The brain is a sacred thing, you can't play with it

2024 Author: Seth Attwood | [email protected]. Last modified: 2023-12-16 15:55

Nobel laureate Eric Kandel on memory molecules, lsd for cats, shellfish training, Vienna in 1938 and Syrian refugees.

Freud lived in a neighboring quarter of Vienna, at Berggasse 19, and the future Nobel laureate had every chance to meet him on the way to school. In a biographical film that will sooner or later be filmed, this meeting will surely take place - somewhere in the background, as an obligatory detail of the urban landscape, the father of psychoanalysis with a recognizable beard and a cigar will certainly flash. In 1938, when the Nazis forced Freud to leave Austria, Candel was eight years old.

Candelu is now 87 and continues to work at Columbia University in New York. On the doorstep of his office, he appears in a bow tie over a dazzling white shirt - as if this was happening in pre-war Europe. “I just flew in from Vienna,” he says. And the imagination - automatically, because exactly this time and this place is devoted to "The Age of Self-Knowledge", the last book translated into Russian by Kandel, - slips a picture of Vienna on duty a hundred years ago with its Secession, Klimt, Wittgenstein, Gödel and Webern, where the professors of medicine were who something like concert pianists, anatomical theaters sold tickets for autopsies, and a new fashionable Freudian theory of the unconscious was popular with artists.

Both Freud and Kandel were engaged in memory throughout their scientific careers - each in its own way. What is our psyche made of? For Freud - from complexes, suppressed fears, repressed memories. For Kandel - from a prion-like CPEB protein, suppressed gene expression and jumps in the concentration of enzymes called "protein kinases" in the processes of nerve cells. The science of the 1930s and 2010s speaks different languages about the brain, but Kandel is fluent in both.

Neurophysiology interested him at the university primarily because it gave him a chance to solve the problems of psychoanalysis. “In 1957, when I first started working, I had to abandon the idea that we could find a place in the brain for functions like the ego. But now, for example, Freud's "it", instinctive drives, is not such a mystery. We know that the hypothalamus plays an important role in this. The amygdala also plays an important role. So we begin to gradually relate these functions to specific areas of the brain,”says Kandel.

At 36, he had to choose - either "it" or the physiology of nerve cells. Kandel was offered the head of one of the most respectable psychiatry departments in the United States, where psychoanalysis was the main method of working with patients, but Kandel did not accept the offer, so that instead of examining memory in laboratory experiments on animals. For these studies, he will be awarded the Nobel Prize in Physiology or Medicine in 2000.

How can you study the memory of animals if they can't share memories? They do not write books, do not go through their childhood photos, do not delve into archives. If they are not capable of this, then, probably, it is necessary at least to take someone who is very similar to a person as a test subject. Chimpanzee? Elephants who - according to a popular English children's song - “never forget”? Whose brain can serve as a good model for ours - with its repressed memories of childhood trauma and the memory of how to ride a bike?

Kandel chose an unexpected hero for the role of the model: the mollusk Aplysia californica, aka the sea hare, a creature similar to a slug, but only half a meter or more long and weighing up to seven kilograms. Aplysia has no brain in the usual sense of the word at all.

A full-length black-and-white portrait of a clam hangs above Kandel's desk. Instead of a brain, Alysia has five pairs of nerve nodes with giant nerve cells - which, in fact, she liked Candela: the larger the cell, the easier it is to look into it. When scared, Alysia releases a cloud of colored ink. For science, the most interesting thing is that the connection between reaction and stimulus is not rigidly fixed once and for all - aplysia knows how to learn new things. In other words, a mollusk without a brain can memorize. And if you look at the work of her nerve cells in the process of memorization, Kandel decided in the mid-1970s, it will help to understand how people remember.

If we know from which molecular parts memories are assembled, we can theoretically count on pills for forgetfulness, and pills that help to forget, as in the movie "Eternal Sunshine of the Spotless Mind", where they go to a neurophysiologist to be treated for unhappy love. This perspective is constantly talked about and written about, but Candel frankly does not like such a formulation of the question of his work.

