( er. The secondauthor Scott R. Granter...)Fundamental Finding Yields Insight into Stem Cells, Cancer; Opens Door to Drug Discovery

er. The second author, Scott R. Granter, MD, is a pathologist at Brigham and Women’s Hospital. The American Cancer Society expects about 55,100 people to be diagnosed with melanoma, the most serious form of skin cancer, in 2004, with an estimated 7,910 deaths. Melanoma can be cured when it is detected and treated early, but if the lesion penetrates deeply into the skin it is often fatal. Sun exposure is a major risk factor in the disease, which has been increasing in the past several decades. Melanocytes, which manufacture and store the pigment that combines with hair-making cells called keratinocytes to color the hair, are specialized cells spawned by colorless melanocyte stem cells. These cells were discovered by Nishimura in 2002. A pool of undifferentiated melanocyte stem cells resides in the hair follicle, and during the hair’s grow-and-rest cycle, the stem cells give rise to color-making melanocytes that journey to the bottom of the hair follicle: That is where they tint the keratinocytes with the person’s characteristic hue. By studying mice at progressively older intervals, Fisher and his colleagues discovered that as the rodents aged and their hair began turning gray, the numbers of stem cells diminished in proportion to the loss of color. The scientists were surprised to observe that, at the same time and the same rate, differentiated, pigmented melanocytes were showing up in the follicle at the location where the stem cells resided. Since they were in the wrong place, the pigmented cells likely did nothing to maintain the mice’s hair color. To see if the cells behaved the same way in humans, the investigators examined human scalp tissue taken at increasing ages, and determined that the same pattern occurred. Since cell survival in general is influenced by an “anti-death?gene called Bcl2, Fisher’s team analyzed mice lacking this gene. In a dramatic fashion, the mice lost their melanocyte stem cells shortly after birth and quickly went gray. It may be that
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