we probably didn’t always know that, and our taboos are more about it being ‘icky’ and ‘creepy’ than about giving birth to unhealthy children. What gave rise to those feelings, which seem to be shared by other apes, and perhaps further down the evolutionary bush?
Let’s look at MHC genes, though I don’t think they’re going to provide an answer that satisfies me. Here are the opening lines from a 2008 PubMed article entitled ‘Major histocompatibility complex alleles, sexual responsivity, and unfaithfulness in romantic couples’:
Preferences for mates that possess genes dissimilar to one’s own at the major histocompatibility complex (MHC), a polymorphic group of loci associated with the immune system, have been found in mice, birds, fish, and humans. These preferences may help individuals choose genetically compatible mates and may adaptively function to prevent inbreeding or to increase heterozygosity and thereby immunocompetence of offspring.
So, yes, I find nothing wrong with this finding, but maybe it’s a bit of a correlation-causation problem for me. I’d like a bit more info on the causal. And obviously all these creatures have no idea whether a potential mate has similar/dissimilar MHC genes, so why mention preference, which is about choice, or intention? But then, doesn’t love, or desire, strike us below the level of awareness? Ain’t love blind? Not to our MHC genes, apparently. And then again, is our preference for sweet rather than sour, or vice versa, really a personal choice or something we find out about ourselves? Do I contradict myself? Very well…
Anyway I’m glad to note the phrases ‘may help individuals choose…’ and ‘may adaptively function to prevent inbreeding…’ here, an acknowledgement, methinks, of the fact that they’ve observed a correlation which hasn’t yet been found as determinative – though probably everyone thinks it is. Meanwhile, we – human and myriad other species – seem pretty good at avoiding inbreeding, mostly, so why worry…
References
https://pubmed.ncbi.nlm.nih.gov/17100780/#:~:text=Abstract,HLA%2DA%20Antigens%20/%20genetics
why is being transgender so controversial?
The first time I lived completely away from family, when I was twenty-one, I shared house with two males, an older homosexual who never wore clothes in the house, and a bisexual who was more sexually interested in me than I was in him, so it was a challenging but fascinating environment. The older man introduced me to his subculture, which included a couple of men, quite elderly, at least from my youthful perspective, who wore dresses and had male partners. I think the word transvestite was used. This wasn’t particularly in-your-face stuff, with heavy make-up, flashy jewellery and fake busts, or whatever, though of course I was a bit nonplussed. These guys were softly spoken, feminine in their gestures, simply but femininely dressed, and clingy with their partners. This was all a revelation to me, and I remember being quite moved, even teary about it all. They seemed so quietly defiant, and contented.
I presume there have always been humans who have felt they were born into the wrong gender. Girls who, even before they really gave it much conscious thought, preferred the shapes, colours, textures and activities that we adults or parents associate with boys, and who, over time, became embarrassingly consistent about their ‘odd’ choices. And maybe it’s just a phase, but sometimes not. And some parents might push their kid to behave more ‘appropriately’, and some might not. And maybe science has an answer for all this, but maybe not.
All of this might involve genetics, epigenetics, pre-natal experience, parental treatment or a host of other causal factors I know next to nothing about. We’re surely the most complex species on the planet, which should make us proud but wary.
Transgender stuff is very newsworthy at the moment, with passions running high. My own position would be to accept people’s deeply felt views about themselves and never mind what the science says. But what does the science say? Can biology and psychology be separated? Is psychology a science? Can the brain and the body be seen as separate? (My answer to that last one is no, obviously).
So in exploring this issue I’d prefer to avoid youtube debates and legal decisions. As described in my previous post, I went through a period, particularly in my mid-teens, of what might be called ‘gender uncertainty’, though I found it more thrilling than disturbing, and tended to be proud of my ‘sophistication’. Perhaps ‘gender fluidity’ would be a more accurate term. But this faded over time and I came to be happy to accept that I was a boringly heterosexual male (cisgender, as they now call it). But I also recognised that this had to do with appearance. Fifteen year-old boys become twenty-five year olds, but not in the same way, physically, that fifteen year-old girls do. You could say that it was the ‘feminine’ side of boys that attracted me, which faded as they became ‘masculinised’. Note that there are many descriptions of boy lovers among the ancient Greeks – Achilles derived strength from his love of Patroclus and Aristophanes spoke favourably of ‘hermaphrodites’ in Plato’s Symposium. We’ve become rather more conservative in our sexual outlook since then, methinks. I blame patriarchal religion.
So, contradicting myself, I want to understand the British Supreme Court’s recent decision on sex and biology and why so many women seem to be very pleased about it – and I’ll start by saying I currently know very little about it. CNN London reports it thus:
The United Kingdom’s Supreme Court has ruled that a woman is defined by “biological sex” under the country’s equality law – excluding transgender women – in a case that is expected to impact accommodations for trans women in bathrooms, hospital wards, sports clubs and more. The court ruling on Wednesday is limited to defining the term “woman” within the country’s Equality Act 2010, meaning trans women are no longer protected from discrimination as women, although they remain protected from discrimination in other forms.
But, as the reporter points out, this will have wider implications, not only for what trans people will be able to do, but for how they’re perceived.
I note that the reporter puts “biological sex” in quotes, which is as it should be. A legal definition of an essentially biological matter is always going to be problematic. There are those who, from an early age, behave in a way that is seen as ‘gender inappropriate’ to what might be expected by noting their genitalia (see Donna the chimp as described in my previous post). They’re generally not doing it to seek attention, it just comes automatically. You could say their brain makes them do it, and not particularly consciously. And the brain is a 100% biological entity.
