Brain organoids are 3D, lab-grown models designed to mimic the human brain. Scientists often grow them from stem cells, combining them to form a brain-like structure. In the last decade, they have become more sophisticated and are now able to reproduce many types of brain cellswhich can talk to someone.
This has led some scientists to question whether brain organoids can achieve this mind. Kenneth KosikA neuroscientist at the University of California, Santa Barbara, recently explored that possibility head of vision. Live Science spoke with Kosik about how brain organoids are made, how similar they are to the human brain, and why he believes that the mind of the brain won’t be possible anytime soon.
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EC: What are brain organoids, and how do scientists make them?
Kenneth Kosik: The brain organoid is made of stem cells. You can take any person and turn skin fibroblasts into stem cells, then differentiate them into neurons. That’s what stem cells are – stem cells are called “pluripotent” because they can make any cell in the body.
We spent a long time before organoid technology came along, taking human induced pluripotent stem cells and putting them in two directions to look at neuronal differentiation.
So that brings us to the middle. But it only gives us two dimensions. And now a great insight, from Yoshiki Sasai Japan and Madeline Lancasterwas to take these neurons that were just beginning to differentiate – cells that are relatively young in development – and put them in a drop of what is called Matrigel – a gel that can be liquid or solid to depending on the temperature.
So the cells are in this drop, and then the magic happens. Instead of growing in two dimensions, they begin to grow in three dimensions. It makes me very happy that when biology starts exploring the third dimension, a whole new field of biology is emerging. Indeed, in two dimensions, these growing neurons could achieve many different types of cells, but they did not achieve any kind of interesting shape.
Once they develop in three dimensions, they begin to form relationships, forms and structures, which bear a very loose resemblance to the brain. And I really emphasize the word “loose,” because there are people who use the wrong name for brain organoids and call them “minibrains.” It is not a brain at all. They are organoids – which means like a brain.
The question that interests us most, and many labs is, if organoids are brain-like, to what extent are they brain-like, and to what extent are they different? And they are very different from the brain, so you have to be very careful with the descriptions of organoids. Not everyone thinks that organoids will help neuroscience because what we get from organoids may be an overstatement. But on the other hand, [it] it forms a three-dimensional structure with some degree of lamination [formation of layers of cells within tissue]it has these roses in which, from the middle of the rosette, you can gradually see the cells grow more and more as development continues, very similar to what happens in the brain.
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EC: Are there brain organoids that capture the whole brain accurately?
KK: No organoid occupies the entire brain. There are methods that try to capture more of the brain than, say, just one area that maybe we and other laboratories are working on. These are called “assembloids.” [Scientists] take the stem cells and divide them in such a way as to make it more ventral [front part of the] the brain, or a bit of the back [back part of the] the brain, and they combine them, combine them, so that you can get a broad fusion – a broad representation, I should say, of the structure of the brain.
There are other ways to make organoids that are more undifferentiated. They don’t direct the stem cells to dorsal and ventral, they connect them all. We do a lot. These are the methods pioneered by Lancaster. And if that’s the case, it’s my opinion that if you do it that way, you get a wider representation of cell types. That’s what you get, but you sacrifice anatomical accuracy because when you make an assembloid, the anatomy isn’t great. But if you do it without distinguishing between dorsal and ventral and put it all together, the anatomy becomes even more difficult.
EC: As you mentioned, these organoids are similar to the human brain, but there are important anatomical differences. Can you explain those?
KK: So, one thing that is common right away is that you see a lot of things going on.
(Editor’s note: Kosik is referring to the fact that, when an organoid is attached to electrodes, this produces electrical spikes, or signals, that are transmitted between nerves.)
It’s amazing, and at the heart of it is the idea, which is probably the most interesting to me, that this whole process is spontaneous: it occurs based on a set of neurons.
And now we can look at the relationships of those spikes. When you do that, you can ask the question, well, if I see neuron A firing, what is the probability that I see neuron B firing? I’m going to look at the binary relationships among all of them and filter them so that when neuron A fires I’ll only look at when another neuron fires within 5 milliseconds. Why 5 milliseconds? Because that’s the time it takes for transmission to occur across the synapse. (Editor’s note: A synapse is a gap between two neurons.)
And when we do that, you can see that they’re creating a network. You put A and B together, then you put C and D together, then A and C. You can see that the neurons talk to each other and this happens randomly.
This is just one example of how an organoid can do something similar to what happens in the brain.
The way I look at an organoid, it’s a vehicle that has the ability to embody experience and information if that experience were present in it – but it’s not. It has no eyes, ears, nose or mouth – nothing enters. But the insight here is that the organoid can create an independent organization of its nerves in order to have the ability to include information, when and if it is available. That is just a theory.
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EC: Do you think brain organoids will ever achieve consciousness?
KK: So that’s where things get weird. I think these kinds of questions are based on this word that people have a lot of trouble defining: knowledge.
[Based on currently fashionable theories of consciousness] I would say, “No, it doesn’t get any closer.”
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EC: You talked about the fact that organoids have shown some ability to encode information, but they don’t have the experience to do this in the first place. What would happen if, hypothetically, a human brain organoid were transplanted into an animal? Can it now reach the mind?
KK: Let’s not spoil that. Before it is implanted into an animal, some people would say that the animal already has a mind and some people say [it does] not. So, immediately, we run into this problem of where does consciousness begin in the animal realm? So, let’s rephrase the question. Now if you were to take an animal, which may or may not be conscious, and put it into a human organoid, would you give that animal a sense or would you I can develop knowledge, or you can find something similar to the human mind. an animal? I don’t know the answer to any of those questions.
We can make these hybrids now – so that’s a good question. But psychoanalysis now, because of all the problems of what psychology is, is still going to be an open question.
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EC: Do we have an idea of hard times – is it something that might happen soon, after, say, a certain number of years, or is it still uncertain at this point?
KK: Technology moves very fast. One place where we can start to push the limit is in the so-called cyborgs, organoid junctions. That might be one direction that might be interesting. Perhaps less about awareness, but more about developing the application of human potential in one of these artificial systems.
EC: Can you think of some obvious advantages and disadvantages of these organoids being able to achieve consciousness?
KK: We know very little about neuropsychiatric conditions. Neuropsychiatric drugs are developed without understanding any deep physiology. All this can be done, I think, with organoids. I think that as examples of diseases, they can be very useful [for them to achieve consciousness].
The dream state I have is to develop them as computer systems because, right now, to do the very expensive computational models that are required for ChatGPT and many of these large language models, these are take hundreds of millions of dollars to develop. They need a powerful server farm to continue. We are running out of computing power. However, the brain does a lot with 20 watts. So, the main interest for me is, “Can organoids, if not solve, contribute to the great needs that we what is done in the energy system by using an efficient way that the brain, and perhaps the organoid, can process the information?”
Editor’s note: This interview has been edited and condensed.
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