But I'm not sure gene editing of the sort provided by the CRISPR-Cas9 system is required for such an application. Transient gene regulation (turning genes on and off) is mostly an epigenetic thing.
Epigenetic changes don't modify the genes themselves. Instead, they modify the level of gene expression by modifying the environment of the gene within the DNA strand. Attaching methyl groups to a segment of DNA can turn it off and detaching them can turn it back on. There are probably other mechanisms as well, but that's the one I know off the top of my head.
Epigenetic changes can be transient, but they can also be long-lasting and even heritable(ish). There's a complicated dance between epigenetics and the DNA regulatory system that we're just beginning to understand.
So clownfish and other serial hermaphrodites don't actually change their own DNA when they switch sexes from male to female. The DMRT-1 gene is still there, in the exact same form as before; it's just switched off (probably by methylation) by some other part of the animal's biology that knows how to do that.
Absolutely true! Unfortunately, the only gene humans (and other mammals with it) have retained which can toggle DMRT-1 is SRY, and that's not a candidate for obvious reasons. Currently, the only successful toggling we've achieved has been using CRISPR. Since that's the only proven technique, I wrote the article under the assumption that, at the very least initially, we'll need to use technology of that general type to trigger the toggle. I hope that you're right in the long run, though, that we'll be able to use even less-intrusive methods in the future.
Kind of bittersweet, like so much is when you're a trans person looking to the future. But it's good to know this is here, and is moving along the (very long) conveyor belt.
Thanks for the breakdown, that was really cool stuff 🙂
Oh yeah. Heck I've been on T for like 8yrs, and there's been a bunch of changes even since then. We're moving in the right direction! Sometimes slowly and always painfully (pain usually provided by others), but we are! 🙂
Fascinating read, and it is something I considered since I started studying biology and first read about those mice experiments, but there are other factors the article didn't touch on.
Like for example, say we find the way to optimize CRISPR or develop another gene editing tool more suitable, and we find a way to use it to change DMRT-1. Even if we could turn testicles into ovaries how would that help trans people?
Reproductively, since embryonic development already happened we can't grow a uterus and the rest of the stuff needed for pregnancy. And as you said, they won't be able to produce eggs. And even if they can secrete hormones, we'd still need to put them in the place ovaries are (especially for the trans women that get SRS) which I don't know if it's possible.
Same with trans men, we'd need to find a way to bring the ovaries-turned testicles out.
They wouldn't be useful for reproduction, sure, but they would secrete the estrogen or testosterone that we currently have to take exogenously. And they don't need to be moved for that; the body can absolutely work with them where they are, because all of the structures that are there to support and transport one hormone (blood circulation, for instance) should work just fine for the other.
Now, pseudo-ovaries for trans women getting bottom surgery need a solution, obviously, but doctors have been embedding testes into mens' pelvises in cases of scrotal cancer, where the sctorum needs to be removed but the testes are clear, for some time now with pretty darn good success. There's no good reason to believe that's not a viable solution for the scenario you're describing.
Sure, it could work. I just wanted to point out that it's another avenue that needs to be investigated.
Of course, this all may not even be necessary. Because we're already on the verge of figuring out how to create organs from stem cells that the immune system won't attack. And if we figure out how to do that with hearts, I don't see why we wouldn't then be able to move into using stem cells to create full reproductive systems of the opposite gender that won't cause issues with the immune system if transplanted (a major setback on why we still can't transplant uteruses to trans women even though a few transplants have already been performed on cis women).
Fascinating stuff.
But I'm not sure gene editing of the sort provided by the CRISPR-Cas9 system is required for such an application. Transient gene regulation (turning genes on and off) is mostly an epigenetic thing.
Epigenetic changes don't modify the genes themselves. Instead, they modify the level of gene expression by modifying the environment of the gene within the DNA strand. Attaching methyl groups to a segment of DNA can turn it off and detaching them can turn it back on. There are probably other mechanisms as well, but that's the one I know off the top of my head.
Epigenetic changes can be transient, but they can also be long-lasting and even heritable(ish). There's a complicated dance between epigenetics and the DNA regulatory system that we're just beginning to understand.
So clownfish and other serial hermaphrodites don't actually change their own DNA when they switch sexes from male to female. The DMRT-1 gene is still there, in the exact same form as before; it's just switched off (probably by methylation) by some other part of the animal's biology that knows how to do that.
Absolutely true! Unfortunately, the only gene humans (and other mammals with it) have retained which can toggle DMRT-1 is SRY, and that's not a candidate for obvious reasons. Currently, the only successful toggling we've achieved has been using CRISPR. Since that's the only proven technique, I wrote the article under the assumption that, at the very least initially, we'll need to use technology of that general type to trigger the toggle. I hope that you're right in the long run, though, that we'll be able to use even less-intrusive methods in the future.
Kind of bittersweet, like so much is when you're a trans person looking to the future. But it's good to know this is here, and is moving along the (very long) conveyor belt.
Thanks for the breakdown, that was really cool stuff 🙂
Yeah, I hear that. But then again, our HRT today is much safer than it was thirty years ago, so step by step, we're getting there.
Oh yeah. Heck I've been on T for like 8yrs, and there's been a bunch of changes even since then. We're moving in the right direction! Sometimes slowly and always painfully (pain usually provided by others), but we are! 🙂
Well, like I said--fast medicine is usually bad medicine. We'll get there.
Fascinating read, and it is something I considered since I started studying biology and first read about those mice experiments, but there are other factors the article didn't touch on.
Like for example, say we find the way to optimize CRISPR or develop another gene editing tool more suitable, and we find a way to use it to change DMRT-1. Even if we could turn testicles into ovaries how would that help trans people?
Reproductively, since embryonic development already happened we can't grow a uterus and the rest of the stuff needed for pregnancy. And as you said, they won't be able to produce eggs. And even if they can secrete hormones, we'd still need to put them in the place ovaries are (especially for the trans women that get SRS) which I don't know if it's possible.
Same with trans men, we'd need to find a way to bring the ovaries-turned testicles out.
They wouldn't be useful for reproduction, sure, but they would secrete the estrogen or testosterone that we currently have to take exogenously. And they don't need to be moved for that; the body can absolutely work with them where they are, because all of the structures that are there to support and transport one hormone (blood circulation, for instance) should work just fine for the other.
Now, pseudo-ovaries for trans women getting bottom surgery need a solution, obviously, but doctors have been embedding testes into mens' pelvises in cases of scrotal cancer, where the sctorum needs to be removed but the testes are clear, for some time now with pretty darn good success. There's no good reason to believe that's not a viable solution for the scenario you're describing.
Sure, it could work. I just wanted to point out that it's another avenue that needs to be investigated.
Of course, this all may not even be necessary. Because we're already on the verge of figuring out how to create organs from stem cells that the immune system won't attack. And if we figure out how to do that with hearts, I don't see why we wouldn't then be able to move into using stem cells to create full reproductive systems of the opposite gender that won't cause issues with the immune system if transplanted (a major setback on why we still can't transplant uteruses to trans women even though a few transplants have already been performed on cis women).
Great article :)
This topic has also been somewhat discussed before on madgenderscience:
https://madgenderscience.miraheze.org/wiki/RNA_interference_with_FOXL2_and_DMRT1
https://madgenderscience.miraheze.org/wiki/SRY_signaling_cascade