The mysteries of the human mind might soon be revealed, now that a consortium of experts has figured out how to render entire brains transparent — meaning that researchers will be able to analyze grey matter with unprecedented levels of detail.
A team of chemical engineers and neuroscientists at Stanford University collaborated on the new federally-funded technique, known as CLARITY, which was described today in the journal Nature. Experts involved in the project suggest it will play a pivotal role in the government's recently announced BRAIN project, a blockbuster venture that hopes to map the mind, much as scientists over the last decade mapped the human genome. The hope is to understand processes like memory formation and learning, and treat ailments like Alzheimer's disease and epilepsy.
"This is huge."
"I can't make any official statement, but I can say that this is exactly the type of technology one would hope to develop for the [BRAIN] project," Michelle Freund, Ph.D., a program manager with the National Institutes of Mental Health who oversaw the CLARITY research, told The Verge. "This is huge."
Right now, researchers conducting analyses of post-mortem brain samples struggle to obtain much in the way of useful information. That's because they're thwarted by lipids, fatty molecules that help the brain maintain its structure — but also prevent chemicals or light from permeating grey matter, barring researchers from getting a closer look at the brain's molecular workings. To circumvent that challenge, researchers slice the brain into thin layers. Unfortunately, that tactic prevents them from understanding how "big picture" brain components, like neural circuits, are impacted by, say, the millions of neurons that interact to control these larger processes.
"Studying intact systems with this sort of molecular resolution and scope — to be able to see the fine detail and the big picture at the same time — has been a major unmet goal of biology," research leader Karl Deisseroth, M.D., Ph.D., said. "[It's] a goal that CLARITY begins to address." Dr. Deisseroth, notably, is one of 15 scientists on a federal working group tasked with establishing priorities for the federal BRAIN venture.
The result? A fully transparent brain
Dr. Deisseroth and his colleagues accomplished what, until now, remained an impossible task: they managed to remove the brain's lipids without destroying the structure of the grey matter itself. To do it, the team infused a brain with a clear gel solution that expanded into a mesh supporting the brain tissue. That process complete, researchers were able to extract the brain's lipids without compromising structural integrity. The result? A fully transparent brain whose components remained available for analysis.
Already, the team has tested the method on a full mouse brain and on samples of human brain tissue. In the mouse brain, they were able to see complex circuitry that winds through the brain, as well as probe into finer details, like the structure of a single cell.
Plus, any brain that undergoes the CLARITY process can be examined over and over: tracer molecules, used to stain specific brain components for analysis, can be flushed out without disturbing delicate tissue. "You could conceivably label and follow 10 or 12 different neurotransmitters in a single brain," Freund said. "With earlier methods, that just wasn't possible — you stained once, that slice of tissue was done."
The implications of the method are myriad. For one, researchers can use the technique for post-mortem study of individuals afflicted with various brain-based illnesses, to better understand how those ailments manifest in grey matter and help determine how we might treat or prevent them. The project is also partly funded by military agency DARPA's Repair program, which endeavors to come up with better treatments for traumatic brain injuries — a problem afflicting both soldiers and athletes, namely NFL players, in devastating numbers.
"Issues with data risk being a bottleneck for the uptake of this technology."
But before the approach can become a mainstay of neuroscientific study, researchers will need to clear one major hurdle: how to handle the huge reams of data that'll emerge from collecting information on these billions of cells, and their complex interactions, that have suddenly become readily accessible for study. "Issues with data risk being a bottleneck for the uptake of this technology," Freund said, adding that several federal agencies and programs (including the BRAIN project) will work to tackle that challenge, though they've yet to announce specific strategies. "This project is a perfect example of why better ways to handle large quantities of data should be a top priority."