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Author Topic: Chiral life concept - creating mirror image synthetic life?  (Read 4926 times)

Offline Jarek Duda

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Imagine mirror image of a living cell - built from scratch using mirror versions of molecules (enantiomers). Symmetry of physics suggests it should work as usual cell, but using e.g. L-sugars instead of our D-sugars: http://wikibin.org/articles/chiral-life-concept.html
There was created first synthetic cells, so maybe it is only a matter of time until they will start building chiral ones - first bags of proteins getting simple prokaryotes, but maybe also complex structure of eukaryotes a few decades later ... or even human?
Some possible applications:
- doubling the amount of possible enzymes we could design and use,
- such organisms would be incompatible with standard pathogens - we could design bottom-up sterile ecosystems for extreme conditions like Mars,
- maybe forever healthy chiral humans immune to our pathogens - which are direct or indirect cause of most of illnesses.

What do you think of such possibility - is it possible to realize? how much time will it take? what other applications could you think of? what would be implications to our society? ...


 

Offline CliffordK

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While there may be some benefits of such an approach, there may be some negative things too.

While a reverse chirality human may have some level of immunity, it may also be unable to eat the majority of the plants and animals on Earth.  In fact, there may be major problems with acquiring adequate amino acids, unless reverse chirality plants are also developed.

Surface terraforming of Mars will be difficult due to lack of heat and lack of atmospheric pressure (and low gravity).  Venus, of course, has too much heat and too much atmosphere, and too slow of a spin.  But, it does have an excellent size, and perhaps it would be easier to reduce the atmosphere on Venus rather than increasing (and maintaining) it on Mars.

The question, however, is about microorganisms. 
It is my opinion that any terraforming attempt would involve flooding a planet with microorganisms.  One could, of course, exclude certain pathogens, especially human and livestock pathogens, if possible. 

Decomposers are just as vital on Earth as the organisms that photosynthesize.  However, any attempt for surface terraforming will necessarily involve production of excess oxygen and hydrocarbons, and thus one may initially populate the planet with an excess of photosynthesizers, and relatively few decomposers. 

With that in mind, there may be benefits of regulating which species colonize the planet when. and perhaps even introduce kill genes. 

However, even without Earth contamination, there will be a tendency to evolve, and fill in niches.  And, it is quite possible that some organisms could develop the ability to thrive even around a primarily reverse chirality environment.

Most of our long-term plans are on the order of decades or centuries.  However, full terraforming of a planet such as Venus may well take thousands, or even millions of years to complete.  Likely it would involve a period of living in a partially terraformed environment, but say over a million years, there certainly will be evolution of both the human colonists, as well as every organism that is imported.
 

Offline Jarek Duda

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Of course there are many issues about such possibility. Indeed it wouldn't be enough to create only humans this way - we would need to recreate bottom up the whole required ecosystem, like plants and symbiotic microbes. The advantage is that we could use only useful organisms for such transformation - avoiding e.g. pathogens.
It could theoretically lead to designing a very harmonious/healthy and so efficient ecosystem ... but in practice it would have many empty ecological niches, which would be probably filled with time in less controlled way. However, even for microbes it could take a few decades - especially if we would avoid DNA sequences of harmful/aggressive proteins: developing them from scratch through evolution would take millenniums.
There are also endogenous retroviruses already built into DNA of organisms - they would need to be removed while transformation into chiral ones. Viruses bring another problem - while creating chiral cell would be extremely demanding task, creating chiral viruses would be relatively simple for some terroristic organizations ...
Another issues we need to have in mind is interaction with standard organisms and their unpredictable evolution ... e.g. creating chiral photosynthesizing cyanobacterias seems to be extreme risk for ecosystem of our planet ...

