Discussion Board

Topic: Immunity by Incompatibility

From: Jarek Duda
Location: Poland
Date: 06/15/2007

I have a concept which will prevent virtually ANY microbe (virus, bacterium, protozoan, etc) from infecting an organism such as the human being  by making humans incompatible to these microbes!

There is a very effective way of achieving this - by reconstructing ourselves using the mirror reflection of our cellular components! Just by replacing left-handed amino acids with right-handed ones, we would get (chiral) mirror reflections of natural proteins. Analogically, we could get reflected sugars, DNA, etc, on which reflected enzymes would work perfectly. Finally we would get a normally functioning mirror reflection of a natural organism - a chiral counterpart organism - with which natural viruses couldnt interact. Electromagnetic force (chemistry) is unchanged under such molecular reflection transformation (P-symmetry). There is a small alteration of weak interactions under reflection, which can produce very small corrections, but these corrections are many orders of magnitude lower than thermal noise - almost certainly too tiny to alter any biochemistry.

Such a chiral organism would obviously need to be feed with reflected food, produced by reflected plants. The great advantage, though, is that such chiral organisms should enjoy a disease-free life, completely immune to all viruses and microbes (which virologists are now beginning to understand underlie a huge number of human diseases). And we would eliminate plagues and epidemics.

Viruses would be completely incompatible with the reflected human cellular structures; and bacteria, protozoa and fungi could not function because they would not be able to find normal sugars inside reflected organisms. The reverse sugars circulating in the chiral human body would be indigestible as far as normal bacteria are concerned, so any bacterium entering a chiral human would simply starve to death. The chiral environment is absolutely hostile for normal viruses, protozoa, bacteria, etc.

In order to infect a chiral human, existing bacteria would have to evolve their own mirror image structure from scratch. This is extremely unlikely to happen (since DNA holds the genes, the alphabet of evolution, but DNA itself is a priori to genes, and therefore untouched by the process of evolution). Terrorist acts, however, are a concern. In the case of sabotage, though, it may be easier control the spread of any terrorist-engineered chiral virus, using anti-terrorist measures already in place today.

How do we create a chiral organism, such as a reflected human? The synthesis of every molecule, a reflected zygote is difficult, because we dont have chiral enzymes. But the real problem is creating the correct structure of membranes with specific concentrations & fill it with life. Nevertheless, with advancing nano-engineering, this could be possible in lets say 50 years, when we could slowly transform our ecosystems, starting from the bacterium E. coli, which will act as our factory, and later plants. Finally, if all goes well, the human being.

But in such a sterile environment, would we have perfect health? Maybe the stresses created by small infections can, like small amounts of radiation, have positive long-term influence? For example, infection helps to get rid of damaged and weak cells in an organism. And the hygiene hypothesis states that the actual absence of exposure to microbes can lead to autoimmune diseases (although more probably, autoimmune diseases are due to chronic underlying infection from viruses and bacteria that have insinuated themselves deeply inside a living organism and its cells, rather than the lack of exposure to microbes; so we should eliminate autoimmune conditions in once we have shifted into chiral life).

There are other dangers too: imagine a reflected unicellular organism, which needs only light and symmetric molecules like H2O, CO2, O2. Such a chiral unicellular organism could spread, evolve, and could even overthrow plant life.

So the main rule from the beginning should be: in the case of chlorophyll organisms: only plants whose population can be controlled should be transformed!

Transformation of our ecosystem would be expensive, but in the future we may need to create completely new ecosystems for populating other planets like Mars. In these situations, the effectiveness of such an ecosystem will be very important. We would need many kinds of microorganisms. Symbiotic ones wouldnt need to have aggressive mechanisms; aggressive microbes would only re-emerge if they evolved from zero. I cannot imagine that chiral viruses would be needed; they wouldnt be transformed at all. Thus chiral viruses would just re-appear if they evolved from zero, like free DNA, which is unlikely. Furthermore, the last time this happened, the viruses evolved in parallel with their targets; now organisms have very advanced specific/non-specific defensive systems, which will make it hard for any chiral virus to appear and establish itself in a chiral ecosystem.

Of course, once our ecosystem is transformed, if in the distant future, we find a new major problem, we can always reverse again!

Re: Immunity by Incompatibility

From: Greg Bear
Date: 06/17/2007

Many fascinating speculations and possibilities here, Jarek. But we NEED many microorganisms (including viruses--or at least virally introduced genes) to stay alive! And if we engineer some of them to join us in this mirror biology (which is possible in some respects, and far less likely in others--not all chiral proteins or other molecules have similar qualities or behaviors) then in time our tiny good buddies are likely to mutate to become pathogens. We might end up right back where we started! (Might make a great story...)

I wonder--if we went to a completely synthesized or reconfigured biological system, how long would it take for unpredictable variations to occur? This leads us into more interesting questions about top-down control vs. bottom-up customization...

Re: Immunity by Incompatibility

From: Jarek Duda
Location: Poland
Date: 06/17/2007

Why do You think that we NEED viruses?
I have a discusion about it - please join us
http://www.scienceforums.net/forum/showthread.php?t=27078
And without viruses, evolution of microorganisms should be much slower...

