Heard part of an interview with the author on NPR a few weeks ago (I think) and he seemed like a genuinely curious person, so I have pretty high hopes for this one.I only have a few more books in mind, so any suggestions are welcome going forward.AmazonWorldCatOverDriveLibgenShort Review: This is an amazing book, an exploration of the mechanics of life approached with a genuine and non-philosophic curiosity that results in some pretty significant insight across the board. This is easily the best biology related book I have ever read (and it’s not even close), and I cannot recommend it enough. I look forward to the author’s future work and definitely am going to work through their prior work. Thank you for the journey Siddhartha Mukherjee.Prelude: Heh, the quote. Not only the basis of one of the most misquoted literary phrases of all time, but a great encapsulation of one of my big communication pain points.
“Each cell leads a double life,” Schleiden would write a year later, “an entirely independent one, belonging to its own development alone; and an incidental one, in so far as it has become part of a plant.”
Nice.Didn’t know his specialty was cancer, this opening seems more obvious in that context. Heh, setup expectations succinctly, nothing bonkers so far. I’m still in.Introduction: Lol, a prelude and an introduction?Man, I wish I could remember the name of the author right now, but every time I read cancer work it always reminds me of the work by a particular author who did lots of work research regeneration in planarians. How planarians not just regenerate their entire bodies from their subdivisions, but how those parts resynchronize their intercellular communication to form essentially a new organism (and what happens when they don’t). I’ll try to remember to look that up.This intro reminds me of the previous book, chasing a cure that the target won’t ever benefit from. We can only build for the future.Hah, and then straight to Emily’s story.A woman with crippling, recalcitrant depression whose nerve cells (neurons) are being stimulated with electrodes.
It’s kind of weird how pervasive this oof is, not really criticizing the author since the sentiment is so pervasive, however the longitudinal success of DBS looks about the same as Sam’s treatment. You can temporarily juice the metabolism, but the underlying expression mechanics are going to catch up eventually (usually no more than 3-5 years for dyskinesia for instance). Stupid nitpick since it’s not his point at all, he’s going for more of a hybrid ship of theseus conceit, but whatever.In a sense, then, one might define life as having cells, and cells as having life.
It’s not that much worse than our current definitions. Really fluid introduction to “behavior” in the context of cells, and how that extends out to the organism.Yes, there was the virus, but viruses are inert, lifeless, without cells.
BOOOOOOOOOOOOOO. Should probably read his other two books tonight if I get a chance.The Original Cell: I often wish I wasn’t so “autistic” that I could understand the need to inject biographical information so heavily in stories, especially in support of “great man” narratives.Heh, this part about the drawings reminds me of how heavily dependent we’ve been up until the last five years or so on these old, hundred year old anatomy drawings. Like I’d bet the average age of a drawing from Gray’s was at least 75 years old.The Visible Cell:In the sum of the parts, there are only the parts. The world must be measured by eye.
Sigh, and this leads to missing the trees for the forest, or seeing the world as a low resolution blob that discards granularity and nuance for convenience.Even though this is another “great man” narrative and it gets retold pretty often, Leeuwenhoek’s story is still pretty cool. I guess it’s because he was in it because we wanted to know rather than for the plaudits.Heh, then we transition to the co-president of the douche club, Hooke. Although it always reminds me of that epic rap battles episode with the other co-president of the douche club (they gave Al Newton’s “Standing on the shoulder of giants line”). (Skrillex beat Mozart, fight me). Damnit, 30 minutes watching those. What’s wrong with me.The Universal Cell: It’s interesting that x-ray crystallography is still kind of the top of the mountain for imaging, despite all of our advances, we’re still stuck on these imaging constructs from more than half a century old. Hot take, Remak (and most polymathic iconoclasts) was a dorsal dominant phenotype with CA2 binding “differences” (contrasted against the ventral dominant Hooke and Newton).I don’t think vitalism ever went away, would actually argue that the “electric brains” construct is a type of vitalist argument.Trying everything to avoid devolving into a broader socio-political argument, but it’s kind of bonkers that we still use the “great man” naming schemes (e.g. Schwann, Muller, etc) rather than a standardized scheme descriptive of function. It reminds me of how 19th century land grands would consist of hundreds to thousands of acres, and we carry this dynastic ownership of land (or thought metaphors like cell names) make it more difficult for future generations to “achieve” what prior generations that essentially lucked into these things did. Breaking these dynastic ownerships of knowledge only creates new dynasties but leaves less canopy for those that follow. We don’t always stand on the shoulders of giants, often we are getting crushed by them.Cells come from cells, but I’m still team RNA world, and the cells came from somewhere (with a nod that there were almost certainly pre-RNA conditions). I really really dislike the “ordered/disordered” conceit, even in this context, especially as it’s been applied to neuroscience (via psychiatry). A “diseased” cell may be executing exactly as programmed, and a sickled cell may be a life saving adaptation tomorrow.The Pathogenic Cell: I can’t imagine washing my hands with chlorine, would be torturous. Had to switch to bromide because chlorine fucks me up so bad. Hey, John Snow again! Didn’t I make a crack about him a couple days ago? OMG, I totally forgot that people used to fucking BURN PHENOL IN THEIR HOMES FOR HEALTH. Ahh, he sorta got around to RNA world.life has only two principal domains—bacteria and archaea—and eukaryotes (“our” cells) represent a relatively recent sub-branch of archaea.
