I think focusing framing against mirror bacteria is harmful for the project, as opposed framing it as protection against any general (synthetic) biology risk. Or even colonization of an alien biosphere.
There are a few classes of commonly-used antibiotics that are achiral and would still work against mirror bacteria (trimethoprim, sulfa drugs). We lose the most commonly used ones, but any human infection could probably be treated with these achiral antibiotics, especially since the growth of mirror bacteria is likely slow due only being able to utilize a small fraction of resources. They could evolve resistance, but they would lack access to horizontal gene transfer from non-mirror bacteria, requiring any resistance mechanisms to evolve de novo.
The main threat of mirror bacteria isn’t direct infection of humans, but how they could reshape the biosphere and impact food security, which hiding in a shelter does not protect you from. Other, more targeted risks, such as bioweapons, pandemics and viral outbreaks would be better served by these shelters (though I’m unsure if your filtration system is designed for viruses).
Note that addition to any achiral antibiotics, we could also use the mirror image versions of any chiral antibiotic. Even more powerful, we could use mirror image versions of toxins to all life (e.g. nucleoside analogs) that are normally hard to use because we share chirality with regular bacteria
To both of you: My knowledge of microbiology and biochemistry is almost non-existent. So I actually very much welcome pushback on the threat itself. I also feel that I should grasp the science behind mirror bacteria at least on some very preliminary level. That said, I always want to understand things “completely” so I started looking for specific places in the immune system where reversed chirality would mess things up and started with the TLR4 receptor and could not conclude that well that chirality would play a role for 2 reasons: 1 - It seems the TLR4 could bind to quite a variety of “form factors” so it is unclear why it would be much less effective for mirror pathogens 2 - I then looked at TLR2 and am hoping to learn from someone expert in this why the binding of NAM (I hope I got that right) and the attached lipid is likely to fail with mirror bacteria. This avenue of study led me to discover 2 things that some bacteria actually uses reverse chirality amino acids in their cell walls exactly to be resistant to degradation, and, that the TLR structures seem to actually flex in space, meaning they have at least some flexibility in the spatial arrangement of whatever they seek to recognize.
The evidence I am now chasing is somewhere scientists actually swapped some lipid or sugar for its mirror equivalent and then looked at the resulting binding or failure to bind to e.g. a TLR.
That said, there is a lot of intellectual power behind that report and it has been peer reviewed so I would be surprised if I find something that invalidates it. And I think the main message is that “we don’t know, but it does not look promising” and the authors state that they would love for people to engage with their assertions.
You cannot completely understand the immune system; that is something you learn early on in immunology.
That being said, the key understanding on mirror bacteria evading the immune system is that the immune system generally relies on binding to identify foreign invaders, and if they cannot bind then they cannot respond. Bacteria generally share a number of molecules on their surface, so the innate immune system has evolved to bind and detect these molecules. If they were mirrored, they would not bind as well, and would be harder to detect and respond to.
That being said, you did find the insight that they are not completely invisible. There are also systems that can detect the damage done by the infection and start a counterattack, even if they can’t see the invaders themselves. But much of the counterattack would not be able to affect the mirror bacteria.
What matters in the report is that the immune system of all animals and plants will likely be (much) less effective against mirror bacteria. This doesn’t mean it’s an untreatable disease, as we have antibiotics that should still be effective against the mirror bacteria. But it does mean that if the mirror bacteria finds its way into the environment it is unlikely that anything can fight back well.
I agree about it being hard to understand the immune system completely, i should have written “understand one single process well enough to have high confidence”. So i just wanted to understand one step, such as the binding of something to just one of the TLRs. And the understanding could be empirical too—I would be confident if researchers could robustly repeat a failure of some mirror component to bind to a TLR, for example.
I was unaware that filters have to be designed differently for viruses. Would you be able to point to where I can read about that? You are the second person I have encountered that has said something along the lines of “filters might work differently for viruses”. I have, as you might see from my post, looked quite deeply into filters and they are tested with both liquids and solids of various forms and this heterogeneity in challenge aerosols, from what I have read, hardly seems to affect their efficiency.
I work with bacterial viruses in liquids, and when we want to separate the bacteria from their viruses, we pass the liquid through a 0.22um filter. A quick search shows that the bacteria I work with are usually 0.5um in diameter, whereas the smallest bacteria can be down to 0.13um in diameter; however, the 0.22um filter is fairly standard for laboratory sterilization so I assume smaller bacteria are relatively rare. The 0.22um filter can also be used for gases.
But as with my usage, they block bacteria and not viruses. I’m working with 50nm-diameter viruses, but viruses of bacteria are generally smaller than those of animals; SARS-CoV2 is somewhere from 50-140nm.
If you use a small enough filter it would still filter out the viruses; but you’ll need to get a pore size smaller than what is sufficient for filtering out bacteria. (and smaller pores requires more pressure, more prone to clogging, etc.)
