Ten years ago, a package arrived at the lab of Dr. Jeff Lichtman, who is a professor of molecular and cellular biology at Harvard University. It contained a small brain sample. The sample was merely 1 cubic millimeter. “It was less than a grain of rice, but we began to cut it and look at it, and it was really beautiful,” Dr. Litchman said.
Despite its diminutive stature, it held thousands of cells and connections, like a mini-map of the human mind. Packed within this tiny piece resided 57,000 cells, 230 milimeters of intricate blood vessels, and a staggering 150 million synapses. This seemingly insignificant has become the “Rosetta Stone” for brain, unlocking a new chapter in our understanding of the brain and embarking on a decade-long odyssey to map its labyrinthine pathways.
The brain sample belonged to a patient with severe epilepsy. Dr. Lichtman's team meticulously sliced the sample into incredibly thin sections using a knife with a blade edge made of diamond. The sections were then embedded into a hard resin and sliced again, very thinly. “About 30 nanometers, or roughly 1,000th of the thickness of a human hair. They were virtually invisible, if it weren’t for the fact that we had stained them with heavy metals, which made them visible when doing electron imaging,” Dr. Litchman said.
These sections were then meticulously imaged using electron microscopy, resulting in a staggering 300 million individual images. Faced with this data deluge, researchers realised they need help with the data. They needed someone with the computational muscle to handle such a colossal undertaking.
Google at that time was working on a digital map of a fruit fly’s brain (released in 2019) and so Dr. Litchman figured that they have the required system for this job. He approached Viren Jain, a senior staff research scientist at Google. Jain saw the immense potential of Lichtman's data, “There were 300 million separate images (in Harvard’s data)”. “What makes it so much data is that you’re imaging at a very high resolution, the level of an individual synapse. And just in that small sample of brain tissue there were 150 million synapses.”
Jain’s team then used Google's vast computing resources and the power of AI. Jain and his team embarked on the task of processing the millions of images. To understand the pictures, scientists at Google used artificial intelligence (AI) to process and analyze them. They identified the types of cells in each picture and their connection. The effort resulted to an interactive 3D model of the brain tissue, which is the biggest dataset ever created at this level of detail. Google named it "Neuroglancer" and shared it online. Following, a study was published in the journal Science, with both Lichtman and Jain credited as coauthors.
The map itself was a box full of surprises. One particularly intriguing finding was the presence of pairs of neurons with an unusually high number of connections – far more than previously anticipated. “This is kind of like if two houses on a block had 50 separate phone lines connecting them. What’s going on there? Why are they so strongly connected? We don’t know what the function or significance of this phenomenon is yet, we’re going to have to study it further,” Jain said.
This unexpected finding hinted at a deeper level of complexity in neuronal communication, raising new questions about brain function and potentially opening doors to a better understanding of neurological disorders.
But what about mapping the entire human brain? Lichtman said that it would require data that's a thousand times larger, totaling 1 zettabyte. To put it in perspective, in 2016, that was the equivalent size of all internet traffic for the year, as per Cisco. Lichtman highlighted that, at present, not only storing such vast data would be challenging, but there's also no ethical way to obtain a perfectly preserved human brain.
While mapping a complete human brain remains a distant dream due to ethical considerations and technological limitations, the success of this project paves the way for future endeavors. The next frontier lies in mapping the entire brain of a mouse, a project estimated to require 500-1,000 times more data than the human sample. This ambitious undertaking will push the boundaries of current technology and necessitate further advancements in data storage and processing capabilities.
The scientific community has received this research with resounding acclaim. Dr. Michael Bienkowski, an assistant professor of physiology and neuroscience, emphasizes the crucial role this project plays in studying the human brain directly, as opposed to relying solely on animal models. Dr. Andreas Tolias, a professor of ophthalmology, highlights the intriguing discovery of highly connected axons, hinting at a previously unknown level of communication within the brain. Dr. Olaf Sporns, a distinguished professor of psychological and brain sciences, sees this project as a crucial step towards mapping the human connectome – the intricate network of connections that forms the very foundation of our thoughts, behaviors, and memories.
