I’m Dr. Alysson Muotri. I can take your stem cells and turn them it into a miniature version of your brain. I use them to help people with neurological disorders like autism and to explore what make us unique. AMA.
Hi Reddit! From May 30-June 2nd, I'll be working on Mainly Mozart's "Mozart and the Mind" series in San Diego which seeks to highlight the genius on every brain. I'm speaking about the differences we observed in autistic brains and how this information can help these individuals to have a better quality of life.
I'm a neuroscientist and professor at UC San Diego School of Medicine, heading the Moutri Lab. We develop protocols to turn stem cells intro brain organoids. These “mini-brains” can be derived from people like you and me, so we can have our own brain avatar in the lab. We use them to understand why the human brain is so unique and to help people suffering from neurological conditions, like autism.
Tickets and info are available here: https://mainlymozart.org/mozart-the-mind-2019-calendar-events/
Further details are available here: https://mainlymozart.org/mozart-the-mind-presents/ Excited to get started!
EDIT: Had such a blast answering all of your questions! I have to run for now, but will do my best to pop back in and answer more today and tomorrow. If you're in San Diego, please check Mozart and the Mind out! If you'd like to stay in touch, you can follow me on Facebook here -> https://www.facebook.com/muotri/
ha! no, but that's a good one!
How does a mini brain cloned from stem cells help those with autism?
What causes autism?
A major factor that causes autism is genetics. However, the genetics is complex, as more than a thousand genes are implicated in the condition.
We can compare how the neuronal network is affected in minibrains derived from autistic individuals to a neurotypical group. We previously found that the "autistic networks" develop in a distinct way. We are learning how we could help that by testing approved medications in these minibrains. We hope to find therapies that are more efficient and specific for people on the spectrum.
Have you damaged a neuronal network and tried to reroute or regrow that section?
yes, it worked in the lab.
As a thing to add about genetics. Apparently the social traits of autism are linked to different genes than non-social traits. Basically, genetically speaking you wouldnt consider autism a single disorder.
correct. There are many different conditions under the umbrella of autism. That's why we call it "spectrum of autisms".
Hello! I’m curious, when you make a brain organoid, is it possible for them to be sentient? Do they display signs of consciousness? How would you look for the signs and record them, if they exist? Also good luck on your research, it’s amazing!
This is a great question and we don't know yet. We are designing experiments to test this possibility. Stay tuned.
I am a high functioning person on the spectrum. I also have Ehlers-Danlos Syndrome and untreated chronic pain. Have you(or anyone you know) done any studies about the differences connective tissue issues can have on the brain or the impact of untreated chronic stimulus(pain in my case, but I assume most stimuli would have an effect) on the development of a brain over time?
Edit: I just wanted to say it is both nice and terrible to see responses from so many people in similar situations. I look forward to reading that dissertation on the 28th and hope that more research will be done in the future on the potential relationships between ASD and other heritable syndromes- specifically but not limited to EDS. If anyone want to contact me please feel free to do so here or on Discord with a DM. I am Daukash#0001 on Discord.
Great question. This is unexplored as far as I know.
How often do you have to deal with anti-vaxxers?
All the time. I hope science education will prevail eventually.
You you believe that if we develop the technology continuously patch the brain, the old portion will continue to rewrite the new parts, much like raid drives when one fails, effectively giving us the ability to replace much of the brain while remaining the same person?
That's an interesting question. I think we can design an experiment using the minibrains to answer it. As for now, I think my answer will be speculative.
What considerations have been given to the potential ethical issues? Such as: is there a threshold in the complexity/scale of these "mini brains" at which point they could be considered alive/feel pain etc.?
We discuss these issues all the time in the lab with my group. Since this technology is quite new, there are many unknowns. However, I must stress that everything we do has to be approved by an ethical research committee. As the technology evolves and we learn more about it, more ethical issues are to appear. That's why is important to let the society know what we are doing inside the labs. BTW, in Oct at UCSD we will have a big symposium to discuss the ethical implications of these mini-brains, stay tuned!
Do you have any idea as to whether these little brains can help other neurological issues, like TBI or chronic migraines? Or is the primary use and focus on mental illness as opposed to physical?
