Duda Jarek

Most believe black holes exist, here we would like to understand their properties from symmetry - existence of white holes is not needed for that. But maybe they exist, e.g. assuming there was Big Bounce, before it I would expect symmetric formation of our white holes, so maybe also before our Big Crunch - while unlikely, I wouldn't be surprised if observing them in some future. Both are coupling of two electrons on both sides of horizon, with photon crossing horizon in the allowed direction - we just switch Feynman diagram between white and black hole, as shown above. But positive/negative radiation pressure seems more intuitive - like revering marine propeller or rotation in EM Barnett effect.

I use white holes here only to better understand black holes - as you say, the former would be trivial to observe - acting with absorption equation on sensor of telescope. If we believe in CPT symmetry, black holes should analogously act with stimulated emission - could reduce the number of excited atoms e.g. in telescope sensor, we might be able to observe: if initially exciting it, and monitoring its population. Sure, maybe CPT is violated and it will not work, but there are not many options to observe lone BH - this one might be slightly more practical alternative to observation of Hawking radiation ... ps. The main diagram again as there are problems with above:

Yes, N1 is the number of ground state atom e.g. in diagram, N2 of excited - absorption equation increases N2 (e.g. outside white hole), stimulated emission decreases N2 (symmetrically should be outside black hole). Usually excited atoms mainly undergo spontaneous emission, but stimulated emission could make it faster - suggesting how to try to observe it: continuously excite the sensor of telescope, and monitor its population. https://en.wikipedia.org/wiki/Barnett_effect can be viewed as EM analog of marine propeller - switching rotation direction to change the sign of created pressure.

From atomic perspective, white holes increase N2 number of excited atoms outside with absorption equation - its T/CPT analog is black hole decreasing N2 number of excited atom with stimulated emission. Regarding radiation pressure, white hole only emits - pushing objects outside, acting with positive radiation pressure ... applying T/CPT symmetry, doesn't it mean pulling, applying negative radiation pressure? Like applying T symmetry to marine propeller situation: Hydrodynamics is mathematically very close to EM, allowing such marine propeller analog:

Including that while white holes should act with positive radiation pressure, black holes should symmetrically act with negative radiation pressure, might resolve the black hole information paradox (?) - showing there was a lot of information exchange before reaching the end of evaporation. https://en.wikipedia.org/wiki/Black_hole_information_paradox :

T/CPT symmetric analog of black hole in Kruskal–Szekeres coordinates is white hole, which only allows photons to cross horizon outside, hence pushing objects around with EM - act with positive radiation pressure p=<ExH>/c vectors outside, absorption equation increasing the number of excited atoms (N2) outside. If so, shouldn't black hole symmetrically act with negative radiation pressure - pull objects around with EM by p=<ExH>/c radiation pressure vectors pointing inside, act with stimulated emission equation decreasing the number of excited atoms (N2) outside? Such looking necessary effect of black hole could be slightly easier to observe than Hawking radiation, maybe even look below the horizon - would need e.g. telescope with excited sensor, monitoring its population - testing if it doesn't deexcite faster than usual by stimulated emission e.g. from black hole.

This is a question of minimal time required for formation of observable objects after Big Bang? If observing earlier ones, wouldn't it mean they had to come from before T=0? My point is that observing extreme Z could offer experimental way to distinguish Big Bang from Big Bounce, e.g. the latter might have no upper bound for Z. What other experimental evidence could confirm there was nothing before?

There are recent claims for observations of up to redshift 25 objects by JWST, which are said too early to be formed by standard Big Bang models, e.g. https://www.scientificamerican.com/article/the-james-webb-telescope-may-have-found-primordial-black-holes/ Probably even higher redshifts will be found in the future, so I wanted to ask if some objects like black holes could e.g. "pass in safe distance" surviving Big Bounce - now being observed as having extreme redshifts? www.youtube.com/watch?v=EOowNVML4_I

Notice you can get all these protein by just copying DNA ... for minimal cells we are talking about hundreds of genes: https://www.nature.com/articles/s41586-023-06288-x - e.g. "493 genes, JCVI-syn3B". Synthesizing the central dogma + DNA, all these proteins will be created themselves ... e.g. enzymes for basic metabolism ... the hard part seem membrane structure, cytoskeleton, replication - which do you think will be technically impossible to recreate in a lab? It is said there are ~10x more bactoriophages than bacteria, coming from infected bacteria ... and this is only one of bacteria natural enemies, preventing exponential growth through e.g. Lotka–Volterra predator-prey cohabitation ... mirror bacteria will have nearly no natural enemies, with exponential growth limited nearly only by resources - taking it from other organisms, dominating succeeding ecological niches ... replacing especially higher organisms: with much slower evolution.

