I think it’s very unlikely that a mirror bacterium would be a threat. <1% chance of a mirror-clone being a meaningfully more serious threat to humans as a pathogen than the base bacterium. The adaptive immune system just isn’t chirally dependent. Antibodies are selected as needed from a huge library, and you can get antibodies to loads of unnatural things (PEG, chlorinated benzenes, etc.). They trigger attack mechanisms like MAC which attacks membranes in a similarly independent way.
In fact, mirror amino acids already somewhat common in nature! Bacterial peptidoglycans (which form part of the bacteria’s casing) often use a mix of amino acid in order to resist certain enzymes, but bacteria can still be killed. Plants sometimes produce mirrored amino acids to use as signalling molecules or precursors. There are many organisms which can process and use mirrored amino acids in some way.
The most likely scenario by far is that a mirrored bacteria would be outcompeted by other bacteria and killed by achiral defenses due to having a much harder time replicating than a non-mirrored equivalent.
I’m glad they’re thinking about this but I don’t think it’s scary at all.
The antibodies not being chiral dependent doesn’t mean there aren’t other fundamental links in the whole chain that leads to antibodies being deployed at all that may not be. Mostly I imagine the risk is that we have a lot of systems optimized for dealing with life of a certain chirality. They may be able to cope with the opposite chirality, but less so. COVID alone showed what happens when something far less alien but that is just barely out of distribution for our current immune defenses arrives: literally everyone in the world gets it in a matter of months, a non-insignificant percentage dies even if the pathogen itself would be no more complex or virulent than others we deal with on the daily. And COVID was easy mode. We have examples of far more apocalyptic outcomes from immune naive populations getting in contact with new pathogens.
Here we’re not even talking about somehow innocuous entities. E. Coli can and will kill you if it gets in the wrong place while your defenses are down, no mirroring necessary. Staph. Aureus is everywhere already and will eat your flesh while you still live if given the chance. The only reason why we coexist with these threats is that we are in an armed truce: they can stay within their turf, but as soon as they try and go where they don’t belong, they get terminated with maximum prejudice. Immuno-compromised people have to fear them a lot more. Imagining a version of them that is both antibiotic resistant (because I bet that’s also a consequence of chirality) and able to evade at least the first few layers of immune defenses, until somehow the system scrambles to compensate and manages to churn out a counter-measure, is terrifying enough. That the immune system may eventually cope with them doesn’t mean it wouldn’t be an apocalyptic pandemic (and worse, one that affects man and animal alike, all at once).
Yes, antibodies could adapt to mirror pathogens. The concern is that the system which generates antibodies wouldn’t be strongly triggered. The Science article says: “For example, experiments show that mirror proteins resist cleavage into peptides for antigen presentation and do not reliably trigger important adaptive immune responses such as the production of antibodies (11, 12).”
The most likely scenario by far is that a mirrored bacteria would be outcompeted by other bacteria and killed by achiral defenses due to [examples of ecological factors]
I think this is the crux of the different feelings around this paper. There are a lot of unknowns here. The paper does a good job of acknowledging this and (imo) it justifies a precautionary approach, but I think the breadth of uncertainty is difficult to communicate in e.g. policy briefs or newspaper articles.
I think it’s very unlikely that a mirror bacterium would be a threat. <1% chance of a mirror-clone being a meaningfully more serious threat to humans as a pathogen than the base bacterium. The adaptive immune system just isn’t chirally dependent. Antibodies are selected as needed from a huge library, and you can get antibodies to loads of unnatural things (PEG, chlorinated benzenes, etc.). They trigger attack mechanisms like MAC which attacks membranes in a similarly independent way.
In fact, mirror amino acids already somewhat common in nature! Bacterial peptidoglycans (which form part of the bacteria’s casing) often use a mix of amino acid in order to resist certain enzymes, but bacteria can still be killed. Plants sometimes produce mirrored amino acids to use as signalling molecules or precursors. There are many organisms which can process and use mirrored amino acids in some way.
The most likely scenario by far is that a mirrored bacteria would be outcompeted by other bacteria and killed by achiral defenses due to having a much harder time replicating than a non-mirrored equivalent.
I’m glad they’re thinking about this but I don’t think it’s scary at all.
The antibodies not being chiral dependent doesn’t mean there aren’t other fundamental links in the whole chain that leads to antibodies being deployed at all that may not be. Mostly I imagine the risk is that we have a lot of systems optimized for dealing with life of a certain chirality. They may be able to cope with the opposite chirality, but less so. COVID alone showed what happens when something far less alien but that is just barely out of distribution for our current immune defenses arrives: literally everyone in the world gets it in a matter of months, a non-insignificant percentage dies even if the pathogen itself would be no more complex or virulent than others we deal with on the daily. And COVID was easy mode. We have examples of far more apocalyptic outcomes from immune naive populations getting in contact with new pathogens.
Here we’re not even talking about somehow innocuous entities. E. Coli can and will kill you if it gets in the wrong place while your defenses are down, no mirroring necessary. Staph. Aureus is everywhere already and will eat your flesh while you still live if given the chance. The only reason why we coexist with these threats is that we are in an armed truce: they can stay within their turf, but as soon as they try and go where they don’t belong, they get terminated with maximum prejudice. Immuno-compromised people have to fear them a lot more. Imagining a version of them that is both antibiotic resistant (because I bet that’s also a consequence of chirality) and able to evade at least the first few layers of immune defenses, until somehow the system scrambles to compensate and manages to churn out a counter-measure, is terrifying enough. That the immune system may eventually cope with them doesn’t mean it wouldn’t be an apocalyptic pandemic (and worse, one that affects man and animal alike, all at once).
Acquired immune systems (antibodies, T cells) are restricted to jawed vertebrates.
You’re saying that we might survive, but our environment/food might not, right?
Yes, antibodies could adapt to mirror pathogens. The concern is that the system which generates antibodies wouldn’t be strongly triggered. The Science article says: “For example, experiments show that mirror proteins resist cleavage into peptides for antigen presentation and do not reliably trigger important adaptive immune responses such as the production of antibodies (11, 12).”
I think this is the crux of the different feelings around this paper. There are a lot of unknowns here. The paper does a good job of acknowledging this and (imo) it justifies a precautionary approach, but I think the breadth of uncertainty is difficult to communicate in e.g. policy briefs or newspaper articles.