How brain organoids are revealing what truly makes humans unique

Since Madlin Lancaster for the first time created organoids of the brain Back in 2013They have become widely used for brain research around the world. But what exactly are they? Are they effectively miniature brains in dishes? Can implantation in animals create super-scart-mossy? How close are we crossing ethical lines? Michael Le Page visited Lancaster in his laboratory in the MRC laboratory on molecular biology in Cambridge, Great Britain to find out.

Michael Le Page: Can you explain what the brain organoid is? Is this a mini-Moscow?

Madlin Lancaster: They are not at all miniature brains. And there are many different types of organoids. The human brain has many parts, and we make an organoid of one part, or maybe a couple. They are very small, as well as immature. They are not like a fully functioning human brain with memories. In terms of size, organoids are similar to insects. But they do not have enough organization that the brain of insects has. I would probably place them below insects.

How did you come to grow the first organoids of the brain?

I began to work with the embryonic cells of the mouse brain, covering them in a Petri dish to allow them to grow. Some of the cells did not adhere to the dish, as they should. They went out and began to attach to each other, forming these beautiful, self -organizing cell balls, which are similar in the early stages of developing brain tissue. Later we were able to do the same with the embryonic stem cells of a person.

Why is the creation of brain organoids with such a big breakthrough?

The human brain is special, it makes us those who we are. It remained a black box for a very long time. If we look at the mouse, we simply cannot capture all the complexity that is the human brain. Organoids of the brain suddenly opened the window into this black box.

Can you give an example?

One of the first things that we did with the organoids of the brain is to simulate a disease called microcephaly, where the brain is too small. In mice, if you introduce the same mutation, you have no effects on the size of the brain. We decided to see if we can see a decrease in the size of the organoids of the human brain. We could – and we could learn anything about the disease.

What are the most important things we still learn from the organoids of the brain?

We began to understand what makes the human brain unique. I am really excited that human stem cells that cause neurons behave differently than that of a mouse or even chimpanzee. It seems that we are developing much more slowly. Stem cells have a longer time to expand and generate more stem cells, and therefore we get many more neurons.

Will such a work have practical application?

Many of the fundamental biology that we do has important consequences for the treatment of diseases. My laboratory is mainly focused on evolutionary issues on genetic differences between people and chimpanzees. But the genes that jump out, participate in human disorders, which makes sense, because if anything is important for the development of the human brain, then if it is mutated, this will probably cause a brain disorder.

What do you think will come out of this?

In the immediate extent, we will see how the organoids of the brain are used to screening drugs. I am especially excited by mental disorders or neurodegenerative diseases, where we do not have new methods of treatment. I mean that we are still treating schizophrenia with 50-year drugs. Organoid models brain models can, I hope, give us several new receipts. In the long run, organoids themselves can be therapy. Maybe not for all areas of the brain, not for the hippocampus or our frontal lobe, parts of the brain that store our memories and make us those who are. But with things such as dopaminergic neurons in black substance, which is lost during Parkinson's illness, we could make organoids, and then transplant them.

I understand that the organoids of the human brain are already implanted into the brain of animals?

Yes, not like therapy, but to improve human organoids. Organoids lack the vascular network, and they lack other types of cells that go beyond the brain, especially in microlytes, which are immune cells of the brain. Thus, to see how these other cells interact with the tissue of the human brain, other groups began transplantation of organoids on mice.

Should we worry about inserting organic organoids into the animal?

The function of the neuron is to connect with other neurons. And therefore, if you put the human organoid in the mouse brain, you begin to see these cells connecting to the mouse. But they are simply not organized. After transplantation, these mice work worse during cognitive measurements. As if you were briefly planned for their brain. Thus, you do not make super-smart-mash.

Can we get to the point that this improves knowledge?

We are quite far away. Our higher order thinking is related to how different parts of the brain are connected, how individual neurons are connected to each other, and then, as groups of neurons are connected to other groups, and then with how all areas of the brain are associated with other areas of the brain. This is about all this structure. Therefore, if it becomes possible to generate something, which is organized in this way, it can be. But you are still encountering problems such as time. The mouse lives only for about two years, but in order for people to become very smart creatures. And one more size. The human brain is so amazing because it is so large. You cannot enter the brain the size of a person into the mouse. So for many such questions, I think, we probably do not need to worry about them in the near future.

When it comes to size, a large limit is the absence of blood vessels, which means that organoids begin to die when they are only a few millimeters on the diameter. How much progress is achieved when overcoming this limit?

I do not want to understand what we did, but it turns out that the brain tissue is actually quite easy to do. It is developing. The vascular network is much more complicated. People began to achieve success with the introduction of vascular cells. But getting real functional perfusion of blood is still quite far away.

When you say far …

I would say for decades. It seems that this should not be so heavy, right? The body does it great. But this is the whole body working together, so, in fact, if you want to suck the organoid, he needs the body. We are not going to generate the whole body in the dish in the near future.

If we manage to achieve this, is it possible to create a full -size brain?

Even if you had a fully formed, vascularized large human brain that develops in a dish, if it has no input or exit, he has nothing to think about. We know that if the animal's eyes are closed during development, and then open later, the eyes still work normally, but the brain cannot interpret visual input, and the animal is functionally blindly. This applies to all feelings and to everything that we interact with in the world. I would say that you need a body at some moment in your development in order to be conscious. There are patients who lose touch input and experience blocked blocked syndrome, and this is terrible. But these are people who had a body, developed ties with loved ones. If the brain has never experienced anything, then he has nothing to think about.

As brain organoids become more advanced, how can we say where this line should not cross?

The field can be quite attested, as you determine and measure consciousness. I’m not sure that we will ever get consent about this, because I don’t even know if you are deliberately – everything I know, I am. But we can say that there are other things that we can measure, which are necessary for consciousness, such as organization, input and output, maturity and size. Many of these criteria can satisfy the mouse, but we do not believe that it has the same level of consciousness as a person, and most of it is a size. Therefore, even if we make human organoids that are completely connected, if they are small, they will not have consciousness at the level of a person. These types of criteria are a more practical way than an attempt to measure consciousness.

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