Episode 80: How do scientists study the brain?

In this episode Dr Bahijja Raimi-Abraham dicusses how scientists study the brain with Professor Alysson Renato Muotri, a professor at the Departments of Pediatrics and Cellular & Molecular Medicine at UC San Diego.

This episode is sponsored by the Black Dementia Company (see the bottom of the article for more details).

Dr Bahijja: Tell us a bit about yourself?

Prof. Muotri: I am part of the faculty at UC San Diego, but I am actually from Brazil. After I finished my PhD in Human Genetics, I moved to California to complete my post-doc in neurosciences and stem cell biology. I eventually decided to stay and established my lab in 2008, and have worked to apply stem cell technology for new applications.

Dr Bahijja: How did you become interested in studying neurodevelopmental disorders and autism?

Prof. Muotri: My interest was very academic, I was very interested in our evolution. When you start looking more at the human brain, you come to realise that we have evolved to be very social. Even compared to other species, we have unique social relationships that are distinct from other social species, such as bees. This is really due to our very sophisticated frontal cortex. One way geneticists will approach this is to actually look at what you might call “mutants” or [essentially conditions that do not follow typical human social behaviour] — that is what initially drove my interest in autism.

Autism is difficult to study as there aren’t any non-human or animal models or autism that we can use in a lab, and as well, it begins during the development in the womb. [Therefore, I cannot simply use mice for my experiments, nor can I get children in the process of developing as it would not be ethical]. So, I have had to find a different approach using stem cells, derived from those with autism.

Using these cells, we develop what are called “organoids”, or small models for organs (in this case, the brain). Using stem cells from those with autism allows us to create a model that closely resembles the early stages of neurodevelopment in individuals in autism and compare it to neurotypicals. That is really the bread and butter of my research.

What is a “neurotypical”? A neurotypical person is an individual who is considered to behave, think, develop and otherwise act normal in the ways defined by society. It is often used to describe individuals without mental illness or neurodevelopmental disorders. Another term for those without autism is “allistic” or “allistic people”.

Dr Bahijja: What is the process of developing organoids?

Prof. Muotri: First, when I started my research, I needed consenting individuals to study. For this, I needed to recruit people to get live stem cells. Usually these are skin cells or dental pulp cells, and we can reprogram them to become pluripotent stem cells. These are similar to embryonic stem cells — and after reprogramming, they are essentially a naive cell with no identity. We can then instruct the cell to become whatever we want, including specific cells within the brain (such as neurons or glial cells). The cells already know what to do and will self-organise, we just need to give them the instructions, and I find that really fascinating.

Dr Bahijja: Is there a risk of this technology being used in an unethical way?

Prof. Muotri: Yes, that is a risk really for any emerging technology, and especially with stem cells. We are always in touch with our IRB board, an ethical board that oversees our research that helps and guides us through our process, to really help us avoid any unethical or borderline unethical issues in our research. In our consent forms we really outline everything we might possibly do with the cells, such as send them to our colleagues, genetically modify them, etc. to make sure the cell donors are aware.

Dr Bahijja: How are organoids different from actual human brains?

Prof. Muotri: That is a great question — I am not a big fan of this nomenclature or this idea of organoids being “mini brains”. We are really far from anything close to that, to be honest. The human brain has over 86 billion neurons, any organoids only have 2.5 million. We also do not have every single cell type — for example we lack many immune cells types (or often any). The brain is also not connected to any other tissues, it does not experience any stimuli in the way a brain does, etc. It is improving over time and many of these limitations will go away, but it is a balance. [It is really more accurately described as a model, meant to mimic the brain, and less of a “mini-brain”.]

Dr Bahijja: Do you think organoids could develop consciousness?

Prof. Muotri: If you had asked me that about that maybe 5–10 years ago, if an organoid could develop consciousness, I would have said definitely no. However, now, I am really unsure. As we develop better and more complex organoids, there is a possibly they could reach consciousness and self-awareness, which brings new ethical concerns. It would be very hard to prove this, however, as there is no universal agreed upon definition of consciousness. There are a couple tasks, however, that me and other colleagues have thought up to perform to determine if the organoid has reached a conscious level.

[Something to keep in mind, is we actually do use animals, which are conscious, very widely in research]. It is possible then, if organoids do become conscious, that they may just be regulated in a similar way (for example, the number you can grow, what you can do with them, disposal methods, etc.). […]

Dr Bahijja: Are there other organs with similar ethical considerations to the brain?

Prof. Muotri: As a scientist, to be honest, I see the brain very similar to the liver or any other organ. The beliefs do change overtime — think about how we used to think the consciousness and the self was contained in the heart. We still say “I love you with all my heart” not “all my brain”. The value we assign to different tissues and organs changes overtime. I mean, individual tissues have no worth on their own, the liver and the brain (and other organs) need all the other tissues to work. There are even theories that consciousness is only possible due to inputs from other tissues, [such as the nerves in our hands, eyes and nose that provide sensory inputs].

To learn more about this episode’s sponsor, the Black Dementia Company, check out their website here or check out shop.alzheimers.org.uk.

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