1. ToeKneeBlack
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    ToeKneeBlack Contributing Member Contributor

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    Genetically engineered people (a question for the biologists among us)

    Discussion in 'Research' started by ToeKneeBlack, Aug 16, 2015.

    I'm doing some research in advance; in a future entry in my series, I plan to reveal one of the villains is a genetically engineered "person" - his DNA is comprised of 8 different nucleotides; 4 naturally occurring, 4 synthetic, but widely used in single cell experiments (in the story). This renders him effectively immune to all naturally occurring viral infections.

    While he was created to look human on the outside, he has various changes to his internal organs, including;

    A gland for producing ATP, along with a bladder which stores it. This allows the rest of his cells to operate without oxygen, as long as his ATP bladder isn't empty. The gland is the only organ which requires oxygen in large amounts.

    Two circulatory systems: One for oxygenated blood from the lungs to his ATP gland, another which carries only ATP and blood plasma around the rest of his body. This requires him to have 2 hearts.

    Would it be possible for him to experience muscle cramps? I understand these are caused by a build up of lactic acid, but without his muscles directly burning oxygen to generate ATP (as the chemical is fed to them by his wider circulatory system), would they generate any lactic acid at all?

    Also, since his genetic code has been built from the ground up, he technically isn't human, even though he creates all of the same proteins and most of the same organs. If you cut his arm (for example), he doesn't bleed red blood, but pale yellow blood plasma; only a deep wound to his ATP system would cause him to bleed red blood, like a normal person. I'll take suggestions for what to call his species (he's the only survivor of his creation experiment out of 6 individuals), and the supplier of the best suggestion will have a character named after them in the series, if they wish.
     
  2. Steerpike
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    Steerpike Felis amatus Supporter Contributor

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    I'm not clear on how the 4 synthetic nucleotides work. They still have to code for amino acids, right? So what do they actually do? Also, how would that stop a virus from inserting its DNA into a DNA strands. If he has the natural nucleotides as well, then it looks like his cells won't have any problem transcribing viral DNA.
     
  3. GingerCoffee
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    The extra nucleotides might work well for a sci-fi book but it's not biologically valid. So you can use it and you can create whatever kind of mutant you want to.

    Once you get that far out from what we know about genetic science, you are completely into fictional territory.
     
  4. ToeKneeBlack
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    The viral nucleotides would still be read and interpreted, but because his ribosomes are looking for different codons to create polypeptides - they can also work with a wider range of peptides, to make use of the extra information storage capacity offered by the extra nucleotide types.
    Since the codon to peptide translation is different in his cells, the virus can infect a cell, but cannot replicate, as proteins different to those in the original virus are created. The original virus dies off, and the infected cell probably dies too, but no new viruses explode out of it; the damage is so minimal that he isn't infected, and likely isn't contagious either.

    Of course, if a virus were engineered using his eight-nucleotide genome in mind, it could successfully infect him.

    I read somewhere that scientists in real life have created a pair of synthetic nucleotides which can be inserted into a strand of DNA or RNA, and will replicate within the cell - however, no ribosomes yet exist that can read these new nucleotides, so until such a ribosome is engineered, we won't be able to use them.
     
  5. Steerpike
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    Steerpike Felis amatus Supporter Contributor

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    There are synthetic or non-standard nucleotides you can incorporate into the genome. Dideoxynucleotides are used in sequencing, for example.

    The rest of this character's biochemical structure would have to go along with it. I guess my question is this: if you have 4 synthetic nucleotides, why not just uses them, since only four are needed to code for the proteins. In that case, the viral genome might not even be read and transcribed.
     