Mirror dogma as complete transcription/translation machinery - just chemistry, done everyday in labs, no problem to enclose it into a membrane ... so where are technical impossibilities for adding further functions like basic metabolism ... finally cell replication? The report is very detailed - if you have lots of concerns, maybe gather more skeptical biochemists and write some detailed critical answer to this report? (would gladly read) It needs sources of energy and materials, natural bacteria has adapted to mirror e.g. sugars so mirror bacteria should adapt to consume e.g. D-sugars ... but there are also lots of achiral molecules both chirality bacteria can directly consume - Table 1.1 of report: Citrate, fumarate, glycolate, glyoxylate, ɑ-ketoglutarate, pyruvate, succinate, Acetate, acetoacetate, butyrate, propionate, valerate, Medium-chain (C6–C10) fatty acids, Long-chain (≥C12) fatty acids, Butanol, ethanol, propanol, Dihydroxyacetone, ethylene glycol, galactitol, glycerol, mucate, Benzoate, m-coumarate, 2-furoate, 3-hydroxyphenylacetate, phenylacetate, phenylpropionate, phenylethylamine, γ-aminobutyrate, putrescine, γ-hydroxybutyric acid, methyl pyruvate, m-tartaric acid, Glycine, Agmatine, γ-aminobutyrate, dopamine, phenylethylamine, putrescine, spermidine, tyramine, Adenine, cytidine, thymine, uracil, Allantoin, urate. One basic question is immune response, and most of its mechanisms are chirality dependent, the report cites lots of research for various types of interactions between natural biology and enantiomers of natural biomolecules ... even if some of them would still work (the report distinguishes certain and unknown), many won't - this would be situation as in immunodeficiencies. Natural bacteria has lots of enemies starting with bacteriophages - mirror bacteria will not have. Also being different many new ecological niches will open for it - what through evolution could drastically change the ecosystem. Regarding Fermi paradox, sure there many dangers coming especially with new technologies - is there a hope our civilization will pass them for the next 10, 30, 100, 1000 years? Very serious question: how to make it more likely? If scientists will not have answers to such question, who to ask?

Like GMO? So you accept synthesizing mirror dogma is reachable (?) and further steps toward mirror bacteria (?), and now say consequences won't be that bad? (otherwise please define your uncrossable barrier on the way) So imagine such mirror bacteria got into the environment, if prepared by malicious player being able to feed on e.g. D-glucose, otherwise still consuming achiral molecules ... not having natural enemies like bacteriphages, being ignored by most immune systems, potentially toxic if consumed ... taking available ecological niches, evolving, spreading ... how do you think it would end? And we are still very early in synthetic life, which will lead to many further organisms relatively easy to create ... then practically impossible to stop spreading, evolving ... you don't see serious dangers to our civilization there? Can they be realistically overcomed? How? And what do you think about Fermi paradox: why, against statistics, we don't see advanced civilizations ... could synthetic life e.g. mirror be the reason?

From Craig Venture Institute, anyway 10-30 years could be also overstatement, and there could be e.g. malicious players paying to quickly get there ... for me it sounds very serious and dangerous, not some abstract SF story, but something really coming and nearly unavoidable (?) ... Can our civilization prevent such fate ? ("Fermi paradox explanation" in 10, 30, 100, 1000 years?) I am thinking about this question since 2007 and the most realistic way I see is another SF sounding technology - from articles observing response before impulse like https://www.scientificamerican.com/article/evidence-of-negative-time-found-in-quantum-physics-experiment/ ... as a physicists I believe in CPT theorem, which also says that causality should work in both time directions, e.g. in the action optimization or Feynman ensembles - in theory allowing for wormholes, but maybe also much more accessible ways to send just information back in time (e.g. using lasers https://arxiv.org/pdf/2409.15399 ) - if getting there, we could send back details about e.g. escaped mirror bacteria, hence physics should action optimize history of the Universe to one without such catastrophe.

I am just listening to discussion about this mirror bacteria report, somebody very serious just claimed that they are planning complete bottom-up synthesis of natural cell in a year(!), they are wondering if there should be moratorium already on mirror ribosome ... very serious, will respond later.

I have some experience in chemoinformatics (e.g. https://link.springer.com/article/10.1007/s11030-022-10589-0 predicting probability distributions of ADMET properties like cardiotoxicity) and yes - excluding various toxicities is extremely crucial and difficult part of drug design, from virtual screening to clinical trials. Some mechanisms should still work (e.g. achiral) and Chapter 5: Medical Countermeasures of the report discusses some approaches like achiral antibiotics, producing mirror antibiotics, or releasing mirror bacteriophages ... but many would not - as in immunodeficient persons we should compare with. From the other side, mirror bacteria would indeed have crippled mechanisms like adhesion, also feeding with natural components - but there are also many achiral sources (Table 1.1: Achiral organic molecules that can be utilized by wild-type or mutant E. coli K-12), and bacteria can adapt to feed on mirror sugars ... the question is if it can get into the bloodstream, e.g. through injuries, if so it could rather easily exponentially grow in population leading to e.g. sepsis for example from released mirror proteins in necrosis. And getting mirror bacteria, it would evolve, take new ecological niches having practically no natural enemies ... also malicious players could easily modify them to become more dangerous.

