"Technical Report on Mirror Bacteria: Feasibility and Risks"
https://purl.stanford.edu/cv716pj4036
The premise reminds me of the "Rifters" trilogy by biologist and science fiction author Peter Watts. In it, an archaic deep sea microorganism "ßehemoth" that outcompetes all other kingdoms of life is brought to the surface and wreaks global havoc as it spreads.
https://www.rifters.com/maelstrom/maelstrom_master.htm
A good premise (along with others) for a hard SF novel series, but it's bleak. As James Nicoll put it, "Whenever I find my will to live becoming too strong, I read Peter Watts."
https://rifters.com/real/author.htm
I see that a substack author has written about this "second kingdom of life" today, under the catchy heading "green goo":
https://denovo.substack.com/p/green-goo-republished
And a commenter there mentioned Rifters also.
A combination of "humans only use 1% of the brain" mythos married to a "super cognition unlocks emergent superpowers" results in something that's more accurately described as an unofficial entry in the Marvel cinematic universe than the hard-scifi it styles itself as.
[1] In the sense that is related to blindsight. Maybe someone with blindsight still has philosophical qualia of the objects they say they can't see, I don't know
> Those sensors can only latch onto left-handed proteins or right-handed DNA and RNA. A mirror cell that infected lab workers might spread through their bodies without triggering any resistance from their immune systems.
It’s clear that RNA wouldn’t be complementary to mirror RNA, but antibody binding is more complex than RNA hybridization. Is it a foregone conclusion that antibodies couldn’t bind to mirror antigens?
(Degrading mirror proteins, as mentioned elsewhere in OP, does seem like a bigger obstacle.)
I wouldn't expect it to, but rather I'd expect the immune system to learn the new antigen just like it learned the old one.
>The downside of having a biology that renders mirror bacteria ‘invisible’ to natural enemies is that they would not be able to consume many of the chiral nutrients found in nature. However, several nutrients, such as glycerol, are achiral (they do not have mirrored forms), and thus could be consumed by mirror bacteria. Well-intentioned scientists could also engineer mirror bacteria that can consume naturally occurring chiral molecules such as sugars and amino acids.
And while the adaptive immune response might not immediately recognise a novel organism, is there something that would prevent it ever adapting?
The problem is the chiral molecules would be difficult to clean up. You’d have this anti-life bacteria torn to pieces, yes, but then the pieces get stuck everywhere and potentially jam things.
Personally—not a biologist—it doesn’t feel like a huge risk, given we accept threats such as microplastics which do much the same thing. However, it’s a completely unnecessary threat with essentially no upsides, and it wouldn’t be possible to undo once created.
I'm confident if we had seen microplastics coming when we first started using plastics, science at least would have tried to prevent their use becoming as widespread as it has.
(By the way, all organisms are made of chiral molecules; what we're talking about is reversing the chirality.)
Some of the things the immune system uses to attack things, such as superoxide, would work fine on mirror organisms. Others, such as antibodies to existing organisms, wouldn't work at all. I don't know what the balance is.
There is no way to effect something that attacks everything it doesn't recognize because a) there is no ooeration that represents not matching and b) if there was such a cell would be a short lived bomb that would blow up your body.
You adaptive immune system learns to and antigen when a short lived immune cell is semi randomly generated that binds to it and becomes a longer lived cell.
Presumably this could still happen but this normally takes days to happen. In between your inate immune system relies on being able to recognize a lot of existing antigens that are out there and common in attackers.
Having the entire library of malicious life become magically unknown means that you are relying on only your adaptive immune system is available to contain the damage.
(biomagnetism is a thing, but I'm not aware of any cases where binding occurs due to magnetic forces)
But I also think it's similar in a way to 'why matter and not antimatter' or 'why ~3d space rather than no structure' (much less obvious the second one!).