These are some of reasons why I don't think chiral humans on Earth would be a very practical idea ... however, if we would get to chiral eucariotes some day, creating chiral humans would be rather unavoidable - e.g. hidden underwater colony of "chiral family" of some billionaires ...
But the situation changes for currently uninhabited places - indeed another planets are extremely hostile for our life, so if we are going to terraform them some day, efficiency of such organisms/ecosystems will be extremely important - no pathogens are allowed and chiral life seems to be the only realistic way for that ... maybe starting ecosystem for later chiral humans ...
To really start this new branch of synthetic biology a single really useful chiral enzyme could be enough - we would need e.g. chiral prokaryote for its mass production. But even without such direct motivation, I think we will create such chiral E.coli e.g. just because we will be able to (about 20-30 years?) ...
 

Offline evan_au

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Conventional chemical processes produce all chiral varieties with equal probability (a racemic mixture).
A racemic mix does not produce the structured helices and sheets that make the familiar enzymes and DNA - I've heard such racemic "proteins" described as "blobs".

However, living systems reliably produce the chiral amino acids and sugars of which they are constructed.

So there are severe problems trying to bootstrap a mirror ecology, without a pre-existing mirror ecology from which to start.

It is still a fundamental mystery about how living things could obtain their chiral "handedness", starting from non-biological materials. One suggestion is that breakdown of radioactive C14 could slightly favour one chiral form over another, see  http://en.wikipedia.org/wiki/Abiogenesis#Models_to_explain_homochirality 
 

Offline Jarek Duda

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Indeed conventional chemistry usually produces racemic mixtures, so there is e.g. question why our life is not the chiral one ...
But personally I think this question is kind of obvious: organisms require the same type of molecules to build themself, so the more one type of organisms there is, the easier their population will grow. It means the symmetric situation is statistically unstable (repelling) and life development just had to broke this symmetry up to the situation when there is practically only one type of life.
I would give similar answer to why we have more matter than antimatter - we don't need CPT breaking for that, statistical symmetry breaking is completely enough - e.g. that while baryogenesis in the presence of nearby proton, there was slightly bigger chance to create proton than antiproton (and symmetrically to create antiproton in the presence of antiproton).

Ok, let's get back to theoretical possibility of synthesizing chiral life ...
As even artificial cell membrane is not a problem now, creating prokaryote would be mainly just filling liposome with the proper molecules ... the question is how to get the chiral ones?
There are ways to directly synthesize them (even using bacterias) or separate from racemic mixture (e.g. use polarized light to ionize only one enantiomer and electric field to separate the ionized ones, like in laser uranium enrichment).

The real milestone will be the chiral ribosome, which would allow for mass production of chiral proteins - tools to make further work faster.
While it is probably too complex for standard chemistry, I think there already exist tools to construct it within a few weeks - AFM/STM which allows to manipulate single atoms:

so we could spread even racemic mixture on a surface, scan positions of molecules and patiently build the RNA sequence base by base (eventually "welding" with electric current) and later help it with the proper folding ... I think directed international program could make chiral prokaryote within a decade (maybe they are already working in some military lab?).
Much more difficult will be eucaryote with its complex cytoskeleton, ER, organelles, but we could target cell division phase when everything is simplified, we could build organelles separately ... and even use a molecular 3D printer to build frozen components of the cell molecule by molecule ... it is extremely difficult and costly, but definitely doable ...
 

Offline CliffordK

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There are many issues.
While people have synthesized short DNA sequences.  Perhaps even a small virus, the human genome, for example, consists of 3 billion base pairs.  We have no ability to synthesize such huge pieces of DNA.  Although, perhaps if a Neanderthal or Mammoth DNA project moves forward in the next few decades, we will at least reach a point where one could build complete chromosomes.

Has anybody ever designed custom proteins, beyond slight modifications? 

For example, could one design a set of proteins that would read normal DNA and produce reverse chiral DNA?
 

Offline Jarek Duda

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First synthetic virus was created about 2002: http://news.bbc.co.uk/2/hi/2122619.stm
Indeed synthesizing long DNA sequences is still extremely difficult, but definitely not impossible and will became cheaper and faster - like sequencing dropping from billions to nearly 1000$ per human genome ... eventually we could e.g. synthesize shorter sequences, take them on a surface and bind manually with AFM/STM ...