I hadn’t thought about it like this. Wow. Hrm. (Still chewing on this one, but the idea of eukaryotes being descendant from archaea, while archaea are dependent on eurkaryotes is some Christopher Nolan shit. Could say they “made their own ecosystem” as a buffer from the external ecosystem. puff puff )The Organized Cell: No knock on Overton, but his name gives me the willies because I see it so often on Gab. This bit is actually a really good reminder of how recent a lot of our understandings are about the mechanics of cells, like 40 years ago what did we know about RNA period? Or the actual structure of cells other than gross morphology? Like we didn’t even have a clue about what mitochodrion did in any fashion until around the 1960s. Eh, there eukaryotes that don’t have mitochondrion.This description of Siekevitz’s work is really cool. Holy shit, Jared at 11 is a billion times more insightful than I’ll probably ever be.The Dividing Cell: So… neurons may not divide, but that’s only because they are hyper specialized cells. Progenitor cells divide constantly and do divide and create new neurons throughout the life of an organism, same with glia and most other cells in our body. This is “hidden” because we are so super focused on visual morphology, but this should be kind of obvious now with the ability to roll back glial cells and re-specialize them into other cell types.Cool, some new jaron, G0/G1 (heh, like CNC code). Wonder how I missed this. He’s super fascinated by IVF. Makes sense though, it’s kind of like magic.Will finish this tomorrow, kids are going apeshit.The Tampered Cell: IMO the hazard of additive gene manipulation is more in how naive we are about the metabolic interactions and how prone we are to trends. Our social mechanics can get a bit out of control, and imagine the Chinese editing for small footed girls, or Americans for height. These trends have hard walls after which they have severe negative impacts, and we’ll keep slamming against that wall hoping to generate that trait even if the environment makes that trait harmful based on social drive. It’s like lemmings, just with humans pushing ourselves over the cliff instead of a shady Disney exec.It occurs to me that CRISPR techniques probably aren’t all that different from mechanics RNP world which led to the creation of DNA as we know it today.That’s pretty messed up that his boy turned him in. Anonymously. How do you say “snitches get stitches” in Chinese?Not sure why multi-cellularity arising on multiple paths is surprising, if the conditions were right we’d expect this right? If it didn’t, it would mean the organism expanded so fast that it consumed all other life, and making something like LUCA pretty obvious.This Travisano/Ratcliff work is pretty cool. Funny story, I knew a biologist who didn’t believe in “evolution” (devoutly religious) even though she worked in a lab that measured fruit fly trait shift over many generations, and later worked in a lab that worked with pathogens. People are weird.The Developing Cell: Yeah, life being the furnace/foundry/substrate for more life is really weird to me. Hah, was thinking about thalidomide at the start of this section, such a classic example of our naive approach the metabolic interactions. I remember the first time I heard that Billy Joel song it said “Children of the little mind”, and assumed it was referring to trisomy or “autism”. We didn’t start the fire, we do the same shit over and over again but believe it’s new isn’t as elegant I guess.The Restless Cell: This book is really making me regret not being more familiar with the initial phases of cellular development, I got some homework to do I guess. Oh god, this story about Greta is pure American HealthCare(tm). She almost had to die before the doctors stopped doing the obvious and lazy push off. Fucking gross.Metal Riff BLOOD MADE OF RUST, FUELING MY LUST metal riff.Later that year, Denys tried to transfuse animal blood into Antoine Mauroy, a man with a psychiatric disorder. The blood of a calf, an animal known for its sober disposition, was chosen in the belief that it might calm the overheated madness in Mauroy—yet again reinforcing Galen’s notion of blood as one of the carriers of the psyche.
