Jennifer Doudna, ARVO/Alcon Keynote Lecture: CRISPR-Cas Gene Editing


Kareem Moussa, MD Mass Eye & Ear / Harvard Medical School

This week I had the distinct pleasure of interviewing Dr. Daniel M. Schwartz, MD, Professor of Ophthalmology and Director of the Retina Service at University of California, San Francisco (UCSF). Dr. Schwartz enjoys a stellar reputation as an astute clinician, beloved educator, mentor, and forward-thinking pioneer in Ophthalmology. We discussed his involvement in the development of the RxSight (formerly Calhoun Vision) light-adjustable intraocular lens and he shared valuable lessons on pursuing a career in ophthalmic innovation.

At what point in your career did you discover your talent for innovation? Were there any aspects of your medical training that fueled this interest?

As an undergrad I majored in philosophy, not science, and learned how to take a fresh look at things, not make assumptions or accept things for the way they are. As a resident I received a solid, broad exposure to ophthalmology at Wilmer, and having this broad exposure helped me to innovate outside of my specialty.

What inspired you to develop the RxSight lens? Can you briefly walk us through how the lens went from an idea to a final product? To what do you attribute the success of this lens?

I was sitting in clinic with one of my colleagues at UCSF and he was frustrated because one of his patients had a high residual refractive error after cataract surgery. This was in the mid 1990s when we were doing a lot of laser in retina for diabetic retinopathy, vein occlusions, and choroidal neovascularization. So, I thought, why don’t we try to use laser to change the refractive power of an intraocular lens? I had only a vague idea of how to approach the problem. After seeking help in the Chemistry departments of UC Berkeley and Stanford and coming up empty handed, l I went down to California Institute of Technology (Caltech) and met Dr. Robert Grubbs, a tremendous polymer chemist (Nobel Prize, Chemistry 2005), who figured out how to do it in a matter of minutes! From there, I got some seed funding from my chairman at UCSF, Dr. Steven Kramer, and we hired 2 post-docs who worked developing the technology at Caltech. Once we demonstrated feasibility in pre-clinical models at Caltech and University of Utah with Dr. Nick Mamalis, we moved the project off-campus and formed a start-up company to further develop the light adjustable lens for clinical use.

dan schwartz 2 The founders of RxSight: Robert Grubbs, PhD (left), Dr. Dan Schwartz, MD (center) and Chris Sandstedt, MD

The development of this took you many years. At what point in those 20 years first realize that the lens was going to be a success?

We had so many times when our hopes were lifted, and then dashed as unexpected technical issues arose, which we’d solve, and then our hopes were temporarily lifted again…. We had excellent and dedicated people in the company who persevered and made the final product successful and ultimately approved by the Food and Drug Administration (FDA) this past year.

What advice do you have for budding entrepreneurs who have a promising idea they would like to turn into a product?

Go for it! Don’t feel discouraged by the fact that you don’t have the scientific expertise to execute a project. I’ve found that scientists in other fields are enthusiastic about using their expertise to develop medical technology. In general, the first steps in developing an invention are to recognize a clinical need, find a novel way of addressing it, and then I think you need to get several reality checks. Go to your trusted friends who are in the specialty you are trying to innovate for. After that, I would talk to people who have been successful in developing projects in ophthalmology or other medical specialties. These people have a good Rolodex of people who can help you. In addition, I would talk to a high level business person to see if this is something industry would be interested in either pursuing in partnership with you or would want to purchase the technology if further developed. Successful former executives in Ophthalmology companies are especially good resources in this regard.

Can innovative thinking be taught or is it an innate talent? How can we foster and promote innovative thinking in the future generation of ophthalmologists?

I think innovation can definitely be taught. When people show you how to do something in Ophthalmology, you should always ask, is this the best way to do this particular thing? Is there potentially a better way to do this? I think you have to always be on the lookout for problems, things that are untoward in terms of affecting outcomes – it’s a mindset. This problem-oriented outlook can be taught to trainees, and I think there’s an important role for people who do innovation to mentor others so they can become successful innovators.

At UCSF one of the things we’ve done to try to foster innovation is we have symposia twice a year with Caltech in which we invite clinicians throughout the university who have an idea they want to develop but don’t know how to do so. And then we have them present their broad-stroke ideas to Caltech professors who say, “maybe we can try this,” and they start off working together kind of like how I did with Bob Grubbs. We’ve found this approach to be quite successful, launching several successful start-ups

Big ideas are often expensive and time-consuming. What strategies do you use to prevent fear of failure from impeding your success?

We had a 20 year history of seemingly endless challenges developing the light-adjustable lens. If you believe the project has merit and it’s something really needed by patients and physicians, you have to have the perseverance to pursue it, against all odds. Once you complete what’s within the scope of your training, namely, coming up with the idea, doing some pre-clinical work to establish feasibility, it’s good to bring in people who are more experienced at getting something through the many regulatory and business hurdles. Developing a project all the way through from an idea to an FDA-approved product is a long way to go. I’ve seen that movie first hand. Maybe, it’s better to pass on your projects at an earlier stage to a strategic partner who can do the heavy lifting to get regulatory approval.

What are 1 or 2 major ways in which you anticipate the practice of ophthalmology will change in the next 15 - 20 years?

I think one of the most interesting innovations in clinical medicine is the application of machine vision to image analysis. When I was training 30 years ago, retinal training emphasized development of  observation skills. I did a medical retina fellowship with Dr. Donald Gass, who carefully described so many clinical entities in retina. Just look at the incredibly detailed descriptions in his atlas. I think with computer vision, the computer will be able to look at a fundus image or an optical coherence tomography (OCT) scan and reveal a multitude of clinical features that would not be apparent to even as superb clinician as Dr. Gass. I think that as computer vision becomes more prominent in our field it’s going to dramatically improve our ability to diagnose and predict clinical outcomes for our patients.

Thank you very much to Dr. Schwartz for your expert, candid, and thoughtful advice on innovation in ophthalmology.