“I'm not interested in pills. Why interfere with the brain at all? Why not just understanding, no interference? You care about mind control, and I care about consciousness. I want to understand how memory works at all levels, and understand where creativity comes from."

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Blood cells, according to the popular science magazine New Scientist, completely renew themselves in 150 days: none of the red blood cells that traveled through our veins a year ago no longer exist. The lifespan of a skin cell is two weeks. Even bone cells live for only 10 years. The tissues of our body are a short-lived thing: they are included in the cycle of constant processing. If the body digests its own blood, skin and bones at a frantic pace, then what biomaterial is capable of carrying detailed memories from 80 years ago?

In his book "In Search of Memory" Kandel describes in detail how in November 1938 the Nazi police came to their apartment and ordered them to clear the premises - to move into another Jewish family for an indefinite period. The next few pages mention the postage stamps that the brother managed to take with him, and the bandage to maintain the shape of the mustache - the head of the family who sheltered them used it when going to bed, and the destruction in the house that they found when they returned.

If all this was recorded on film, it would have had time to dry out and crack from 1938. But somewhere in the head, mysterious perishable organic molecules store this information better than film.

The mollusk aplysia gave a chance to approach this issue at least from afar. Kandel began by examining short-term memory, where the impressions of the last few seconds live. A second is already a very long time by the standards of a nerve cell, which during this time has time to charge itself with electricity many hundreds of times and fire an electrical impulse at its neighbors. Where, in the midst of this electrical storm, processes a thousand times slower come from? It took more than fifteen years to describe the causal relationships behind this.

The first is the auxiliary neuron, which acts as a kind of volume knob for electrical cannonade. The closest qualitative analogue of this "loudness" in the mollusk is stress in humans, which dulls emotional reactions. What does "twist the handle" mean? To isolate the molecules of the neurotransmitter serotonin, which, like a key in a lock, lie in the receptors waiting for them on the surface of the target cell and affect the processes inside it. What are these processes? Synthesis of special molecules called "cyclic AMP" that live in the cell for much longer than electrical impulses. The rate of synthesis is controlled by enzymes, the work of enzymes is regulated by genes, the activity of genes depends on the gene regulatory network - and so on: the chain of cause and effect is long.

To clarify the details, it was necessary to dissect the goldfish and bring out - this has already been done by other scientists - the genetic line of mutant flies with the official name "dunce" (dunce): they were unable to remember what it smelled like before being hurt. And to figure out how serotonin, the same “volume control”, binds in the visual cortex, Kandel gave LSD to cats: he began working with this substance back in 1955, before the first hippies tried it.

What about human experiences? The same LSD, although researchers were banned from using it as early as the 1960s, returned in the 2000s to the laboratory along with mescaline and psilocybin, where healthy volunteers take them under the supervision of scientists. And then, and now Kandel is categorically against: “The human brain is a sacred thing. You can't play with him."

* * *

When the book "In Search of Memory" was first published in English in 2006, Kandel wrote that even the most routine operations of our brain - for example, recognizing faces and objects - are tasks of unimaginable computational complexity: computers ". Since then, something has changed: in 2012, a graduate student from the University of Toronto, Alex Krizhevsky, invented a neural network that, with a record low error rate, managed to classify 1.3 million pictures per thousand classes in the ImageNet competition. It was necessary, in particular, to distinguish geckos from iguanas, and Yorkshire terriers from Norfolk ones - and the computer program itself, without explicit instructions, learned to find subtle differences between lizard species and dog breeds.

Complicated versions of this neural network by 2014 began to solve the problem of image recognition better than a person. “They are doing a great job with it,” Kandel nods his head: now we need to illustrate the superiority of a living brain over everything else with something new. Where is artificial intelligence still inferior to natural intelligence - and now what does this latter need to do to surpass the brain?

