Innovator Banks on 'Truly Smart' Robotic Lasers in Dermatology

Doug Brunk

September 15, 2020

It's hard to think of a clinician who has had more of an impact on dermatology in recent decades than R. Rox Anderson, MD.

Dr. R. Rox Anderson

Dr. Anderson, director of the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston, conceived and developed many of the nonscarring laser treatments now widely used in dermatology. These include selective photothermolysis for birthmarks, microvascular and pigmented lesions, and tattoo and permanent hair removal. He also contributed to laser lithotripsy, laser angioplasty, photodynamic therapy, and optical diagnostics. The highest-resolution imaging device approved for human use, an infrared confocal microscope, came from his laboratory. Dr. Anderson has also contributed to basic knowledge of human photobiology, drug photosensitization mechanisms, tissue optics and laser-tissue interactions. In this Q&A with Doug Brunk, he reflects on his achievements and on the future of lasers in dermatology.

In published interviews you have described yourself as more of a problem solver than an inventor. How did your upbringing foster your affinity for problem solving?

I grew up in Central Illinois during the 1950s and early 1960s, an area known for corn, soybeans, and hogs. At an early age I learned to be interested in other things because it's possible to die of boredom there. By the time I was 12 years old, I was an amateur radio operator, and I was building rockets to see how high they would go.

Problem solving comes naturally to me. I enjoy very much finding a problem that is worth solving, which means getting passionate about it and brainstorming. Half the time you don't come up with a potential route to solve the problem. I attended the Massachusetts Institute of Technology at the age of 17, which was a real eye-opener. I had never been east of the Wabash River prior to that. I studied physics for a while, then decided to flip into biology. That combination has served me well. My special sauce is to have some intuitive and academic rigorous feeling for physical processes. But we physicians have a front row seat to nature's human drama. There is no lack of problems to solve. I can sit around and obsess about things theoretically, but at the end of the day I want to work on things that ultimately benefit people.

What inspired you most early in your career as a physician scientist?

After I made a commitment to medicine, Dr. John A. Parrish, and Dr. Thomas B. Fitzpatrick were key mentors to me. I was 30 years old when I started medical school, but they took me under their wing even before that. I took a part-time, temporary job with them, which turned into a permanent job. That turned into a love for the work they did. Instead of going into a graduate program in a laboratory and studying bacteria and genetics, the whole idea of working with people and on people was awesome. Dr. Parrish really mentored me. I won a lifetime achievement award from the American Academy of Dermatology a few years ago. I found myself on stage and it rolled out of my mouth that John Parrish believed in me before I believed in myself. It's really true. He somehow recognized that I had some talents. I was very young and a combination of naive and humble, I guess.

What was the initial genesis for your idea of selective photothermolysis?

I was interested in going to medical school and working with Dr. Fitzpatrick and Dr. Parrish on things related to light. They were mostly interested in PUVA and UVB; it was the heyday of modern phototherapy. I attended a lecture at the Beth Israel Hospital in Boston given by a plastic surgeon, Dr. Joel Mark Noe. He was talking about using lasers to treat port-wine stains in children. The gist of the talk was that argon lasers were being used, and that the results were sometimes decent, but not great. Often children would have burn scars after the treatment. Dr. Noe was talking about how you had to choose the color of the wavelength of the laser to be absorbed by hemoglobin, but he wasn't talking about what happens to the heat once it's created. My background in physics led me to recognize that he wasn't capturing the full picture. Selective disruption of a target in the skin by light is half of the story. The confinement of heat in the target is the other half of the story. Literally on a bus on the way home from that lecture to my apartment in Cambridge, I hatched the idea for selective photothermolysis and wrote down some equations. I also wrote down the ideal wavelength region, how much energy was needed, and what the pulse duration would have to be like to damage target vessels that small. I showed John Parrish what I had written. He took me seriously and said, "Let's see if we can find a light source that can accomplish this." We traveled around the country looking at various lasers, but we wound up building the first pulsed dye laser for treating port-wine stains. To me, the surprise was that we didn't kill the skin. If you treat an area of skin with a laser and hurt all the blood vessels, you think, "Wait a minute. Are we going to kill the skin because it has no blood supply?" The questions of the day were so basic, and we just got lucky. It took 6-8 years before we ramped up the clinical studies showing efficacy and safety of this technology.

I presume that you experimented on your own skin while developing some of the nonscarring laser treatments now widely used in dermatology. What "war story" stands out to you most from that part of your work?

I'm right handed, so I'd grab a laser with my right hand and treat my left arm, so that arm sports a bit of history. In 1994, while working with Dr. Melanie Grossman on the development of laser hair removal, I used a ruby laser to self-treat a patch of hair on my left arm. I still have the world's oldest laser-induced bald spot on that arm. It's been 26 years now. I still look at it and count the hairs, because one of the big questions is, is laser hair removal permanent? In all these years I have grown two hairs.