But I think the real answer here is touched-on by nmstoker in a sibling comment: We're so far down the energy-gradient of the current-default-chirality on earth, that it would take exploration of an insanely-deep valley for all molecules in a cell (there are zillions even in a bacteria!) to flip the the whole thing to the alternate chirality.
It's a bit like the idea that a good chunk of matter (like even a whole amino acid) could all spontaneously-convert to antimatter at once, sure it's possible in theory but the chances are so low we might as well say it's impossible.
But over the course of the entire evolution of life on earth...
It's hard to argue that the step from chirality A to B is larger than all the other insanely unlikely steps evolution has taken. From earliest proto-life to complex multicellularity and beyond.
>as there are no natural mirror aminoacids. Normal bacteria will quickly evolve to consume mirror aminoacids.
There are and they already have:
>D-amino acids are toxic for life on Earth. Yet, they form constantly due to geochemical racemization and bacterial growth (the cell walls of which contain D-amino acids), raising the fundamental question of how they ultimately are recycled. This study provides evidence that bacteria use D-amino acids as a source of nitrogen by running enzymatic racemization in reverse. Consequently, when soils are inundated with racemic amino acids, resident bacteria consume D- as well as L-enantiomers, either simultaneously or sequentially depending on the level of their racemase activity. Bacteria thus protect life on Earth by keeping environments D-amino acid free.
https://pubmed.ncbi.nlm.nih.gov/24647559/
On the one hand, this does indicate that the "mirror bacteria" might not starve immediately, but on the other hand it shows that "non-mirror bacteria" would already be there in large numbers.
This is covered in the article in 2 ways though: It says that some nutrients (like glycerol) are achiral - this might mean they could still find a food source in a regular-chirality world. It also mentions that the mirror-bacterial nonstandard-chirality might 'cloak' them from regular-chirality predators (or immune-systems).
I dunno, it does seem pretty far-fetched and I am not a professional scientist so I find it hard to evaluate the risk in any worthwhile way.. but I think it still seems worth considering?
But multicellular organisms would be at a huge disadvantage. We don't have offspring every second, so adapting to the mirrors would be nearly impossible. They'd be able to cause havoc in plant and animal life that has mechanisms for dealing with regular bacteria.
This is a function of how easy it is to do the banned thing, how easy it is to detect when it is being researched and what are the benefits of researching it.
Imagine as an example that we live in a world where there are no firearms, and we decide to ban their research and development. All three factors would be against the ban. It is relatively easy to make primitive firearms (all you need is metal working tools). It is hard to detect when someone is doing it (they can keep their firearms secret, and the tools and activity disguised as something else) and the firearm once developed will be of great benefit to whoever developed it.
So a blanket ban against firearms would be unstable. It wouldn't work.
Let's look at an other example. Nuclear weapons. They are much harder to create (you need a whole industrial project to develop the tech, lot of engineers, and lot of energy consuming processes), there are pre-cursor technologies you can monitor to have an early warning (uranium enrichment, centrifuges, etc), it doesn't have immediate benefits unless you also develop a reliable delivery mechanism for it.
And these are the factors while nuclear weapons don't proliferate everywhere. You can't buy them in the mall, smaller countries don't have them etc.
I don't know what the answer to these questions are for "mirror life" but the framework is the same.
How hard is to develop it? If a single dude in a shed can do it, there is probably no point banning it. It will happen sooner than later. If it requires coordinated effort from multiple research groups and industrial partners, then a ban might work.
How hard is detect when someone is developing it? Can they hide it? Is the process using common materials and equipment? Do they need to get stuff only people who develop mirror life would need?
But the final question is the most important: What do they win? If there is some military benefit to developing "mirror life" then we are lost, and it will be developed. If there is some big economic benefit a ban might work, but it will be an uphill battle. If there is no benefit to it, and it is just cool and interesting to do, it will be a lot simpler for a ban to hold.
