Fair-skinned people who yearn for a suntan -- even though they know it's hopeless and unhealthy -- may one day have cause for celebration.

Harvard scientists have discovered new information about how the skin tans or -- in the case of fair-skinned people -- stubbornly refuses to tan due to a genetic defect. Using a skin treatment, they have turned pale skin dark, while also protecting it from ultraviolet-induced skin cancer.

"Darkening a person's skin may mimic the protective benefit seen in people who otherwise make a large amount of pigment," says researcher David E. Fisher, MD, PhD, director of the Melanoma Program at Dana Farber Cancer Institute in Boston. And that could translate into a reduction in the toll of the potentially deadly skin cancer melanoma, expected to be diagnosed this year in 62,000 people in the U.S. and to result in 8,000 deaths, according to American Cancer Society projections.

The study appears in the Sept. 21 edition of the journal Nature. Fisher cautions that the study was done only in animals. Using a topical cream instead of the sun's rays, Fisher's team was able to switch on the tanning mechanism in the skin cells of fair-skinned mice, turning them into olive-skinned animals.

"This has not been demonstrated in people and there is a lot that needs to be proven before it's ready for even a first attempt in clinical subjects," Fisher says.

Even so, the study was called intriguing by Meenhard Herlyn, DVM, PhD, a tumor biologist at The Wistar Institute, a research center on the campus of the University of Pennsylvania.

"What he clearly has shown is … you can induce a pigmentation, tanning, and the purpose is that people who are very susceptible to skin cancer, including melanoma, can be protected."

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'Accidental' Discovery

Like much of science, the finding was accidental, Fisher says.

"We were attempting to generate mouse models to study the ability of ultraviolet radiation to induce melanoma in the skin," Fisher says. They used mice whose fair skin came from the same genetic roots as fair-skinned people. "We ran into this technical difficulty, that no matter what we did, the red-haired mice sunburned. We've proven what people had known for thousands of years -- redheads don't tan."

But the finding, Fisher says, was much more rigorous evidence than the long-standing observation. They decided to take a closer look at what happens when the skin tans -- or in the case of fair-skinned people, doesn't tan.

In fair-skinned people, a receptor for the melanocyte-stimulating hormone, which induces pigment production from melanocyte cells, often has small changes in the genetic sequence, which make it function poorly. Fisher's team studied mice that were engineered to have this mutation.

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Role of UV Radiation

In their experiments, they found that UV radiation doesn't act directly on the melanocyte cells, as experts believe, but rather on neighboring skin cells called keratinocytes.

"The keratinocytes responded to UV radiation by making a huge amount of melanocyte stimulating hormone," he says. "It then secreted that and that hormone needed to find its receptor on the surface of the melanocyte." But if that receptor is faulty, as it is in fair-skinned people, tanning doesn't occur.

Then, they used a plant extract called forskolin, found in India, which bypassed the mutated receptor and starts the pigmentation process. The plant extract is known to activate an enzyme "one step past the receptor" involved in pigment production, Fisher says.

"We applied forskolin once a day, five days a week," Fisher says. "Within a few days we could see the skin was starting to get dark. One hundred percent of them got dark. We extracted the melanin, and it was true melanin. We looked at it under the microscope. Everything about it was the same as a dark person's melanin."

Mice treated with the forskolin developed six tumors, while those not treated with it developed 11 tumors. At the end of the 50-week follow-up, the skin of the mice treated with the forskolin was still dark. Treatment of forskolin also prolonged the time until development of tumors as well from an average time of four weeks to 25 weeks.

Next, says Fisher, he hopes to validate that the pathway to tanning works the same in people. "We suspect there is a very good chance that is the case."

Herlyn calls the study "intriguing" because "it brings many pieces of a puzzle together in a very elegant way. If this bears out in humans, you can activate your pigmentation machinery without having to go into the sun."

While the study will have an impact on our understanding of how tanning occurs, practical applications are probably "years off," cautions Martin A. Weinstock, MD, PhD, chair of the American Cancer Society Skin Cancer Advisory Group and a professor of dermatology and community health at Brown University in Providence, R.I. "It's not like next month we will have the component that will make all this theoretical stuff possible."

Fisher emphasizes he's not suggesting anyone smear their skin with forskolin. Like Weinstock and Heryln, he recommends the use of sunscreens and other sun-protective measures, such as wearing a hat and long-sleeved clothing when out in the sun.

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SOURCES: David E. Fisher, MD, PhD, director, Melanoma Program, Dana Farber Cancer Institute; professor of pediatric hematology/oncology, Harvard Medical School, Boston. Meenhard Herlyn, DVM, PhD, tumor biologist; professor and chair of the Program for Molecular and Cellular Oncognesis, The Wistar Institute, Philadelphia. Martin A. Weinstock, MD, PhD, chairman, American Cancer Society Skin Cancer Advisory Group; professor of dermatology and community health, Brown University, Providence, R.I. Fisher D. Nature, Sept. 21, 2006; vol 443: pp 340-344.