Science Gene editing to end autism - Or how I learned to stop worrying and love CRISPR

https://www.telegraph.co.uk/science...nificantly-reduced-breakthrough-gene-editing/

Autism traits may be “edited” out using new genetic techniques, scientists have said, following a successful trial.

Researchers are hailing a breakthrough after they used cutting-edge gene editing to to significantly reduce repetitive behaviour associated with the disorder.

The technique, which was performed on mice, could also be developed to treat conditions ranging from opioid addiction and neuropathic pain to schizophrenia and epileptic seizures.

Scientists injected gold nanoparticles covered in a “forest” of DNA chains to alter the the genetic code of mouse models with a form of autism called fragile X syndrome (FXS).

The technique, CRISPR-Cas9 gene editing, resulted in in a 30 per cent drop in repetitive digging, and a 70 reduction in leaping, both indicative of autistic behaviour.

Because the editing DNA was introduced attached to gold particles, the team were able to control how much of the crucial Cas9 protein was delivered, in contrast to previous failed attempts using viruses.

"There are no treatments or cures for autism yet, and many of the clinical trials of small-molecule treatments targeting proteins that cause autism have failed," said study leader Hye Young Lee, an assistant professor of cellular and integrative physiology at the University of Texas Health Science Center at San Antonio.


"This is the first case where we were able to edit a causal gene for autism in the brain and show rescue of the behavioral symptoms."


Autism spectrum disorder is a complex developmental disorder, with a strong genetic component, which manifests during childhood.

It is characterised by deficits in the domain of social interaction and communication, stereotyped behaviour, delayed speech and language and can also be associated with intellectual disability.

There are around 700,000 people on the autism spectrum in the UK - more than one in 100 - and when including families, it is a part of daily life for 2.8 million people.

The results are published in the journal Nature Biomedical Engineering.

 

[kinglordsupreme19]

I wonder what it would really feel like to an autistic person to suddenly lost their autism. Maybe it'd be something like the delirium of a fever subsiding?

Yet as @Ravenor said, even if someone had their autism removed, it looks like they'd still have to "catch up" to "normal" as the damage has already been done.

Forgive the P-levelling here, but I think I can offer a response. I am autistic and was diagnosed at a young age. I've been interested in understanding my condition for quite a few years, and even have corresponded with a few psychologists in the field and have attended a fair few clinical trials (I'm in the lucky position of being able to articulate my phenomenology and make substantive comparative judgements to the norm). From this, I'm inclined to say that autism cannot be understood as a simple mental handicap or a developmental block. Instead, autism is better seen as a substantive neurological difference that is intrinsically tied to the nature of the subject.

Implicit in the idea that it is possible for an person to 'lose' their autism is the idea that there is some sort of unencumbered non-autistic self underneath who, upon being cured, would finally overcome empathic deficits and begin to hit the developmental milestones. However, the evidence (see the work of Baron-Cohen on this, especially on his analysis of the Empathising-Systemising concept of human cognition and its relation to the autist) and personal anecdote strongly suggests to me that this is not the case. Autism is not just social impediment; one of the best articulations of the autistic mind was made by Temple Grandin, who put it best when she described it as being equivocal to being a computational unit that had traded off most of its RAM, and in many cases had traded the neurological resources for it for faster raw computation or data storage (hence why many autists, despite having horrid working memory and motor skills are able to still do high-cognition work or have a prodigious memory).

An autistic person does not just lack the programming of intuition, empathy, or social norms. The neurological resources that allow that in the first place simply are not present. And if you were to try to change their neurology to have those resources, it would erase their existing cognitive resources.

What I'm hitting at is that autism is not a 'disability' in the sense that it's equivocal to a broken leg where if we just fix it they'd be able to carry on as fine (although autism is often co-morbid with heavy impediments), but is instead a completely different mode of being that is a necessary part of the autist's identity. To erase it would be equivocal to killing the autist.

As a pretty high-functioning case, most of my difficulties arise not necessarily from my autism but from the fact that I am an autist in a world populated mostly by non-autists (whose mode of being relies on intuition on empathy, whereas mine consists almost exclusively of sysemisation). Personally, I'd prefer to stay the way I am since it seems that changing that would likely be equivocal to death.