It seems to me that to a degree nuclear weapons show some of the problems with a research ban. I think that it's possible that nuclear weapons are proliferating just very slowly. The problem seems to be that once someone engages in forbidden research, then their rivals feel the need to as well. E.g. we allowed China to get a nuclear weapon so India decided they needed one which led to Pakistan needing one. More currently, we allowed Israel to get nuclear weapons so now Iran is likely trying to get them.
It's also notable that the two instances where people gave up nuclear weapons, Gaddafi and Ukraine; have both ended poorly for the people who gave them up.
All this to say, I wonder if it might be possible to slow research on a subject but not to stop it completely.
You unleash green too ensuring your targets liquidation in 6 weeks they inform you to share your own defense against it or get nuked tomorrow. You share it but it adapts and everyone dies.
Also, there are numerous examples throughout history of people performing evil human studies; so while people may not have studied children falling from planes, people have studied equivalent things.
Research bans do not inherently work.
Treaties need enforced, and the Streisand effect and arms-race dynamic play into the game theory as well.
Someone's going to need to work it out, because if the problem of "how to ban existentially dangerous things" is not solved, eventually we'll be fucked.
And realistically, we're probably fucked, because humanity probably simply lacks the maturity to not fuck itself over at some point (e.g. because of the logic "if we don't do it someone else will" is scarily effective, and some people are just unhinged for really stupid reasons). We probably only made it this far because of external constraints limited what we could do.
Part of me thinks it may turn out that a that a full-scale nuclear war that knocks out industrial civilization (especially if it's followed by A Canticle for Leibowitz-style anti-intellectual social changes) may not be such a bad thing in the long run, if it buys humanity a few more millennia.
After understanding what "mirror bacteria" is I have one word and that's "Yikes"
This appeals to me both as a defensive/protective measure and as a deterrent to others who might look to weaponize such organisms.
They aren’t going to be mirror copies of terrestrial organisms, there’s no guarantee that mirror copies of our antibiotics will work (AFAIK it’s actually very unlikely). Protein binding sites change when mirrored because it’s not just mirror image but a change in how the proteins twist when folding, which is why most of them are sensitive to chirality. Only very simple molecules are likely to behave the same.
Stuff like bleach will still work by denaturing proteins and disrupting the bilipid layer in cell membranes but anything like tetracycline and penicilin that targets peptidoglycan enzymes or ribosomes or other complex biochemistry almost certainly won’t.
Wouldn't this pretty much rule out the synthetic creation of mirror bacteria? We should not just be able to rewrite a simple existing lifeform in mirrored version; we should recode all its proteins from scratch so that they keep their function in a mirror version, assuming that that's even possible.
"The baddies will use this as a weapon, so we need to get ahead of this, and manufacture the nastiest variants we can come up, so that we know how to DEFEND against them. It's defense, I say!"... Then eventually there is a lab leak, and there is a pandemic on your hand.
there is currently ~no risk because generating mirror life is such a monumental task. we dont have a full biological bootstrap sequence currently. even syn1.0 which was a synthetic genome transplant and rebooting operation, required a living host cell to transplant the DNA into, and the genomic dna does go from a computer file, but only the smallest ~100 bp fragments are made by robots and chemistry; intermediate fragments are assembled and amplified in enzyme reactions, bacteria, and yeast.
in principle you could get these to be entirely in vitro, but the yields would be nearly nil. and the expense of mirror dna monomers is... i can't even imagine. you'd probably bankrupt a midsize nation on that. and theres no motivation to decrease the cost because there's not really any other practical use for mirror dna outside of fucking around scientifically. and thats just the DNA. our ability to synthetically make proteins taps out at around 150-200 residues (maybe 2-4x that if you can get clever with native chemical ligation) and the purification and isolation at that length is truly a nightmare, not to mention refolding longer sequences is also hard.
- It would still have antigenic properties, just not the ones we are familiar with, because antigens are proteins or proteins bound to sugars. Both have "left" vs "right" variants.
- It can't eat any ordinary food, except simple fats. Common proteins and sugars won't fit it's enzymes. That means it can't digest sugars, proteins or any combination that contains them. It also means it can't attack and decompose our tissues, so it would have no way to enter our bodies.