Energy effectiveness can be essential for our civilisation, before we learn to terraform other planets, and in such difficult enviroments this effectiveness is even more essential...
I think we will make such simple sterile ecosystems and slowly replace our own.
I imagine that they will select, combine best human genomes and create chiral elite... after a while the richest will be able to adopt them, maybe based on inywidual DNA ... and after a long time they will be a significant percent of the population...
I don't have to add that it will be very interesting social/political time... :)

Re: Immunity by Incompatibility

From: Terran
Location: Winter Park, FL
Date: 06/18/2007

I'm sure I read a story based on this, but the details are escaping me. Does anyone else remember it?

I believe the main concept was an accident with a teleportion device - someone got transported, but reassembled backwards and then starved because they could not digest any food. Maybe it was a Larry Niven short story?

Re: Immunity by Incompatibility

From: Greg Bear
Date: 06/18/2007

As I've pointed out in both the DARWIN'S books and in papers on this web site, we actually use at least one gene supplied by viruses to get born. That's pretty essential! Viruses are far from just "poison." They're Fed-Ex for genes of all sorts, and contribute greatly to evolution and probably to chromosome management within cells, and perhaps even between individuals in species--or species within ecosystems!

Re: Immunity by Incompatibility

From: Greg Bear
Date: 06/18/2007

It's an Arthur C. Clarke story, I'm pretty sure--but I looked through my collections and can't find it! Any readers out there who remember? The man starves to death because is mirror-reversed and he can't absorb sugars.

Re: Immunity by Incompatibility

From: Jarek Duda
Location: Cracow
Date: 06/19/2007

"we actually use at least one gene supplied by viruses to get born" - it's very interesting, I couldn't find it...?
I agree that viruses helps the evolution, but if we made precise, customized ecosystem - evolution is rather something unwanted - it's difficult to predict, control and can throw out of the stable point.

I've got to this idea by my previous one - to became incompatible 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 haven't read this novel and I belive that chiral life is to 'simple' to be new idea. I want to show that it can be quite realistic possibility and danger - it should be widely discussed.

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 stay 'alive' 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 its 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 the rest 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.

Re: Immunity by Incompatibility

From: Greg Bear
Date: 06/19/2007

Take a look at this paper on the web:

http://www.pnas.org/cgi/content/abstract/102/3/725

Mirror-reversing complex proteins strikes me as a very difficult procedure to get right, since how they fold and interact with other molecules is key to their functions. What you're talking about is completely re-engineering nearly all the components of a cell. That would be possible, certainly, but let's call it what it is--creating a new form of life!

Re: Immunity by Incompatibility

From: Jarek Duda
Location:
Date: 06/20/2007

If I correctly understood, the problem is that we cannot replace all ERVs to something neutral, because we use eg their capsids in some of our mechanisms.
Over this millions of years, this capsids have been optimized for our purposes. Maybe it's good point for viruses to begin evolution again, 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 evoluted last time...

People are talking about nanorobots - isn't a new life?
I'm young(27) theoretics (MS physics&math&computer science), grown up on SF, RPG, so for me it's 'easy' to sketch such procedures :)
But I realize that it's not so easy ... but it's imaginable ... possible? ...
So someone, sometime will try to do it ... we should discuss to help him or how to prevent ...
And if You are looking for the author of this idea ... maybe Carroll and his Alice ... :)

Re: Immunity by Incompatibility

From: patrick
Location:
Date: 06/20/2007

As is evident in biology, and homeopathy is confirming, regardless of whichever institutions want to think otherwise, symbiosis is the most balanced form of existence.

Re: Immunity by Incompatibility

From: Jean Lagarde
Location: Ridgecrest, CA
Date: 06/23/2007

Re the Arthur C. Clarke story, I would not remember something like that, but I am reasonably adept at searching the Internet: The story is "Technical Error", available in "The Collected Stories" (ISBN 0-312-87821-4).

Re: Immunity by Incompatibility

From: Greg Bear
Date: 06/26/2007

I have no doubt we'll be doing some substantial deconstruction and reconstruction of biological systems--and not just in the far future. Near-term proposals are being researched now. But any such system will have to take into account the unpredictable consequences even of simple changes--in one instance, new and different kinds of viruses. Complete control is likely out of the question!

Re: Immunity by Incompatibility

From: Greg Bear
Date: 06/26/2007

Symbiosis is what happens after you've exhausted all attempts to expunge and purify, and discover that your enemy can be your friend.

Re: Immunity by Incompatibility

From: Greg Bear
Date: 06/26/2007

That's the one--thanks, Jean!

Re: Immunity by Incompatibility

From: Jarek Duda
Location:
Date: 06/26/2007

I completely agree that this idea has maaany aspects - both possibilities and dangers.
I only want to show that it looks achievable and it's better to think about it now than in eg 30 years, when required technology could be generally accessible.

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

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.

Re: Immunity by Incompatibility

From: patrick
Location:
Date: 06/27/2007

"Symbiosis is what happens after you've exhausted all attempts to expunge and purify, and discover that your enemy can be your friend."

This indicates a psychological inconsistency. It has no bearing on its efficacy.

"I have no doubt we'll be doing some substantial deconstruction and reconstruction of biological systems..."

Have been doing for decades. This is one reason for 'scientific ethics'.

Re: Immunity by Incompatibility

From: James
Location: pittsburgh
Date: 07/16/2007

I believe that this idea is not very realistic. We interact with millions of organisms every day. It is impossible to say which of these hurt and which help. One example is the bacteria in our digestive track. The idea is rather close minded.

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