Changing DNA?

Changing DNA creates a mutant, by definition. However, just how mutated from the 'norm' is a subjective thing. We all differ from each other by DNA...are we all mutants? And what is 'normal'? You can see where this goes.

Most DNA just sits there, doing nothing. If you change it, it will probably still do nothing. In order to create changes, it must be 'expressed'. You could give him the DNA of a turtle, that doesn't mean he'll become one. And the changes aren't instantaneous, either. In my WIP, DNA changes figure as the central problem. But I change only a little part of the genome. Change too much, and everything dies.

Good luck!

Mutations happen naturally in genetics, so it's plausible that someone with the appropriate technology and resources could force them. (In a future world where gene therapy can be used to re-code some's RNA, which would then re-code their DNA.... I think. It's too early for genetics.)

The problem you're going to have with plausibility here is that zombies, by definition, are dead things. Dead things have no cellular replication/reproduction. Mitosis has stopped. Even with living things, there's the matter of the brain. By the time someone is grown, their brain has set pathways. Screwing that up by drastically altering the physical nature of the body to which that brain is attached would have serious - and most likely unpredictable - consequences... I think. It's too early for neurology, too.

It completely depends how much you want to subvert the laws of science in your book! In real life, it wouldn’t happen with a grown human. There are 10 billion cells in the human body - that's 10 billion copies of the genome you would have to change. And even if you did change the DNA in every cell, most of the cells in a person have already decided what kind of cell they are and have lost the capacity to change from, say skin to scales. But you could do it with an embryo.



Your idea could work though – most superheroes rely on altered DNA after all. Unfortunately, it also means it is not the most original idea and needs to be done really well to work.



The most scientifically accurate way to change a person’s DNA would be via gene therapy using a virus that gets into every cell and inserts itself into the DNA, over-riding some but not all of the genes that are already there. This is the principle of gene therapy where a virus is used to add a gene into the cells of certain organs to replace a defective one. A version of gene therapy has been used in lots of books and films already (I am Legend uses it with zombies).



I think a zombie book based on prions would be good by the way. Prions are infectious proteins that cause brain diseases like mad cow disease. They bind to certain proteins in the brain, causing them to misfold and stick together, destroying the brain bit by bit. How cool would it be to use this to explain zombies? You could have certain parts of the brain getting destroyed, starting with everything required for higher functions such as thought and knowing not to eat your mates. Not that this helps you one bit with your idea though!

Wasn't Kuru (the laughing sickness) a prion-like disease amongst the cannibals of Papau New Guinea? There's a great proto-zombie disease for you!

BillPatt said:

Wasn't Kuru (the laughing sickness) a prion-like disease amongst the cannibals of Papau New Guinea? There's a great proto-zombie disease for you!

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There was a version of vCJD that some cannibals developed due to eating the brain of the deceased. Wahay for Google: http://www.nhs.uk/news/2009/11November/Pages/brain-eating-cannibals-CJD-mad-cow-disease.aspx

In theory, it's possible. But every cell has its own copy of your DNA and this chemical weapon would have to change all the cells that matter the same way, which is unlikely (when a chemical substance is mutagenic, it usually causes all kinds of damage that usually result in cancer or deformed babies). But don't worry. No one expects this kind of story to be plausible. You just have to be convincing.

scottishpunk said:

Their mutation (brought on by chemical warfare and amplified over generations of inbreeding)

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Given enough generations, that'll give you mutations on its own. Shrink your gene pool and the number of naturally occurring mutations increases.

I disagree that such a disease would have to attack every cell in the body. Once the body is done forming, the cells pretty much stay put, unless they are blood cells. To affect behavior, you'd really only have to attack cells in the brain and central nervous system, and possibly a few glands. The trick would be to keep the immune system from attacking these mutated cells. If it also attacked the gametes, this would ensure heritability.

In fact, all the initial disease would have to do would be to attack the gametes. Then you would have seemingly normal people giving birth to mutants.

I disagree that such a disease would have to attack every cell in the body.

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That's why I wrote all the cells that matter instead of all the cells in the body.

Cellular DNA isn't like software. What genes do is to create chemicals - proteins that a cell needs to function. If you have an already living organism and you change its DNA - even if you change the DNA of all its cells at once - the cells that have already been "built" were built using the old proteins, and won't recognize the new ones. They will treat a lot of the new proteins and new cells as infections. The body's immune system will go to war against them, creating the processes we see in host/graft syndrome, mysthenia gravis, lupus, and all the other autoimmune diseases.