- With only simple lipids as food, it would need to take all Nitrogen from the atmosphere or inorganic compounds, which means it can't really be a pathogen for humans (or any animals) even if it could somehow enter our organisms. However, it could live on the soil and possibly be a plant pathogen.
- It's "mirrored" toxins won't have any effect on us. (But compounds that are normally benign possibly could be toxic if "mirrored" - I can't say for sure if it's possible.)
Most critically, metabolic pathways.
But that isn't to say there isn't already varied chirality in nature [0]. The primary reason life is generally aligned to one chirality is because its very purpose is to interoperate with the living environment around it.
That sounds like a good thing but... Our food chain starts at the bottom with bacteria turning nutrients into bio-molecules right? These bacteria are eaten by other things going up the food chain ultimately to us. What if some bacteria got loose at that bottom level and started eating all the nutrients with no natural predators? What if it out-competed those with predators? That might be game over for life as we know it.
I'm NOT saying this would happen, just that it one of thousands of possible scenarios one can come up with that go very badly. No one can say with certainty which things would or would not happen.
The parts would be similar enough to form bonds and trigger receptors, but different enough to become permanently stuck, unable to be processed.
Why wouldn't it work in the other direction though? The mirror cells would be competing for the same ambidextrous resources (for my lack of a better term). Sugar is chiral isnt it? Would they be able to digest normal chiral resources?
so the sides of key, and reflection are switched relative to the key.
if you could somhow pluck the reflection from a mirror and try to use it, the left side is right, and right side is left.
when this happens with molecules, there is different parts of the molecules being brought together, leading to alternate interactions, thus different reaction path
The only major non-chiral nutritional molecules are fatty acids.
That's not the problem. There's a recent patent on synthesizing L-glucose cheaply.[1] The problem is that L-glucose turns out to be a strong laxative.[2]
Levoglucose (L-glucose) is the stereoisomer of D-glucose. L-Glucose does not occur naturally in higher living organisms, but can be synthesized in the laboratory. L-Glucose is indistinguishable in taste from D-glucose, but cannot be used by living organisms as source of energy because it cannot be phosphorylated by hexokinase, the first enzyme in the glycolysis pathway. Levoglucose may be used as diagnostic aid. It has been investigated as a non-nutritive food sweetener. However, L-glucose produced significant laxation, with an average of 4 to 5 loose watery stools in a 24-hour period. This laxative property clearly reduced the use of L-glucose as a food additive. The mechanism of laxation after L-glucose ingestion is unknown, but malabsorption of the compound with secondary osmotic diarrhea is likely. L-glucose is a well-tolerated, safe, and efficacious means of cleansing the colon for colonoscopy.
Since that thread didn't make the front page, we'll merge those comments hither. Interested readers may want to look at both articles.
People forget that blue-green algae caused a global climate apocalypse, polluted the oceans and atmosphere with deadly oxygen, caused all exposed iron to rust massively changing ocean chemistry, and threw the entire globe into an ice-age that lasted 300 million years.
I wonder how we would stop something like that. It'd be like the algae bloom from hell. Plankton likely wouldn't be very successful in attempting to eat it.
Once the mirror creature is big enough, it will not matter that it is an indigestible mirror creature, as the predator will eat it regardless. So we only need to create mirror predators up to a certain level.
"No, that's the beautiful part. When wintertime rolls around, the gorillas simply freeze to death."
Unfortunately, even in the aftermath of a massive global disruption directly due to the creation of organisms which are supernaturally able to defeat human immune systems, it's still the wild west. There's effectively very little limitations on research that could quite literally end humanity and disrupt all life on earth, and the limitations that do exist are actively skirted, ignored with violations covered up after the fact.
On the other hands mirror amino acids already exist in nature, so I find the argument that a mirror bacteria would rampage the ecosystem unchecked sensationalist. Click-bait even. More likely than not, the mirror bacteria itself would be heavily outcompeted in the wild.
