confidence level: I am a physicist, not a biologist, so don’t take this the account of a domain level expert. But this is really basic stuff, and is very easy to verify. Recently I encountered a scientific claim about biology, made by Eliezer Yudkowsky. I searched around for the source of the claim, and found that he has been repeating versions of the claim for over a decade and a half, including in “the sequences” and his TED talk. In recent years, this claim has primarily been used as an argument for why an AGI attack would be extremely deadly. I believe this claim is factually incorrect.
Organic chemist there
bucket o' nitpicking incoming
I think that chemistry 101 classification of bonds is a tad useless here. Instead, you can go from first principles: there are things that happen when atomic orbitals overlap (covalent bonds, metallic and such), there are interactions that are mostly electrostatic in nature (ionic, dipole-dipole, quadrupole-quadrupole - important biologically as pi-stacking, also ion-quadrupole etc) and there are things that are a result of exchange interaction (van der Waals and steric repulsion). Hydrogen bonds would be a mix of dipole-dipole and van der Waals interaction. You don’t have to transfer electrons in order to have ionic interaction, most of the time in biologically relevant situations it’s proton transfer, or charges just were there previously. Hydrophobic interactions are almost entirely a solvent effect and aren’t a bond strictly speaking
In water, i’m pretty sure that proteins are mostly held by hydrogen bonds and hydrophobic interactions. EY is correct in that some proteins hold shape by mostly noncovalent interactions, but these are mostly hydrogen, ionic, hydrophobic interactions and the proteins that actually provide mechanical strength run in continuous covalent strands through entire length of them anyway (collagen, keratin). I don’t think that counting bonds and saying that something is 90% bound covalently is a meaningful metric, because long series of hydrogen bonds or even vdW forces (in things like UHMWPE fibers) can be stronger than single covalently bound strand, ie if you tried to pull out a single strand of kevlar or collagen from bulk material, above certain length you won’t pull it apart, you’d just break it because collective energy of hydrogen bonds will be greater than single covalent bond holding it together, that’s why these fibers are strong in the first place
There is another kind of flexibility that you haven’t mentioned: proteins are made out of single covalently bound strand, yes, but these aren’t straight C-C chains. Making and especially breaking C-C bonds in controlled way is hard, proteins can be just hydrolyzed at amide bonds. If protein breaks in some way, and in real world everything breaks, it can be recycled into aminoacids (+ any cofactors etc) and then put back in a pretty straightforward way; you can’t do this with diamondoids, when it breaks, it breaks hard, and you’re done unless you’re picking everything apart atom by atom which would be much harder and more energy intensive. As it happens you can buy bulk adamantane, but it’s just made in conditions where C-C bonds are weak (high temperature) and it’s preferentially formed because it’s most stable thermodynamically among its isomers (that are starting materials). Conversely, if you use weaker bonds, you can make pieces conform to some template, or to each other without breaking everything at once - this is basis of dynamic combinatorial chemistry. There’s also entire field of self-healing materials that is based almost entirely on these either noncovalent or reversible covalent bonds
You actually don’t have to do that, and there are some small organocatalysts that are entirely covalently bonded and do the same job. However you can’t make them from from aminoacids, these don’t have secondary structure (too small) and are generally less active. The bare minimum is to provide a receptor for transition state, and you can make it work without drastic changes in conformation. You could make your catalyst as stiff as you like, and it’ll even make activity higher - but only if none of these stiff parts interfere with binding of substrates, and your options are limited. It’s often better to leave some wiggle room. Short peptides aren’t really stiff enough in ways that matter there and instead it’s secondary and tertiary structure that puts important bits in the right place
Feel free to pick my brain any time you like
Hey, thanks so much for looking through it! If you’re alright with messaging me your email or something, I might consult you on some more related things.
With your permission, I’m tempted to edit this response into the original post, it’s really good. Have you looked over Yudkowsky’s word salad in the EA forum thread? Would be interested in getting your thoughts on that as well.