What technology that you conceived of or developed has most surprised you, in term of its ultimate clinical impact?

I would say confocal microscopy. In the mid-1990s I worked with a physicist named Robert H. Webb, who invented an imaging system for the retina. We got together, noodled about it, and decided we would modify his ophthalmoscope system to see if we could get images from inside the skin. It worked pretty well. It was truly surprising from many points of view. First, it wasn't clear at all that we'd get any images this way. Now, reflectance confocal microscopy is a standard tool in both clinical and research dermatology. But there were odd discoveries early on. For example, the darker your skin, the brighter it appeared in the microscope. You might think that melanin absorbs light and that you would get poor images in dark skin. It was the exact opposite; melanin acts as a natural contrast agent.

We worked with a small company to make the first confocal microscope. Initially, it had no clinical applications but what was fascinating to me was the incredible value of being able to see inside human skin harmlessly, and just see what's going on. It became a potent research tool, and recently CPT codes were established for its use in evaluating skin cancer margins. I wouldn't be surprised if 30 years from now, taking a skin biopsy is seemingly barbaric. A forerunner of all these new imaging tools for the skin was the confocal microscope developed in my lab in 1994.

During a 2011 TED talk, you said that nevus of Ota is your favorite thing to treat, because the outcome is usually perfect skin. Are there other technologies or devices you played a role in developing that make you proud at this stage in your career?

The reason I love treating nevus of Ota is that you have a lifelong facial disfigurement, and the only treatment for it is a laser we came up with, and it always works. How perfect could it be? The flip side of the same coin is, there are lesions of the skin that just don't respond. One of the things we don't know enough about is the connection between the biologic aspects of repair of various lesions and the treatments that we come up with. The most recent example of selective photothermolysis is a new laser we're building right now for acne that is based on sebaceous gland injury. You'll see this coming out in the next year or two. My heart goes out to people with nodular cystic acne. For young men it's highly associated with suicide. So, I'm excited about optimizing and learning what happens when we target sebaceous glands.

One of the other big stories in laser dermatology is the fractional laser. I developed this with Dr. Dieter Manstein when he was a postdoc in my lab. One of the most pleasing things from this technology is how well you can rehabilitate scars, particularly burn scars in children. Over the last few years, I have trained plastic surgeons at the Shriners Hospital for Children in Boston on how to use fractional lasers to improve the lives of these kids. Another technology I developed with Dr. Manstein is cryolipolysis, which is removing fat from the body by cooling it. There are no lasers involved with this technology. I like to say that I've spent most of my career studying light and heat, and now we've come up with something that's cold in the dark. We are now working on derivatives of cryolipolysis, to determine if what we've learned about targeting fat that might be applicable elsewhere.

Who inspires you most in your work today?

In addition to Dr. John Parrish and Dr. Thomas Fitzpatrick, the late Dr. Albert M. Kligman also influenced me. He never accepted dogma and he loved to ask questions, like, "What if?" as opposed to just accumulating a fund of knowledge. Understanding things is not just based on how much you know. It's based on critical thinking and the ability to question. I also admire Albert Einstein, his ability to sit down with nothing more than pencil and paper and change our view of the universe. I love physics because it's the science of everything. I also love poetry. My favorite poet is Stanley Kunitz. He had amazing insight and was named United States Poet Laureate in 1974 and in 2000. I have plenty of antiheroes as well, mostly politicians.

I understand that you play the banjo. How long have you been playing, and what do you enjoy about it?

You cannot sit down and play the banjo and have your mind on much else. It's a wonderful moving meditation. Before my medical career, I was a schoolteacher in Vermont. There was a guy on the staff there who played banjo. He came from a small town in Georgia. I just picked it up and started plunking. It's a happy instrument. It's awfully hard to make the banjo sound melancholy.

What novel use of lasers and light in dermatology are you most excited about in the next 5 years?

The marriage of therapeutic devices with diagnostic and imaging devices has not happened yet. They are not even in the honeymoon moment. But I think that having truly smart robotic systems in our hands for treating patients will become a reality. These days, dermatologists have to buy a certain type of laser to treat a certain type of lesion. For example, the Q-switched alexandrite laser you buy for treating Nevus of Ota won't do anything for a port-wine stain; it's the wrong pulse duration. This means that clinicians who practice a lot of laser dermatology end up with a dozen lasers in their practice. In the future, I think it will be possible to have a software laser, so when you want to acquire another target, you load an App as opposed to buying a new laser. This means that you would have software programmable targeting, and you would not have the requirement of having selective absorption. So, I'm excited by the idea of guided fractional lasers. None of them exist now. We have to start from scratch.

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