The visible brain has arrived - the consistency of Jell-O, as
transparent and colorful as a child's model, but vastly more useful.
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.
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
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."
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.
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.
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.
are several ways to make tissue transparent. The key to the new
technique is a substance called a hydrogel, a material that is mostly
water held together by larger molecules to give it some solidity.
said the hydrogel formed a kind of mesh that permeates the brain and
connects to most of the molecules, but not to the lipids, which include
fats and some other substances. The brain is then put into a soapy
solution and an electric current is applied, which drives the solution
through the brain, washing out the lipids. Once they are out, the brain
is transparent, and its biochemistry is intact, so it may be infused
with chemicals, like antibody molecules that also have a dye attached,
that show fine details of its structure and previous activity.
like this, said Insel, "should give us a much more precise picture of
what is happening in the brains of people who have schizophrenia,
autism, post-traumatic stress disorder, bipolar disorder and
The tricky part was getting the right combination of
temperature, electricity and solution, and it was very tricky indeed,
Chung said. Over the course of years spent trying to make it work, he
said, "I burned and melted more than a hundred brains."
paper's publication, the recipe is available to anyone who wants to use
it, and, he said, "I think it will be relatively easy."
technique has its limits, of course. Chung said more work needed to be
done before it could be applied to a whole human brain, because a
human's brain is so much larger than a mouse's and has more lipids.
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.
© 2013, The New York Times News Service