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In HG Wells’ 1897 science fiction novel, “The Invisible Man,” the main character invents a serum that makes the cells in his body transparent by controlling how they bend light.
More than 100 years later, scientists discovered a real-life version of the substance: A commonly used food coloring can temporarily make a mouse’s skin transparent, allowing scientists to see the function of its organs, of according to a new study published Thursday in the journal Science.
This breakthrough could revolutionize biomedical research and, if successfully tested in humans, could have far-reaching applications in medicine and healthcare, such as making veins more visible for drawing blood.
Researchers made the skin on the skulls and bellies of the living mice transparent by applying a mixture of water and a yellow food coloring called tartrazine. By washing away any remaining solution, the process was reversed, which did not harm the animals. The fur of the mice was removed before the solution was applied.
“For those who understand the basic physics behind this, it makes sense; but if you’re not familiar with it, it’s a magic trick,” Zihao Ou, an assistant professor of physics at the University of Texas at Dallas, said in a statement.
Dye molecules that absorb light
The “magic” uses insights from the field of optics. Light-absorbing dye molecules improve the transmission of light through the skin by suppressing the tissue’s ability to scatter light.
When mixed with water, the refractive index — a measure of the way a substance bends light — of the aqueous portion of the tissue is modified to better match the effect of the proteins and fats in the tissue. The process is like a cloud spreading fog.
“We combined the yellow dye, which is a molecule that absorbs most light, especially blue and ultraviolet light, with skin, which is a scattering medium,” said Ou, who conducted the study as a postdoctoral researcher at Stanford University in California. .
“Individually, these two things block the most light from getting through,” he said. “But when we put them together, we were able to achieve the transparency of mouse skin.”
When the dye had completely diffused into the skin, the skin became transparent.
“It takes a few minutes for the transparency to appear,” Ou said. “It’s similar to the way a face cream or mask works: The time required depends on how quickly the molecules diffuse into the skin.”
The team experimented on chicken breast before working on live animals.
In mice, the researchers were able to observe blood vessels directly in the surface of the brain through the transparent skin of the skull. The mice’s internal organs were visible in the abdomen as well as the muscle contractions that move food through the digestive tract.
The transparent areas take on an orange color, Ou said, similar to the color of food.
FD&C Yellow No. The synthetic color is often used in orange or yellow colored snack chips, candy coating, ice cream and baked goods. However, a 2021 study by the California Office of Environmental Health Hazard Assessment linked the coloring to behavioral difficulties and reduced attention among children. A state bill, if signed into law, would ban the use of food coloring in food served in California public schools.
Ou said it was important that the dye be biocompatible – safe for living organisms. “Also, it is very cheap and effective; we don’t need much of it to work,” he said.
Potential biomedical applications for humans
The researchers have not tested the process on humans, and it is unclear what dye dose or delivery method would be necessary. Human skin is about 10 times thicker than mouse skin, according to the researchers.
“Going forward, this technology could make veins more visible, facilitating … the procedure of drawing blood or giving fluids through a needle – especially for elderly patients with hard-to-find veins,” said senior author Guosong Hong, an assistant professor at Stanford. material science, by email.
“Furthermore, this innovation could aid in the early detection of skin cancer, improve light penetration for deep tissue treatments such as photodynamic and photothermal therapies, and make laser-based tattoo removal simpler.”
Christopher Rowlands, a senior lecturer in the bioengineering department at Imperial College London, said he was “kicking himself” not to have the same insight as the Stanford-led team, which is based on widely studied physics and has been around for a long time. a principle known as the Kramers-Kronig relationship: When a material absorbs a lot of light of one color, it will bend more light of other colors.
“It’s pretty obvious when someone notices it, but nobody thought about it for 100 years and something,” said Rowlands, who was not involved in the study but wrote a commentary published alongside the research.
Along with Jon Gorecki, an experimental optical physicist at the same institution who was also not involved in the study, Rowlands wrote that the approach offered a new way to safely visualize the structure and activity of deep tissues and organs in a living animal. , a temporary and non-invasive method.
“It just works. You rub it on a mouse, and you can see what it had for breakfast. It’s so powerful,” he said.
Rowlands and Gorecki said existing methods for turning tissue transparent use solutions that have side effects such as dehydration and swelling and can alter the structure of the tissue. However, tartrazine was used at a low concentration, and its effects were easily reversed, which could facilitate long-term study of biological processes in living animals, they wrote.
Both noted that the discovery is an example of life imitating art, with the dye solution echoing the serum imagined in “The Invisible Man”.
“The main character (in the story) invents a serum that will make the cells in his body transparent by precisely controlling their refractive index to match the surrounding medium, air,” they wrote.
“One hundred and twenty-seven years later … biocompatible dyes make living tissue transparent by tuning the refractive index of the surrounding medium to match the index of the cells.”
However, Ou and Hong said that a completely invisible mouse was a stretch: The current approach cannot make bone transparent.
“Until now, we have only tested soft tissues, including brain, muscle and skin. We haven’t done much research with hard tissues like bone, so I’m not sure if we’ll be able to make the mouse completely invisible,” Ou said via email.
“However, a partially transparent mouse (mouse) will already enable many research opportunities to answer questions related to development, regeneration and aging.”
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