Invention in Dermatology: A Review

The development of new medications can take many years. An example of the extended time frame for development of new pharmaceuticals is the story of vismodegib, with scientific research dating back to the 1960s when cyclopamine was identified as a responsible compound for one-eyed lambs resulting from the consumption of corn lilies by the mother.¹⁴ In 1995, the Nobel Prize in Physiology/Medicine was awarded for the identification of genes including Hedgehog that control embryonic development.¹⁵ In 1998, Genentech conducted a search of compounds that inhibit the Hedgehog pathway, and in 2004, Genentech identified vismodegib and conducted preclinical research in collaboration with Curis. An investigational new drug application for vismodegib (GDZ- 0449) was filed with the U.S. Food and Drug Administration. After a multi-phased development process, the FDA approved vismodegib for the treatment of adults with metastatic basal cell carcinoma or with locally advanced basal cell carcinoma that has recurred following surgery, and who are not candidates for surgery, and who are not candidates for radiation in January 2012, twenty-four years after Genentech initiated their search for compounds that inhibit the Hedgehog pathway.¹⁶ Inventing new therapies takes significant time and resources.

Medical Devices
In the arena of medical devices, dermatologists have been very inventive and productive. The history of phototherapy dates back 3,500 years when plant extracts and seeds were combined with sunlight to treat “leukoderma”.¹⁷ Modern phototherapy was initiated in 1903 when Niels Finsen received the Nobel Prize for Chemical Rays Lamp Therapy of Tuberculosis.¹⁸ In 1974, Drs. Parrish, Fitzpatrick, Tanenbaum, and Pathak published their experience with photochemotherapy of psoriasis with oral methoxsalen and long-wave ultraviolet light in the New England Journal of Medicine.¹⁹

The development of lasers has been fruitful ground for dermatologists, as well. In 1959, the laser was invented by physicist T. H. Maiman with the development of the flashlamp pumped ruby crystal laser.²⁰ Laser therapy was brought into clinical practice by Dr. Leon Goldman with the use of continuous-wave ruby laser followed by the introduction of argon, carbon dioxide, and neodynium-YAG laser. In 1983, the seminal therapy of selective photothermolysis was advanced by Drs. Rox Anderson and John Parrish.²¹ In 2003, Anderson and Manstein developed the concept of fractional thermolysis, a new concept for cutaneous remodeling using non-continuous application of energy to cause controlled thermal injury.²²

Health Care Information Technology
In health care information technology, the development of the Melanoma Outcome Calculator by the Laboratory for Qualitative Medicine at Massachusetts General Hospital allowed rapid access to patient-specific melanoma prognostic information based on SEER database.²³

The invention of the Contact Allergen Replacement Database by James Yiannias, M.D., from Mayo Clinic in Arizona turned on its head the usual questions associated with avoidance of contact allergens. Prior to the development of the Contact Allergen Replacement Database, physicians would share information with patients, advising what to avoid. In a clever twist, Dr. Yiannias developed a database which catalogued all ingredients within common commercial topical products allowing patients to receive answers to the more important question: “What can I use safely?”

Diagnostic and Prognostic Assays
Developments within the field of dermatopathology have allowed more precise refinement of disease prognosis and outcomes for patients based on skin biopsies including the iconic contribution of Alexander Breslow, M.D., in the paper “Thickness, Cross-Sectional Areas and Depth of Invasion in the Prognosis of Cutaneous Melanoma”.²⁴

Recently, molecular based testing and analysis of melanocytic lesions and melanoma have become significant fields of interest. Emerging technologies include DermTech’s Adhesive Pigmented Lesion Assay, Myriad’s myPath Melanoma test, and Castle’s DecisionDx-Melanoma gene expression profile test designed to identify high risk Stage I and II melanoma patients based on biologic information from tumor tissue.

The Future of Invention in Dermatology
Opportunities abound for invention in the future within the field of Dermatology. From digital health solutions to molecular diagnostics, precision and individualized medicine, regenerative medicine, and effective behavioral medicine interventions, dermatologists have many practice gaps that can be filled with innovative and creative solutions. Participating in the “virtuous cycle of invention” allows dermatologists to maximize their positive impact on society while engaging in a stimulating and challenging career endeavor.

1. [No author listed.] United States Patent and Trademark Office. General information concerning patents. (October 2015). Retrieved from https:// www.uspto.gov/patents-getting-started/general-information-concerningpatents# heading-2

2. [No author listed.] “First American Medicine Patent- Today in History: April 30.” ConnecticutHistory.org, Connecticut Humanities, connecticuthistory. org/first-american-medicine-patent-today-in-history-april-30/.

3. U.S. Government Accounting Office (GAO) Report to Congressional Committees. May 7, 1998. "Technology Transfer, Administration of the Bayh- Dole Act by Research Universities"

4. The Bayh-Dole Act: It’s Working. Association of University Technology Managers website. https://www.autm.net/AUTMMain/media/Advocacy/ Documents/BayhDoleTalkingPointsFINAL.pdf. Accessed April 4th, 2018.

5. Fischer S. BIO Study Quantifies Economic Contribution of University & Non-Profit Inventions. Biotechnology Innovation Organization website. https://www.bio.org/media/press-release/bio-study-quantifies-economiccontribution- university-non-profit-inventions. June 21, 2012. Accessed April