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Viral Contraception for Men

A specially crafted virus partially shuts down the testicles until...
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This Idea involves something we don't yet know, but are definitely going to know in the not-distant future.

We start with the topic of stem-cell research. A stem cell has the ability to produce multiple types of other cells. When a sperm fertilizes an egg, the resulting zygote is a "totipotent" stem cell, meaning it can generate any other type of cell in the body. It is an important fact that any cell descended from a stem cell has ALL the DNA of the stem cell.

An ordinary specialized cell, like a muscle cell, normally only pays attention to some of the overall DNA code in the cell. That is of course the code that tells it how to be a muscle cell. What stem-cell researchers are trying to do is locate the DNA code that can tell an ordinary specialized cell to behave like a stem cell, and stimulate the cell to actually start processing the stem-cell DNA code.

We know that various aspects of the goal can be done; an ordinary virus, for example, can tell a cell to stop paying attention to its normal DNA code, and start running the code in the virus (which causes many copies of the virus to get made, until the cell dies from exhaustion). And when the DNA of a normal specialized cell is extracted, and used to replace the DNA in an ovum, somehow that event causes the stem-cell/zygote code in that DNA to get processed, such that a clone begins to exist.

Imagine a specially crafted virus. It infects an ordinary cell, and tells the cell to stop processing its normal DNA code, and to start processing stem-cell code. The goal of stem-cell researchers could in theory be that simple.

But that is only the beginning of this Idea. Imagine identifying all the blocks of DNA code normally associated with all the different types of cell in the body. Want to be more muscular? Get a specially crafted virus to tell fat cells to start processing muscle- cell DNA code! And yes, a virus can be that specialized, such that it can infect only one type of cell. (This implies someone must specially craft one virus for each cell, but perhaps we could make the virus first tell the cell to make just a couple copies of the virus, before switching DNA gears from fat-storage DNA to muscle DNA.)

Now consider the testicles. They contain specialized cells that manufacture sperm, and possibly other specialized cells that produce hormones like testosterone. I'm not completely sure about all the specializations; maybe one type of cell does both (and more). Anyway, what we want here is a custom virus that can tell the appropriate testicular cells to stop running -- perhaps by skipping-- the DNA code that causes them to make sperm. Think of it as doing the equivalent of inserting a JUMP instruction into a block of computer code. If only sperm-production is affected, then the man will be perfectly healthy otherwise, and yet is now basically sterile, with respect to having offspring (or will be after the backlog of previously-created sperm has left his system).

It doesn't have to be permanent, though. Another custom virus could be made, which removes that JUMP instruction.

Vernon, Jan 31 2016

testicles+valves+surgical+implanted https://www.google....es+surgical+implant
images of mechanical on off valves [popbottle, Feb 01 2016]

[link]






       Customizable sterility sounds like a convenience. And a weapon. Perhaps even a weapon of convenience? I'll bun that [+]
whatrock, Feb 01 2016
  

       Not sure I want a virus running around my balls that tells them to become sterile, and another one that is trying to shut it off. Who knows what damage they'll do during the O.K. Corral shootout.
RayfordSteele, Feb 01 2016
  

       (marked-for-tagline)   

       " This Idea involves something we don't yet know "   

       I think that takes it into the category of "magic".
normzone, Feb 01 2016
  

       Vernon has a unique lack of regard for the perils of producing a virus that could cause human extinction.
WcW, Feb 02 2016
  

       [WcW], nonsense! Some humans are always immune to a given virus. But, yes, the population might go down a lot if this Idea was mis-used.
Vernon, Feb 02 2016
  

       A few strains of Vernon's magical elixir "accidentally" lost in ISIS-controlled countries might slow the production of future terrorists and help develop a following for fried food, sugar and a lethargic lifestyle. Better than a bomb.
whatrock, Feb 02 2016
  

       I think it would be pretty trivial to use a lenti virus to CRISPR out fertility, targets and specific promoters are pretty easy with such a specialized tissue. You should be able to transiently put it back, with a scrotal injection of adenoviral rescue DNA. I can't be bothered with the details right now, but viral delivery of a drug-inducable system to switch fertility on and off should be pretty doable.
bs0u0155, Feb 02 2016
  

       Did anyone else notice the phrase "scrotal injection" just then?
MaxwellBuchanan, Feb 02 2016
  

       //Some humans are always immune to a given virus.//   

       So far, no readily transmissible and sterilising (or highly lethal) virus has been human-to-human infectious enough to spread to any highly connected human population and become pandemic. That's not actually the same thing, and there have been some diseases which have been close.
Loris, Feb 03 2016
  

       [Loris], even the AIDS virus has run up against a few humans who were immune to it. I do need to be clear that it is different humans who are immune to different viruses; not one group immune to all. We could be wiped out by enough different-and-fatal viruses.
Vernon, Feb 03 2016
  

       I'm a bit sceptical about the computer code analogy. Computer code is generally executed in a linear way. DNA is more ... 3D ... isn't it?
pertinax, Feb 05 2016
  

       The immune system is not some sort of infinitely diverse magical system which (within the species) has enough diversity to fight off any possible attack. While I don't know of evidence of any species driven to extinction by a virus, I'd be surprised if none had.
Loris, Feb 05 2016
  

       //I'm a bit sceptical about the computer code analogy. Computer code is generally executed in a linear way. DNA is more ... 3D ... isn't it?//   

       DNA is a 3D molecule, but then, so are the computer chips where computer code functions.
DNA is however an essentially linear store of information (some DNA molecules are circular; this doesn't affect the basic point). A linear series of the four standard bases encodes the information required to produce RNA, most of which encodes for various proteins (some is functional directly as RNA). The DNA holds both the expression information (whether to produce a protein) and the amino acid sequence of that protein. DNA molecules can be very long, and encode many proteins. The structure of a protein molecule depends on its sequence - different amino acids flex and attract each other in different ways. So the one-dimensional DNA sequence encodes the 3D shape of proteins.
  