(though for air, it’s quite rare for bare viruses to be floating around; they’re usually in aerosols (bacteria are often also in aerosols, which may be easier to filter out)
Filtering liquids is pretty different from air, because a HEPA filter captures very small particles by diffusion. This means the worst performance is typically at ~0.3um (too small for ideal diffusion capture, too large for ideal interception and impaction) and is better on both bigger and smaller particles. The reported 99.97% efficiency (2.5 logs) is at this 0.3um nadir, though.
This seems largely correct but I must admit I have never seen an experiment that clearly demonstrates that diffusion is the main feature. Perhaps such experiments have been carried out but if so I think one would have to do something extremely challenging like filming the process at extremely high FPS rates with something like a scanning electron microscope. My sense is that the “performance curve” of filters is mostly empirically deduced while we are actually only extrapolating when making statements about what exactly causes these empirical results.
For example, another process I intuitively feel is different between air and water is the density and thus the force of the fluid on contaminants. If you travel in a boat, it is so much harder to stick your hand in the water compared to the air. Similarly, a particle that could potentially attach to a filter fiber in water is unlikely to stay attached as the water would exert such a high force on it that it detaches. This is why one washes one’s car with a water hose, not an air hose.
I would be interested in any experiment that has looked at the micro scale physics involved in air filtration but my impression after looking at a lot of filter literature is that there are few, if any such studies.
Absolutely, if anything I trust decades of consistent, empirical results way more than something arrived at by armchair mathematics, or even worse, a mixture of intuition and extrapolated theories.
Other, more targeted risks, such as bioweapons, pandemics and viral outbreaks would be better served by these shelters
I think they could maybe be appropriate for some bioweapons, but for most pathogen scenarios you don’t need anywhere near the fourteen logs this seems to be designed for. So I do think it’s important to be clear about the target threat: I expect designing for fourteen logs if you actually only need three or something makes it way more expensive.
Just a note here—I am not sure e.g. 5-log reduction would be much less expensive. The counterintuitive design with serial filtration fed into a positively pressurized bubble is already cheap even at the >10 log level. The reductions in cost by removing logs would stem from:
-Lower power demands, meaning one might get away with a somewhat smaller power system, and/or smaller dimension air supply. However, nothing like a 50% cost reduction, more like 5%-10%
-One would need to buy less filters. But these are not extremely expensive, I would guess removing one filter would decrease overall cost by <5%
Said differently, the “performance-cost curve” is kind of jumpy: Below 3-5 log it is very cheap, like just a regular HEPA air cleaner in your room and some sealant at windows and doors. Then the next step is this bubble with relatively flat costs from 3-5 logs up to 13-16 log. After that I think one is looking at something markedly different and much more expensive, if such logs even make physical sense.
I think focusing framing against mirror bacteria is harmful for the project, as opposed framing it as protection against any general (synthetic) biology risk. Or even colonization of an alien biosphere.
There are a few classes of commonly-used antibiotics that are achiral and would still work against mirror bacteria (trimethoprim, sulfa drugs). We lose the most commonly used ones, but any human infection could probably be treated with these achiral antibiotics, especially since the growth of mirror bacteria is likely slow due only being able to utilize a small fraction of resources. They could evolve resistance, but they would lack access to horizontal gene transfer from non-mirror bacteria, requiring any resistance mechanisms to evolve de novo.
The main threat of mirror bacteria isn’t direct infection of humans, but how they could reshape the biosphere and impact food security, which hiding in a shelter does not protect you from. Other, more targeted risks, such as bioweapons, pandemics and viral outbreaks would be better served by these shelters (though I’m unsure if your filtration system is designed for viruses).
Note that addition to any achiral antibiotics, we could also use the mirror image versions of any chiral antibiotic. Even more powerful, we could use mirror image versions of toxins to all life (e.g. nucleoside analogs) that are normally hard to use because we share chirality with regular bacteria
To both of you: My knowledge of microbiology and biochemistry is almost non-existent. So I actually very much welcome pushback on the threat itself. I also feel that I should grasp the science behind mirror bacteria at least on some very preliminary level. That said, I always want to understand things “completely” so I started looking for specific places in the immune system where reversed chirality would mess things up and started with the TLR4 receptor and could not conclude that well that chirality would play a role for 2 reasons:
1 - It seems the TLR4 could bind to quite a variety of “form factors” so it is unclear why it would be much less effective for mirror pathogens
2 - I then looked at TLR2 and am hoping to learn from someone expert in this why the binding of NAM (I hope I got that right) and the attached lipid is likely to fail with mirror bacteria. This avenue of study led me to discover 2 things that some bacteria actually uses reverse chirality amino acids in their cell walls exactly to be resistant to degradation, and, that the TLR structures seem to actually flex in space, meaning they have at least some flexibility in the spatial arrangement of whatever they seek to recognize.
The evidence I am now chasing is somewhere scientists actually swapped some lipid or sugar for its mirror equivalent and then looked at the resulting binding or failure to bind to e.g. a TLR.
That said, there is a lot of intellectual power behind that report and it has been peer reviewed so I would be surprised if I find something that invalidates it. And I think the main message is that “we don’t know, but it does not look promising” and the authors state that they would love for people to engage with their assertions.