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  6. Hubardo
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    Hubardo Contributing Member Contributor

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    Good ol' @Wreybies referenced this book in another thread and now I'm reading it:

    [​IMG]

    I'm about 35% into it and one of the central features of the book is around genetically modified people (called New People). Doesn't answer your technical question but here is one example of how this can be integrated very well into a story. In the tradition of any good sci-fi, he makes the reader stretch the bounds of what human is or can be. Some of the technical aspects touched on have nothing much to do with molecular biology and as a reader you don't need to know the details of how the person was successfully engineered. One character is more or less a Geisha, bred for traits of extreme submissiveness, smooth skin, tiny pores. Parts of the story are told from her perspective, which humanizes her. Others view her as less than or at least other than human, so you get to explore that and relate to it as her existence seems somehow icky. As with genetic engineering sometimes there are phenotypic issues that come up you couldn't predict because while x and y variables have been modified, you didn't realize they would also impact a and b variables. So she also walks funny, like a windup doll. She has all the desired traits the company wanted to produce, except the strange way she walks and moves. Also, because of her extremely tiny pores, she does not let out heat efficiently or sweat enough so she overheats and needs access to cold water or ice often. On the more macro scale I hope this is helpful in regard to what you might want to think about if you write genetically modified people. Bacigalupi has a very interesting writing style and dips you into this fictional future earth setting very convincingly and I highly recommend the book.

    Edit to add: Sorry if I'm overly excited about this. I've never read a book about genetically engineered people so to me it seemed relevant to mention this although I know it doesn't address your question much directly.
     
    Last edited: Aug 16, 2015
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  7. ToeKneeBlack
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    ToeKneeBlack Contributing Member Contributor

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    The "father" of the character wanted to create a compressed genome - using fewer nucleotides to represent the same amount of data in a regular human genome, he can speed up the rate of growth, since the DNA coping phase of mitosis is reduced by a factor of at least 4 (or is that 16? That would be even more impressive).

    That's not a problem, but simply more inspiration.

    After Googling about lactic acid and muscles, I've found that the answer to my original question is no, he wouldn't have muscle cramps caused by lactic acid, though he could still overwork them. But he would have a vastly increased level of stamina when compared to a regular human.
     
  8. AspiringNovelist
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    AspiringNovelist Contributing Member

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    I didn't get too deep into your process, but as a general question -- how would his (its) muscles even fire without oxygen? I recall from biology class that in order for muscle (or any cell I think) to convert glucose to useful energy, requires oxygen.
     
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  9. ToeKneeBlack
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    Good question. The oxygen and glucose are "burned" to convert ADP into ATP by the mitochondria - the "power stations" - present in the vast majority of human cells. This ATP (Adenosine TriPhosphate) is then used by almost every other cellular process that requires energy.

    I came to the conclusion that, if there was an organ that could generate and store ATP, then this store could be released gradually into the body, without the need to circulate other stuff like haemoglobin (to carry oxygen) all over the body. This results in the requirement for a smaller heart, since the blood is effectively thinner. Plus, oxygen is fairly dangerous stuff to a cell - immune cells can use it as a weapon to destroy bacteria! Circulating less of it in the body would result in less damage from "free radicals", so he would age more slowly.

    That said, his white blood cells would have to carry their own oxygen to kill germs, as they cannot take it from the red blood cells in his "wider" circulatory system. These immune cells would have a little haemaglobin, but not as much as a regular red blood cell as they exist in real life. Effectively, this would result in his immune cells being nicknamed "pink blood cells" ;)

    Which brings to mind this little tale:
    A biochemist walks into an English pub, and asks the barman for a pint of adenosine triphosphate.
    The barman says, "Certainly sir, that'll be 80p."
     
  10. Aaron DC
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    Aaron DC Contributing Member

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    I'd be wary of using lactic acid as the culprit for cramps, as it doesn't fit my experience or understanding.
    Are you envisaging the ATP pouch like a spleen? Storing until required then squirting it into the system?
    What happens when he gets injured? If he's bleeding ATP? Will that system have coagulents also?
    How will the blood vessels delivering the ATP get access to the mitochondria? Exclusively or in some manner of shared access with the normal circulatory system?

    An interesting premise. I would have thought it would be easier to have 2 hearts for pumping normal blood, and increase the oxygen absorption and use.
     