my DMs are open, but lemmy’s DMs seem to be janky, matrix should be more reliable
no issues with that
i’ll have a closer look tomorrow, for now i’d just say that that steel chain protein analogy is okay, however if you wanted to convey directionality of hydrogen bonds, then every link is magnetized, and really these links are not welded shut, but instead bolted, so you can disassemble them and put them together again with some effort. continuing this analogy, diamondoids would be elaborate welded assembly of stiff H-beams or something like that
i see that EY tries to “get” materials science from first principles, in true aristotelian fashion, never reading first year BSc level chemistry textbook, fails badly and can’t even comprehend that he can be wrong. in other words, another tuesday
update 2: i’m not doing that, he sounds like a straight up cultist in this one
update 3: unfortunately i had some time to look back at this, and the longer i thought about that “bacteria but stiffer” thing the more aggressively stupider entire thing becomes. get yourself a mean drink like i did, because it’s long. for your sneering pleasure (and if you want to use it, just rephase relevant bits it’ll be shorter):
here i'm talking out of my ass about psychology, so don't listen to me because i'm not a psychologist
Zeroth of all, let’s take a few steps back and look at the bigger picture. University allows you to learn, teaches you how to learn, but here one underappreciated thing is that it lets you fail non-catastrophically. Let’s say you know some things, and you arrive at a hypothesis. When you are in some professional environment dedicated to learning, you might be - should be - incentivized to test it: look up some literature, design an experiment, or just ask someone who actually knows. When you are right, you don’t really learn anything new; but when you’re wrong, you learn limitations of your method/approach/reasoning, how to fix them, new things etc but more importantly you learn some humility and nuance, and you learn to answer “it depends”. This of course doesn’t have to happen at university, but I suspect it’s pretty good at it. When you don’t have that, when you never are proven wrong, you might end up sniffing your own farts so hard that you refuse all criticism in the future, never admit that your ideas could be possibly faulty and you become EY. I know that because I’ve come too close for comfort to that path however at the uni some half year in where i had to do actual lab work cured me of it irreversibly when reality proved me wrong. I’ve also seen one case of exactly that on /r/chemistry, in that case there also was a complete lack of self-awareness about their own limitations, not really unlike of EY’s in principle, but he had more time to learn it. I can elaborate in DMs if anyone is so inclined
Everything breaks 1
For reasons that might be related to the above all rat’s nanomachines are perfect, never malformed, work flawlessly, fibers are infinite and without defects etc etc. Bitch, in real life everything breaks all the time, and yet reality and real things work. To illustrate this consider single kevlar fiber.
When taken alone, single molecular strand of kevlar is not significantly stronger than polyester, polyethylene, or PVC. However we don’t really use kevlar this way, and what makes kevlar kevlar is how it interacts with itself between strands. Every unit makes 4 rather strong hydrogen bonds perpendicular to strand direction, and perpendicular to both there are 4 quadrupole interactions between aromatic units. This all arranges single strands into sheets and sheets are then stacked parallel to each other. Now, let’s try to pull a single strand out of bulk material. When strands are short, it’s the hydrogen bonds and quadrupole interactions that break - strands just slip off and separate. However, above certain length, it’s easier to break single strand than to pull it out.
That length turns out to be quite small. Going for a ballpark figure, benzene C-H bond has dissociation energy of some 113 kcal/mol, while (quite similar) beta-sheet hydrogen bonds have some 4-9kcal/mol, depending on who you ask and how you measure. That works out to some 4 to 7 fully hydrogen-bonded diamine-diamide units are already held in place with more force by hydrogen bonds than single covalent bond can withstand, and that’s without considering quadrupole interactions. This has interesting consequence: as long as you can make sure that at least some of the time neighboring strands have these 30 or more hydrogen bonds between them, under tension they don’t slip - failure mode shifts. This means that kevlar tolerates some breaks, a very important property in a world where everything breaks. There’s still benefit to strands longer than that - it allows for increased tensile strength, to a degree - but it’s these weaker hydrogen bonds that make kevlar what it is, an interaction that EY dismisses outright as some superfluous bullshit not worthy of attention.
Exactly the same thing applies to peptide beta-sheets and collagen, keratin and such, which have similar hydrogen bonding pattern but this time after 3 strands it wraps over, making 3-strand helix. As it happens, alpha-aminoacid based peptides pack pretty much as many amide bonds per chain length as humanely possible, so these hydrogen-bonds-collevtively-are-stronger-than-strand segments are even shorter than in kevlar. These are actual structural proteins that are part of the reason that cells hold shape. Same goes for cellulose, chitin and to some degree lignin. The above is also the reason why i think that this bond counting metric is pretty useless, and that’s before ionic and vdW interactions swamp the entire picture. You can arrive at something more useful by counting bond energies by type, but this still makes sense only in context, because you might break single covalent bond vs bunch of hydrogen like above, so shape is also important. Even this wouldn’t be massively useful, but that could be better. But i digress
Nanomachines, son
EY makes a big point of how living thingies lack wheels, and his imaginary nanomachines have wheels, which makes them superior (yes i know about ATP synthase, this is not the point). I’m not convinced on how adding wheels on perfectly wheelless bacteria would improve them in any way, especially when what you need is something else. Square-cube law is binding here and in full effect - noncompliance is punished by inefficiency, and energy is something that will be very useful. There are already strings, levers, shuttles, springs, elastic membranes, one-way and two-way pumps and valves, some gated by external signal, and even a tiny conveyor belt at this scale. We don’t need no wheels where we’re going