But predatorless photosynthetic self-replicating gray goo that grows exponentially across the planet, resulting in a drastic change in CO2 and oxygen levels across the globe? Wouldn't be the first time. [1]
> At long last, we have finally created the Torment Nexus from the classic sci-fi novel "Don't Create the Torment Nexus".
> The doctor seemed to be struggling for words. 'What, dammit?' 'Something came up out, of the water, Like a parrot beak, but about a hundred times bigger. It took - Rosie - with one snap, and disappeared. We have some impressive company here; even if we could breathe outside, I certainly wouldn't recommend swimming -' 'Bridge to Captain,' said the officer on duty, 'Big disturbance in the water - camera three - I'll give you the picture.' 'That's the thing I saw!' cried the doctor. He felt a sudden chill at the inevitable, ominous thought: I hope it's not back for more. Suddenly, a vast bulk broke through the surface of the ocean and arched into the sky. For a moment, the whole monstrous shape was suspended between air and water. The familiar can be as shocking as the strange - when it is in the wrong place. Both captain and doctor exclaimed simultaneously: 'It's a shark!' There was just time to notice a few subtle differences - in addition to the monstrous parrot-beak - before the giant crashed back into the sea. There was an extra pair of fins - and there appeared to be no gills. Nor were there any eyes, but on either side of the beak there were curious protuberances that might be some other sense organs. 'Convergent evolution, of course,' said the doctor. 'Same problems, same solutions, on any planet. Look at Earth. Sharks, dolphins, ichthyosaurs - all oceanic predators must have the same basic design. That beak puzzles me, though -' 'What's it doing now?' The creature had surfaced again, but now it was moving very slowly, as if exhausted after that one gigantic leap. In fact, it seemed to be in trouble - even in agony; it was beating its tail against the sea, without attempting to move in any definite direction. Suddenly, it vomited its last meal, turned belly up, and lay wallowing lifelessly in the gentle swell. 'Oh my God,' whispered the Captain, his voice full of revulsion. 'I think I know what's happened.' 'Totally alien biochemistries,' said the doctor; even he seemed shaken by the sight. 'Rosie's claimed one victim, after all.' The Sea of Galilee was
But I have seen it as a short story about how the world ends, some synthetic bacteria that was meant to be reversed chirality for safety, but eventually it went wild and could eat everything without itself being eaten by anything.
This is it: https://laprade.blog/your-dietbet-destroyed-the-world
(where "fairly recent" means part of Ryan North's excellent run)
Most D-amino acids are known to bind MHC poorly and lead to reduced TCR recognition. I imagine this could increase the chances of evading immune surveillance.
If you 3d print a mirrored house key, the bitting may line up with the original, but the warding wouldn't fit anymore. I think that's a reasonable analogy to the way proteins match up.
Whether an antibody raised against one structure interacts with a different structure is irrelevant to the question of whether an antibody can be raised to the other structure.
These fears were unfounded.
(Granted, atmospheric nuclear weapons testing has its own set of subtle consequences that are gradually becoming more well known.)
Exactly.
I suspect mirror-image molecule life hasn't evolved because it wouldn't be fit enough to be self-sustaining.
Sure, but it's good to prove that one out before pressing the button.
Seems like the risks of this research are similar to prions.
It's full of his own fetish, misogynistic sadism, and without kink shaming, I can say this makes these books—which are otherwise interesting and memorable—literally unrecommendable.
Caveat lector
If there was an advantage to being opposite-handed, some bacterium would have done it by now. The article even says that researchers just found out that e-coli can consume different-handed food.
I’m guessing that the first discovery in this area, the ambi-vory of e-coli, is not really all that unique. Medical and biological science is still just scratching the surface. They’re still cataloguing new components of human anatomy, things you could have found with a microscope centuries ago… It is highly unlikely that out of the universe of billions of years of bacteria, e-coli is the singular organism that went down this route to the furthest extent that was advantageous. The fact that they found one example with their limited resources tells me that this is not so improbable.