  11. Aaron DC
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    Aaron DC Contributing Member

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    Like natural hematide or something?
     
  12. Aaron DC
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    Aaron DC Contributing Member

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    (I am not a biologist, just interested in biology).
     
  13. Sifunkle
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    Sifunkle Dis Member

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    Wow, you've got quite the imagination! I'm not sure all your ideas will work if it's to be scientifically realistic (based on our current understanding anyway), but they'd be really interesting for a less rigorous sci-fi. My comments:

    Synthetic nucleotides - Doesn't seem feasible for him to be engineered this way to me. They'd need to have completely rewritten his genetic code (which would be similar to creating life from scratch). They'd also need to concurrently design a whole array of new proteins to deal with the new DNA (polymerases, helicases, ligases, histones, etc + ribosomes). I suppose all the new proteins would preclude viral infection: they wouldn't be set up to transcribe or translate 'classic' viral DNA/RNA, and pathogen evolution to deal with new nucleotides seems a stretch even by viral standards.

    ATP gland and bladder - Seems very risky. As it stands, ATP production occurs within pretty much every cell of the body to some extent (via oxidative phosphorylation, linked to the Krebs/TCA/citric acid cycle). This means that ATP is widely distributed, so instantly available on demand (as is necessary: when your cells need energy, they need it now!). If you had its supply dependent on circulation, you'd create a delay whenever there was a sudden increase in energy requirements. You'd also apply all the shortcomings of our existing circulatory system (heart attacks, emboli, bleeds, etc) to something that is needed instantaneously. Any minor circulatory hiccup could completely knock out something very important. And the gland/bladder (and potentially any one of the vessels...) would be an incredible vulnerability in fights/accidents/etc.

    2 heart system - I don't see the advantage. You'd need the same overall amount of oxygen/haemoglobin, it would just be redirected. All you'd have is an extra heart to pump (= extra energy required), plus additional vessels prone to damage, blockage, etc (+ maintenance costs) - given you've removed ATP production from cell, your new circulatory system would need to reach every cell in the body, which is far more comprehensive than the current setup. And your oxygen system would still need two circuits (pulmonary and to/from the ATP gland) to separate oxygenated from deoxygenated 'blood' (or it would be very inefficient).

    Whether lactic acid would build up would depend on how effective your oxygen supply to the ATP gland was. If oxygen supply was inadequate, the body would have to rely on anaerobic metabolism to generate ATP (far less efficient than ox phos), which produces lactic acid via fermentation. So overall, this is another catastrophic risk of your setup - if the sole oxygen supply was disrupted for some reason, because your ATP production is concentrated in one area, there would be a sudden, drastic increase in lactic acid. Rather than mild cramps or whatever, he'd be more likely to develop a fatal metabolic acidosis.

    Those are my thoughts anyway. You might already have workarounds to some points, but I think it's a hard sell overall (if you're aiming for plausibility). This has certainly tested my biochem!
     
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  14. psychotick
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    Hi,

    What you're describing is not just a long way beyond what geneticists will be able to do say within the next century. It may be completely impossible. In essence you've created an entirely new not just species but genetics. This guy you've built wouldn't be human at all.

    If I can put this into simpler computer terms. Say instead of using silica / sand for chips, I decided to use a different substrate altogether. One with different chemical properties. Say carbon. Then say I decided I wanted to build a computer out of carbon chips. Everything is different. The charges carried through wires, the logic diagrams, every single piece of equipment in the machine from the hard discs to the fans and of course the speed. Everything has to be.

    But now as if that isn't enough I want to build a computer that works and looks like my old one. So somehow I now have to know how every interaction between different parts will affect every other part. I have to know that all in advance so I can then make my new carbon computer match my old one in terms of how all the parts function together so that they work the same.

    And then the final straw. You want to build new parts. Things that have absolutely no counterpart in the original, but still fit them into the carbon copy and make them at least look like they might fit.

