Dye used in snacks can make rats’ skin transparent, study says

In H.G. Wells’ 1897 science fiction novel, “The Invisible Man “, the protagonist invents a serum that makes your body cells transparent by controlling how they bend light.

More than 100 years later, scientists have discovered a real-life version of that substance: A commonly used food coloring can temporarily turn a mouse’s skin transparent, allowing scientists to see the workings of its organs, according to a new study published last Thursday (5) in Science magazine.

The discovery could revolutionize biomedical research and, if successfully tested in humans, have wide-ranging applications in medicine and healthcare, such as making veins more visible for blood sampling.

Researchers made the skin on the skulls and abdomens of live mice transparent by applying a mixture of water and a yellow dye called tartrazine. The mice’s skin was shaved before the solution was applied, and washing off the remaining solution reversed the process, which caused no harm to the animals.

“For those who understand the fundamental physics behind this, it makes sense; but if you’re not familiar with the concept, it seems like a magic trick,” Zihao Ou, lead author of the study and an assistant professor of physics at the University of Texas at Dallas, said in a statement.


Time-lapse of blood vessels in the brain, just below the skull of a sedated mouse, revealed by staining the tissues with tartrazine; the process involves no surgery, incisions, or damage to the mouse's bones or skin

Light-absorbing dye molecules

The “magic” uses knowledge from the field of optics. Dye molecules that absorb light increase the transmission of light through the skin, suppressing the fabric’s ability to scatter the glow.

When mixed with water, the dye changes the refractive index — a measure of how a substance bends radiation — of the watery part of the fabric to better match the index of proteins and fats in the skin. The process is similar to the dissipation of a cloud of fog.

“We combined the yellow dye, which is a molecule that absorbs most light, especially blue and ultraviolet, with the 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 most of the light that passes through them,” he said. “But when we put them together, we were able to achieve the transparency of mouse skin.” Once the dye had completely diffused into the skin, it became transparent.

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

The team experimented with chicken breasts before working with live animals.

In mice, researchers were able to observe blood vessels directly on the surface of the brain through the transparent skin of the skull. The mice’s internal organs were visible in the abdomen, as were the muscle contractions that move food through the digestive tract.


Photos showing the difference in transparency of chicken breast tissue after immersion in tartrazine solutions with increasing concentrations

The clear areas take on an orange color, Ou said, similar to food coloring.

The dye used in the solution is commonly known as FD&C Yellow No. 5, which is certified for use by the U.S. Food and Drug Administration (FDA). This synthetic dye is often used in orange or yellow snack foods, 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 span in children. A state bill, if signed into law, would ban the use of the food dye in meals served in California public schools.

He stressed that it is important for the dye to be biocompatible — that is, safe for living organisms. “In addition, it is very cheap and efficient; we don’t need much for it to work,” he said.

Possible biomedical applications for humans

The researchers have not yet tested the process on humans, and it is unclear what dosage or method of application would be needed. Human skin is about 10 times thicker than that of a mouse, the researchers said.

“Looking ahead, this technology could make veins more visible, making it easier to draw blood or administer fluids via needle — especially in elderly patients with hard-to-find veins,” senior author Guosong Hong, an assistant professor of materials science at Stanford, said in an email.

“In addition, 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 simpler.”


Before-and-after images show how the dye allows researchers to see a mouse's organs by making its skin temporarily transparent

Christopher Rowlands, a senior lecturer in the department of bioengineering at Imperial College London, said he was “bummed” that he had not had the same insight as the Stanford-led team, which relied on a long-standing and widely studied physical principle called the Kramers-Kronig relations: When a material absorbs a lot of light in one color, it bends more light in other colors.

“It’s totally 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 research.

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

“It just works. You rub it on a mouse, and you can see what it had for breakfast. It’s so powerful,” Rowlands added.

Rowlands and Gorecki explained that existing methods for making tissue transparent use solutions that cause 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.


The dye FD&C Yellow No. 5 was used at a low concentration in the study and its effects were easily undone, according to the researchers.

The pair noted that the discovery is an example of life imitating art, with the dye solution echoing the serum imagined in “The Invisible Man.”

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

“One hundred and twenty-seven years later… biocompatible dyes render living tissue transparent by adjusting the refractive index of the surrounding medium to match that of the cells.”

However, Ou and Hong said a fully invisible mouse is still unlikely: the current approach cannot make bones transparent.

“So far, we have only tested soft tissues, including brain, muscle and skin. We haven’t investigated hard tissues, such as bones, much, so I’m not sure if we would be able to make the mouse completely invisible,” Ou said in an email.

“However, a partially transparent mouse will already allow for numerous research opportunities to answer questions about development, regeneration and aging.”

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This content was originally published in Dye used in snacks can make rats’ skin transparent, says study on the CNN Brasil website.

Source: CNN Brasil

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