Duda Jarek

From today: https://www.theguardian.com/world/2020/mar/16/first-participant-us-coronavirus-vaccine-trial-moderna-dose

"Researchers rush to test coronavirus vaccine in people without knowing how well it works in animals" https://www.statnews.com/2020/03/11/researchers-rush-to-start-moderna-coronavirus-vaccine-trial-without-usual-animal-testing/ Good video about mechanisms of COVID-19: https://www.youtube.com/watch?v=Eeh054-Hx1U

Sounds like you are writing about capsid (?), viral envelopes are rather not made of proteins: https://en.wikipedia.org/wiki/Viral_envelope They have some glycoproteins, which could be put on a liposome to get a fake virus ...

I am not saying about just releasing random proteins, but trying to recreate its viral envelope - doesn't it look like liposome? - part of the membrane of cell which produced it. Doesn't this viral envelope have something additional like proteins for targeting? If so, couldn't we just put these external proteins on a liposome to get a fake virus? Wanting to target enveloped virus in bloodstream, we need to target the envelope - or maybe it is just too difficult for immune system, so in practice it can only target infected cells? I thought ribosomes are mainly in nucleus and ER (...mitochondria, chloroplasts), that free ribosomes in cytosol are relatively rare in eucariote (?) and capsid's purpose is usually to get material to the nucleus(?) But still - how to get this mRNA into cells? If using other viruses, I believe it is extremely difficult/time consuming to make it work, and seems nearly impossible for mass production in millions (?) I have seen hypothesized that in November, being nearly identical suggests single point of origin - like jumping from an animal host (bat?). Fresh Science article: https://www.sciencemag.org/news/2020/01/mining-coronavirus-genomes-clues-outbreak-s-origins

Sounds interesting, but from one side delivering mRNA to cell's nucleus seems extremely difficult without viral envelope+capsid (?) Ok, they probably use envelope+capsid of other viruses, e.g. used in gene therapy (?) - but it's probably extremely difficult to take it scale required here (?) From the other side, this way immune system can only learn targeting infected cells (assuming they expose some material) - wouldn't it be better if it could directly target virus in bloodstream? Coronavirus is enveloped - where is the difficulty in just mounting its external proteins on a liposome to get a fake virus for immune system training?

Sounds interesting - some interfering RNA? The situation does not look optimistic here, exponential population growth continues ( https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6 ) and standard vaccine development needs a year. In this moment the virus is still nearly identical: "The researchers also found that the eight complete 2019-nCoV genomes were more than 99.98 percent identical, " https://www.genomeweb.com/genetic-research/coronavirus-genome-sequencing-finds-distinct-genetic-differences-2003-sars-virus what is a big advantage for training immune response, but quickly mutations can start - especially with population growth. What other defense options are there? Wouldn't e.g. just putting its external proteins on a liposome work as provisional vaccine?

Developing a standard vaccine for coronavirus will take at least a few months - what might be too late. However, its sequence is already known, and is nearly identical - suggesting recent single point of origin for human host. So the question is if/how there could be quickly started production of some provisional vaccine - not perfect but fast to introduce? Also exploiting the fact that these viruses are now nearly identical. For example synthesizing its outside proteins and putting them on liposomes - would its introduction to blood have a chance to prepare immune system for the real virus?

I don't doubt that free-cell synthesis can get high production ... assuming you have a good source of e.g. polymerase, which are the real problem here - without mirror cells and ribosomes ... Beside industrial applications, mirror life will be also a crucial milestone in development of synthetic life - the first really different and reasonable (in contrast to e.g. additional nucleotides), and natural development will make it in reach in a few decades, e.g.: 2002 - synthetic virus: https://en.wikipedia.org/wiki/Synthetic_virology 2010 - synthetic cell: https://en.wikipedia.org/wiki/Artificial_cell#Synthetic_cells 2013 - synthetic ribosome: https://en.wikipedia.org/wiki/Synthetic_ribosome 2016 - large mirror protein (polymerase) Will we be really able to contain it then forever? - with human factors, antibiotics resistance, accidents, etc. ... it seems a matter of time when it will finally reach natural environment and start searching an ecological niche to populate, evolve, diversify ...