We think we’re really far removed from this kind of batshittery… but we aren’t. I hope in 100 years we have the opportunity to see ourselves as equally dumb and barbaric. Ugh, his American HealthCare(tm) stories are starting to get depressing.The Healing Cell: Wow, hadn’t really thought of that, but prior to cardiovascular research modernization, people literally just dropped dead all the time and no one had any clue why, like the hand of god or magic. And not that long ago either, we didn’t start understanding heart attacks or strokes until the 1950’s and didn’t get decent consistency with resuscitation techniques until after that.Like a growing collection of trash and silt on the edge of a river, coronary plaque usually builds up over decades—bulging out toward the center of the hollow vessel and slowing down blood flow, although never obstructing it entirely.
Lol, what a metaphor. Ageing is being full of the garbage of life.The Guardian Cell: It’s kind of bonkers that we define many cell types by how they look under a stain developed hundreds of years ago. This idea of haggling for pustules is kind of mind blowing. The elimination of most types of “pox” infections is probably our greatest medical achievement, I can’t even fit it in my brain how pervasive and devastating these things were.The Defending Cell: Heh “wrong constructed out of many rights” is kind of the story of medicine isn’t it? Oh god, that’s amazing, “So bad that it was not even wrong”. Them’s fightin’ words.Rather, natural selection chooses the individual finch that happens to have an ideal beak for the natural disaster.
Sigh (not author’s fault, is a quote). Heh, B Cell spam is our greatest frenemy, really cool to see them here. On a side note, Wellcome/Sanger is doing some really exciting stuff, everyone should have them followed in their papers filter.The Discerning Cell: Heh, this author is way more “human” than me, kind of interesting. It’s like a perpetual haze of nostalgia that colors everything. Man the author really loves embryos. Still don’t agree with this argument that function is visually discernible or that it usually takes a visually discernible form.This chapter is REALLY important, and I wish more nervous system researchers understood how this interaction between internal peptide/protein signalling worked. We’re so dead ended and fascinated by the whole electrochemical gradient that the actual mechanic is right there under everyone’s nose. Cells work with fundamentally the same mechanics, regardless of their function. Huh, I still haven’t read anything by Salman Rushdie, he was a bit before my time I guess.I don’t know how oncologists manage, these stories are just so damn grim. Gotta pick this up again in a bit.The Tolerant Cell: Lol, “a clown car of questions”, that’s amazing. Hrm, this section is a little dicey in the context of the previous chapter talking about how yeast very much enjoy mixing their cellular selves (and that eukaryotic cells themselves are probably the product of several different types of mixed cells). Not disagreeing with the concept, cell walls are cell walls, but I think the answer is more about the metabolic impossibility of massive intercellular bodies. Cells do very clearly try to create a single shared environment, and this is the foundation of organisms from bacteria forming films to human skin. It’s may be this property that IMO histones are based on, ensuring that cells can create cooperative environments while excluding competitive cells.Maybe it’s just confirmation bias, but the presentation of cells as a part of a repeating, larger pattern is appealing. I think this conceit could be carried into literally anything we have epistemological constructs for very well. Even the quanta have quanta, at least from our reference frame.The Pandemic: The thing I remember most about the early days of the pandemic was that everyone was really sick WAY before anyone realized what was happening. I distinctly remember the cough running through the area in February, and people who hadn’t taken time off work in years suddenly taking time off.I think I chalked it up to “must be a really bad flu variant” until a friend started wiping literally everything down everything with alcohol. He is one of those “doing things they can’t talk about types”, aka the bomb squad meme “If you see me running, try to keep up”. Shortly thereafter videos from China started leaking of the extreme measures being taken there and I couldn’t help but think of the Spanish Flu.Wow, I had no real concept of how much drug development is focused on immune function, that’s nuts. It’s a fortunate/strange coincidence that the same freakish astrocytes that likely insulate me from many social external functions, also insulate me from disease. Even the quanta have quanta. I know the author is immune focused, but I’d be interested in seeing how his view has changed with recent evidence of glial tropism being the root of the metabolic chaos (e.g. cytokine storms) that accompany COVID in susceptible individuals.The Citizen Cell: Ugh, this reminds me of how absurd “heartbeat” laws are.The Contemplating Cell: Heh, and more of the drawing madness. Like so much of our knowledge is built around that single source of information. This is probably the greatest advantage of “AI”, that it incorporates many different data points comparatively to draw insights (only usually to be largely quashed by a researcher if they don’t fit the researchers expectations or goals). It’s interesting that both Cajal and Golgi were both more wrong than they were right (but the “great man” cult limited challenging either until recently).I guess this answers the question about his opinion on glial contribution to COVID pathology, he doesn’t really know much about it. Heh, this bit about Galvani is probably a bit too on the nose for me, a clearly wrong idea that was experimentally verifiable. Yeah, straight into the mechanics of neurons. Oh man he’s so close, it’s frustrating to me that we can recognize that chemicals are the purveyors/maintainers of inter-cellular signalling, that chemical processes within the cell are not dependent on electric signalling, but still feel the need to conform back to electrical signalling as the driver.Of all cells in the body, the neuron is, perhaps, the most subtle and the most magnificent.
