The title suggests Magritte has escaped from his exhibition at the Museum of Modern Art in New York and is writing this week’s post. Recently, in the Bali Bird Park near Ubud, Indonesia I saw a remarkable hornbill bird from Africa with what looked like eyelashes; really looked like eyelashes. Yes, of course I know that eyelashes are limited to mammals and that they are hairs made up of alpha keratins, and that birds do not have alpha keratins, and that feathers have beta keratins. I have known that since I was a resident in Howard Baden’s laboratory at Massachusetts General Hospital. Howard is interested in many aspects of skin biology and chemistry, and I was a junior researcher there, dodging the X-ray diffraction beams and studying the patterns of human epidermal keratins and their associated lipids. Howard had hundreds of grams of desquamated snake skin in the laboratory for his comparative keratin research.
Many hornbill species have tiny cylindrical eyelid feathers that mimic eyelashes and serve the function of eyelashes — keeping foreign material from the eyes. In hornbills it is suggested that they may also serve as mini-hats, shielding the eyes from sunlight.
It is unknown, but unlikely, whether many of our readers have seen the “Hunger Games,” in which Effie Trinket, who escorts the female tributes, has feather-like eyelashes. This has started a fashion trend in those many generations younger than this blogger, and Effie, her clothes, and the eyelashes, will surely be featured on some trick-or-treaters. Applying those feather-like eyelashes is harder than one might expect, so leave yourself enough time.
Thinking about this blog for the past year, I recognize that hair, feathers, and birds appear as topics more than would be randomly expected. Why is that? I can see at least two reasons: my early experience in Howard Baden’s laboratory and growing up in Brooklyn, within walking distance to Prospect Park and its zoo, where my eyes and mind could contemplate the wondrous skin and appendages of many zoo animals. Certainly an ideal upbringing for someone who spends his personal and scientific life searching out the wonders of the natural world.
Two articles in Science Translational Medicine (Sept 25: Wolk et al, 2013; Clark, 2013) triggered a stream of consciousness response and lead to this proposal. There are not enough productive jamfests between clinicians and scientists to keep advancing research. The articles related to skin TH17 cells in psoriasis producing IL-29 (a gold cytokine on the cytokine hit parade); Il-29 triggers production of several antiviral proteins, whose abbreviations are well known to their friends but not others. This research was stimulated by the clinical observation, known forever (meaning before I trained), that patients with atopic dermatitis often have disseminated herpes simplex infections, while patients with extensive psoriasis do not. This old (no, very old) observation now may have a scientific basis. Why did it take decades to perform this research? The most obvious reason is that methodology in cell and molecular science needed to reach a certain stage just to perform the studies. The other, more subtle, point is that no one thought of, or had funding and a group on which to test, such a hypothesis. A German group gets the gold ring for these findings.
Just as interesting is the accompanying perspective by Rachael Clark, reviewing several aspects of the skin’s immunological response. In addition to scientific detail are the author’s remarks about whether mouse models will be completely applicable to human disease. This was the topic of a previous post in this space (January 15, 2013) which yielded many comments from our readers. Dr. Clark is in Boston, home of the Red Sox, and she uses an analogy that mouse studies bring us to third base but may not be sufficient to bring the runner home for understanding human disease. I realize this may not be the most international sports model and would appreciate a soccer analogy to complement the baseball one.
Thus, my idea: there is a need to bring physicians and laboratory scientists together to brainstorm and be creative. This could be at local (institutional), national, or international levels, to share what each group of individuals knows and what they need and desire to know. This should be an ego-free zone, for most productivity. National clinical and/or scientific societies can convene the meetings and set ground rules. Sure, involve industry. The need for rapid progress is too compelling to let the naysayers overrule the usefulness of this proposed jamboree. I hope our commenters will refine and continue these discussions.
