Sometimes you wonder about the way scientists hit upon discoveries. The man who discovered phosphorus, for instance, realized he had struck on something important when the buckets of urine he had stored for ages started glowing during his experimentation. Even though he must have been disappointed as an alchemist when his “light-bringing” substance failed to bring immortality or transmute metal into gold, as a scientist, he became fascinated by the element he had discovered. I can imagine him telling his family, “See, I told you storing buckets of putrid urine would eventually pay off.” But I cannot imagine the series of thoughts that--even in the 17th century--led him to suspect urine had mystical qualities.
A team of scientists at Stanford have embarked on a similar journey that leaves me impressed, fascinated and extremely curious about how that first conversation went, the one where one researcher turned to the other and said, “You know, if we could turn a brain transparent, wow! imagine all the cool science we could do without ever having to cut into the organ.” But even in bioengineering, the trickle of an idea is just a sci-fi writer’s bread and butter, unless you can transmute “What if...?” into “Eureka!”
That Eureka moment must have been fantastic. Imagine coming into the laboratory, to take a quick peek at the mouse brain you had prepared two days earlier, and finding it completely transparent. I imagine the scientist spluttering on coffee, taking a second look, wondering aloud, “Okay, who stole the mouse brain? Oh, oh wait, no it is there! It worked! It worked! The mouse brain has gone transparent!”
The image above perfectly demonstrates the startling transformation. Where an opaque mound of grey matter had sat two days prior, a pale outline of cranial matter rested in its place. Once held in place by opaque lipids, the brain’s components--from its axions to its synapses--now owed their structure to hydrogel polymers.
The replacement process required clever maneuvering. Dunked into a hydrogel solution, the brain absorbed the molecules, soaking the monomers into its tissue. Scientists then warmed the system to a temperature close to body heat, and the monomers began attaching to each other, forming long polymer chains and maintaining the integrity of the brain’s elements. With the polymers in place throughout the organ, the scientists could then eliminate the lipids, which had previously supported the brain’s structure and simultaneously blocked curious eyes from examining the inner workings.
Peering into the brain’s intricate structure, rather than slicing and dicing, will give scientists a three-dimensionality advantage, allowing them to study the brain’s anatomy in its entirely, rather than segment by segment. They can begin mapping the brain and making sense of the neurological networks inside. The Stanford team’s paper, published this month in Nature, has invigorated the medical community. Bringing transparency to an organ that still poses millions of mysteries in the medical world means prospects of finally gaining clarity about how the brain functions and how to treat brain diseases.
Another strange route to scientific advancement? Definitely. But the most fascinating science discoveries have an interesting way of also being the most useful.
Photo courtesy of the Deisseroth lab/STANFORD