Pictures from the little black box

Scientists often describe the brain as a black box - we know what it can do, but we don't really understand how. We know about 3.300 types of neuron cells in the human body the brain, but we assume that there are dozens of times more. In addition, we do not know why they occur, nor how to cure diseases of the nervous system, which are among the greatest medical challenges of today: Parkinson's disease and Alzheimer's disease.

We don't really know what exactly is in the brain. Until now, no one has scanned the human brain in such a way as to examine, identify and determine the roles of cells within it. That endeavor is still a long way off. But, in the meantime, scientists are "practicing" this kind of research on another named creature Drosophila melanogaster – fruit fly.

Neuro-researchers networked in a group that includes several dozen laboratories around the world, after years of painstaking work, made a real research feat. They were able to explore and map the entire brain of a fruit fly. It sounds like a mockery or an understatement, but in that little brain, the size of a poppy seed, there are as many as 8.453 types of nerve cells, almost three times more than we know of in the human brain.

Before the brain of the fly was mapped, researchers managed to do the same work in a worm that has only 302 neurons, but that work was neither that complex nor expected to make a big contribution to help us get to know the human brain better. The brain of a fruit fly larva, which has about 3.000 neurons, was also mapped, which is still incomparably simpler than the brain of an adult wine fly with about 140.000 neurons and tens of millions of synapses connecting them.

Why the wine fly and what does its brain have to do with ours?

SCIENTIFIC MODELS

The first animal to be launched into space was not Laika, which orbited the Earth in 1957, but fruit flies. In 1947, American astronauts packed them into a rocket and launched them to a height of 100 kilometers, and then they landed on Earth with a parachute. The goal was to examine how radiation and weightlessness affect flies.

Drosophila melanogaster was at that time already used for more than half a century for various researches as a model organism. The fruit flies lived on the International Space Station, their genome was sequenced before that of humans, and the formation of their eyes is controlled by genes equivalent to those of humans. In fact, fruit flies share 60 percent of human DNA, including genes for learning and Down syndrome. As much as two-thirds of the genes that cause disease in humans are also found in the fruit fly. However, their genome is much simpler than ours and therefore more suitable for research and manipulation.

Although all this became known only in this century, the wine fly became important to researchers much earlier. The American evolutionary biologist Thomas Morgan, who later won the Nobel Prize for explaining the role of chromosomes in inheritance, proposed in 1901 that fruit flies should be used as a model organism. And not only did Morgan win the Nobel for research related to midges, but so far the observations of this insect have won a total of six Nobel prizes.

Such model or model organisms - among which mice are probably the best known - are used for detailed studies of certain biological phenomena such as the effects of drugs, the mechanisms of disease development or the epidemiology of infections. The development of organ transplantation, the discovery of insulin and its use in the treatment of diabetes, as well as many other procedures in medicine would not be possible or so effective if animals were not sacrificed instead of human experimentation (see the box "Mandatory testing"). Ideal model organisms are small, have a short life cycle, reproduce quickly, are readily available, and have specific characteristics suitable for a given study. When Thomas Morgan experimented with fruit flies and identified chromosomes as the vector of inheritance for genes, the public appreciated how Morgan contributed to transforming biology into an experimental science.

Among the frequent model microorganisms are, for example, bacteria Escherichia coli which is part of the microbiome of humans and many other creatures, as well as baker's yeast, Saccharomyces cerevisiae, which is widely used to investigate DNA damage and repair. The first plant whose genome was sequenced and on which numerous researches are carried out is Arabidopsis thaliana. This unsightly, multi-continental flowering annual was long thought to have the smallest genome among angiosperms, but it turns out that there are others with smaller genomes, such as some carnivorous plants.

LIFE IN SUGAR AND RESIN

photo: sanjay acharya / wikimedia commons

The wine fly is very small, only about two and a half millimeters, and lives a short time. She is comfortable at room temperature and her diet is quite simple. In nature, we most often see wine flies near overripe fruit and fermented drinks, so their needs can be easily and cheaply met in the laboratory as well. Only 50 days pass from the creation of the egg to its death. During that time, he gave birth to about 2000 offspring.

