Mark S. Blumenkranz, MD, MMS, H. J. Smead professor of ophthalmology, emeritus, is the 2019 Hewlett Award Winner

Hewlett Award Winner Mark S. Blumenkranz, MD, MMS: “I love what I do. It’s like a dream.”

The Albion Walter Hewlett Award is a Department of Medicine-sponsored award honoring an exceptional physician with ties to Stanford. It is named for Albion Walter Hewlett, professor and executive head of the Stanford Department of Medicine from 1916 to 1925, who was renowned for his outstanding contributions to patient care and medical science.

The 2019 winner of the Hewlett Award is Mark S. Blumenkranz, MD, MMS, H. J. Smead professor of ophthalmology, emeritus, for whom the word “polymath” might have been coined. An extraordinarily gifted eye surgeon with a focus on vitreoretinal diseases, he has also succeeded in such administrative roles as head of the vitreoretinal service; department chairman for 18 years; and involvement in the planning, fundraising, and construction of the Byers Eye Institute of Stanford, which he served as founding director between 2010 and 2015.

In addition to his medical, surgical, and administrative skills, Blumenkranz has academic talents that span service on journal editorial boards, as president of specialty ophthalmology societies, on the steering committee of the Audacious Goals Initiative of the National Eye Institute, and as a Fellow of the Corporation of Brown University, his alma mater, where he chaired the Medical School Committee for a dozen years.

How It Began

He has done all of this atop bachelor’s, master’s, and medical degrees from Brown; internship and residency at Stanford; and fellowship at Bascom Palmer Eye Institute, after which he joined the faculty there in 1980. This was followed by his founding a highly regarded vitreoretinal fellowship training program at William Beaumont Eye Institute in 1985. Finally, in 1992, he returned to Stanford to head the vitreoretinal service before stepping up to become chairman of the department in 1997.

His professional trajectory was impressive from the start. He chose Brown University in part because it offered an integrated undergraduate and graduate program in medicine and additionally was one of the few coed Ivy League schools at the time (and it happens that he met his wife Recia there): “I was particularly interested that Brown did a good job of focusing on its undergraduate education. Rhode Island has been known as a free-thinking state since colonial times, a place where you could be your own person with less need to be a conformist in religious or secular matters. The year I was a freshman Brown changed to an open curriculum where you had a lot of freedom to experiment and create your own major, and there were no mandatory grades. You were in charge of your own education, which suited my instincts to be self-directed.”

What led him to select ophthalmology as his specialty? “As I got into general surgery as an intern, I realized that I liked microsurgery the most, and of all the microsurgeries ophthalmology was to me the most interesting in terms of fine motor control required for successful results and the elegance of the eye as a finely tuned-optical and neurosensory system. One thing I noticed on my ophthalmology rotations was how grateful patients were and how much immediate gratification you experienced as a surgeon. Coupling that with basic science, which I was always interested in, as well as  the advantages and challenges of working in a one-inch sphere, I stumbled on this idea of combining biochemistry and pharmacology with the more mechanical aspects of problem solving.”

“I had recognized that many of the major advances in medicine at that time had their earliest roots in ophthalmology including medical laser systems, novel microsurgical techniques, advanced medical imaging systems, and even the concept of large multicenter randomized clinical trials, of which the Diabetic Retinopathy Study was a good example. I reasoned that working in ophthalmic and vision science research would be a bridge to impacts in other medical specialties.”

From Lasers to Drugs to Gene Therapy

Between the 1970s and 2005, Blumenkranz, with his longstanding collaborator and colleague at Stanford Daniel Palanker, PhD (professor of ophthalmology), worked extensively with lasers, including inventing the Pascal photocoagulator and the Catalys Femtosecond Laser, to treat vitreoretinal diseases and cataract. “There was no field of pharmacology for retinal diseases when I started,” he says. “There were no drops or pills for the retina: drops didn’t get to the back of the eye, and there wasn’t a pill you could take that would improve a retinal disease. That changed dramatically when intravitreal antibiotics and steroids came along – the first effective retinal therapeutic. Now that has been further expanded to the remarkable advances in retinal disease treatments with anti VEGF agents in which I have been a very active participant while at Stanford.”

