Brain Organoids These 3D lab-made models are designed to mimic the human brain. Scientists usually grow them from stem cells and guide them to form brain-like structures. Over the past decade, they have become increasingly sophisticated and are now capable of mimicking the human brain. Multiple types of brain cells,this is Communicate with each other.
This has led some scientists to question whether brain organoids are even feasible. Awareness. Kenneth KosickNeuroscientists at the University of California, Santa Barbara recently explored this possibility. PerspectiveLive Science spoke with Kosick about how brain organoids are made, how similar they are to the human brain, and why he thinks it’s unlikely they’ll become conscious anytime soon.
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EC: What are brain organoids, and how do scientists make them?
Kenneth Kosick: Brain organoids are made from stem cells. Anybody can turn, say, a skin fibroblast into a stem cell and differentiate it into a neuron. That’s what stem cells are all about. Stem cells are called “pluripotent” because they can make any cell in the body.
Before the advent of organoid technology, we spent a lot of time studying neural differentiation by harvesting human induced pluripotent stem cells and coordinating them in two-dimensional arrays.
This is half the battle, but it only gets you to the second dimension. And the big insight is Yoshiki Sasai Japan and Madeline LancasterThe study involved taking neurons that had just begun to differentiate (cells at a relatively early stage of development) and placing them in a drop of a substance called Matrigel, a gel that can become either liquid or solid depending on the temperature.
The cells are in this drop, and magic happens. Instead of growing in two dimensions, the cells start growing in three dimensions. I’m really fascinated by this: when biology starts to explore three dimensions, very new biology emerges. Certainly, in two dimensions, these neurons that are growing can achieve a huge variety of cell types, but the interesting anatomical structures didn’t.
As they grow in three dimensions, they begin to form relationships with each other, structures and anatomy that are very similar to a brain. I emphasize the word “loose” because some people mistakenly call cerebral organoids “mini-brains.” They’re not brains. They’re organoids, they’re brain-like.
The question that we’re very interested in, and that many laboratories are very interested in, is, if organoids are like the brain, how similar are they to the brain, and how different are they? Organoids are very different from the brain, so we have to be very careful in interpreting them. Not everyone thinks that organoids are useful for neuroscience, because what we find in them can be over-interpreted. But on the other hand, [it] It forms a three-dimensional structure with a certain degree of layering. [formation of layers of cells within tissue]The brain has rosettes, and from the center of the rosette you can see the cells gradually maturing as development progresses, which is very similar to what happens in the brain.
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EC: Do brain organoids already exist that accurately capture the entire brain?
KK: There are no organoids that capture the whole brain. There are approaches that we and other labs are working on that try to capture more of the brain, not just parts of it. These are called “assembloids.” [Scientists] Taking stem cells and differentiating them down a path to become a little more ventral oriented. [front part of the] Brain, or a little more dorsal [back part of the] And by combining and fusing them together, we get a more comprehensive fusion, a broader representation of the brain’s anatomy.
There are also ways to make organoids that are a little bit more promiscuous. Instead of directing stem cells dorsally and ventrally, you put them all together. That’s a lot of what we do. It’s a technique that Lancaster came up with. In that case, my opinion is that if you do it that way, you get a broader range of cell types represented. You get that, but you sacrifice anatomical precision because if you make assembloids, the anatomy is not very good. But if you combine them all together without directing them dorsally and ventrally, the anatomy becomes even more problematic.
EC: As you mentioned, these organoids resemble the human brain, but with some key physiological differences. Can you explain them?
KK: So one of the similarities you can see right away is that there are a lot of spikes happening.
(Editor’s note: Kosick is referring to the fact that when the organoids are connected to electrodes, they transmit electrical spikes, or signals, between the neurons.)
This is quite remarkable, and underlying it is the notion that all of this activity is spontaneous and occurs on the basis of an ensemble of neurons, which is perhaps what is most interesting to me.
And then you can look at the relationship between those spikes. And then the question arises: if you see neuron A firing, what is the likelihood that you’ll see neuron B firing? I look at the binary relationship between all of them. And I use a filter that says, when neuron A fires, I only look at when another neuron fires within 5 milliseconds. Why 5 milliseconds? Because that’s how long it takes for transmission across a synapse to occur.Editor’s Note: A synapse is the gap between two neurons.)
And then you see a network form: you connect A to B, then you connect C to D, then A to C. You see neurons communicating with each other, and this happens naturally.
This is one example of how organoids can spontaneously do something similar to what happens in the brain.
My view of organoids is that they are vehicles that have the ability to encode experience and information. But they don’t get experience. Organoids don’t have eyes, ears, noses, or mouths. Nothing comes into them. But the insight here is that organoids can set up a spontaneous organization of neurons and have the ability to encode information as it becomes available. This is just a hypothesis.
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EC: Do you think we will ever see brain organoids acquire consciousness?
KK: So, things get a little bit puzzling. I think these kinds of questions are based on the term “consciousness,” which people have a very hard time defining.
[Based on currently fashionable theories of consciousness] I would say, “No, not at all.”
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EC: You said that we know that organoids have the ability to encode information, but they don’t have the experience to do so. What would happen if we were to implant a human brain organoid into an animal? Would it then acquire consciousness?
KK: Let’s take a closer look at it. Some say that animals already have consciousness before it is implanted in them. [it does] No. So right away we’re faced with the conundrum of where in the animal kingdom consciousness begins. So let’s reframe the question: If you take an animal that may or may not have some level of consciousness and transplant a human organ into it, does that give the animal consciousness, or does it enhance consciousness, or does it give you something resembling human consciousness in the animal? I don’t know the answers to these questions.
We can do these hybrids now, and that’s a good question, but assessing consciousness is an open question right now because there are so many issues with what consciousness is.
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EC: Do you have any idea of the general timescale? Is consciousness something that could happen in the near future, say a certain number of years, or is it still uncertain at this point?
KK: Technology is evolving rapidly. One of the places where we can start to push the boundaries is the so-called cyborgor organoid interfaces. This would be an interesting direction, perhaps getting us a little closer to consciousness, but even more so, to developing one of these synthetic systems with human capabilities.
EC: Can you think of any obvious advantages or disadvantages to allowing these organoids to gain consciousness?
KK: “We know very little about neuropsychiatric diseases. Drugs for neuropsychiatric diseases are developed without a deep understanding of the physiology. I think that with organoids we can achieve all of this. I think they can be very useful as disease models.” [for them to achieve consciousness].
My dream is to develop them as computational systems, because right now, doing the very expensive computations that ChatGPT and many of these large language models require would cost hundreds of millions of dollars to develop. You need the energy of server farms to run them. We’re literally starved of computing power. But the brain does a lot of these tasks on 20 watts. So the big question for me is, “Can organoids contribute to, if not solve, the enormous demands on our energy systems by leveraging the very efficient ways that the brain, and maybe organoids, can process information?”
Editor’s note: This interview has been edited and condensed.