But the UK Supreme Court has chosen to consider ‘biological sex’ in a more reductive way, as have many conservatives. The Skeptics’ Guide to the Universe, a science and skepticism podcast that I’ve been listening to regularly over the past 15 years, recently featured an interview with Dave Farina, a popular science communicator on YouTube, in which the transgender issue was briefly discussed. It seems there are some other science communicators, notably Richard Dawkins and Jerry Coyne, who take a strong line on ‘biological sex’, largely based on gametes. And shamefully, I had to look the term up, though I’ve doubtless written about them before. Gametes are the sex cells – ova in females, sperm in males, which combine with their opposites to produce offspring. So, according to Dawkins, Coyne et al, the whole gender controversy can be reduced to these haploid cells (cells containing half the genetic material of diploid cells, the somatic cells of all mammals). You are what your gametes reveal. According to these scientists, this isn’t reductive, but entirely determinative, regardless of thoughts or ‘gender-affirming’ surgery. Farina and the principal host of The Skeptics’ Guide, Steven Novella, firmly disagreed, and more or less dismissed Coyne and Dawkins as members of a ‘passing generation’. We shall see.
So what to do with these trans people, with their wayward thoughts, their fantasies? And why was the Supreme Court’s decision met with such glee, by so many women? A spokeswoman for the campaign to prevent transgender women from being recognised as women, on being interviewed after the decision was handed down, expressed ‘great sympathy’ for their position, but common sense had prevailed, and – what? These people, a tiny proportion of the population, have been left in no man’s land, and no woman’s land either. If this is sympathy, I wouldn’t like to experience her hostility. What solution has been offered, apart, it seems, from forcing them to recognise that they’re deluded?
This is obviously not going to be the end of the matter, and indeed it will create greater acrimony within and between genders than there ever was before.
Meanwhile, I’m still wondering about those unisex toilets. I like the suffix uni-. I like to think it stands for ‘united’.
References
https://www.apa.org/topics/lgbtq/transgender-people-gender-identity-gender-expression
https://edition.cnn.com/2025/04/19/europe/uk-supreme-court-biological-woman-intl/index.html
on gender, and bonobos
the gender agenda, and other positives
It’s New Year resolution time, which I try not to pay much attention to, and yet… I’m thinking of/resolving to focus on the biggest issue that bugs me, rather than trying to expand my understanding every-which way (corals, dark matter, Milankovich cycles, the cryosphere…), and that’s our culture and politics, in the broadest sense, including our existence as primates, mammals, forms of life. Dominators of the biosphere.
So that’s why gender is important to me, because one gender, in the sexually reproducing world, nurtures and brings forth life from her own body, and so, it reasonably follows, has a greater regard for life than the other. Yet, reasonable though this observation might be, it often meets with resistance, sometimes mounting to hostility, from members of the other gender. In the case of Aristotle – and no doubt his idea was formed from the ancient Greek zeitgeist – it was the male’s seed that produced the next generation, the female being nothing more than the incubator.
I’m interested in exploring why humanity came to be, by and large, patriarchal, and how we can be less so – much much less so, because I’m deeply convinced that this is our best path to the future. A long and winding road, I suspect.
I’ve retitled this blog a few times, but it has been called ‘A bonobo humanity?’ for some time now. I’ve wondered occasionally about changing the title again, as people have looked quizzical, or chuckled, and even sneered. For those who know at least something about bonobos, the general impression I’ve felt has been – ‘yes, cute, but really what has this got to do with us?’
So yes, bonobos are hairy, more or less ugly (to us), forest-dwelling, sex-obsessed frugivores who will never express themselves in a complex language, never invent a complex device, never play a musical instrument or wonder where those twinkling lights in the night sky came from. They have nothing to teach us.
And yet, we study them, just as we study other primates, and mammals, and our own human history, and so on and so forth. To learn about, and to learn from. And in the process, we’ve discovered, as we have with so many species we’ve turned our attention to – complexity. Remember the term ‘bird-brain’? Those brains in those tiny heads that enable their owners to build complicated nests of all kinds, to communicate all sorts of tuneful messages to their kin, to use humans to crack nuts for them, to fashion tools from twigs to spear tasty morsels for themselves and their chicks?
Yes, we’re smart to have uncovered these smarts in other species, which has helped us to respect the cleverness and complexity of life itself, its amazing development from the earliest archaea or whatever. But the neurological developments that led to H sapiens, the massively dominant species on this planet, in destructive as well as productive terms, are of the greatest interest. How is it that this most complex species, which has divided its billions of specimens into hundreds of nations, can allow individuals like Donald Trump, Vladimir Putin or Xi Xinping (and many other repugnant characters) to wield power over millions of their obvious intellectual and pro-social superiors? Why is one gender, the more pro-social of the two, given so much less power than the other? I like to think that the situation is changing, but if this is so, it’s at such a heart-rendingly slow pace that it really is painful to bear.
Even so, I tend towards optimism. We’re programmed to survive, not just individually – no species survives individually – but by working out what’s best for us all. And I do mean all, and that’s an endless learning process.
What I’m doing here, in this first post for the new year, is trying to work out how to put my queer shoulder to the wheel. I’m being inspired by writers such as Frans de Waal, Cat Bohannon and Rutger Bregman, by positive texts such as Glimpses of Utopia by Jess Scully and The Future We Choose (as yet unread!) by Christiana Figueres and Tom Rivett-Carnac, and by the work of all those in the field, protecting wildlife, providing education, supporting effective solutions, promoting hope and thoughtfulness. But enough of this sludge, it’s 2025, let’s see what we can do!
References
Jess Scully, Glimpses of utopia, 2020
Frans de Waal, Different, 2022
Rutger Bregman, Humankind:a hopeful history, 2020
Christiana Figueres & Tom Rivett-Carnac, The future we choose, 2020
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: