Since this idea has been mentioned a few times on other threads, I thought it deserved its own thread.

For those not yet familiar with this idea, you can read this wired article, this H+ Magazine article, or just read the original scientific paper, as proof of principle.  In a nutshell, two adult male members of a species of squirrel monkey in which the males are mostly colorblind (called Daltonism) recently gained the ability to distinguish between red and green due to gene therapy.  What this team of scientists did was genetically engineer a harmless virus to carry the gene that the females have for distinguishing the two colors, and injected it into these monkeys.

The most interesting thing, in my opinion, about these results is that these squirrel monkeys were adults, and therefore presumably their brains were past their most "plastic," yet this therapy still worked.

So, the purpose of this thread is:

a) to discuss some of the potential enhancements that we could do with this type of gene therapy, and

b) to discuss some of the ways we can make this type of enhancement more open-source, or more accessible to the public.

I shall start by discussing two potential uses.  First, as described in the H+ magazine article, the gene that birds use to code for sensing UV light is similar in size to the genes we use to code for sensing red, green, and blue light.  Presumably, we could do the same thing with this gene; engineer a harmless virus to carry it, and inject the virus into humans.  It is also worth pointing out that many nocturnal mammals can sense IR light.

Second, there is evidence that some women can sense two versions of red.  This allows them to better differentiate between different red colors.  Presumably, this is due to the fact that our "red gene" is located on our X chromosome.  Since women have two of them, there is a chance that, due to mutation, their two "red genes" are different enough that they effectively sense two different colors.  If we could take the genes that code for green and blue and mutate them as well, we could improve our ability to distinguish between the colors we already have.

So, that's my two cents for now.  Have at it!


  • If you are thinking of modding now, you're best bet is an Adeno Associated Virus. 
    (It is a lot to read but it's best we know exactly what we're doing before we start modding)

      "These viruses can insert genetic material at a specific site onchromosome 19 with near 100% certainty. There are a few disadvantages to using AAV, including the small amount of DNA it can carry (low capacity) and the difficulty in producing it. This type of virus is being used, however, because it is non-pathogenic (most people carry this harmless virus). In contrast to adenoviruses, most people treated with AAV will not build an immune response to remove the virus and the cells that have been successfully treated with it."

       We should also get acquainted with the proteins necessary for colored vision - two good sources for this are the International Protein Data Bank and the RCSB Protein Data Bank.  Another thing you guys might be interested in is Cryptochrome, which allows birds to see magnetic fields ( )
  • Actually there are several good reasons not to use viruses....
    First: you can only do one type of a virus once, after that the immune system is trained for it.
    Second: You have to be so very carefull because viruses (what is the english plural of virus??) mutate so unbelieveably quickly...
    Third: you need to use retro viruses, the most dangerous type of all. Not only, that they may not be pathogenic themselves, it is crutial where they implant the new genomic material. There are lines and sines buried in our genes (old viral genetic information, silenced by our defences but they can be easily activated) that should not be interfered with!

    There are however new approaches, as well as the viral approach. One is called mitch (or similar, it was only an appreviation)

    If the viral approach stays the only one fitting, however, there are several precautions to be kept. For what I know the assembly lines of bacteria are state of the art, used to assemble the genome of the virus, rendering it unable to procreate on its own. That should be the lowest limit of safety taken...

    Viruses is probably the best word to use ^_^
  • @Ben:  What vector do you suggest, then?  
  • BenBen
    edited January 2011
    Actually, I just thought virii looks a bit like it could be right (latin always confuses me) but ok, no skript kiddie blabber xD.

    The one new approach I was talking about (not mitch... midge) eg.
    What they basically do is to create an rna vector, seal the ends chemically, so the rnases (and simple enthropie) don't destroy it and coat it in a way, so the cells take it in. I'm not exactly sure how advanced this particular technique is, but it was shown by a professor as a new approach to create safer vaccines.
    The main feature here is, that there shuldn't be any immune reaction to the vector itself, plus you don't bring in some biological legacy no one really understands so far.

    Yes, this would not be a permanent mod, but considering the experimental state: at least at the beginning there actually shouldn't be any permanent modifications. As long as we don't know about the side effects I consider the effect wearing off more as a feature. After that a more permanent solution is probably quite useful, but one step at a time.

    The difficult parts being (in any method used): make the vector, whatever technique is used, only modify the cells we want, modified rhodopsin in a liver cell is useless and might lead to complications.
    And hey, just came to me: bringin in a modified Protein (almost) ALWAYS triggers the immune system. The MHC I (or II, always mix them up) complex takes parts of all the proteins a cell produces and presents them on the cell membrane. There immune cells check if they know it to be somehow altered. That is fine if your goal is to produce antibodies as in a vaccine. I'm not sure how to solve that. In a small possibility this might not be a problem if the frequency is determined by parts that very much are alike (eg repeats in the protein) but still, you never know what the immune cells react to, so this is hard to predict and if it goes wrong results in the body killing all modified cells.
    Once I thought about implanting chloroplasts into human skin (still not given up that one ;) ) but there the same problem occures. One solution I came up with was to do it in a very young age, before the immune systems "imprinting" is finished (the process where it determines what belongs to the body and what is alien matter) or to somehow trigger some sort of re-imprinting, the latter one being the only solution allowing me to modify myself...
  • @Ben  I too want to work on a photosynthetic mod.  Anyway, I thinking about the problem with the immune system today.  I have no idea what processes would mark one protein as harmful and another as 'normal'.  The answer would not only have implications for gene therapy but also for autoimmune disorders (which I have).

    Anyway, for temporary mods we might want to go with plasmids - I'll do some research into immunology to see what I can dig up. 
  • @Ben the problem with getting chloroplasts into skin cells is that by the time they get out from under your natural sunshade, the skin cell has died. I can't pronounce on the idea's "doableness," but I'm not sure how useful it would be if it worked.
  • I think using fungi styled radiotrophism would work better, as humans already have melanin in their skin

  • Instead of tanning, thicker skin? That could be very interesting indeed...
  • You'd have a lot of extra energy to do stuff with, which can be quite useful if you want to add on energy consuming mods.
  • Ok, I can explain to you how the immune system decides that.
    Actually I already did, but:
    {"Code":401,"Exception":"You don't have permission to do that."}
    Hope it is ok if I rewrite that rather long text later...

    And the chloroplast thing was more some silly idea in a "'cause I can" kind of way.Maybe one day I will do that, but I don't consider it some real hack...
    Oh, and the starting point was the similarity between chloroplasts and metochondria.
  • So, finally. First of all: sorry, it is not rhodopsin (that is apparently only for black/white) but photopsin. Not that much of a difference, though.

    And bad news as well, the absorbed (and therefor seen) wavelenght (color) is not determined by a repeated are of a protein, that only differs in lenghts. Apparently it is a pigment that can contain some non-protein pigment or different amino-acids. Bad news because this way it will be harder to find something the immune system does not attack.

    So, here the explanation how the immune system determines if something is dangerous. The big problem is: it does not. If it did we wouldn't have such a hard time bringing stuff in (and less issues with auto-immune diseases). All it does is look for something it does not know.
    The immune cells use anti-bodies to determine what they know and what they don't know. These anti-bodies are (spoken simplified) little antennas on the surface. They (a bit like a key) only fit to special surfaces. In our genome we got very very many of them coded, so almost anything you can imagine fits to one of them. Now I said they look for something they do not know. That means, they look for something they can bind to. If the anti-body can bind to it, they will attack it.
    Why they don't (usually) attack normal functioning body cells? Because the anti-bodies fitting to the proteins coded in our genome are sorted out. That is the process I call imprinting (not sure about the real name right now, probably not imprinting, more likely something like maturing). In the thymus (do not fix me on that one, it is one organ connected to the immune system, I remember it being this one) cells produce everything there is in our genome.  Then the immune cells wearing the anti-bodies test if they can "grab" any of the normal body and if so, they (the immune cells) are destroyed. After this there should be no more cells left having anti-bodies against anything we usually have in our bodies. This is not done all the time but once. Sometime during the childhood.
    They are rather restrict.That is why you can't just take blood or another organ out of one human and put it into another one. You have to supress the immune system, because it fights anything from anyone having a different set of dna...a
  • edited January 2011
    @Ben - thank you.  Are there any sources that you can direct me to? 
  • Instead of chloroplasts, take a look at the natural photovoltaic cells these hornets have. (i'm imagining a hornets morphology has more in common with ours than a plants. I could be wrong)
  • Soooo, if we want a body to accept modified or new tissue then we need to work out how to add the modified genome to the thyroid's "Do not touch" list? Yes?
  • @ Lukas: sry, that it always takes me so long, just your questions usually take a bit more thought to answer than the small remarks I make...
    A good starting point is (believe it or not)
    Wikipedia might not be great as a scientific ressource, but for uni it usually suffices, so you should be just fine. Some of it is quite scientific and written more complicated than it has to be. If you have any questions, feel free to pm me or write here.
    I will have a look into those "protection-proteins" you wrote about, just two small thoughts before any research done: keeping a cell from destruction is not the same as silencing the immune system on one matter. you can keep a cell save from killer cells and still start an inflamatory process. Not, that these proteins do that, just one little thing, that could happen.
    Second thought: what once has been called legacy of evolution. There is one thing often destroying hopes of researchers: cancer. Protecting modified cells (usually modified by random mutations) from destruction is one of the early steps in the lifetime of every tumor.

    On the "do not touch list": if only it was that simple. this list is not one centrally kept and updated list but rather a big bunch of paranoid officers, running around. you have to get to each one individually and make sure they forget about you. Or you kill them all. Considering allergies still being an issue, this obviously isn't that simple.
  • @firedust:
    I did read about that, too. Couldn't remember why I didn't go more into that back then, but now I do. It is very hard to find any useful information about this.
    The core of this photo-electric element is: Xanthopterin
    Looking a bit more into this one I found:
    Bad news being: we already do have it in our bodies BUT it "is known to inhibit the the proliferation and growth of conconavalin-stimulated lymphocytes."
    That is to say: it inhibits our immune system.
    Might not be a big problem, but kind of a bad start. Good news being: we can create this stuff under physiological circumstances.
  • Hey all, I'm a medical geneticist and thought I would throw in my 2 cents into this discussion.  

    For the original topic of correcting colorblindness, this is something we could do right now, with our current technology, in a matter of weeks.  AAV's are great vectors as they tend to have no immune response, high tither amounts, expression lasting for several years, and can be targeted to specific cell types.  Thus it wouldn't take much for a proper medical genetics lab to build an AAV vector that could correct red-green colorblindness.  I would theorize that it would also be easy to insert cones that could see UV light from say a bird species or insert the gene for Cryptochromes as mentioned earlier.  Naturally, we don't how these foreign proteins would react with native proteins but it would be interesting to see what would happen.

    On a general note about gene therapy, we have actually gotten pretty good delivering and correcting single gene defects with viral vectors.  My genetics center already uses it to treat recessive metabolic disorders, X-SCID's, cancer, etc without much in the way of immune responses or causing additional issues. The real problems with gene therapy isn't delivering a gene, or the immune system, but that a lot of genes need specific regulation of how much protein to produce and when to produce that protein.  Right now we just cannot do that as genetic control mechanisms are quite complicated (SiRNA's and epigenetics).

    A few of people here have also touched on naked nucleotides like plasmids or RNA vectors.  The problem we have with plasmids, RNA, or liposome vectors is that cells don't readily take them up.  Even when we alter the chemical structure so they aren't degraded as quickly (such as Morpholino's) the transfection/efficacy rates are extremely low.  So you really do need a viral or targeted approach to make it worth your wild.

    So to sum this all up-  we could use viral vectors like AAV or Lentivirus to genetically modify people with little in the way of immune response.  We would just have to have a gene that doesn't need much regulation, fairly small in size, dosage independent, and know which tissue it needs to be in.  Why we don't do this on people, even if someone wants to, is because right now laboratory PIs and staff would be fined/placed in jail for "unnecessarily" screwing around with the genetics of someone.  Unless you are curing an existing disease the regulating bodies would go after you with an iron fist for doing any type of gene therapy.  Not that I don't intend to experiment on myself one day.....

    @Lukas  you mentioned you had an autoimmune disorder, I too am a sufferer of an autoimmune disorder.  You might be interested to know that research is starting to look at epigenetics as the cause/progression of a good number of autoimmune disorder diseases.  Mutations, such as those in MHC's, are really only involved in familial cases of autoimmune disorder.  The research in the field of autoimmune disorders is starting to pick up and books like this might be of interest to you.
  • @Ben Correct me if i'm wrong, but lymphocytes are grown and proliferated from the bone marrow. Is there any kind of way we could isolate the Xanthopterin in areas of higher-concentration of Xanthopterin on the skin so that it doesn't come into contact with the bone marrow. After all, the skin is where we need it to be. Seeing as it is not carcinogenic to lymphocytes once created I think this would keep you healthy while being able to have your own built in power supply.
  • Welcome Crazyivan. 

    I am severely color blind.  You know those tests they give you that have a number hidden in all of the dots?  I scored 2 out of 30 correctly.  I volunteer as a lab rat if someone can make something for me.  :)
  • You would trust us with your eyes? You are a braver man than I.
  • I'd trust you with one of them.  I have one eye that needs to be operated on.  It is nearly worthless for long distances, but I can see close up.  I figure I can experiment with it and if something goes wrong I will be on the operating table at some point anyway.  If it works I can always try it on my other eye.

    Of course this all assumes that I can do one eye at a time.
  • With a gene therapy? My guess would be: no. (on the one eye at a time thing)

    @ Firedust: sounds interesting to seperate those areawise, I'm a bit worried about diffusion, but it might work (even though not all the profileration is done in the marrow!)

    @crazyivan: interesting, I'm happy to get information!
    I got some reasons against gene therapy via viruses, though. Even if you have one that is not causing too many issues with the immune system (can you use them more than once? I'd think even without sickening it will trigger the immune response making a second "infection" impossible) it is a lasting effect. Especially with experiments I would prefer something that is reversible or even better wearing of. That is why I was suggesting the midge thing, and I found some info about it.
    Not sure how realistic this approach is for us, but it seemed fitting.

    Also I'm not sure if we can build a three line assembly for the vectors (to my knowledge you use three colonies of bacteria to build the parts of the virus due to safety regards, wouldn't cut down on safety...) Then again, creating a vector isn't that simple for us either...
  • Since @DirectorX was talking about the whole modding only one eye in another thread, I thought I'd revive this dead sucker.

    Instead of only modding one eye (which I can't imagine would work very well anyway), @Ben mentioned, earlier in this thread, a different potential way of testing this mod:  use what he called the midge method of taking a RNA vector and directly using that.  Unlike using a Human Adeno-Associated virus to do the job, this version wouldn't be permanent.  So, if you're willing to settle for temporarily modding both eyes instead of testing it out on one eye, this might be the method to use.

    As for me, I gotta relearn all this crap; all this time away from my DIYbio lab has caused my brain to atrophy...

  • @Ian

    Hm! A temporary mod is an interesting idea. A test to make sure that the gene is effective at all before making any permanent adjustments seems to be exceptionally prudent.

    I'd love to see someone come up with a working, practical theory on doing this that could be implemented in a year or two. This mod is one of the most fascinating to me, and I would love to be able to try it out someday. Perhaps I'll start doing some research so that I can actually contribute useful information to help the project progress.
  • @Oak - Give me a little while longer, I am working on it
  • Bumping this. Any new input on cheap ways to do this?
  • @DirectorX:  Yes and no.  We have discovered a cheap way to get foreign molecules (such as vectors) into cells; namely, electroporation.  After we at Grindhouse have gotten some of our current projects ready for release, I hope to start work on an electroporator.  However, I can't think of a single practical way to use electroporation on our retinal cells (maybe someone else can, though?).

  • only possibility would be to have small injection needle with an additional core needle with isolation inbetween. injecting and pulsing at the same time. it would only affect a very tiny area but might be enough to get a few cells done. neither terribly save, nor efficient tho.
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