In the year 1600, a landmark moment in the history of science occurred. Tycho Brahe, a Danish nobleman obsessed with accurately measuring the movements of the stars, met Johannes Kepler in Prague, a German of humble origins with an inclination toward mysticism and science that seems contradictory today. Kepler, inspired by Copernicus, felt that the solar system with the star at the center made more sense, but he needed data to support his model. At this time, astronomers made navigational maps and astrological predictions from crude observations collected centuries earlier, and few found it necessary to collect accurate measurements. Brahe had collected these measurements, but he kept the Earth at the center of his solar system and hid his observations from Kepler, who was only able to see them after the Dane’s death in 1601. This data allowed Kepler to mathematically describe the movements of the planets around him. the sun and paved the way for Isaac Newton to use gravity to explain to us why they move the way they do.
Four centuries later, scientists are striving for a scientific revolution at least as significant as those who discovered Earth’s position in the cosmos. Despite advances in neuroscience since the years of Santiago Ramón y Cajal, there is still much unknown about the brain, how it generates consciousness or memory, or how many neurological diseases can be cured. Today, Science magazine is publishing a series of articles that illustrate the effort involved in obtaining the data that forms the basis of every significant advance in knowledge.
The work is part of the Brain Initiative Cell Census Network (BICCN), a project launched in 2017 by the US National Institutes of Health (NIH). The project involves hundreds of scientists using cutting-edge technologies to locate cells in the brains of humans and other animals and characterize them individually based on their genetic expression, shape and other characteristics. They have already done this with more than 3,000 types of human cells, uncovering aspects that distinguish them from those of other primates and that allow them, for example, to identify which of them are more susceptible to certain mutations that cause neurological diseases.
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One finding of the collaboration is that, just like in the kitchen, different stews can be prepared with the same ingredients. Although there are cells specific to some brain regions, there are many differences between regions because they have different proportions of the same cell types. As Alyssa Weninger and Paola Arlotta from the Universities of North Carolina and Harvard explain in one of the articles, there are exceptions to this general rule. For example, the primary visual cortex contained certain types of inhibitory neurons. The data shows that evolution has not led to the emergence of new types of brain cells that justify the brain’s different functions, but rather that it is small variations within the same cell types and changes in the frequency of these cells per region that create circuits. different brains.
There is no human brain
Juan Lerma, a researcher at the Institute of Neuroscience in Alicante, points out that the enormous amount of data obtained with the new techniques “will not provide us with a solution to the knowledge problems of the human brain and will reveal things that were already known.” but that is the way to show that knowledge is solid.” One of the highlights for Lerma is the large variability between brains, “something that has been observed in non-invasive brain imaging tests in humans.”
“This shows us that it is important that human studies include a large number of cases, because you can do a study on 500 brains that gives some results, and later you do an analysis of 30 of those brains and the results are…” different,” illustrates. A study led by Nelson Johansen of the Allen Institute in Seattle, USA, analyzed the genetic expression of individual cells in the cerebral cortex of 75 people and found only small differences caused by factors such as age, gender, ancestry or whether it was from healthy or comes from sick people. “There is no prototypical person,” summarize Weninger and Arlotta.
“The knowledge gained from these studies will be fundamental to answering some classic questions in neuroscience, such as what are the fundamental differences between the human brain and that of our closest relatives such as chimpanzees,” says Ignacio Sáez, a researcher at Mount Sinai Hospital, New York.
One of the papers published today by Science, signed as first author by Nikolas Jorstad of the Allen Institute, analyzes the genetic expression of the cells of the middle temporal gyrus, a region crucial for language comprehension, in humans, chimpanzees, gorillas and macaques and marmosets. The researchers found that all of these primates share largely the same cell types that appeared at one point in evolution and were conserved as new species appeared. Only a few hundred genes showed expression patterns that only occur in humans. These data suggest that the apparent differences between a marmoset and a human are due to some molecular and cellular changes.
Among the Science articles are also papers that analyze cells at key moments in brain development before and shortly after birth. Knowing these moments can also help create better models for studying the human brain, something that is very difficult to do with flesh-and-blood volunteers, or better understand which animal models may be useful to advance knowledge of the expand the organ of consciousness. Arlotta is an international reference in the construction of organoids, three-dimensional models made from stem cells that simulate the structure of the brain.
Javier de Felipe, a CSIC researcher who has participated in large international collaborations such as the Human Brain Project, believes that projects of this kind help “improve communication between scientists” by allowing them to define exactly “how many species of neurons there are”. in the brain.” Brain, what we do not know, and also see the connection that these genetic or morphological properties of the cells have with the function that they develop.” “These types of projects give us a lot of data that we then have to understand “, he explains. Juan Lerma agrees that this is “a map in a similar way to sequencing the human genome.” “Once you have a map of an area, the next thing you need to do is start exploring that area,” he says.
As with Brahe and Kepler 400 years ago, the data and the expensive and precise tools required to harvest them will precede the great discoveries that will change the way we see the world, even those who do not understand transcriptomics or planetary motion. Because behind this project to know all the cells of the brain, their location and their functions, there is a tycoon’s money. Paul Allen, the co-founder of Microsoft who died in 2018, founded the Allen Institute for Brain Science in 2003, the organization that leads the initiative along with the NIH. Unlike the Danish nobleman, the institution created by the techno-millionaire will make the data obtained in this project available to all new Keplers who will use them to try to understand reality.
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