I don't have education in biochemistry (physics, cs, math), but it seems highly unlikely that you could produce macroscopic (e.g. grams) amounts of large molecules this way (?) Especially proteins requiring mirror ribosomes, often complex post processing, help in folding ... Cell-free synthesis might be useful for extremely rare diseases, but finding some promising drug for a common disease in this huge mirror world, there would be needed kilograms, tonnes to synthesize - what is completely unrealistic without mirror life ... which should become easier every year due to natural development of technology. Anyway, I think it is a matter of time (less than a century) when, due to ambition/money incentives/"because we can", somebody will open this Pandora box, e.g. secretly in a lab in China like for CRISPR babies ...

Hello, the Nature article mentions aptamers as direct application, which are length 30-80 oligonucleotides. Enantiomers of the small ones probably can be directly synthesized in negligible quantity. Now they have mirror polymerase allowing to speed it up, but being relatively costly to synthesize, how many copies can produce a single molecule of polymerase? For mass production there is needed mirror life. And aptamers are just the beginning - mirror life would literally double the space of possible large molecules we can mass produce. Starting actively searching this space, we can find many valuable ones. Especially enzymes - complex and effective nanomachines, optimized for very sophisticated tasks. Anyway, there are extremely strong incentives, not only financial, to go toward finally synthesizing mirror life - like CRISPR babies, there might be no way to stop it (?) What we can do is trying to prepare - understand it well, try to protect from the dangers. And there are many of them - earlier than mirror cyanobacteria dominating our ecosystem due to less prepare natural enemies, potentially killing us all in a few centuries. Bacteria has extremely fast evolution - already can consume l-sugars, and can quickly adapt to others. Mirror E. Coli might already find unusual ecological niches, disturbing ecosystem in an unpredictable way. I wouldn't be surprised if synthesizing mirror life was a factor in Fermi paradox - it is a natural possibility in development of civilization ... which might lead to its extermination.

A decade has passed, moving this topic from SF to synthetic life: https://en.wikipedia.org/wiki/Chiral_life_concept One of the most difficult tasks seemed to be able to synthesize working proteins ... and last year Chinese have synthesized mirror polymeraze: Nature News 2016: Mirror-image enzyme copies looking-glass DNA, Synthetic polymerase is a small step along the way to mirrored life forms, http://www.nature.com/news/mirror-image-enzyme-copies-looking-glass-dna-1.19918 There are also lots of direct economical motivations to continue to synthesize mirror bacteria, like for mass production of mirror proteins (e.g. aptamers) or L-glucose (perfect sweetener). So in another decade we might find out that a colony of mirror bacteria is already living e.g. in some lab in China ... ... taking us closer to a possibility nicely expressed in the title of WIRED 2010 article: "Mirror-image cells could transform science - or kill us all" ( https://www.wired.com/2010/11/ff_mirrorlife/ ) - estimating that it would take a mirror cyanobacteria (photosynthesizing) a few centuries to dominate our planet ... eradicating our life ...

But water molecule has mirror reflection - the same molecule In physics taking mirror reflection is called P-transformation. This transformation isn't perfectly conserved, but the corrections are many orders of magnitude smaller than thermal noise in biochemistry - they shouldn't alter biology. http://wikibin.org/articles/chiral-life-concept.html

Thanks for constructive arguments. I'm not saying that we should do it, but that there can be possibilities - if it's true, somebody, sometimes will anyway do it! So I believe that it should be discussed to understand dangers and possibilities ... and hoped that I can find it here...