The fear-mongering just sounds like a funding push to me. The basic research will be enriching for humanity, if it doesn’t create the very thing from which it purports to save us, though I’m thinking this messaging is a bit out there. Could you engineer a super-bioweapon this way? Probably. But there are easier ways to do that with information that’s already in the textbooks.
Is it possible to mix chirality in, say, a protein?
I.e. have a portion of one chirality and another of the other?
Thanks! I think that was the notecard in a dusty corner of my mind that was nagging.
its basically impossible (but not totally impossible) for a living creature to be able to generate any protein with mixed chiralities.
this is because a ribosome with a chamber that can support both chiralities is likely to be less efficient at protein extension. but also you need so much more trna if you want to support arbitrary d-amino acids, etc.
Individual chiral molecules can happen naturally, sure, but not entire organisms. From the report: In a mirror bacterium, all of the chiral molecules of existing bacteria—proteins, nucleic acids, and metabolites—are replaced by their mirror images.
In the fitness landscape there is an absolutely enormous gulf between standard and mirror bacteria, large enough that no amount of incremental evolutionary pressure could flip the ~billion chiral bonds in a given bacterium simultaneously.
That sounds simpler to do than, say, evolving a cogwheel (which does happen occasionally) or actually developing some of these molecules in the first place. It'd be weird for evolution to struggle so much on trying such a simple concept somewhere. This is a process that naturally figured out solar power, a bunch of mechanical engineering properties, various chemical techniques, all sort of fluid dynamics and statics, radiation resistance, sensing and control systems, etc, etc. If it doesn't build things backwards, more likely than not it is because it doesn't work well. The process knows how to do quite complex engineering tasks.
> If bacteria haven't figured out how to use mirroring
It's unclear bacteria have ever "attempted" it. The synthesis of DNA is incredibly intricate and complex, and the set of proteins that do it are believed only to have ever evolved once. In order for a bacteria to have "attempted" this, it would have to evolve an entirely new set of proteins from scratch.
Personally I think a self-replicating photosynthetic cell with mirror DNA is as scary as self-replicating photosynthetic plastic.
They have: https://pubmed.ncbi.nlm.nih.gov/24647559/
Cellulose? It did cause quite the stir, I'll grant you.
> would have to evolve an entirely new set of proteins from scratch.
Mirrored amino acids already exist in some organisms.
Related:
Technical Report on Mirror Bacteria: Feasibility and Risks (stanford.edu)
Mirrored bacterias are still just scifi. It's too hard to make one of them for now and some normal bacterias will eat them anyway becuase there are a lot of weird bacterias that can eat some specific varity of crap. One of them will save us [1].
The normal bacterias can have trouble eating the reversed proteins, RNA, DNA and even sugars. But oil/fat don't have this problem! In the worst case, normal bacterias will just steal all the oil and fat from the reversed bacterais and kill them, and we will have to sweep the discarded reversed proteins and burn them.
https://en.m.wikipedia.org/wiki/Gray_goo
AI paperclips
https://cepr.org/voxeu/columns/ai-and-paperclip-problem
Prions getting into food supply
Nuclear holocaust.
I’m definitely not sleeping tonight. I can see why Gen Z is thinking not to have kids…
In the mean time, they tried using mRNA vaccines that did mimic our own mRNA, but they caused immune reaction. Substituting a different nucleoside and made the vaccine more stable. The way pseudouridine is used in mRNA vaccines isn't found in nature, ergo people who have been vaccinated are already carrying around bit bit of a form of life never seen before on the planet.
From: https://en.wikipedia.org/wiki/Transfer_RNA
> A large number of the individual nucleotides in a tRNA molecule may be chemically modified, often by methylation or deamidation. These unusual bases sometimes affect the tRNA's interaction with ribosomes and sometimes occur in the anticodon to alter base-pairing properties.