Sure one can synthesize proteins from single amino acids, but comparing with its production by bacteria, what would be the difference in cost and volume? A thousand? A million? My point is that there will be large financial incentives for such cost reductions and scaling up, and there is a quickly growing number of potential applications, e.g. from the report: > Are you also worried about naturally occurring mirror molecules? For naturally appearing around us, evolution should generally prepare us for. But for others it did not, what does not automatically mean toxicity, but that there is a probability of various toxicities due to looking random interactions (again thalidomide example) ... and the number of potential interactions grows with the square of number of chiral biomolecules, so multiply this probability by millions e.g. for necrosis of mirror bacteria in human bloodstream - for me it sounds worrying.

Sure a company could now produce mirror protein drug for maybe thousans of customers ... but what if millions would like to buy it? If we agree synthetic central dogma is doable, why they couldn't build on it adding further features? Where exactly is your boundary you believe they will not be able to cross?

Just watching a week old presented by Yutetsu Kuruma from Japan Agency for Marine-Earth Science and Technology: Design and construction of artificial cells based on cell-free system - mentions the most difficult is cell replication, where I completely agree ... but just recreating (mirror) central dogma looks doable (?) - and might be sufficient for safe mass production of mirror biomolecules (?) ... or will become the first step toward replicating mirror cells ... George Church Synthetic genomes & tRNAs in vitro & vivo (Nov 2024):

While as a physicists I can say FTL is forbidden by special relativity (but in theory allowed by general relativity) ... I honestly cannot imagine obstacles for recreating cell chemistry - generally easily made outside cell ... so recreating original cytosol composition of some minimal cell, why wouldn't it work? Which chemical processes? They would work individually, but couldn't synchronize like in a living cell? Anyway, looks like these are your words against their. Searching for "boot synthetic cell" I see lots of positive examples. Could you support your view with some references? ps. Lots of talks from Build-a-Cell seminar (tomorrow about mirror bacteria I plan to visit): https://www.youtube.com/playlist?list=PLb2LmjoxZO-gKWXZZadcko8tHHkPuEeJT E.g. 2020 John Glass from J. Craig Venter Institute (e.g. minimal genome: 483 kbp, 432 proteins, 39 RNAs):

Yes, they use this vague "boot" verb for kind of bringing life to a synthetic cell - but what exactly is it? Naively there is just chemistry - statistical reactions in cytosol as a dense soup of biomolecules ... recreating composition of this soup (for some minimal cell with just central dogma), what more is needed to make it alive?

There are programs searching for minimal cell (e.g. https://www.nature.com/articles/s41586-023-06288-x ) but for full synthesis it is not needed. Being able to synthesize mirror ribosome and DNA/RNA, they could get all required enzymes - then enclose it into a membrane ... and why wouldn't such minimal cell work? (to be further extended with more functions) From fig 2.4 of the report: This is bottom-up approach, but the report also discusses top-down: trying to stepwise convert natural cell into mirror one through various approaches, e.g. genetic code reprogramming like replacing tRNA with carrying mirror amino acids. Section 2.3 of report: "1. Production of mirror-image proteins in vivo by creating a crossover pathway made of natural-chirality components. 2. Production of mirror-image proteins in vivo by creating an entirely mirror-image central dogma. 3. Delivery or assembly of a full mirror-image DNA genome in vivo, and removal of the natural-chirality genome, to create a mirror bacterium."

> We have been just a few years away from synthetic life for a few decades now There is continuous progress (timeline from 2019 https://elifesciences.org/articles/45379 ), synthetic cells are created since 2010 ... where do you think will be the main difficulty for complete synthesis of natural minimal cell? I completely agree interactions between both chiralities are very complex, recommend in the report: "Table 1.1: Achiral organic molecules that can be utilized by wild-type or mutant E. coli K-12", "Table 1.2: Utilization of ʟ- and ᴅ-amino acids by E. coli", "Table 1.3: Utilization of the enantiomers of common monosaccharides by E. coli". And reminded thalidomide example - toxicity from basically random interactions, there would be a huge number of them e.g. from necrosis of mirror bacteria in human bloodstream - there is a large chance for various toxicities.

