Duda Jarek

Immunity by incompatibility – hope in chiral life

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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?

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could you explain a bit further with your asymmetric amino acids with examples using currently existing amino acids?

By the way, even if you success in changing a living organism to its so-called mirror form, as a matter of fact, pathogens such as virus and bacteria have an extremely high reproductive rate and very short reproductive cycle, I doubt if such 'mirror form' could survive without disease or any other infection or disturbance for thousands years. I don't support this due to that I don't that it would be valuable for us to invest with the profit of just a short period of peace after all. Besides, I doubt if there would be any side-effects, which would cause extra harm to the body and make the matter worse.

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I would have to agree with dttom, pathogens would find a way to infect organisms after they "mirror". You must also remember that there are many good microscopic organisms we might not know about exactly that could be lost if accidently considered "unwanted life".

It is also important to note that some compounds we see as harmless at the moment, could be harmful in their reverse form. In other words, for the amount of testing it would not be worth trying this kind of thing.

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You also have to consider how this would affect our relationships to mutualistic symbiotic relationships we have with many microorganisms.

 

 

I don't think the future of immunity lies with the type of complete genetic engineering you're talking about.

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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.

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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...

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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.

 

Why should we start with chiral? Like you have mentioned yourself, the whole environment would need to be changed before you could even create chiral life. Wouldn't it be much more intelligent to begin with something like nanorobots for example, which are being designed to work with life in the current form?

 

The whole idea that chiral life we give us health can be seen as a good thing, which is the view you have taken. But, if we are to have this perfect health, no pathogens to infect us, etc. wouldn't organisms be living longer and be using more resources than they would have in their normally shorter, diseased life? This would mean the environment would probably be destroyed/used up a lot faster. Or if not that, wouldn't it be a lot more crowded with all these organisms living longer?

 

And why would chiral life allow better use "of the most clean and powerful source of energy - sun"? If you make the world chiral the sun will still be sending out the same stuff which will still hit earth in the same way.

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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 ...

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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...

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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

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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

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Dear Iwannaplaygodandreseedtheearthwithrighthandedmoleculesandorganismsofmyowncreation,

Please put down the comic books, stop taking illicit drugs and read a biochemistry book and a microbiology book.

I suggest starting with anything that contains "..for Nurses" somewhere in the title.

 

After that and a good basic ecology course, hopefully, you will see the complexity of ecological systems.

Please pay particular attention to any parts that mention how organisms have evolved over billions of years to depend on each other; and that they are involved in, for example, complex food chains and symbiosis.

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This thread has been dead for over a year. Kinda makes the ranting twice as useless, doesn't it?

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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...

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One practical problem is mirror bio-material is not chemically active. So even of you could set up an entire mirror cell, perfectly, it would just sit there. If you do an energy balance most bio-chemical mechanisms don't add up using the biomaterial alone. It takes water. Water doesn't exactly have a mirror image. The H20 molecule in solution only lasts about 1 millisecond, so it would revert back to stable steady state. The water push will be to revert the mirror back so it can be functional again where the energetics are able to add up right. If not, the mirror becomes food for life that has the energy engine.

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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 ...

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Posted (edited)

Hi all.  I think we don't even have to make a cyanobacteria to do the job. Even E.coli can grow on minimal media with only mineral salts and glycerol, which is symmetric, as a single source of organic carbon. So does mirrored E.coli. And there is plenty of potential food for the Mirror Life in our environment. Although triglicerides (fats) are technically not symmetric (if all three radicals are different) their (+) and (-) forms may be digested by enzyme of any chirality, leading to glycerol(symmetric) and fat acids (also symmetric). Glycine, citric acid, acetic acid and many other molecules are all symmetric and can be the source of carbon.  A potential pathogen doesn't have to be able to digest its host completely (and none of them actually do).  From the point of view of a mirrored microbe we are Petri dishes, with a relatively inert medium soaked with tasty solution of low-molecular food. Natural nucleosides and nucleotides contain D-sugars, but nucleotide bases are symmetric and could  be used as a building block for RNA and DNA of Mirror life.

Non-photosynthetic Mirror life can deplete oceans and atmosphere of CO2 as well. Their lipids can be digested, but D-proteins are much more prone to hydrolysis, and carbohydrates of the cell wall will be probably almost undigestible. Something like 100 kg/m^2 (quick calculation, could be wrong) of deposits on the seabed and it's over. 

Edited by AlexSorokin
typo

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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.

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Posted (edited)

One molecule of thermostable DNA-polymerase can incorporate about 10^5 nucleotides into DNA during routine polymerase chain reaction. And the only limiting factor here is that 92-95°C is too high even for thermostable enzyme. Taq-polymerase is very cheap, so reaction is optimized for speed, not for the effectiveness per molecule. Anyway, mass production of nucleic acids enantiomers is possible even with chemical synthesis.  Proteins (especially big ones, and those needed post-translational modification) are muck harder to be made. I think it is something like reiterated solving of an "chicken or the egg" problem: you need to decide what is cheaper to create first. 

Fully artificial cell-free protein synthesis systems will be a huge step forward. Presently such systems are made from cell extracts (so it's more like an omelette,not  egg or chicken).

By the way, take a look at https://doi.org/10.1093/nar/gkx079. PCR with a bacterial mirror polymerase. Twice bigger than that virus polymerase, much more effective.

 

And Racemic crystallography is another motivation for producing mirror proteins. 

Edited by AlexSorokin

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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 ...

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For cell-free systems yield is about  1g/L, scalable. https://doi.org/10.1016/j.coche.2017.10.003 So cell-free is somewhere between chemical and microbiological production. 

And it allows to synthesize many different proteins in one test tube.

When an assembly of artificial cells (of normal chirality) will become possible, it's time to stockpile antibiotic enantiomers in your medical kit... Some antibiotics are produced as racemic mixture, so it it won't be a problem.

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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 ...

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