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Ten years ago, Dr. Jeff Lichtman – professor of molecular and cellular biology at Harvard University – a small brain sample in his laboratory.
Although small, the 1 cubic millimeter of tissue was large enough to contain 57,000 cells, 230 millimeters of blood vessels and 150 million synapses.
“It was less than a grain of rice, but we started cutting it and looking at it, and it was really beautiful,” he said. “But as we collected the data, I realized we simply had way more than we could handle.”
In the end, Lichtman and his team had 1,400 terabytes of sampled data – roughly the contents of more than 1 billion books. Now, after a decade of close collaboration between the lab team and Google scientists, that data has turned into the most detailed map of a human brain sample ever created.
300 million images
The brain sample came from a patient with severe epilepsy. It’s standard procedure, Lichtman said, to remove a small part of the brain to stop the seizures, and then look at the tissue to make sure it’s normal. “But it was anonymized, so I knew virtually nothing about the patient other than their age and gender,” he said.
To analyze the sample, Lichtman and his team first cut it into thin slices with a knife with a diamond blade edge. The sections were then embedded in a hard resin and again sliced very thinly. “About 30 nanometers, or roughly one-thousandth the thickness of a human hair. “They were virtually invisible if we hadn’t stained them with heavy metals, which made them visible on electron imaging,” he said.
The team ended up with several thousand slices, which were picked up with a custom-made tape, creating a kind of film strip: “If you take a photo of each of those sections and align those photos, you get a three-dimensional piece of the brain microscopically. level.”
That’s when the researchers realized they needed help with the data, because the resulting images would take up a significant amount of storage space.
Lichtman knew that Google was working on a digital map of a fruit fly’s brain, released in 2019, and that he had the right computer hardware for it. He contacted Viren Jain, a senior staff researcher at Google who worked on the fruit fly project.
“There were 300 million individual images (according to Harvard data),” Jain said. “What makes it so data-rich is that you’re taking images at a very high resolution, the level of an individual synapse. And there were 150 million synapses in that small piece of brain tissue alone.”
To understand the images, Google scientists used AI-based processing and analysis, identifying what type of cells were in each photo and how they were connected. The result is an interactive 3D model of the brain tissue and the largest dataset ever created at this resolution of a human brain structure. Google made it available online as “Neuroglancer,” and at the same time a study was published in the journal Science, with Lichtman and Jain as co-authors.
Understanding the brain
The collaboration between the Harvard and Google teams resulted in colorized images that make the individual components more visible but are otherwise a true representation of the tissue.
“The colors are completely random,” Jain explained, “but other than that, there’s not much artistic freedom here. The whole point of this is that we’re not making it up – these are the real neurons, the real wires that exist in this brain, and we’re really just making it convenient and accessible for biologists to view and study.”
The data contains some surprises. For example, instead of forming a single connection, pairs of neurons have more than fifty. “This is like if two houses on a block had fifty separate telephone lines connecting them. What’s happening there? Why are they so strongly connected? We don’t know yet what the function or significance of this phenomenon is, we will have to study it further,” he said.
Ultimately, observing the brain at this level of detail could help researchers understand unsolved medical conditions, Lichtman said.
“What does it mean to understand our brain? The best we can do is describe it, and hope that from these descriptions will emerge, for example, an awareness of how normal brains differ from brains that are disordered, in adult psychiatric diseases or developmental disorders such as the autism spectrum – that kind of comparison will be very valuable “, he said. “Ultimately it will give us some insight into what is wrong, which in most cases we are still in the dark about.”
Lichtman also believes the dataset may be filled with other amazing details that have not yet been discovered due to its size: “And that’s why we’re sharing it online, so everyone can look at it and find things,” he says. added.
Next, the team behind the project wants to create a complete map of a mouse’s brain, which will require between 500 and 1,000 times the amount of data from the human brain sample.
“That would mean 1 exabyte, which is 1,000 petabytes,” Lichtman said. “A lot of people are thinking hard about how we’re going to do this, and we’re in the first year of a five-year proof-of-principle. I think this would be a turning point for neuroscience, if we had a complete wiring diagram of the mammalian brain; it would answer many, many questions. And of course it would reveal many more problems, things we didn’t expect.”
What about mapping an entire human brain? That would be another thousand times larger, Lichtman explained, meaning the data would be 1 zettabyte. In 2016, according to Cisco, this was the size of the entire internet traffic of that year. At this point, Lichtman said, not only would it be difficult to store even that much data, but there would also be no ethically acceptable way to obtain a pristine, well-preserved human brain.
Pioneering new territory
Researchers in the same field who were not involved in the work expressed their enthusiasm when contacted by CNN for comment.
“This study is great, and there is so much to learn from this kind of data,” said Michael Bienkowski, assistant professor of physiology and neuroscience at the University of Southern California Keck School of Medicine.
“Much of what we think we understand about the human brain has been extrapolated from animals, but research like this is critical to revealing what makes us truly human. Visualizing neurons and other brain cells is challenging due to their enormous density and complexity, and the current dataset does not capture the connections over longer distances,” Bienkowski said.
“What other brain areas does this input come from, and where does the output go once it leaves the area? But it is incredible to see all these different cell types and their interactions and it makes you realize what an architectural masterpiece life has given us,” he added.
Andreas Tolias, a professor of ophthalmology at Stanford University in California, agrees. “This is a remarkable technical study that reconstructs the structure of the human cortex at high resolution,” he said. “I was particularly excited about the discovery of rare axons that can form up to 50 synapses. This finding is intriguing and raises important questions about their computational role.”
The brain mapping project opens the door for future research, according to neuroscientist Olaf Sporns.
“Each human brain is a vast network of billions of nerve cells,” says Sporns, a professor of psychology and brain sciences at Indiana University. “This network allows cells to communicate in very specific patterns that are fundamental to memory, thinking and behavior. Mapping this network, the human connectome, is critical to figuring out how the brain works,” he added, noting that the study breaks new ground toward this important goal and provides exciting new offers opportunities for exploration and discovery.
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