    It's simply going too far without a godlike intelligence or billions of years of evolution to help you. And why do it?

    Go the easier route. Use DNA. Stick with the templates. And tinker. Why do you want an ATP producing organ? Why not simply have cells with a very slight shift so that they all produce more ATP. Same effect, more immediate effects physiologically, and easier to achieve.

    Two complete circulatory systems - again why? Again I get that you need two because you want your ATP to be delivered seperately. But if your ATP is already in the cells waiting for a chemical messenger to tell it to be released, then why the needless complexity of an entire extra pump and tubing? Just tweak a gene so that certain glands produce more of certain hormones under certain circumstances.

    You want him to be able to go without oxygen for a while? There are easier ways. Simply look at some whale genes.

    Cheers, Greg.
     
  15. Aaron DC
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    Aaron DC Contributing Member

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    Look up things like AICAR and GW5o156 and consider how you could genetically modify a human to produce those sorts of substances naturally, perhaps?
     
  16. ToeKneeBlack
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    I'm going to refer to the genetically engineered person as a "Gep" just to make it faster to type - unless that's an offensive word anywhere. I'll stop using the term if it is.

    For context, the story is set in the early 23rd century, where a medical technology called the "biode" exists - this is an engineered bacterial cell with nanoelectronics, which uses the same 8-nucleotide template as the Gep. These biodes are effectively his ancestors.

    A disgruntled medical genius, desperate for more time to prove his theories, has created a machine capable of converting human synaptic connection patterns into a computer program; he has used this to cheat death AND hijack a large number of computers to run his consciousness. This is established in the first book in the series.
    With the colossal processing power available to him, he has taken the humble biode genome and expanded upon it, creating a being that grows and develops very much like an ordinary human externally, but much more efficiently internally.

    I get what you're saying about centralising the production of ATP being a bad idea - would it be feasible to have an ATP gland and bladder in addition to the production of ATP in every cell in the body? The contents of the ATP bladder could then be released into the bloodstream during times of extreme physical exertion, effectively giving him a temporary boost in physical strength.

    Sticking with a single circulatory system, would reducing the size of a red blood cell while retaining its classic shape be any good? This would increase the overall surface area of the red blood cells for a given mass of them, reducing the stress on their cell membranes as they pass through capillaries and giving them a longer lifetime. Would this, in theory, reduce the viscosity of the blood?

    Probably the most unrealistic aspect of the Gep would be the "memory" chromosome, which was engineered by his creator. This chromosome contains a default synaptic layout which gives the Gep the same memories as his creator at the time of the creation of said genetic material. The results wouldn't need to be perfect, but I'm assuming a human's instincts are the result of default synaptic patterns common to everyone through our DNA. While improbable, I think this could be possible, given the time period.
     
  17. Aaron DC
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    I think you are going too detailed even discussing ATP. My suggestion would be to give it a general / generic energy delivery system, handwave then describe the effects / outcome.

    ATP and its process is not well known, so maybe that is the generic delivery system, but if someone goes looking and expects it to make sense they may be disappointed?

    Dunno.

    I have not seen or read someone go into that much detail before. It's usually glossed over mostly.
     
  18. Aaron DC
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    Aaron DC Contributing Member

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    PS. I love the premise you just set up, @ToeKneeBlack - it sounds brilliant. Let me know if you're after beta readers, I'm interested.
     
  19. ToeKneeBlack
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    ToeKneeBlack Contributing Member Contributor

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    I guess I am looking into it too deeply. I once saw a behind the scenes special where the writers of Star Trek discussed their favourite fan questions, some of which asked them to describe how the technology works.

    I didn't want to be caught out, but I do also have people who can change into crystalline humanoid insect creatures - I won't even start to try to figure out how that would work.

    Thanks for being interested in the story. I'll message you with more information.
     