Changing the DNA of an embryo is a lot less problematic.
Or creating a chemical compound to deal with the symptoms of the zombie mutation, as opposed to reversing the genetic mutation itself (in adult zombies, that is).

Smiling Ted said:

Cellular DNA isn't like software. What genes do is to create chemicals - proteins that a cell needs to function. If you have an already living organism and you change its DNA - even if you change the DNA of all its cells at once - the cells that have already been "built" were built using the old proteins, and won't recognize the new ones. They will treat a lot of the new proteins and new cells as infections. The body's immune system will go to war against them, creating the processes we see in host/graft syndrome, mysthenia gravis, lupus, and all the other autoimmune diseases.

Changing the DNA of an embryo is a lot less problematic.
Or creating a chemical compound to deal with the symptoms of the zombie mutation, as opposed to reversing the genetic mutation itself (in adult zombies, that is).

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The B lymphocytess might have their DNA changed so they won't make antibodies against the new proteins, for instance. In fiction everything is possible.

Dr Swann said:

It completely depends how much you want to subvert the laws of science in your book! In real life, it wouldn’t happen with a grown human. There are 10 billion cells in the human body - that's 10 billion copies of the genome you would have to change. And even if you did change the DNA in every cell, most of the cells in a person have already decided what kind of cell they are and have lost the capacity to change from, say skin to scales. But you could do it with an embryo.



Your idea could work though – most superheroes rely on altered DNA after all. Unfortunately, it also means it is not the most original idea and needs to be done really well to work.



The most scientifically accurate way to change a person’s DNA would be via gene therapy using a virus that gets into every cell and inserts itself into the DNA, over-riding some but not all of the genes that are already there. This is the principle of gene therapy where a virus is used to add a gene into the cells of certain organs to replace a defective one. A version of gene therapy has been used in lots of books and films already (I am Legend uses it with zombies).



I think a zombie book based on prions would be good by the way. Prions are infectious proteins that cause brain diseases like mad cow disease. They bind to certain proteins in the brain, causing them to misfold and stick together, destroying the brain bit by bit. How cool would it be to use this to explain zombies? You could have certain parts of the brain getting destroyed, starting with everything required for higher functions such as thought and knowing not to eat your mates. Not that this helps you one bit with your idea though!

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My thoughts exactly. I especially love the idea of zombies caused by prions.

To be more specific about what I'm looking for, my "zombies" in my story are actually mutated human beings. Their mutation (brought on by chemical warfare and amplified over generations of inbreeding) basically reduced people to their most primative, animal form. It manifests itself primarily through an overactive metabolism (thus the constant need to feed), sensitive skin (which facilitates the need to avoid direct sunlight) and, of course, a mental disconnect reducing them, essentially, to beasts.

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This will take a lot longer then you think it will, more than just generations. Unless you give a plausible explanation that these chemicals will cause a mutation in a specific region of the DNA, the mutations will be random. And if these chemicals are extremely mutagenic, which the would have to be, there is going to be a lot of nonviable fetuses and deformities in the population. The resulting "zombies" would come from only a few individuals, and who is going to want to mate with them.

But then again, most movies and tv shows get evolution wrong anyway, so we are used to it.

My MC is a human who is doing research to discover/create a cure for them, and turn them back into humans. Kinda I Am Legend style. Most ideal for my story would be a cure that can be implemented in the form of a drug of some kind (although I like the "good virus" idea)-- perhaps dispersed as a gas.

Any more ideas?

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If your MC is a scientist, this is going to be tough to do if you want it realistic. I would suggest reading up on genetics.

Whether or not a cure is realistic depends on what gene was mutated. Every cell stores all of the genetic information but doesn't express every genes. Many genes are turned on at specific moments in development and/or in specific cells. If your gene of interest is expressed during embryo development, then changing the gene in a mutant won't cure them, but would save any potential offspring. For example: if there is someone with a genetic defect that gives him three arms, fixing that gene won't make the third arm go away, right. So don't give your zombies physical abnormalities and curing them with gene therapy; it just isn't possible.

So the mutant gene would have to code for a protein that is continually expressed, like sickle cell anemia.

Gene therapy is a good route to go to try to cure the mutation with your "good virus." Gene therapy is being research but hasn't been very successful against genetic disorders like cystic fibrosis (I think, but you can google it). There is a lot of information on this process for you to research.