 

[kinglordsupreme19]

While you're technically correct in that there's no inherent link between autism and intellectual functioning (pattern recognition, application of concepts), as measured by IQ, it does make a major impact on how that intelligence can be fostered and utilized. A major part - arguably the majority - of human learning comes from receptive learning by watching and interacting with other humans. Basically our process of knowing things, such as language, comes from bouncing ideas, knowledge, etc. off of one another and building a wider knowledge pool between each other. This is due to what are called mirror neurons, and it has been suggested that autism might be due in part to a disruption or underdevelopment of these neurons. So autism often hinders the learning potential of people who would otherwise be brilliant contributors to society, in the case of autistics with high IQ. I'd argue that IQ is a relatively small part of overall human intelligence, especially when social and emotional intelligence are taken into account. So autism overall, I think, does hinder intelligence, depending on your definition of intelligence.

This is an interesting point. Autists usually end up, even if they have a high IQ, at the bottom of hierarchies because of their inability to convince, collaborate, negotiate, and share ideas. I'm of the school that intelligence = IQ, and 'social and emotional intelligence' are better referred to as intuition and empathy. The consequence is certainly still the same regardless of what you call 'intelligence' (which, as you use it, I would consider to better mean 'capacity to succeed') - autists tend to not be able to enjoy the same fruits of social cooperation as normal humans, which include adequate learning or divisions of labour. So they typically find their natural talents squandered.

But, as I said above, my belief is that autism is inextricably tied up with personal identity in a profound psychological and philosophical sense. You can't just remove it. The best I think we can hope for to solve the autistic problem is possibly screening it out of newborns. Which I don't inherently oppose, since it's clear that social cooperation (which arises from empathy and intuition) does profound good for humans.

 

[ToroidalBoat]

it seems that changing that would likely be equivocal to death.

So you're saying that even if an autistic person had the neurological cause of autism magically removed, they'd still think autistically?

Wouldn't having a "normal" brain after a "magic cure" allow them to change their thinking and develop differently afterwards?

 

[kinglordsupreme19]

No, I was trying to say that the removal of the neurological cause of autism would wipe away the identity of the agent.

Imagine if you developed a benign brain tumour a few years ago (without your knowledge), and that said tumour had completely changed your interests, personality, way of seeing the world. If we wish to locate the self in psychology, it seems that removing it would be equivocal to killing the patient. For another example, consider the Phineas Gage case. Phineas Gage changed extensively after losing a large part of his brain. Imagine if we were able to correct the damage ten years after the damage, and he had stabilised into his new personality. It would be likely that we would be wiping away that 'Gage' and replacing him with a new 'Gage'.

Or, even more so, imagine taking a healthy person and rewiring their brain such that their interests, passions, personality, and capabilities were the complete opposite of that of the person who came in. That's what people propose when they argue we can 'cure' autism (rather than the conditions it's often comorbid with); we could have a new agent after that, but we have effectively killed the old one. So the person who occupies the body that belonged to the autist could develop normally, but they are no longer identical with the autist (unless we wish to claim that personal identity is found in something non-psyschological, which seems counter-intuitive to me).

 

[Broseph Stalin]

This might be the doomsday weapon that destroyes /pol/. Anyone sperging out over this yet?

 

[Wallace]

While I don't think it's going to happen any time soon, I still wouldn't rule out the possibility of the neurological causes of autism being treatable someday.

@kinglordsupreme19 , if I may ask, have you ever been on any SSRIs? And if so, when and for how long?

 

[kinglordsupreme19]

@kinglordsupreme19 , if I may ask, have you ever been on any SSRIs? And if so, when and for how long?

3-4 months in 2016 (well after diagnosis, was diagnosed as a child). Prozac/fluoxetine. No noticeable effects, although I probably only was fully consistent with dosage for around a month and a half. If they did produce a change, it would be unsurprising if I didn't notice the effects; autists often have difficulty identifying all but the most extreme changes in mood (imo an interesting connection to the empathic deficit - the same mechanisms that are used for empathic recognition of others may also be used by the self to identify mood). I'd be interested in taking them again in the future, however occupational reasons are preventing me from doing so at the moment.

Ironically I think I may be a case where maternal SSRI intake contributed to my case. My mother popped and pops those pills like candy.

Why'd you ask?