Yes, we have some other projects in the lab. Migraine is one that we are just starting.
Is cord blood storage a useful practice for parents to protect their children against the possibility of a future disease that can be treated with stem cells? Or is it $125 a year down the drain?
Cord blood can be used for diseases like leukemia. The clinical use for other conditions, including autism, is still experimental (in clinical trials now). So, if you have a history of blood disease in the family, I would highly recommend it.
Aside from spending time exercising, mindfulness, and practicing a healthy lifestyle, what are other things that may not be as commonly known that someone can routinely do to help strengthen mental health or combat depression? I'm not at all knowledgeable about neuroscience but I am curious whether there is any correlation between stem cells and brain plasticity and maintaining strong mental health?
Yes, socialization. If you can combine your exercise, mindfulness and healthy lifestyle with a better social life, your brain will love it. Our brains are programmed to be highly social.
As i am on the spectrum, i know aspergers has its strong feats. Do you see a possibility that in the future we can 'take out' the downsides like decreased social capabilities and keep in the good stuff?
That's exactly my goal!!! If we understand what are the network defects related to the downsides, we can design specific treatments for that, leaving out the good stuff.
Hello! In one of my neurobio courses in undergrad, I learned that autism is oftentimes caused by an excess of synaptic connections, and that some of these connections are not "pruned" or trimmed during early development, which can lead to autism. Would there be any way in the future to treat this during early development?
Yes, the idea of not pruned connections is still a theory and might be true for a fraction of autistic individuals. We believe, our minibrain technology can be used to find treatments that could help to compensate for this lack of pruning during early days. In fact, others have shown that autistic-like symptoms in adult mice could be reversible. There is no reason to believe otherwise for humans. We just need to learn how to do this.
Are there any potential applications for stem cell therapies in patients with relapse-remitting MS?
I am not aware of any. I don't think so.
How easy are stem cells to get?
Easy but time-consuming and expensive.
How do you use this application to help autism? As someone that struggles with autism, I'm quite interested in hearing what it could do for somebody like me.
We compare how the neuronal network is affected in minibrains derived from autistic individuals to the neurotypical group. We found that the networks develop in a distinct way. We are learning how we could fix that by testing approved medications. We hope to find therapies that are more efficient and specific for people like you.
Curious as to what inspired you to pursue this work?
Initially, I was interested in finding what makes the human brain so unique compared to other species. Our brains are incredible from the perspective of socialization and technology. However, we don't have human models, thus, I decided to use stem cells to create one. Later, I become the father of an autistic boy. He is now my major inspiration!
My step-son inherited a genetic disorder called "Fragile-X". Is there any chance gene-therapy or stem-cell treatments might one day help him or others with this malady?
Yes, we do have minibrains from Fragile-x individuals and we are currently testing a novel drug treatment and a potential gene-therapy approach. It is early days but looks promising. fingers crossed!
How valuable do you think stem cell research is and will continue to be in the future?
This is a very powerful technology, we are just starting to learn about it. The future is very promising for stem cell research. There are many fundamental research applications and clinical trials going on.
Could AI ever truly be conscious?
There is a huge debate about this topic. Right now, I don't think we are close to that. However, if we modify AI to learn how the organic brain does, then I think there is a possiblity.
What does a mini brain look like? Is it cells in a petri dish? Or are we talking mini brain in a jar type thing?
In a petri dish. They look like small white balls floating in a red solution. You can see them at naked eye. They reach 0.5 cm by 6 months of age and you can keep them alive for years.
I hadn’t heard of this before. Do you know of any other labs that are using stem cells in a similar way to help people with schizophrenia?
Yes, there are. We do have some schizohrenia-derived mini-brains in my lab too. I like to compare them with the ones derived from autistic individuals.
My whole family has Autism Spectrum Disorder to some extent. Clearly it’s genetic, but are their any “nurture” elements that can be used to treat autism? Or does the whole thing stem (forgive the pun) from the “nature” side, including treatment
Thank you for the work you’re doing
Although the genetic factor is quite strong in autism, it is not deterministic. Therapies, like ABA, have shown that the autistic brain is still very plastic. Moreover, our own data suggests that, in the right environment, even neurons with severe genetic alterations can thrive. The challenge is to translate this to the real world. Keep your heads up, we will see better treatments for autism in the coming years.
