Huntington’s Disease
Molecular Neurogeneticist David Rubinsztein on the Kennedy disease, CAG repeats, and autophagy
I am a mammal. You are a mammal. Everybody here, in this room, is a mammal and possibly many people watching this video are mammals. I am very happy to be a mammal: who wants to be a toad, or a fish, or a worm? We, mammals, are very successful animals. We, mammals, captured the whole globe: wherever you go on this earth you will see mammals. You will see them in the Arctic, you will see them in the sea, in the jungle, in the woods and in the water. And wherever we, mammals, are we are very successful.
Why are we so successful? The reason is possibly very simple: we, mammals, are very smart animals. Our intelligence is a function of our brain, and the mammalian brain is a very different one from the brains of birds, frogs, reptiles and fish. As you possibly know, only we, mammals, have a cortex. The cortex is a fantastic structure of our brain: if you look at the mammalian brain and take a little bit out of it you’ll see that this cortex is divided into different layers, six layers altogether, and that there are different neurons specialized to do different jobs in the cortex. No other vertebrate has such a brain.
The cortex is a fantastic machine because of one architectural feature. All information comes in vertically arranged, so that each nerve cell along that vertical path receives the same kind of information, but each cell processes this information in a different way. When you see a specific color, hear a specific sound, feel a specific touch on your skin, it is analyzed in all details along the vertical dimension. All of this information is then exchanged horizontally with all of the other areas of the brain. You have a vertical arrangement with detailed analysis and a horizontal exchange of information. This is the machine of thinking. I have it, you have it, and this is the reason why we, mammals, are so smart.
This is a theory that emerged about a hundred years ago and since hundred years we believe that this is true, but I will tell you now that this is wrong. Why is this wrong? Because this theory has a certain implication which is that an animal without such a cortex should not be able to be smart because this is the only arrangement that makes animals smart. This is position one of this old theory, but there is a second position: brains have to have a cortex and they have to be large. Our brain is about 1.3 kilogram: it’s a big brain. Most other animals (for example, birds) have very small brains of 5 grams, 2 grams, 10 grams, and they have no cortex, so birds, for example, should not be able to be so intelligent.
And now we have a problem: birds are as smart as we, mammals. Take, for example, crows and ravens. Ravens can plan into the future as good as chimpanzees do. They can combine information logically as good as chimpanzees do. Let’s take another task: are you able to inhibit your motives? What do I mean by that? For example, let’s take two different kinds of food, the one that I like and the one for which I’m crazy. I like the first one but not as much as the second one. Now, I give the animal (a raven, for example) the first kind of food, and the animal has learned that it has to look at that without eating it. It looks, and looks, and looks, and it is not allowed to eat it. How long will the animal be able to constrain itself from eating? Ravens can do that for about ten minutes. When they wait ten minutes, they get the better food and they eat it. Chimpanzees can do that for four minutes only. Grey parrots can do that for fifteen minutes. Our children cannot do that for fifteen minutes.
So all aspects that we call cognition are equal between birds and mammals, and if you take the top birds (parrots and corvids) you can see that they are as intelligent as primates. And now we are back to the brain problem. A raven has a brain of 15 grams or usually even less, about 12 grams. A chimpanzee has 400 grams of brain, so it’s 12 grams versus 400 grams. In these 12 grams the raven is doing the same as the chimpanzee with 400 grams.
So what is the brain of the raven? What we see inside is that there is no lamination, so here we see a small brain that is not organized whilst in mammals we see a large brain that is beautifully organized. How is this possible that an unorganized brain is the better design than our brain?
You possibly want to have an answer to this, but I have to tell you that I’m only giving you half an answer because I don’t know the second half of it. But at least we learned a little bit on this mystery in the last years. First, it seems that in the evolution of vertebrate brains – of bird brains and mammalian brains – both groups started with a primitive cortex with just three layers. We, mammals, doubled the numbers of layers, but birds gave up the layers. Why did they give it up? Now comes the second point: their brain is much denser packed with neurons than our brain. They have about four times more neurons per unit volume. That means that if you take a certain part of the birds’ brain out and you take the same part of the mammalian brain, the same volume, you’ll have more neurons in the birds’ brain. Depending on where you look, the difference can be large (for example, four times) or very small, like two times, but still, it’s more densely packed. So birds have small brains, but they have brains with much more neurons than we expected. The second implication of that is that the birds’ neurons are very close to each other, but the mammalian neurons are far away from each other. So the birds’ neurons can communicate faster with each other because they are very close by.
These are possibly some of the reasons why birds have such superior abilities – abilities that we did not expect from these birds. But the bottom line is the following: there must be more of what makes them so smart, and the majority of this answer I cannot give you yet. But there are two implications of that. First, the next time that you look out of your window and you see a crow, say ‘Hello, feathered chimpanzee!’ It’s a chimpanzee with feathers. Isn’t that beautiful? And it visits you, it’s out there. Secondly, per neuron birds are able to come up with more intelligence then we are able to do, so they have a better design than us. But then you can ask the critical question: why are we, humans, ruling the world, why do we shoot crows and they don’t shoot us? The reason is possibly the following: we have really huge brains, so we might not have the best design, but we compensate the lack of it by sheer size, just by number crunching power of a huge brain. This is how we got smart enough to capture the world. And now imagine another world where birds would have developed large brains and remember that birds are the surviving dinosaurs. The dinosaur with the largest brain was T-Rex: it had 110 grams of brains. Maybe T-Rex was not as dumb as we usually think.
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