 

[Wallace]

Just wondering. SSRIs have been shown to affect neuroplasticity. When I have some time, I should read up on the neurology of ASD.

 

[The Great Chandler]

Welp. It's been a wild ride. I anticipate the close down of this forum.

 

[kinglordsupreme19]

Just wondering. SSRIs have been shown to affect neuroplasticity. When I have some time, I should read up on the neurology of ASD.

This is a good overview.

https://www.omicsonline.org/open-ac...tism-a-review-1234-3425.1000113.php?aid=31135

 

[ToroidalBoat]

No, I was trying to say that the removal of the neurological cause of autism would wipe away the identity of the agent.

I'm still not convinced autism is so ingrained that curing it kills off an autistic person's entire identity and completely changes who they are.

I still think if one were cured of autism, the person could still have their memories and personality. But the way of perceiving the world could be changed. From then on they could develop skills that were previously impaired. Interests and personality could change, but naturally as a result of the new way of perceiving.

 

[kinglordsupreme19]

I'm still not convinced autism is so ingrained that curing it kills off an autistic person's entire identity and completely changes who they are.

I still think if one were cured of autism, the person could still have their memories and personality. But the way of perceiving the world could be changed. From then on they could develop skills that were previously impaired. Interests and personality could change, but naturally as a result of the new way of perceiving.

Definitely not their personality. Autism is necessarily a condition which causes unusual emotional and behavioural responses to fairly common stimuli, and all definitions of personality take it as the set of emotional and behavioural responses to stimuli. Thus, autism seems to be integral to the autist's personality.

I think the premise that I made - that rather than being a mere impediment, autism is an aberrant wiring of neural circuitry - suggests that the only way to cure autism is to radically rewire the brain rather than just change a few 'problem areas' such as those related to perception.

 

[TowinKarz]

I think you'll see what you saw when a lot of first-generation psychotropic medications were invented.

Everyone thought "A pill that makes the schizophrenic not hear voices anymore? This is wonderful, mental illness is cured!"

And what actually happened was, it wasn't making the voices go away selectively. It was "deadening" the part of the brain that generated those. And unfortunately, that part of the brain was responsible for other functions too, and those who took them found the trade-off for not hearing voices was that they suddenly couldn't function, either, losing the ability to do their jobs, or enjoy their hobbies, or do much of anything except vegetate in a chair until the dose they took wore off.

It's why so many people with mental illness who went on those meds in the 60's and 70's just as rapidly went off them, they didn't want to be insane, but they also didn't want to be sane and non-functional to the point they might as well be a potted plant.

"removing" autism I suspect, would have a similar result, you wouldn't be "autistic" after the treatment, you'd just be messed up in a different non-autistic way.

Think of having autism as having a favorite color... the "treatments" don't make you not have that favorite color anymore, it just removes your ability to see it, the underlying personal predilection for it cannot be removed from the brain by a pill or a therapy, the best you can do is find a way to make it so devotion to that color doesn't consume your life.

 

[ToroidalBoat]

[...] suggests that the only way to cure autism is to radically rewire the brain [...]

Do you think the amount of change could vary with the severity of the autism?

 

[One Man Bland]

"removing" autism I suspect, would have a similar result, you wouldn't be "autistic" after the treatment, you'd just be messed up in a different non-autistic way.

Eh, I don't think the effects of schizophrenia medication to potential treatment are really a fair 1:1 comparison.

While a schizophrenic's are the result of certain functions of the brain are put into overdrive, autism is mostly the result of parts of different parts of the brain not communicating properly. Or even flat out non-responsive in the cases of severe autism. While still not an accurate comparison, curing autism would kinda be more in the opposite direction of schizophrenia where instead of finding a way to gets sections of your brain to calm the fuck down, a lot of studies to treatments regarding autism seem to suggest the most effective methods would be encouraging an increase in neural pathways between areas of the brain that show a deficit - which at the moment can't be treated with medication.

 

[Fork Cartel]

ITT: People desperately grasping at straws in vain hope of a ‘cure’ for autism.

Face it. It’s just like the upthread posters have pointed out. There is no postnatal treatment for a fundamental effect of brain structure, and there’s no guarantee that the cure wouldn’t be worse than the disease even if it did. The best we’ll likely ever be able to do is screen fetuses early enough to switch it for another embryo.