Have you tried giving cerebral organoids psychedelic compounds like psylocybin or LSD?
What would be the possibility of using stem cells to regrow certain parts of the brain that may be damaged, like an optic chiasm that was damaged removing a glioma?
Yes, this is regenerative medicine. I do think we will be doing this in the near future using cell reprogrammed from the patients.
What are the notable result differences between male/female duplicate brains if any; are there notable differences between blood types?
We have not explored yet, differences between male and female. We see no differences regarding blood types.
What is your feeling about using CRISPR/cas9 on children to prevent diseases in the future? Do you think it is feasible?
Yes, this is a very promising technology. However, we are not quite there yet. The current enzymes have off-targets and in the next years or so we will learn to make it better. There is no return for this application in medicine.
can you make tiny clone humans with those brains?
These minibrains are actually clones of the real ones. So, if I use your cells, there will be your minibrain in my lab because the cells capture your genomic content.
What if my microbrain is secretly concious and I could be dooming them to a existence of torture like that Black mirror episode with the bear
It is hard to determine if a minibrain is conscious or not. We are testing some possibilities. If yes, scientists and ethicists will need to work together to create rules for their use, the same as we did with animal research.
Have you ever heard of Rett Syndrome (genetic mutation in the X chromosome of the MECP2 Gene) and if so would this type of research be beneficial in finding a cure?
Yes, we do have models for Rett sydnrome. and MECP2 duplication syndromes. Check this out: https://health.ucsd.edu/news/releases/Pages/2015-09-08-stem-cell-derived-mini-brains-reveal-drug-target.aspx
Are mini brains unique to each persons stem cells that were used to create it?
Ok that sounds amazingly cool and scifi. What is the most unexpected development from this technology?
We don't know how the human brain is formed during early stages in utero. To me, the most unexpected development is to learn how organic human innate intelligence is born. With this information, we can make AI more human-like! My lab is working on this as we speak!
Please install something like Asimov's Laws of Robotics!
A human-like AI sounds like it could also be disturbingly human-like in cruelty and capacity for wanton destruction.
(But seriously, that's awesome! We really do live in the future now)
All technology can be used for good or bad. It is up to us to guide it. You might enjoy this article: http://blogs.discovermagazine.com/crux/2018/11/02/lab-grown-brain-organoid-robot/#.XN13tC_MxBw
Hi! Is there any way this could also help people with Epilepsy? If yes, how so?
Yes, we have created minibrains from people suffering from epilepsy and we are now testing if they show any sign of seizures. then, we can test drugs to block that. What I like about this, is the possibility of personalized medicine, ie, creating drug combinations that are specific for the individual.
How common are savants? What causes an autistic person to be a savant as opposed to low-functioning?
Savants are rare. There are several theories about what causes an autistic person to be a savant as oppose to low-functioning. To me, the most attractive idea is about genetics, the genes that are mutated in one vs the other.
Do these mini brains have a conscious?
Likely not but we have not formally tested it yet.
is there a possibility in future that whole brain be replicated??
Can memories also be recreated??
I love this question. I don't know. The brain is formed in uterus with input and output from other organs and tissues. Our current technology can create minibrains with no other body parts, yet. As the protocols evolve, we will need to add stimulation so the brain can record memories. For this to happen, we need first to recreate a fully functioning brain with all regions (cortex, hippocampus, etc).
Can I send in a sample like those dna heritage tests and you send me back a little mapped out version of my brain?
no. We actually need live cells to create an avatar of your brain in the lab.
have you had any practical break throughs? for example have you been able to mitigate TBI by promoting new brain cell pathways? Any effective treatment of CTE to reverse brain atrophy? Anything like that? Having a miniature brain in the lab is cool and all... but.... you know.... not very tangible results for us non brain scientists....