Montagna Symposium on the Biology of the Skin
Sunday October 13, 2013
By Guest Bloggger Sancy Leachman, MD, PhD
Welcome to the final day of the Montagna Symposium on the Biology of the Skin 2013. The dinner speaker last night was John Parrish (in absentia via video), complemented by symposium co-leaders Barbara Gilchrest, Rox Anderson, and Steve Jacques. It was powerful. John took us through a tour of his adventures in the development of photo-related innovations, from the development of effective sunscreens to therapeutic lasers, and he shared social context along the way. The sustained level of energy and impact he has brought to our field is remarkable. What was clear is that he has been simultaneously driven and humbled by his role as an innovator in dermatology; and the level of intensity he communicated seemed to be fueled by the success he had in making a meaningful contribution for patients. It was also clear that he actively selected important and interesting problems to solve. The video resonated with so many in the audience because we glimpsed the opportunity to apply similar principles to our own work with the possibility of making a difference in the pain and suffering of patients. Our challenge, and one that was tackled in the final session of the meeting (Provocative Problems and Questions), is to harness the energy of the best and brightest minds in our field toward a unified vision to benefit our patients.
Of the provocative presentations, one that struck a chord with me was by Richard Weller, who suggested that despite our understanding that UV radiation causes skin cancer, there is no definitive data to prove that it shortens lifespan. In fact, exposure to UVA may lead to NO2 and NO3 release by the skin that could lower blood pressure and extend life. The presentation of his data and the lively discussion surrounding the pros and cons of sun exposure that ensued was invigorating. It was a fabulous example of the power of academic discourse, where opposing points of view can be clearly articulated and critiqued. Dr. Parrish’s presentation on the previous evening emphasized skepticism by the dermatology community when he first presented data demonstrating the beneficial effects of UV radiation on psoriatic skin. I can imagine this being similar to the skepticism that Dr. Weller experienced today.
Additional lively discourse occurred around the role of business in dermatology and the development of partnerships between industry and academia during the last session in the conference. At the time when Dr. Parrish completed his studies, there was little funding available for clinical trials from the NIH, but there was more support available from the hospital and discretionary clinical income. Now, both NIH funding and clinical revenue are diminishing, and to continue to support innovation and clinical trials for the benefit of our patients, it is going to be necessary to identify additional support, perhaps through industrial partnerships and patient-based philanthropy. Future dermatologic advances must be driven by innovation and the development of devices and treatments that create value, that help make our patients better.
These and other topics will be continued and extended at next year’s Montagna Symposium on the Biology of the Skin on Aging of the Skin to be held at the Salishan Resort on the Oregon Coast, Oct. 9-13, 2014. Don’t miss it!
Montagna Symposium Blog
Skamania Lodge, Stevenson, WA
Saturday, October 12, 2013
By Guest Blogger Sancy Leachman, MD, PhD
Good morning from Skamania Lodge as we start day two of the Montagna Symposium on the Biology of the Skin 2013. I want to share a “quintessential Montagna” experience I had last night at the faculty dinner at Nora’s in Hood River (where only local food and wine are served!). I sat directly across from Rox Anderson and we returned to a conversation we had started about 4 years ago. I had explained my frustration with performing autologous pigment cell transfers for vitiligo and the need for a device to simply and easily transfer non-scarring epidermal grafts to a prepped affected surface. Last night, I found out that he (and his wonderful team) created such a device and that it became commercially available about 6 months ago!! Not only that, the story behind it is inspiring. Rox gave this project to an engineering student that came to him through a program for developing countries. Once the device was created (Momelan, derived from “more melanin”), it was licensed to KCI with the stipulation that a portion of the product be supplied to developing countries at a substantially discounted rate. Wow – from a problem, to an idea, to a mentorship, to a product, to a venture-based solution – this is the way it is supposed to work! I will be purchasing one of these devices next week.