SF writer, Greg Bear (http://www.gregbear.com/blog/display.cfm?id=982), pointed me out that we need viruses - the point is that we use some parts (eg capsid) of REV (retrovirus which is in our DNA) in some essential mechanisms, so we can't replace it to something neutral. But over this millions of years, this capsids have been optimized for our purposes. Maybe it's good point for viruses to begin evolution, but there is still a long way, counted in thousands-millions of years. Viruses for evolution requires friendly environment - cells. Ours has quite good protection, much better then when viruses evolved last time. We can also think about transforming only eg human, and use original bacterial flora, which could be compatible (after teaching the immune system)? I've received a long letter from Steve Winter. One of many things he mentioned was that " there was a study where a group fed some bacteria chiral food, and it eventually evolved the ability to eat the food". It's large problem, but I think they should have much more problems with evolution of interactions (like aggressiveness) with chiral organism, and in supported by us chiral ecosystem, they should be dominated... And they usually die with the carrier. But the largest benefit from chiral life are viruses - let's say that we can manage with microorganisms, but elimination of viruses looks hopeless http://virology.wordpress.com/ And the lack of them should slow down the evolution of bacterias, making the creation of stable ecosystem easier. What are the costs of such project? The most of the cost is to transform a few cells of each needed specie - I think that required technology should be standard in a few dozens of years. Then we have to replace seeds for a few fields, clone some cattle ... and humans for adoption... The replacement process can be very slow. And the income ... HEALTH ... crop production ... pests ... maybe to be or not to be for natural Martian life until terraforming

How to make such prokaryote? Huge problem is to create chiral enzymes, I will sketch in a moment how how I imagine that. Now take a solution of phospholipids, it will automatically create a bubble, fill the membrane with proteins, pump DNA, ... , ATP ... and voilla About the other parts of it... The cell should 'live' in specyfic, precise conditions, without most of them. Then it should try to stabilise itself, rebuild what's needed (like the wall). This would give us time to do something to allow it to reproduce. Having this small factories, synthesis of elements will be simple. But the real problem is with eukaryote. I think we could use the original cell and just replace/add what we need... Most of the proteins work with symmetric molecues, the other we could block or do nothing with them - if we place the cell in good conditions, feed it (even artifically with eg ATP), it should be stable while 'slowly' adding chiral molecues, replacing DNA ... and after some time/generations it will replace everything itself. Here is a sketch of production the (chiral) string of protein(/DNA): Prepare a surface with with oriented lattice of something that can adhere amino acids and that they can be easly released (by light, electric current, pH, temperature...). Then 'just' print (like ink printer) or litograph (use different solutions of aminoacids and light specyfic pattern to adhere) given patterns of strings of amino acids... Then use some catalysis to join neighbours. We would have maaany copies full of errors at one time. For selection process, we can use something the correct ones would adhere to. Now we can slowly recreate bottom-up customized ecosystem... But how to do it more effective and stable? Maybe we need viruses? I have a discussion about it on http://www.scienceforums.net/forum/showthread.php?t=27078

There is a problem - for example we have human endogenous retroviruses (HERVs) in our DNA. Before transforming organisms, we should identify any dangerous parts in our introns, virus's capsids, and replace them with something neutral. If not - they can be used as a good start for evolution... I was thinking about projecting ecosystem based on harmony - there are maaaany problems to take under consideration - I've decided to start new thred. Generally - let's say we can manage with most of microorganism, there are some concetps for viruses too, http://virology.wordpress.com/ but they looks a bit hopeless for me...

why with chiral? Becouse there has been everything made ... a few billions years of evolution, just take what you need... Of course there is possible much more 'perfect' life, in devalopment of which we will make huge steps, not possible while evolution, like exchanging neurons with something based on conductors - with much higher speeds ... But devalopment of it, is unimaginary difficult ... much easier, for the beginning, is to copy (reflect) the nature About overpopulating, population becaming older ... it's already inaviodable social problem... In this way You can say to go back a few hundreds years... Science can give tools to make life easier, longer ... but what do people do with it...? About effectiveness... Look at the ecosystem - it's neverending domestic war, most of energy is 'waste' on competition, fights... And we would like to change it into something closer to harmony, by removing some organisms, so the energy (solar) would be mainly used to production of proteins, sugars and reproduction ...