Another idea, but in a less developed stage in scientific research, is antisense or RNA interference. This is a way to "turn off" any gene by delivering an RNA sequence that is complimentary to mRNA (the molecule that takes the message of the gene from the DNA to the site of protein synthesis). The result is that the intererence RNA (iRNA) binds to the mRNA and is degraded by enzymes so that the protein the gene codes for is never made. Of course this wouldn't be a permenant cure. The mutants would have to take their iRNA medication or they would revert to the "zombie" state. iRNA could also be delivered by engineered viruses.

If this method is used, your mutant gene would have to be a gain in function mutation, and would only need to be turned off not altered. I believe most gain in function mutations (not sure if that is the official terminology) are dominant.

Do some research and have fun with this. Don't stress about getting everything right. I love X-men and Heroes and they pretty much butcher evolution and DNA. Just tell a great story. If you have more questions, feel free to send me a PM.

Good luck.

Edited to add a gas would not work for either of these methods. You would need to inject it into the mutants like a vaccine. You could always gas the "zombies" and once they were sleeping, inject them with the cure.

Smiling Ted said:

Cellular DNA isn't like software. What genes do is to create chemicals - proteins that a cell needs to function. If you have an already living organism and you change its DNA - even if you change the DNA of all its cells at once - the cells that have already been "built" were built using the old proteins, and won't recognize the new ones. They will treat a lot of the new proteins and new cells as infections. The body's immune system will go to war against them, creating the processes we see in host/graft syndrome, mysthenia gravis, lupus, and all the other autoimmune diseases.

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Ted, there might really be a way out. Cells are constantly dying and being replaced. I read somewhere reputable that the kidneys essentially replace every cell in them once every seven years. Seems implausible, but what the hey - it could be true.

Of larger import, though, is the nature of mutation. There are two ways that a mutated cell would get past the immune system: acting normal, or fooling the system. If the mutated cell does not change its surface antigens (those proteins on the surface that say "Made in BillPatt"), then the immune system does not recognize that its different. The downside, though, is that most mutations alter the surface antigens. So, over to Plan B.

Plan B is to divert, confuse, or just defeat the immune system. The problem here is that white blood cells just swarm - even if the cell resists engulfment, eventually it is cut off from the flow of nutrients, and dies in its own waste.

The big issue, of course, is always the immune system. You'd have to include at least a little datadump in your work to explain how it was outwitted. Of course, you could just start with the zombies - and part of the puzzle is how they got that way, eventually explicated through the work by the MC working on the cure.

BillPatt said:

Of larger import, though, is the nature of mutation. There are two ways that a mutated cell would get past the immune system: acting normal, or fooling the system. If the mutated cell does not change its surface antigens (those proteins on the surface that say "Made in BillPatt"), then the immune system does not recognize that its different. The downside, though, is that most mutations alter the surface antigens. So, over to Plan B.

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Huh? I am not sure where you are getting this idea that I bolded.

Yes, there are genes that are responsible for the glycoproteins (I think they are glycoproteins) that identify the cell as yours. So changing those specific genes might make the immune system attack those cells, but the vast majority of genes aren't involved in this at all.

Changes in most genes won't alter the surface of the cell. There are many proteins that work inside the cell, from proteins that regulate DNA activity to enzymes involved in cellular metabolism.

There are also genes that code for proteins that make, store, and control the release of chemical messengers like hormones and neurotransmitters. I don't see changes in these genes changing the cells enough to cause an immune response in every individual. So it really depends on what type of gene has been mutated.

Honestly, I don't think you need to be worried about the immune system attacking the cured cells, unless you want that to happen. There is a lot of room to play since this gene is imaginary.

I should clarify. I am NOT a microbiologist or anything like that, just a general interest in the field. First, I want to acknowledge that all the points you raise are valid AFIK.

However, I do recall reading where most genetic changes that turn a cell cancerous do result in changed cell surface markers, initiating an immune response. Otherwise, we'd be overwhelmed with cancers at a relatively young age. At least that was the theory.

I'll be more careful.

BillPatt said:

I should clarify. I am NOT a microbiologist or anything like that, just a general interest in the field. First, I want to acknowledge that all the points you raise are valid AFIK.

However, I do recall reading where most genetic changes that turn a cell cancerous do result in changed cell surface markers, initiating an immune response. Otherwise, we'd be overwhelmed with cancers at a relatively young age. At least that was the theory.

I'll be more careful.

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I believe you are correct that tumor cells can be attacked by the immune system. It is also true that cells are complex and making a small change to a gene can have unforeseen consequences, but this isn't always the case. There is a lot of leeway when your gene is fictional.