Such a simple insect performs many complex functions at the same time. As the researchers from Princeton who participated in this research explain, in that tiny body some of the simple actions take place such as fast movement, navigation, searching for food, avoiding predators, reacting to light and darkness, but also some very complex ones such as communication with romantic partners, because it is well known that males sing to females in the heat of love.

To map the fruit fly's brain, the researchers removed its brain, barely visible to the naked eye, and immersed it in resin where it hardened. They cut that piece of resin into 7050 microscopically thin pieces, slices. Each of them was photographed through an extremely high-resolution microscope. Then they repeated that process more than a thousand times and got about 21 million pictures. A global team of 287 individuals from 76 laboratories, led by researchers from Princeton University, the University of Vermont, and the University of Cambridge, set to work reviewing those images. They worked for a decade to identify each distinct neuron and each synaptic connection.

As a result, they found that the fruit fly has a total of 139.255 neurons that are classified into 8.453 types. Each type of neuron was described and named. They also discovered about 50 million chemical synapses, and then showed how all the parts of the brain are networked and connected – how they work together to process signals that turn into actions. Thus, with the help of a supercomputer, a complex, fascinating, three-dimensional map of millions of synaptic connections was created and a computer model was built that will be used for further research.

"What we've created is, in many ways, an atlas," said Sven Dorkenwald, first author of the fly brain mapping paper. "Just like you wouldn't want to drive to a new place without Google Maps, you don't want to explore the brain without a map. We created a brain atlas and added annotations for all businesses, buildings, street names. Researchers are now equipped to thoughtfully manage the brain as we try to understand it.”

At first, the result of this feat is only that map, but in fact, it is only the starting point from which we now expect - with much less effort - to follow numerous important discoveries that speak not only about the wine fly but potentially also about man and his brain. . "Each brain that we really understand tells us something about all brains," explains Sebastian Seung, professor of neuroscience and computer science at Princeton, showing how with a network diagram we have the potential for "unprecedented, detailed and deep understanding."

But the human brain is infinitely more complex - we have billions of neurons (who knows how many types!) and trillions of synapses, which makes it the most complex neural network that exists. Only a complete understanding of how neurons connect will help us shed light on the black box and find answers to some of today's most puzzling questions.

Mandatory testing

In the thirties of the 20th century, for the treatment of streptococci, doctors massively prescribed the drug sulfanilamide in the form of tablets and powder. In the summer of 1937, the large pharmaceutical company "Masengill" from Bristol (Tennessee, USA), which at that time employed about 200 people, was informed that there was a demand for the same medicine in the form of syrup. The chief chemist and pharmacist at this company, Harold Cole Watkins, did a little experimenting and came to the conclusion that sulfanilamide dissolves nicely in diethylene glycol. This organic compound is odorless, colorless and has a sweet taste. The only thing Watkins didn't know was that it was also very poisonous.

He dissolved the sulfanilamide in diethylene and added a little raspberry flavor – which is usually done when making children's medicine. In the control laboratory, the taste, smell and appearance were tested and the mixture was confirmed to be good. They called it "elixir sulfanilamide" and poured it into 633 vials that were sent to pharmacies in different parts of the United States in September 1937.

Already in October of that year, the first information arrived that this "elixir" had caused the death of several people. In the following period, at least 100 people died as a result of poisoning with the "medicine".

The owner of the "Masengil" pharmaceutical company, Samuel Masengil, denied that the company was responsible, and the chemist Watkins committed suicide while awaiting trial. The company was punished with a symbolic fine, with the explanation that it is forbidden to call the product an elixir if it does not contain alcohol.

However, due to public pressure, Congress passed the Food, Drug, and Cosmetic Act the following year, requiring companies to test all their products on animals and submit the results to the Food and Drug Administration (FDA) in order to obtain approval for manufacture. In the meantime, this regulation has been significantly improved, but animal drug testing is still part of the testing process for any drug.