For me Chapter 2 is quite detailed, bottom-up, top-down and other approaches. If reaching first synthetic cell, what seems a matter of a decade, mirror one would just need to use enantiomers - and their synthesis is quickly developing, especially that there are financial motivations, like mass production of mirror proteins, DNA/RNA ... and there could be some malicious players, like nihilist terrorists, or AGI wanting to get rid of humans ... Chapter 4 is indeed extremely detailed, and difficult without immunology background, but basic scenario is such mirror bacteria getting into the bloodstream, and freely multiply being nearly invisible for immune system - reaching sepsis or different problems. Anyway, I agree this is still early (10-30 years away) - good time to discuss, understand, try to find protections if possible.

This is entire Chapter 4: Risks to Human Health of https://purl.stanford.edu/cv716pj4036, maybe take a look there. For example for macrophages looks like nearly nothing would work:

Below Table of Contents of https://purl.stanford.edu/cv716pj4036 itself allows to imagine our situation in ~20 years, when such synthesis should be relatively simple ... and deadly - how to prevent it? Chapter 2: Pathways to Mirror Life 26 2.1 Advances in chemistry permit the synthesis of mirror biomolecules with diverse applications 28 2.2 Progress in synthetic biology could allow the assembly of a mirror bacterium from non-living mirror components 33 2.3 A natural-chirality bacterium might be converted into a mirror bacterium in a stepwise fashion 41 2.4 Other approaches to creating mirror bacteria are plausible 50 2.5 The feasibility of mirror life will increase as related technologies advance 51 Chapter 3: Engineering, Biosafety, and Biosecurity of Mirror Bacteria 54 3.1 The creation of any mirror bacterium could enable the generation of diverse mirror bacterial strains and species and their modification by routine genetic engineering 55 3.2 Biocontainment approaches might reduce accident risk, but they would face challenges 60 3.3 Creating robustly biosecure mirror bacteria is not feasible 62 Chapter 4: Risks to Human Health 65 4.1 Innate immune detection of mirror bacteria could be significantly impaired 67 4.2 Mirror bacteria would likely be resistant to most innate immune responses 72 4.3 Adaptive immunity to mirror bacteria would likely be impaired 81 4.4 Mirror bacteria could plausibly pass barrier surfaces and translocate into the bloodstream and tissues 91 4.5 Mirror bacteria could plausibly replicate in blood and cause lethal systemic infection 98 Chapter 5: Medical Countermeasures 107 5.1 New antimirror compounds could be developed to target mirror bacteria, but most existing antibiotics would not function 108 5.2 Conjugate vaccines could plausibly be developed against mirror bacteria 113 5.3 The efficacy of other countermeasures against mirror bacterial infection is unclear 116 Chapter 6: Animal Infection 119 6.1 Vertebrate susceptibility to mirror bacterial infection would likely be similar to that of humans 120 6.2 Many invertebrates would likely be susceptible to mirror bacteria 123 Chapter 7: Plant Infection 134 7.1 Mirror bacteria are likely to evade plant innate immunity 135 7.2 Mirror bacteria could plausibly establish chronic local infections within leaves and roots 138 7.3 The extent to which mirror bacteria could spread through and colonize plant vascular tissue is unclear 145 7.4 Countermeasures for agricultural plants 151 Chapter 8: Environmental Survival and Spread 156 8.1 Mirror bacteria would be inherently resistant to many biological controls 157 8.2 Mirror bacteria could colonize natural environments outside of multicellular hosts 165 8.3 Invasive mirror bacteria could rapidly disperse through the environment 175 8.4 Invasive mirror bacteria could rapidly evolve and diversify 178 8.5 Invasive mirror bacteria could cause irreversible ecological harm 181 8.6 Countermeasures to invasive mirror bacteria might lessen but would not halt the ecological damage 187

Regarding time estimates, the report says: "We estimate that if substantial resources were invested in a concerted effort, the creation of a mirror bacterium might still be 10 years away; and if research continues on its current trajectory, mirror bacteria might be created in the next 15 to 30 years." Regarding dangers, basically mirror bacteria could be able to adapt to our e.g. sugars, especially thanks to very fast evolution, and immune system of standard life could be nearly defenseless - from the report: "In addition to functioning as a dangerous “accidental pathogen” to a wide range of natural-chirality species, mirror bacteria could persist within and potentially colonize external environments. Unlike their natural chirality counterparts, mirror bacteria would be completely resistant to all bacteriophages, partially evasive of and largely indigestible to predators, and largely resistant to antimicrobial compounds released by competing microbial species. These potentially decisive competitive advantages could allow sufficiently robust mirror bacteria to successfully invade many ecological niches despite lacking specific adaptations for them. Because predators would not be able to digest most mirror macromolecules, a growing mirror bacterial population would not be controlled by any commensurate increase in predation, which could allow populations to reach high abundance." It is hard to find better sources than this report now - I am slowly reading. It is around the Build-a-Cell community, but I got disclaimer "This Science paper does not represent any official position of the Build-a-Cell community", also with "Mirror Biology Dialogues Fund": https://www.mbdialogues.org/ and information about open discussion this Thursday.