“Think creatively,” says Kandel. Neural networks already know how to compose texts similar to Letov's poems and redraw photographs in the style of Van Gogh, but all this, according to Kandel, is not the same: "Imitating is one thing, coming up with new styles is another."

Least of all, a Nobel laureate can be suspected of not believing in such a possibility. His book "The Age of Illumination" is about how to discern in an artist's work specific methods of influencing the brain, the ability to pull the right lever of the mechanisms of empathy at the right time. Kandel is a collector and a big fan of Viennese Art Nouveau, therefore the main characters of his book, the reasoning about the nature of creativity which he extends to all artists in general, are Klimt, Schiele and Kokoschka.

Kokoschka's paintings "act on the amygdala like an electric shock." The nodal lines in his paintings repeat the gaze movements that were sketched by the Soviet psychophysiologist Alfred Yarbus (he fixed tight-fitting contact lenses connected to a motion recorder on his eyeballs). And the angularities and distortions in expressionist portraits are signals that perfectly read the multiple face recognition zones in the brain.

Realism, with its aspiration to reproduce the geometry of the three-dimensional world as literally as possible, is in this sense not the best way to force our brains to turn on empathy. With photographic accuracy, it makes no sense to redraw a person centimeter by centimeter if the brain is completely disproportionate to the areas responsible for the perception of faces, hands - and the rest of the body.

What will happen if you move away from classical painting even further? Kandel seems to be skeptical about art after the 1950s: for example, actionism - even Viennese, no matter how warmly he feels about Vienna - leaves him indifferent. What neurophysiology has to say about emotions like disgust or fear that Marina Abramovich and Valli Export work with,when doing experiments on their own body? “That doesn't interest me,” he says shortly and changes the subject.

* * *

What political subjects should the authorities first of all discuss with scientists? Migrants, Kandel immediately replies. “Trump has banned people from different countries from entering, and I find it very dangerous,” he recalls a presidential decree that in January made it impossible for citizens of Iran, Iraq, Syria, Yemen, Libya, Somalia and Sudan to enter the United States. The ban, later overturned by the court, was unconditional - even those with a family in America, a contract with Microsoft or a department at the Ivy League University were or were about to deploy at the border.

What could science say to this? Kandel says: "I will give you a personal example." Nobel laureate - a migrant and the son of a migrant. His family had to leave Vienna almost at the same time as Freud. But first, Father Kandel, along with other Viennese Jews, was forced to scrub the anti-Anschluss slogans off the sidewalk with toothbrushes. Then they took away and transferred the father's toy store to the new Aryan owner. Then Kandel himself was expelled from the school where he studied with non-Jewish children, and transferred to a new one, only for Jews, on the outskirts of the city.

"I, an American celebrity, and myself a migrant" is a popular argument: when journalists found Sergey Brin, the co-founder of Google, among the protesters against Trump's decision in January, he reasoned the same way. But if Brin came to America from the USSR in 1979 as the son of a professor of mathematics, then the Kandel family in 1939, by all formal criteria, did not fall into the category of immigrants who are welcomed with open arms. His father was born in a tiny Ukrainian town near Lvov and had an incomplete schooling. And Kandel himself, upon his arrival in America, was sent to a religious school - to study Hebrew and Torah.

The closest analogue of this situation now is an eight-year-old Arab boy, the son of an uneducated worker from Syria, who immediately after moving goes to study in a madrasah. From the point of view of the European or American right, this is the perfect example of someone who should under no circumstances be allowed into the West.

Kandel is confident that his case is more the rule than the exception. When people say about American science that it is the work of European immigrants, they usually imagine celebrities like Einstein or Fermi who have already taken place in Europe. But there were only a few of them: “Most of the immigrant scientists came here not because the government hoped for their future contributions to science. Many of them were very young and were saving their lives: if they, Jews, had stayed in Europe, they would have simply been killed. This is especially true for Germany and Austria. But they took advantage of the United States and grew up in this wonderful environment. And they achieved everything they wanted."