Modern medicine is intended to build custom proteins to e.g. block a specific site, but they are indeed rather small modifications nowadays - while molecular simulations treat most of the folded protein classically and only the interacting part in quantum way, we are still far from simulating well the folding process.
It is extremely difficult to design a complex protein from scratch - to make it fold, interact exactly as we would like. Their optimization took billions of years of evolution - we will probably be able to design them from scratch in a few decades. Now the only way to make a really different synthetic life is just to take a mirror image ...
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For example, could one design a set of proteins that would read normal DNA and produce reverse chiral DNA?
Such "reflecting polymerase" looks extremely difficult, especially that base enantiomers probably are no longer complement, what standard polymerazes use.
I think the simplest way to create chiral life is to synthesize it from scratch ...
 

Offline CliffordK

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It might be possible to make a hybrid protein, half normal chirality, half reverse chirality, so that it could, for example, read normal DNA, and produce either reverse chirality DNA or RNA.

One of the problems is that most of the tools that synthetic molecular biologists use are proteins and enzymes.  Thus, it may be exceedingly difficult to synthesize the first reverse chirality protein, or piece of DNA or RNA.

==============

While I understand the desire to produce life different than what is on Earth, I would still question the benefits of creating two environments that are mutually toxic to each other, especially in our solar system where we may eventually colonize most of the planets, and may have some interplanetary transportation.

If we terraformed a planet around a distant star, it is possible that there would be little interstellar transportation, and thus making the environment toxic to Earth life might not be a problem.  Could it prevent a war if in a million years, neither planet would be capable of supporting life from the other one?
 

Offline Jarek Duda

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It might be possible to make a hybrid protein, half normal chirality, half reverse chirality, so that it could, for example, read normal DNA, and produce either reverse chirality DNA or RNA.
Of course such enzyme/nanomachinery is theoretically possible, but seems unimaginably difficult to design.
Standard polymerase works thanks to that complementary bases fit together (hydrogen bonds), what would no longer apply if you would like to copy into mirror images ... you would need to create some kind of interface to couple them - a mobile protein part working perfectly as you need ... maybe in a century ...
Besides, creating such enzyme would make the chiral life concept useless as it would automatically translate our viruses ...
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One of the problems is that most of the tools that synthetic molecular biologists use are proteins and enzymes.  Thus, it may be exceedingly difficult to synthesize the first reverse chirality protein, or piece of DNA or RNA.
Indeed, it is exactly why I have written that the first milestone would be synthesizing chiral ribosomes (e.g. using AFM/STM) - each such factory can produce thousands of proteins from single mRNA strand - which can be used to further automate the process ...
Synthesizing chiral ribosomes might be simpler than I thought as it turns out they have already synthesized standard one 4 years ago: http://www.sciencedaily.com/releases/2009/03/090309104434.htm
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While I understand the desire to produce life different than what is on Earth, I would still question the benefits of creating two environments that are mutually toxic to each other, especially in our solar system where we may eventually colonize most of the planets, and may have some interplanetary transportation.
We often consume synthetic organic substances, which are often racemic mixtures. It doesn't generally mean they are toxic, but there could be some very subtle unwanted interactions (thalidomide?).
Of course I would be afraid of eating chiral meat/plants, especially it would taste and smell very strange, wouldn't be very valuable ... but most importantly: could be toxic.
But there are many other casual substances around that are toxic - it is probably only a matter of labeling/separation ... however of course even e.g. chiral pollen could be toxic, so we would need to be extremely careful while trying to mix such populations ...

Situation with terraforming other planets is much safer and chiral life is probably the only way to ensure sterility to maximize efficiency so needed in such harsh environments. There are many issues of creating colony of chiral humans, but in the history of life diversity was often the key to survival ...
 

Offline Jarek Duda

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Another milestone: "A right-handed molecule can only copy left-handed ones."
http://arstechnica.com/science/2014/10/researchers-evolve-a-molecule-that-flips-the-orientation-of-life/

Maybe we could use artificial selection to get from building blocks of our life also other tools for the synthesis of the first chiral organisms ...
I bet we will have chiral E. Coli before 2040.
 

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