This is a bizarre ass statement from an immunologist. Whoa, Ed Wilson name drop, was not expecting that. Alright, he’s just leading me on. Of course he dives into glia. I’ll stop playing with my jump to conclusions mat.It’s hard to locate an aspect of neurobiology that doesn’t involve the glial cell.
Fer-real. Although he’s still mostly talking about microglia here.Neuronal signaling from one cell to the next instigates profound biochemical and metabolic changes in the recipient cell. An elaborate cascade of chemical changes is sparked off in the recipient neuron: alterations in metabolism, in gene expression, and in the nature and concentration of chemical transmitters that are secreted into the synapse.
Modify this with “astrocyte” and that’s how brains work.Heh, he’s digging into electric brains now. THEY LITERALLY DON’T FUCKING MAKE SENSE, lol. Yeah, I don’t know that surgery for 31% effect rates is… good. The biggest problem with DBS schemes is that they are modifying downstream targets, which eventually get metabolically corrected. Until we start hitting brainstem/cerebellar targets, the cascade will always recover back to homeostasis.The Orchestrating Cell: Ah shit, the title of this chapter probably means I have a fucking shoe to eat.The lab was barely equipped, and the heat was oppressive. Banting, dripping with perspiration, cut off the sleeves of his lab coat.
This is the type of stuff that I have a hard time with, the hell does this have to do with the information itself. Human context is weird.Sometime in the future we might encounter a new kind of diabetic patient with no injections, batteries, or beeping monitors (instead, the batteries and monitors will be worn, like those getting deep brain stimulation for Parkinson’s disease or depression).
Hopefully much better than that, and not at a million dollars a pop. AHHHH HE SAID IT.It is the metabolic cascade—and the restoration of chemical balance—that is the small miracle of cell biology that unfolds in your body as you walk back to your hotel.
And that’s how biology works. Lol. I’m going to find out his email address and spam him a piece of work about astrocytes every single day until he publicly denounces me. Thank goodness I didn’t have to eat my shoe though, that was a close one.The Renewing Cell: Heh, this whole embryonic vs induced pluripotent cells is a really, really great summary and also really illustrative of some of the amazing advances made over the past decade. It also illustrates a frustrating aspect of this behavior, that people got so locked in on endothelial cells (because of the original work) that until very recently the idea that nearly any cells can be manipulated metabolically into other cell types.The result was an utter shock to biologists—a Loma Prieta that shook the Earth plates of the stem cell world.
Would anyone but a local really get this reference? Heh, ship of Theseus probably isn’t appropriate here, since every cell is the whole boat. Unless we modify the genetics of the DNA, then it’s the same boat.The Repairing Cell:Short, intense, energetic, and driven by a single purpose, he was like an Ozzie-made hand grenade.
Heh, I read this as like “Ozzy” instead of Australian and thought “so, full of cocaine?” which I think works here as well. Reading about the results of animal experimentation is interesting, reading about animal experimentation itself is awful. Wonder why he hasn’t made the connection between osteoblasts and neurons?The Selfish Cell: Ah, dangit, oncologist not immunologist. Although it’s hard to be great at the former without the latter considering most cancer treatments are immunosuppresive I imagine. Heh, this section seems silly and answerable by the “metabolic cascade”. Whenever stuff like this seems a mystery, it’s usually because the initiation point is upstream and that our assumptions of visual similarity are tripping us up.The Songs of the Cell: I wonder what the ratio of people who fell off their horses and got messed up to people who get messed up in car accidents is? Are they similar rates, driven by the same factors (e.g. inattention or mechanical/biological issue) or do they have completely different rates? I imagine this might be greatly skewed by modern vs. pre-2010 era cars. Hrm.Epilogue: NO. Dangit, I feel a bit recalcitrant seeing that word.I cannot imagine us cloning and sacrificing humans to act as organ donors.
Yeah, it would be stupid and inefficient to do so. We will eventually get to the point where we can induce growth along particular cellular lines, e.g. we will understand exactly which parts of the metabolic chain are necessary to start growing a liver or kidney, but more importantly we’ll likely get to the point of creating artificial organs which beat the snot out of our biological ones. Thinking of that movie Bicentennial Man here. Speaking of which, why did that robot really need to commit suicide? So short sighted for a bicentennial man (uh spoiler).I think only people who aren’t suffering from a debilitating or socially ostracized condition can take the whole “respect your genes for what they are!” argument seriously. Human societies are not tolerant of such things.