Oh yes. Recently, we create a minibrain model for Aicardi Goutieres syndrome, one of the most dramatic neurological disorder. Guess what, there is no animal model for this condition, so progress was not made for this condition. With our human model, we could generate minibrains from them, find what causes the problem and developed a treatment that is currently in clinical trials. You can learn more in this short video: https://www.uctv.tv/shows/32743
Are you familiar with the neurological condition Misophonia?
Some research suggests it might have some relevance or connection with autism?
Any insight would be greatly appreciated.
Yes, misohphonia, similar to other synesthesias, is likely caused by mixed sensorial connections in the brain during development. Some theories suggest that a fraction of autistic individuals might have different forms of synesthesias in different levels.
what are the main differences between a brain organoid and a regular brain?
These minibrains or brain organoids, are smaller so they don't have the same number of neurons. They are also not vascularized and they grow in the absence of a body, so they are not connected to anything. They are very different from the real brain, they are a model. Even with all these limitations, it is a useful model for science.
Probably a dumb question but how do you know that the stem cells turn into a miniature version of the donor's brain? Couldn't it turn out differently?
Yes. althought these minibrains do capture the genetic information from the donor, the way they develop is different from the real brain. So, all the data must be analyzed with this limitation in mind.
This is amazing and also very complex stuff. When you were a child did you like to play with Jigsaw Puzzles?
For conditions that are neurological but physical manifestations like tinnitus and visual snow can we expect any success in the field of fixing these often rare tricky neurological problems?
Yeah, absolutely. One application we have going on is to connect these mini-brains with mini-retinas, to study how the visual cortex is formed. We hope this will be platform to study these neurological conditions and ways to fix it.
Where do you see this research helping in other brain fields? TBI/PC's?
Absolutely, this technology can be used to study and help many neurological conditions.
Yes, virtually, all neurological conditions could be modeled by this technology.
Have you done any studies on narcolepsy?
not yet. A very interesting topic though.
As someone on the spectrum, I'm rather interested in what actually makes my brains tick. What differences in structure do you usually look for?
We have noticed some alterations in cell migrations at early stages (embryonic, fetal stages). There are also alterations on the morphology of the neurons. They look less arborized, more like immature neurons when compared to the same stage from neurotypicals. The good news is that none of these differences are permanent and could be reversible (at least in a dish).
Has Cartman ever offered you some aborted fetus’?
Funny, but a nice opportunity to clarify something! Scientists on serious academic institutions have constant ethical board supervision. Fetal material is a sensitive subject and regulated in many instances, as it should be.
Hello, what's the processing power of "mini-brains" and can we one day surgically insert, or even stimulate further growth of, a "mini-brain" directly onto our own?
We are still learning what is the processing power of these mini-brains. Our data indicate that they follow what is expected for human development so a 6 month old brain organoid might have network similarities to a newborn brain: https://www.spectrumnews.org/news/mini-brains-show-realistic-neuronal-firing-rhythms/
We are now stimulating them to see if we could improve the maturation. Regarding creating a mini-brain directly onto your own, I would say this is possible but might be dangerous because we don't fully understand how it will connect with the host brain.
Is it possible for the tiny brains to experience anything at all themselfs?
We don't know yet. I think it might be possible if we have the right conditions.
What cells need to be replaced/added in the brain to affect autism?
Autism is not a neuro-degenerative condition. We don't see cells that are dying or need to be replaced. The neurons are there, we just need to find ways for them to work at their best. We can do this by providing a nice environment for them, for example, using medicine that improves synaptogenesis (brain cell connections).
Are these new medications that you’re trying or one that are already on the market but used in a different way.
yes, some are, others are novel.
How do you extract the initial stem cells?
We "reprogram" somatic cells, such as your skin or hair cells. This cellular reprogramming is a simple step by activating 4 genes in any cell type and making them behave like embryonic stem cells. From them, we developed robust protocols to make minibrains.
what did you study to end up with this career?
Biological sciences as an undergrad and human genetics for my PhD. My postdoc was on stem cells and neurosciences.
You think your better than me ?
For laughs, do you ever turn to a lab assistant and cackle "Igor, fetch me the brain?"
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