You cannot completely understand the immune system; that is something you learn early on in immunology.
That being said, the key understanding on mirror bacteria evading the immune system is that the immune system generally relies on binding to identify foreign invaders, and if they cannot bind then they cannot respond. Bacteria generally share a number of molecules on their surface, so the innate immune system has evolved to bind and detect these molecules. If they were mirrored, they would not bind as well, and would be harder to detect and respond to.
That being said, you did find the insight that they are not completely invisible. There are also systems that can detect the damage done by the infection and start a counterattack, even if they can’t see the invaders themselves. But much of the counterattack would not be able to affect the mirror bacteria.
What matters in the report is that the immune system of all animals and plants will likely be (much) less effective against mirror bacteria. This doesn’t mean it’s an untreatable disease, as we have antibiotics that should still be effective against the mirror bacteria. But it does mean that if the mirror bacteria finds its way into the environment it is unlikely that anything can fight back well.
I agree about it being hard to understand the immune system completely, i should have written “understand one single process well enough to have high confidence”. So i just wanted to understand one step, such as the binding of something to just one of the TLRs. And the understanding could be empirical too—I would be confident if researchers could robustly repeat a failure of some mirror component to bind to a TLR, for example.
I was unaware that filters have to be designed differently for viruses. Would you be able to point to where I can read about that? You are the second person I have encountered that has said something along the lines of “filters might work differently for viruses”. I have, as you might see from my post, looked quite deeply into filters and they are tested with both liquids and solids of various forms and this heterogeneity in challenge aerosols, from what I have read, hardly seems to affect their efficiency.
I work with bacterial viruses in liquids, and when we want to separate the bacteria from their viruses, we pass the liquid through a 0.22um filter. A quick search shows that the bacteria I work with are usually 0.5um in diameter, whereas the smallest bacteria can be down to 0.13um in diameter; however, the 0.22um filter is fairly standard for laboratory sterilization so I assume smaller bacteria are relatively rare. The 0.22um filter can also be used for gases.
But as with my usage, they block bacteria and not viruses. I’m working with 50nm-diameter viruses, but viruses of bacteria are generally smaller than those of animals; SARS-CoV2 is somewhere from 50-140nm.
If you use a small enough filter it would still filter out the viruses; but you’ll need to get a pore size smaller than what is sufficient for filtering out bacteria. (and smaller pores requires more pressure, more prone to clogging, etc.)
(though for air, it’s quite rare for bare viruses to be floating around; they’re usually in aerosols (bacteria are often also in aerosols, which may be easier to filter out)
Filtering liquids is pretty different from air, because a HEPA filter captures very small particles by diffusion. This means the worst performance is typically at ~0.3um (too small for ideal diffusion capture, too large for ideal interception and impaction) and is better on both bigger and smaller particles. The reported 99.97% efficiency (2.5 logs) is at this 0.3um nadir, though.
This seems largely correct but I must admit I have never seen an experiment that clearly demonstrates that diffusion is the main feature. Perhaps such experiments have been carried out but if so I think one would have to do something extremely challenging like filming the process at extremely high FPS rates with something like a scanning electron microscope. My sense is that the “performance curve” of filters is mostly empirically deduced while we are actually only extrapolating when making statements about what exactly causes these empirical results.
For example, another process I intuitively feel is different between air and water is the density and thus the force of the fluid on contaminants. If you travel in a boat, it is so much harder to stick your hand in the water compared to the air. Similarly, a particle that could potentially attach to a filter fiber in water is unlikely to stay attached as the water would exert such a high force on it that it detaches. This is why one washes one’s car with a water hose, not an air hose.
I would be interested in any experiment that has looked at the micro scale physics involved in air filtration but my impression after looking at a lot of filter literature is that there are few, if any such studies.
While it’s nice to know the mechanism, I think all we really need in this case is the empirically determined performance curve.
Absolutely, if anything I trust decades of consistent, empirical results way more than something arrived at by armchair mathematics, or even worse, a mixture of intuition and extrapolated theories.
I think they could maybe be appropriate for some bioweapons, but for most pathogen scenarios you don’t need anywhere near the fourteen logs this seems to be designed for. So I do think it’s important to be clear about the target threat: I expect designing for fourteen logs if you actually only need three or something makes it way more expensive.
Just a note here—I am not sure e.g. 5-log reduction would be much less expensive. The counterintuitive design with serial filtration fed into a positively pressurized bubble is already cheap even at the >10 log level. The reductions in cost by removing logs would stem from:
-Lower power demands, meaning one might get away with a somewhat smaller power system, and/or smaller dimension air supply. However, nothing like a 50% cost reduction, more like 5%-10%
-One would need to buy less filters. But these are not extremely expensive, I would guess removing one filter would decrease overall cost by <5%
Said differently, the “performance-cost curve” is kind of jumpy: Below 3-5 log it is very cheap, like just a regular HEPA air cleaner in your room and some sealant at windows and doors. Then the next step is this bubble with relatively flat costs from 3-5 logs up to 13-16 log. After that I think one is looking at something markedly different and much more expensive, if such logs even make physical sense.