Member SpotlightsA Reasoned Approach Links Medical Training and Scientific Thinking: A Personal Memoir from Iran Behrooz Kasraee, MD A Member Since April 2002  I was born in 1974 in Shiraz, Iran. After successfully passing the annual examination, Konkoor, I was accepted as a medical student at the Shiraz University of Medical Sciences. Out of the 25,000 students who had participated in the examination in 1993, I was ranked 10th. I was thirsty to learn medicine and valued the opportunity to examine new ideas and to discover new ways for treating diseases.However, at the university things were slightly different from what I expected. As medical students, we were solely encouraged to memorize the information given -- or "injected into our brains" by our professors. The better we memorized, the better students we were. There was no room for new ideas. After three semesters of studying medicine this way, I had totally lost interest in learning this knowledge. At this time, I decided to pursue what I was interested instead and decrease my efforts towards learning what I did not like. I believe that humans can make great progress only when they pursue what they love to do rather than what they see only as a duty. Three years before entering medical school, my grandmother died of malignant melanoma, and I used to dream about discovering a new, effective drug capable of killing melanocytes and curing melanoma. I was therefore personally motivated to study about melanocytes and became interested in melanocytotoxic and skin depigmenting agents. Depigmenting agents are used for the treatment of skin hyperpigmentary disorders and, at present, safe and effective skin depigmenting chemicals are lacking. The enzyme tyrosinase, commonly considered as the sole enzyme involved in melanogenesis, has long served as a target for the development of melanocytotoxic and depigmenting agents. Like other investigators in this field, I focused on tyrosinase substrates and searched for inhibitors to such agents. Since tyrosinase initiates melanogenesis, skin depigmentation would occur if melanogenesis is inhibited. In theory, my hypothesis seemed quite straightforward. I began to topically apply tyrosinase inhibitor chemicals to black guinea pig skin, but -- to my surprise -- no skin depigmentation occurred. The next time I repeated the experiment, I chose chemicals with more potent tyrosinase inhibting ability, but the result was still the same: no changes in pigmentation. Every time that the experiment failed, I felt greatly disappointed, but I continued to examine other agents. During my five years of work on depigmenting chemicals, I tried many agents -- from benzoic acid to the potent tyrosinase inhibitor, alpha-methyl-p-tyrosine -- but all were ineffective. I finally came to the conclusion that something may be wrong. "Do the existing skin depigmenting chemicals really act by the inhibition of tyrosinase?" "If so, why couldn’t I produce skin depigmentation by this way?" After carefully reviewing the literature, I recognized that there was not a good correlation between the depigmenting activity of chemicals and their ability to inhibit tyrosinase. There were some skin depigmentors that had the ability to inhibit tyrosinase, however, not all depigmenting agents had such an ability. Neither were all tyrosinase inhibitors capable of producing skin depigmentation. I thought that the traditional way of using tyrosinase inhibitors to find skin depigmentors was not very productive and tried to focus on melanogenesis pathway targets other than tyrosinase. The enzyme peroxidase was once believed to play a major role in initiating melanin synthesis by only a few investigators such as Dr. Milton R. Okun, but this idea was discounted by several studies and eventually ruled out. However, other studies indicated that peroxidase actually plays a role in the final steps of melanin synthesis. Therefore, peroxidase might indeed be an important enzyme in melanin synthesis, although it was never used as a target for identifying new depigmenting or melanocytotoxic agents. Through my research, I discovered that there was a good correlation between the skin depigmenting ability of different chemical agents and their ability to inhibit peroxidase activity. Surprisingly, the unknown depigmenting mechanism of many agents, such as glucocorticoids and indomethacin could be convincingly explained by their ability to inhibit peroxidase activity. The ability to inhibit peroxidase was also exhibited by the tyrosinase inhibitors which could produce skin depigmentation. The enzyme peroxidase was once believed to play a major role in initiating melanin synthesis by only a few investigators such as Dr. Milton R. Okun, but this idea was discounted by several studies and eventually ruled out. However, other studies indicated that peroxidase actually plays a role in the final steps of melanin synthesis. Therefore, peroxidase might indeed be an important enzyme in melanin synthesis, although it was never used as a target for identifying new depigmenting or melanocytotoxic agents. Through my research, I discovered that there was a good correlation between the skin depigmenting ability of different chemical agents and their ability to inhibit peroxidase activity. Surprisingly, the unknown depigmenting mechanism of many agents, such as glucocorticoids and indomethacin could be convincingly explained by their ability to inhibit peroxidase activity. The ability to inhibit peroxidase was also exhibited by the tyrosinase inhibitors which could produce skin depigmentation. My results were accepted for presentation at the "The 9th Congress of the European Academy of Dermatology and Venereology" in October 2000 in Geneva, Switzerland. It was in Geneva that I had the opportunity to meet and discuss my work with some of the most famous investigators in the field such as Professor W. Westerhof, Professor K.U. Schallreuter and Professor J.H. Saurat. After my discussion with Professor Saurat, who is the head of the department of dermatology of the Cantonal University Hospital of Geneva, he kindly provided me with an extendable one-year study grant for research and training in his department. My article about the depigmenting potential of methimazole is published in the Journal of Investigative Dermatology (Kasraee B, J Invest Dermatol, 2002; 118:205-207). My hypothesis about "the involvement of peroxidase-mediated mechanisms in the melanocytotoxic and melanogenesis inhibiting effects of chemical agents" has also been sent for publication in the journal, Dermatology. I think that peroxidase may serve as an effective target for the discovery of melanocytotoxic/depigmenting chemicals. I also believe that peroxidase might play a more important role in melanogenesis than what is currently believed. In the near future, I am planning on moving to Geneva to continue my research on new types of depigmenting and melanocytotoxic agents and to be trained as a dermatologist. I am also very interested in furthering my dermatology training in the United States. When I am not conducting experiments, I enjoy painting and surfing the Internet. ### << Previous Next >> [ View All Member Spotlights ] |
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