  20. Aaron DC
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    Aaron DC Contributing Member

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    I think it's good to work out the behind the scenes stuff, for sure. Have some semi-plausible foundation for what you're doing. But keep it there, and focus more on story and effects vs causes at a biological level.
     
  21. Sifunkle
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    I still have trouble accepting an entirely new genetic code, even for something as 'simple' as a bacterium (still incredibly complex when starting from nothing). And to produce a humanoid from a bacterium... without billions of years of intermediary steps... The time scale the evolution of life occurred over is unfathomably immense, and I'm sceptical that even the global processing power of your 23rd century digital consciousness could compensate (although computers aren't my field, so maybe I'm not fathoming that ;) I also know nothing about nanotechnology and what that might contribute). Having stated those concerns - pinning it on the processing power of your digital man, I'd probably suspend my disbelief and enjoy the story :) so good idea.

    Talking evolution, biosecurity would have to be pretty tight to prevent the biodes leaking out and diversifying via natural selection, which would probably result in plenty of 'New DNA' pathogens that might affect the Gep (when not busy wreaking havoc on the rest of Life). With no other 'New DNA' organisms around as competition, no 'New DNA' bacteriophages, etc, I think the biode would have incredibly dangerous evolutionary potential, and if it's bacterial (short generation times), it could happen quickly.

    I'm with @Aaron DC : maybe steer away from ATP. I could be wrong, but my impression of ADP/ATP is that it's a fixture within mitochondria that periodically has phosphate molecules tacked on (stores energy in the bond), and broken off (releases energy as needed). I don't believe it's something that's circulated like you're proposing. Maybe you could work with insulin (a hormone that drives blood glucose into cells, where it's used to ramp up ATP cycling, etc) or erythropoietin (EPO; stimulates red cell production, so increases oxygen delivery; the hormone that cyclists, racehorses etc get in trouble for 'blood doping' with).

    Reducing RBC size would definitely improve surface area:volume ratio thus oxygen delivery. I think would reduce viscosity too (need to revise fluid dynamics). To some extent this is what already happens in RBC development: the precursors have a nucleus and are big, then they lose the nucleus and are still big, then they mature and shrink a bit. If you lose blood cells, the 'juniors' get sequentially released from bonemarrow (better than nothing). Your idea might be good though (but to develop, they'll still be starting large with a nucleus, so to produce heaps of small ones, you'd probably need more bonemarrow).

    I agree that 'genetic memory' is fairly unbelievable (unfortunately what you're suggesting isn't really how development works - if you want to study, look up evolutionary development = evo devo), but it's a darn cool idea (one I've toyed with myself).

    Despite how much I've talked shop, I was also going to suggest what Aaron DC has: that you should 'handwave' some stuff and just let Rule of Cool outweigh realism. Brainstorming and study is a great source of plot/setting inspiration, and it's nice to have some idea of the background of what you write, but write an entertaining story rather than a textbook. I think a lot of the time, if you don't draw attention to dodgy details, readers won't notice, so don't get bogged down :) I know I poked a lot of holes (only because you asked; I'd have rolled with it if I was reading), but I also think your ideas have a bright future!
     
  22. Aaron DC
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    Aaron DC Contributing Member

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    Dune had genetic memory. Or awakening. Plenty of examples there for description and impact.
     
  23. Shadowfax
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    Shadowfax Contributing Member Contributor

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    Similar idea as was used in Host by Peter James.

    I'm with @Aaron DC about the handwaving...ATP is unstable, unlike something like blood, so wouldn't store well without a major change in biochemistry, so you'd end up with a different mechanism for converting oxygen and carbohydrates into work, so you may as well go straight to hydraulic fluid and build a robot!...there's about 250g of ATP in the body, and is recycled something like 300-400 times per day...
     
  24. Sifunkle
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    On this note, Rupert Sheldrake's idea of 'morphic resonance' may be worth a Google for story ideas (widely regarded as pseudoscience though).
     
  25. Aaron DC
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    All those banned TED talks are worth a listen :D
     

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