To create a stable ecosystem, we would have to transform a large part of ours. We would do it to reduce maximally competitiveness, aggressiveness - to maximize its effectiveness by harmony. Of course there will be many empty, profitable ecological niches and organisms would want to evolve to use them. But... 1. I cannot imagine that viruses would be needed - they wouldn't be transformed at all - they would have to evolve from zero, like free DNA. But last time it evolved pararelly with its victims, now organisms have very advanced specific/non-specyfic defensive systems ... 2. We would need many kinds of microorganisms. Symbiotic ones rather wouldn't need have aggressive mechanisms - they would have evolve them from zero. The problem would be with eg. saprotroph, but without viruses, evolution should be much slower and we humans can make it much more difficult for them. 3. Higher organism would need enormous large time to evolve... And if we would have new large problem, we can reverse again. There are some problems with living in sterile environment. There is the hygiene hypothesis that it can lead to autoimmune diseases. We would have to weaken the immune system or give it something else to do, learn it good responses. The other thing is that small amounts of stress (like radiation or infections) is positive - it eg. helps to get rid of damaged - weak cells. But I think we will understand better this mechanisms and learn to use them more effective artificially. Maybe transformation of our ecosytem would be to expensive, but in some time we would need to create completly new ecosystem eg. on Mars, and its effectiveness will be veeery important...

About finding the way by pathogens... Evolution is a process of finding local fitness maximum by small steps... Let say that a virus get into chiral cell ... what next? Bacterias would eg need normal sugars... Chiral enviroment would be hostile for them, there is no way that eg virus could just transform naturally into chiral form. They would have to evolve from zero. Or by sabotage... but then we could easier controll their population, and they couldn't reach actual level. The danger I've found is that eg unicell which is able to photosynthesis wouldn't have many natural enemies ... it could evolve...dominate our enviroment. Very important priniple for the beginning would be: from chlorophyll organisms we can transform only plants which population can be controlled! About problems of sterile life... there is quite sensful 'hygiene hypothesis', that it would increase susceptibility to allergic diseases. But I think we would be able to manage with it...? About symbiotic organisms... Of course finally it would be needed to transform large part of our enviroment. We could start with eg ecoli and use them as a factories on the beginnig. Plants... and finally maybe human... Question if such chiral cell would function normally? I've found an article arxiv.org/ftp/cond-mat/papers/0507/0507347.pdf which says in abstract that corrections for P-symmetry would be 10^-17(...?). I could'n find more pricise formulation, but this number suggests that it would be many orders of magnitude smaller than thermal noise. It could be essential in symmetry breaking, but not in funtioning. We humans like to show our power and it's rather unavoidable that some day, we would be able to create a new life (what is the whole talking about nanorobots?) ... I think we will start with chiral... They could give us not only health, but I think they could allow us to increase efficiency of our ecosystems, of the most clean and powerful source of energy - sun.

A while ago I thought about some concept, which should which should allow us, to get rid of all unwanted life. This is – by becoming incompatible. Previously I thought that we could do it by changing the language which encodes nucleotide triples into amino acids (be replacing eg tRNA), but it could result in enormous number of problems with gene regulation. I’ve just found the “safe” way – take mirror reflection! If we replace left-handed amino acids with right-handed, we would get mirror reflections of natural proteins. Analogically we could get chiral DNA, sugars, etc. on which new enzymes would work perfectly. Finally we would get normally functioning mirror reflection of natural organism, on which natural viruses couldn’t interact. We know, that there is a small violation of such symmetry (P), but it shouldn’t change the biochemistry. Such organism would have to be feed with reflected food, produced eg by reflected plants, which use to production symmetric (not chiral) molecules and unpolarized light. In such world natural hostile organisms, if wouldn’t be translated by a terrorist organization, wouldn’t have chance to transform into chiral versions. They could evolve from zero, but we would have many thousands years of peace. How to make it? We can imagine synthesis of every molecule, such reflected zygote is made of. The problem is to create the correct structure of membranes with specific concentrations … fill it with life… What with actual trends in nano-engineering should become possible in at most 50 years, I think. Then we could slowly transform our ecosystems. In that way we could get rid of any plagues. But if in such sterile environment, we would have perfect health? Maybe stresses created by small infections can, like small amounts of radiation, have positive long term influence…? What do You think about this concept?