I’m not sure how this entire thing would maintain integrity and remain isolated from external environment. Actual biology uses for this lipid bilayer, which can’t be easily damaged in some ways because it’s literally liquid, what’s more it can absorb some insults, it can conform to surface, it can replace its components at will - all you need to do is to overcome these weak interactions (hydrophobic in this case) and you can pull out some protein, shred it into aminoacids, and make it anew. You can’t do any of this with stiff, crosslinked sheets of graphane (or something)
Lipid bilayer has a very important function that even a small break kills catastrophically - it stores energy by way of electrical and chemical gradient across it. When it breaks, you’re proper fucked - fortunately, these weak interactions allow for membrane to reform where it was punctured. This fails badly when membrane is stiff for obvious reasons. Membrane also needs to be thick: we’re talking about some 150mV across some 5nm of membrane of a living bacterial cell, which in already existing biological systems means 30kV/mm, and can withstand much more. What was that supposed benefit? Higher energy/power density? You would need to think really hard about making materials that can withstand this and higher fields. Note: real life example already uses pretty much the best material for the job
Everything breaks 2
In real life everything breaks. Proteins misfold, denature, get pieces chopped off by hydroxyl radical. This is not something you can magic away: reactive oxygen species form wherever there is oxygen and some heavy metals in biological systems, and more generally everywhere where there’s water and ultraviolet at the same time. Nature has a solution: just shred everything exposed periodically, at random. This way, as long as the cell is alive, no critical protein lives long enough to accumulate too much damage. Fortunately, proteins aren’t disassembled into atoms - building blocks can be put back with some limited effort into new intact copies (
1 ATP per residue, + some extras for folding, transport, unfolding DNA, let’s say conservatively 1.5 ATP per residueactually looked it up, it’s 4.2 ATP per residue. point still stands).This rather economic recycling allows a living cell to absorb damage that would be catastrophic when you just assume that everything works forever just as you imagined. I don’t have a guess how much more energy would be expended in reassembly of diamondoids, @[email protected] might have an estimate, but i guess it’s some 1-2 orders of magnitude more. Disassembling and assembling everything at random would be most likely prohibitively expensive in terms of energy, and detecting fault could be very easily hard to impossible. (There are some pathways that are responsible for shredding misfolded proteins, again, you can’t do this with stiff things)
Assorted shit
Nowhere is explained where energy comes from, this is probably the biggest issue in all of this. From what i understand, all this assembly by manipulator magic also only ever happens in high vacuum, at cryogenic temperatures (?) at tip of AFM, and on top of all of that entire surface to be worked on has to be uncapped (ie covered in radicals). This is not exactly a condition directly transferable to something that has to survive in air or even worse, in water. Nowhere is also explained where, or how, information about structure is stored.
Somebody in the comments made a point about how they’re sure that you can make something like a protein but held entirely by covalent bonds - while possible in principle, i find notion of such thing absurd and detrimental to fitness - you can’t easily make or hydrolyse such densely, permanently crosslinked protein in usual ways, it would require special proteases. Even some cyclic peptides resist digestion, that’s because normal proteases turn proteins into unfolded string of aminoacids first and chop it one by one. You can’t do this when there’s no end. This gets much worse when it’s an entire 3d mesh of mess that you can’t even move, and there’s already an actual biological problem with this - it’s linked to nonspecific reaction of glucose with proteins, most commonly, tying permanently lysine and arginine side chains. These are quite appropriately abbreviated as AGEs https://en.wikipedia.org/wiki/Advanced_glycation_end-product
Why don't organisms make diamond bones? Are they stupid?
This is so fucking wrong i had to quote this. I don’t even know where to begin, calcium atoms have charge +2 in hydroxyapatite and pretty much in any other non-pathological edge case. The bigger (heavier) you make an atom, the less surface charge becomes, this is a bad thing if you want strong ionic bonds
Because it’s already here and making diamond bones is both pointless and prohibitively energy expensive. I guarantee there would be enzymes running on lanthanides, were these more common in, say, seawater
Ionic bond is not really a bond in some senses of this word. It’s better to say ionic interaction - bond in some meanings has defined shape, that is there is a geometry that obtains minimum energy. This works in salt crystal, where any disturbance of ion position has to happen along sharp energy gradients. It doesn’t really mean anything in proteins, where charges are fuzzier, further apart, and there’s water around blanketing every charge and shielding it from others. Here, there might be some things that are attached directly to hydroxyapatite crystal by ionic interactions, I expect some phosphorylated proteins, but don’t quote me on that
Yeah, I’m pretty sure that would be rather pretty fucking hard, especially when you don’t have things like palladium or platinum. Making C-C bonds in controlled way is hard enough, making them in regular lattice without any functional groups nearby makes it significantly worse
Nobody should think about anymore, none of that nanomachine drivel makes sense. When in doubt, don’t
Thanks, I love these answers! I’ll drop a DM on matrix for further questions.
The DMS researchers were estimating something on the order of 5 eV for mechanically dropping a single pair of Carbon atoms onto the surface of diamond. I’m not sure how to directly compare this to the biological case.
so we’re looking at something in the order of 2x more energy for pair of carbons than for putting single aminoacid in protein, and aminoacids are much larger. (some 4.2x70kJ/mol per ATP -> AMP + 2Pi), and that’s including everything around protein synthesis except aminoacid synthesis, compared to just deposition of carbons (that’s without picking them up?), and it’s when you have clean prepared surface, in real life this also takes some considerable energy
re: energy requirements, there’s a bit about dissipative systems here that i never could get fully because it’s some harder thermodynamics that i’ve been used to. pretty neat stuff https://en.wikipedia.org/wiki/Dissipative_system