The visible brain has arrived — the consistency of Jell-O, as transparent and colorful as a child’s model, but vastly more useful.
Scientists at Stanford University reported Wednesday that they had made a whole mouse brain, and part of a human brain, transparent, so that networks of neurons that receive and send information can be highlighted in stunning color and viewed in all their three-dimensional complexity without slicing up the organ.
Even more important, experts say, is that unlike earlier methods for making the tissue of brains and other organs transparent, the new process, called Clarity by its inventors, preserves the biochemistry of the brain so well that researchers can test it over and over again with chemicals that highlight specific structures within a brain and provide clues to its past activity.
The researchers say this process might help uncover the physical underpinnings of devastating mental disorders like schizophrenia, autism, post-traumatic stress disorder and others.
The work, reported Wednesday in the journal Nature, is not part of the Obama administration’s recently announced initiative to probe the secrets of the brain, although the senior author on the paper, Dr. Karl Deisseroth at Stanford, was one of those involved in creating the initiative and is involved in planning its future.
Dr. Thomas Insel, director of the National Institute of Mental Health, which helped fund the research, described the new work as helping to build an anatomical “foundation” for the Obama initiative, which is meant to look at ongoing activity in the brain.
Insel added that the technique works in a human brain that has been in formalin, a preservative, for years, which means that long-saved human brains might be studied.
“Frankly,” he said, “that is spectacular.”
Kwanghun Chung, the primary author on the paper, and Deisseroth worked with a team at Stanford for years to get the technique right. Deisseroth, known for developing another powerful technique, called optogenetics, that allows the use of light to switch specific brain activity on and off, said Clarity could have a broader impact than optogenetics.
“It’s really one of the most exciting things we’ve done,” he said, with potential applications in neuroscience and beyond.
“I think it’s great,” said Dr. Clay Reid, a senior investigator at the Allen Institute for Brain Science in Seattle, who was not involved in the work. “One of the very difficult challenges has been making the brain, which is opaque, clear enough so that you can see deep into it.”
This technique, he said, makes brains “extremely clear” and preserves most of the brain chemistry. “It has it all,” he said.
In the mid-2000s Reid was part of a team led by Dr. Jeff Lichtman at Harvard that developed a process called Brainbow to breed mice that are genetically altered to make their brain neurons fluoresce in many different colors. The new technique would allow whole brains of those mice with their rainbow neurons to be preserved and studied.
“I’m quite excited to try this,” Lichtman said.
Chung said he planned to start his own lab soon and to work on refining the technology. But he pointed out that it was already known that it works on all tissue, not just brains, and can be used to look for structures other than nerve cells.
On his laboratory bench, he said, “I have a transparent liver, lungs and heart.”
Reid agreed that Clarity had applications in many fields.
“It could permeate biology,” he said.