The progression from lasers to drugs, while welcomed, left room for more innovation. Blumenkranz explains: “It occurred to me that we could use gene therapy to improve upon monthly anti-VEGF injections for patients with these diseases. We formed a company, Adverum Biotechnologies, which developed a way of substituting a gene therapy approach with DNA that would trick or program patients’ own pigmented  cells underneath the retina to secrete an anti-angiogenic protein. It’s in human trials now, and I’m encouraged. I hope it will be one of my lasting contributions: a durable therapy that could be curative as opposed to only ameliorative, but it is still early in the game and we’ll have to wait for the clinical results to know more.”

“With the recent introduction of Luxturna as the first FDA-approved gene therapy product in the United States, I feel that same extension from ophthalmic research to other areas of medicine is still occurring. I take particular pleasure in knowing that one of my fellows in vitreoretinal disease, Albert Maguire, MD, and his wife and collaborator Jean Bennett, MD, PhD, were the translational scientists who successfully introduced that therapy into human use. They did the very earliest exploratory studies in retinal gene therapy during that fellowship year and have since remained close friends and collaborators.”

And then there are the many other startup companies Blumenkranz co-founded: Peak Surgical; Optimedica Corporation; Oculeve, and Verana Health, that have products on the market that improved health care outcomes for patients. Most have been acquired by large medical device and pharmaceutical companies. For a decade he was Chairman of the Board of Adverum Biotechnologies. He is still a director of Verana Health, a health analytics and mobile ophthalmics diagnostic company, and Lagunita Biosciences LLC, an early stage biotech and medical investment company which has a number of younger startups in the area of ophthalmology and protein therapeutics in its pipeline.

Creating an Incubator for Innovation

How does a talented ophthalmologist with a full career of operating and inventing, merging ophthalmic science with pharmacology, designing essentially better mousetraps approach retirement? In his own way, contributing, passing along his learnings, coming up with yet more new ideas. In his words, “Now that I have just officially retired from Stanford I’m still active with the university. I felt that we could use something that was akin to Biodesign but specific to ophthalmology. So my principal focus the last three years has been working to assist the new Chairman, Jeff Goldberg, MD, PhD, in terms of teaching, mentoring, and philanthropy, and then creating a program in ophthalmic innovation. It’s built upon the principles of the Biodesign program which I believe in very deeply and have been a small part of. But it is specific to ophthalmology and it takes up where residency and clinical practice end and extends it to include all the things that you think about when you really want to take translational medicine to the next level and make it readily available to patients.”

“It’s a way to help to institutionalize some of the basic principles that go into the introduction of products into clinical practice: the regulatory piece, the clinical trial design, the strategic marketing, the reimbursement channels, the protection of intellectual property, the development of a high-performance organizational structure, all those things that are really not taught in medical school or in residency.”

“We take fellows every year who have already been trained either in vision science or in ophthalmology who are headed toward a career typically in academic medicine but possibly in industry or clinical practice and we teach them those principles. I’m going to spend the last part of my career trying to foster innovation and to teach some of the basic principles: the better ways to do things and the worst ways to avoid; the principles of organizational behavior and how you create high-functioning teams. These are very valuable skills particularly because a lot of promising therapies never make it to patients, not because they are not intrinsically worthwhile but because you have to get a lot of things right and in the right order. It’s a complicated dance.”

Not only has Mark Blumenkranz’s career been professionally worthwhile but, in his words, “I still really enjoy myself. I cannot imagine having had a more interesting and personally rewarding career. I get to help people and I get to teach and do research. It’s a gift to be here at Stanford.”