A study has shown that a common food dye can make mouse skin transparent.

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In H.G. Wells’ 1897 science fiction novel The Invisible Man, the protagonist invents a serum that makes the cells in his body transparent by controlling the way they refract light.

More than 100 years later, scientists have discovered the real thing: A common food dye can make the skin of mice briefly transparent, allowing scientists to watch their organs work, according to a new study published Thursday in the journal Science.

The breakthrough could revolutionise biomedical research and, if successfully tested in humans, could find wide application in medicine and healthcare, for example by making veins more visible for blood sampling.

Scientists made the skin on the skulls and bellies of live mice transparent by applying a mixture of water and a yellow food coloring called tartrazine. Washing off the remaining solution reversed the process, which did not harm the animals. The mice’s fur was removed before the solution was applied.

“For those who understand the basic physics behind it, it makes sense; but for someone who isn’t familiar with it, it looks like a magic trick,” the study’s first author, Zihao Ou, an assistant professor of physics at the University of Texas at Dallas, said in a statement.

“Magic” uses insights from the field of optics. Light-absorbing dye molecules enhance light transmission through the skin by suppressing the tissue’s ability to scatter light.

When mixed with water, the dye modifies the refractive index—a measure of how a substance bends light—of the water portion of the tissue to better match the ratio of proteins and fats in the tissue. The process is like a cloud of fog dissipating.

“We coupled a yellow pigment, which is a molecule that absorbs most light, especially blue and ultraviolet light, to the skin, which is a scattering medium,” said Ou, who conducted the study as a postdoctoral researcher at Stanford University in California.

“These two things individually block most of the light from coming through,” he said. “But when we combined them, we were able to make the skin of the mice transparent.”

Once the dye had completely penetrated the skin, it became transparent.

“It takes a few minutes for the clarity to appear,” Ou said. “It’s similar to how a cream or face mask works: the time it takes depends on how quickly the molecules diffuse into the skin.”

Before the team began testing on live animals, they experimented with chicken breast.

In mice, scientists were able to observe blood vessels directly on the surface of the brain through the transparent skin of the skull. The internal organs of the mice were visible in the abdominal cavity, as well as the contractions of the muscles that move food through the digestive tract.

As Ou explained, the transparent areas turn orange, similar to the color of food coloring.

The dye used in the solution is commonly known as FD&C Yellow No. 5, certified for use by the U.S. Food and Drug Administration. The synthetic dye is often used in orange or yellow chips, candy coatings, ice cream and baked goods. However, a 2021 study by the California Office of Environmental Health Hazard Assessment linked the dye to behavioral difficulties and decreased attention in children. The state bill, if signed into law, would ban the food coloring from foods served in California public schools.

Ou said it’s important that the dye is biocompatible—safe for living organisms. “It’s also very inexpensive and efficient; we don’t need a lot of it to make it work,” he said.

Scientists have not tested the process in humans, and it is not clear what dose of dye or method of administration would be necessary. Human skin is about 10 times thicker than mouse skin, according to the researchers.

“Looking forward, this technology could make veins more visible, making it easier to…draw blood or administer fluids with a needle—especially for elderly patients whose veins are difficult to locate,” senior author Guosong Hong, an assistant professor in the Department of Materials Science and Technology at Stanford University, said in an 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 tattoo removal easier.”

Christopher Rowlands, a senior lecturer in bioengineering at Imperial College London, said he was “kicking himself” for not having thought of the same idea as the Stanford-led team, which relies on a widely studied and long-used physical principle called the Kramers-Kronig relations: When a material absorbs a lot of light of one color, it will refract light of other colors more.

“This is perfectly obvious when someone points it out, but no one has thought about it for over 100 years,” said Rowlands, who was not involved in the study but co-authored a commentary published alongside the study.

Rowlands wrote with Jon Gorecki, an experimental optical physicist at the same institution who was also not involved in the study, that the approach offers a new way to visualize the structure and activity of deep tissues and organs in a living animal in a safe, transient, and noninvasive way.

“It just works. You rub it on a mouse and you see what it ate for breakfast. It’s that powerful,” he added.

Rowlands and Gorecki said existing methods for making tissues transparent use solutions that have side effects, such as dehydration and swelling, and can alter tissue structure. But tartrazine was used at low concentrations and its effects were easily reversible, potentially facilitating prolonged study of biological processes in living animals, they wrote.

The duo noted that the discovery is an example of life imitating art, and that the dye solution references the serum imagined in “The Invisible Man.”

“The hero (in the story) invents a serum that makes the cells in his body transparent by precisely adjusting their refractive index to match that of the surrounding environment, the air,” they wrote.

“One hundred twenty-seven years later… biocompatible dyes make living tissues transparent by tuning the refractive index of the surrounding environment to that of cells.”

But Ou and Hong say a completely invisible mouse is overkill: current approaches cannot make bones transparent.

“So far, we have only tested soft tissues, including the brain, muscle and skin. We haven’t done much research on hard tissues like bone, so I’m not sure we could make the mouse completely invisible,” Ou said in an email.

“But the partially transparent (mouse) will already enable numerous research opportunities that will help answer questions about development, regeneration and also aging.”