The hike on Eagle Creek Trail was strategically scheduled after a very exciting, but sophisticated session on imaging and microscopy led by Steve Jacques. Again, this session was “quintessential Montagna,” but in a completely different way. Biomedical optics, photonics, and technical details of non-invasive imaging devices are “over my head” scientifically, but I have always loved science fiction. When I was a kid, I read every Jules Verne book I could find – I loved the idea that dreaming about using a technology that didn’t exist could inspire someone to create that technology (think “Nautilus” in 20,000 Leagues Under the Sea). For me, that’s the way this Montagna session felt, like I was living in the development phase of a science fiction novel. The technology presented in this session will undoubtedly revolutionize the way that we practice dermatology, and I feel lucky to be here to learn about it at the ground-level, directly from the inventors and developers. In today’s world of super-sub-specialization and information overload, cross-fertilization between diverse specialties is priceless because it is the foundation of team science. Team science will be mandatory as we choose to solve increasingly difficult problems requiring diverse expertise. This session is a jump-start to that process. As a concluding thought for the day, I would also add that this marriage between medicine and technology is likely our best strategy for reducing health care costs in the long-term. Only by doing it “better, cheaper and faster” can we hope to simultaneously improve health care and reduce costs.
Montagna Symposium on the Biology of the Skin
Skamania Lodge, Stevenson, WA
By Guest Blogger Sancy Leachman, MD, PhD
Greetings from the Montagna Symposium! As many of the “old-timers” in dermatology know, this topic-directed symposium on the biology of the skin has a tradition of identifying the most important scientific breakthroughs in dermatology and of recruiting leadership to develop a cutting-edge program around that topic. All of this intellectual excitement occurs in relative seclusion (this year in the Columbia River Gorge) to foster an atmosphere of reflective collegiality and collaborative problem solving.
This year’s selected topic is “Light and the Skin: How Light Sustains, Damages, Treats, Images, and Modifies Skin Biology” and the program has been developed by four world-renowned leaders in the field of photobiology and pigmentation: Rox Anderson (Program Chair), and David Fisher, Barbara Gilchrest, and Steven Jacques (Session Chairs). Together, they have worked with Molly Kulesz-Martin (Symposium Director) to create a thought-provoking program exploring the biological effects of light and how light can be used to image and treat the skin. My motivation to blog throughout this meeting is to transmit some of the energy and excitement we are experiencing to dermatologic scientists that are unable to be present this year, including our friends from the NIH who are unable to attend secondary to the government shutdown.
One of the topics that struck me as being particularly intriguing or paradigm challenging was that of pigmentation diversity. Why is there so much diversity of human pigmentation and how does that impact the risk for skin cancer including melanoma? I found it quite thought-provoking to consider the multiple functions of MC1R, not just in pigmentation, but also in the oxidative stress/DNA damage responses, apoptosis, and curiously, in the role it appears to play in addiction and pain sensation. These multiple cellular and molecular roles suggest that melanocytes play roles in the skin beyond production of pigment and may be important mediators of other neurological (e.g. pain) or light sensing processes. There is clearly a complex interaction between pigmentation genes, skin phenotypes, and environmental exposures to UV that, as Dr. Gilchrest mentioned, “are likely to be coordinately regulated toward a common purpose and selected by nature to safeguard and protect the genome, which in skin translates into cancer prevention. Unfortunately one of these safeguards is phtoaging.” Some of the most interesting conversation I heard on this topic was “off-line.” Nina Jablonski’s work was discussed from the perspective of a strong evolutionary pressure for lightening of the skin (via MC1R heterogeneity) as human migration extended into Northern, light-poor regions. It was suggested that part of this evolutionary pressure might be related to decreased maternal/fetal survival in individuals with rickets. It struck me that MC1R polymorphism effects on both pigmentation and pain might represent a remarkably efficient biological use of a single molecule, simultaneously reducing vitamin D deficiency and pain associated with sunburn. Finally, concern was expressed that investigation of pigmentation diversity has been hampered by a fear that such research may be interpreted as racial or discriminatory in nature. Spanning the fields of genetics, biochemistry, medicine and evolution highlights the purpose and strength of the Montagna.