       However, one big difference between computer code and DNA is that biological processes are very probabalistic (from the perspective of the 'DNA program'). If a particular event has to happen reliably then quite a lot of work has to be done to ensure that.
Loris, Feb 05 2016
  

       [Loris], one reason some species are considered "endangered" is because their gene pools have shrunk so low that they are indeed susceptible to extinction by disease. Humanity, however, is not currently suffering from that danger.
Vernon, Feb 05 2016
  

       What I am saying is that this:   

       //Some humans are always immune to a given virus.//   

       is an rash claim.   

       For what it's worth, humans are high in numbers, sure, but are not particularly genetically diverse.
Loris, Feb 05 2016
  

       Thank you, [Loris].
pertinax, Feb 07 2016
  

       Actually, while I'm here, flaunting my ignorance, there's something else that I may have misunderstood about DNA-editing.   

       I'm picturing a virus spreading, from cell to cell, through some tissue. Let's say it's the "off" Vernovirus, in someone's testicle. Presumably its spread would be limited, in a somewhat unpredictable way, by the person's immune system. If cell-division is still happening in that part of the body, then infected cells will make new infected cells, while uninfected cells will make new uninfected cells (with the old "factory-settings" DNA).   

       What mechanism causes the infected cells to win out over the uninfected ones? And how do you know when they have? And, once they have, how do you clean up the infection? (That is, once the virus has delivered its payload to all relevant cells, I assume you wouldn't want a permanent viral infection using up immune-system resources).   

       In this case, you'd probably want a very high level of confidence about whether you were fertile or not - but my curiosity is more about the general practicalities of CRISPR-ing stuff in multi-cellular organisms such as myself.
pertinax, Feb 07 2016
  

       So, the editing is a separate technology from the delivery. The delivery is what you'd have to get right here. The most commonly used virus technologies, are adenovirus, adeno-associated virus and lentivirus. The're all engineered to be replication deficient, that is a viral protein necessary for building more viruses is missing. That means that the virus now enters the cell, delivers the DNA then stops short of making millions of new viruses and breaking open the cell like a wild-type adenovirus would do. Instead the replication has to take place in special lab grown cells which have the missing protein. So instead of a disease, you now have a breathtakingly efficient DNA delivery system. Adenovirus is pretty non-specific and will infect almost any cell it runs into, infecting a whole body would be tricky, but individual tissues with a well understood blood supply (like balls) should be pretty easy. Then there's the question of specificity. Because adenovirus will infect practically anything, how do you target your effect? The answer to that is in the DNA you put int he virus, you need something called a "tissue-specific promoter". Choosing these is sometimes easy, sometimes hard, but you essentially want to find a gene that is only expressed in your target tissue. If you're lucky, on the front end of this will be the promoter, a region of DNA recognised and read by the cell. For example, insulin is only made by the pancreatic beta cells. The DNA for insulin is in every cell, but on the front of that DNA is a promoter only recognized by beta cells. So if you wanted to selectively build proteins in beta cells, you'd copy the insulin promoter and the beta cells will make whatever you put behind it. So your virus can infect many types of cells, but largely nothing happens because non-beta cells will just ignore the insulin promoter.   

       So, if you find yourself a good, sperm specific promoter, you can put the CRISPR system in behind it, targeted to break a gene necessary for viable sperm. Then, package it all up in an adenovirus. Adenovirus efficiency is >95%, and CRISPR is around the same, once its in the cell, so you might miss 10% of cells. But you can just re-dose a few times, remember the virus doesn't replicate, and the DNA doesn't even get read in most cell types.   

       I mentioned adeno-associated viruses, these are a group of viruses which have some specificity, they are physically able to infect some cells, but not others. For example, AAV8 preferentially infects the liver, this is great, because you can inject the virus into a vein, and the viruses won't just jump into the first cell they meet. They hang around until the encounter a liver cell. The specificity is useful if you can't get privileged access to the tissue you are interested in. Not really an issue with balls.   

       The last virus type is lentivirus. This is a retro virus. It infects, integrates itself into the host genome and from there becomes just like a regular gene, only you get the choice of what that gene is. After infection, the host cell will just crank out the proteins you told it to make forever. Theoretically, this is great for putting a working copy of a gene into cells to offset the effect of a broken one. The downside is that we don't get to choose where the DNA gets integrated. It' a roll of the dice whether the new DNA inserts itself in a gene critical for preventing cancer. It's pretty unlikely, but with billions of cells and billions of viruses, you're rolling the dice a lot, and you only have to get unlucky once.
bs0u0155, Feb 07 2016
  

       Excellent explanation. Thank you very much, [bs0u0155].
pertinax, Feb 08 2016
  
      
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