I had the pleasure of interviewing Dr. Shawn Carbonell, a physician-scientist who dropped out of neurosurgery residency to start his own biotechnology company, OncoSynergy. He has a degree in psychology from the University of Washington and a PhD in neuroscience as well as an MD from the University of Virginia. He then did his postdoctoral studies at the University of Oxford in the United Kingdom before starting neurosurgery residency at Cedars-Sinai Medical Center in California. He dropped out of neurosurgery residency (his Instagram account is @brainsurgerydropout) to work full time on fighting glioblastoma with science, and now, in 2019, his company is finally starting their first clinical trial, using OS2966 to treat glioblastoma. Dr. Carbonell’s story is absolutely fascinating and quite inspiring, and it is nothing short of a pleasure to be able to share it.
Why did you want to become a doctor, and what do you think are the traits of a great one?
It is personal for everyone. I realized early on that I enjoyed giving back. I was pre-med in college, but I did not really have my heart into it. I was pre-med initially because I was smart, and my parents wanted me to be a doctor. However, I had not owned it for myself until I started volunteering. That gave me a sense of purpose and insight into what medicine is really like. Before that, in my sophomore year, I was not doing too great, at last gradewise, but once I started volunteering, everything fell into place, and I knew that I found my calling at that time. From there, my grades completely turned around, and I became really active in the pre-med society.ving others is what did it for me. The second part of the question is like a classic medical school interview question: put scientific knowledge, technical skill, and compassion in order of priority and explain why you chose the order that you did. For me, number one was compassion and empathy, number two was technical skill, and number three was knowledge. I do it that way because the last two can be learned or practiced. Compassion and empathy, on the other hand, need to be innate to make a great doctor.
What was your medical school experience like, especially considering that you did the combined MD/PhD medical scientist program at the University of Virginia?
The MD/PhD program, the MSTP (Medical Scientist Training Program funded by the NIH) was a really unique and great opportunity. Of course, there were a lot of distinct challenges with the program because you had to do the first two years of medical school, and then, all of a sudden, stop that and then do a PhD and then, all of a sudden, stop that. Then, you go back to the clinic and actually see patients when you probably have not seen a patient in several years. It was definitely something that helped me grow as a person though. From a time perspective, it was obviously long, but, rather than see that as a problem, I saw it as an opportunity and a challenge. The opportunity there was that I got to become friends with more than one medical school class; I actually became friends with three different ones. It was also a little weird to be back in the clinic after my PhD and see that some of the people I was working with were now my attendings. However, I highly recommend doing an MD/PhD program since I believe that it is the best preparation to be a physician-scientist, but, of course, it is not the only one as most physician-scientists are MD only. What I have been seeing lately, though, is that more people are doing their PhD during residency which is a little frightening and unique, but I think it may be a better way of doing it since then you are tailoring your PhD to your ultimate clinical interests, making it a little more applicable in that case. All in all, not everyone has the time to get a PhD along with an MD, but I recommend it.
What motivated you to do your residency in neurosurgery?
It really was a love for the brain. My initial major in college was microbiology as it was during the Ebola craze after The Hot Zone was published, but I did not really have my heart into it. Then, I took a Psych 101 class on basic human behavior, and that piqued my interest a great deal. Within two weeks, I switched my major to psychology as the University of Washington, despite being a big university, did not have an undergraduate neuroscience program in the mid-90s. Regardless, I think that was an advantage because psychology is ultimately what the brain does. The brain is behavior and motor. Actually, psychology is a perspective of the brain that is often neglected in medicine. That is what got me interested in behavior, the science of behavior on the cellular and molecular level, and the biophysics. I loved it all. Going into medical school, I saw three options for myself: neurosurgery, neurology, and psychiatry. What really did it for me were my mentors. For example, I found a great mentor, who was a professor of neurosurgery at the University of Washington. He basically took me under his wing, and he took some chances with me. It ended up being a really great experience as we published three papers together, and I was the first author as an undergraduate. He really supported me, and I really appreciated it. We remained friends through all these years, and twenty years later, he sits on the scientific advisory board of my company as a founding member.
What were the factors that led to you dropping out of your neurosurgery residency at Cedars-Sinai?
This is a tough one. I had a very romantic view of what neurosurgery was like. For example, I was obsessive of neurosurgery history with Harvey Cushing among others and read all of their biographies. Additionally, at the time in the 1990s, the University of Washington was the best neurosurgery program in the country, if not the world, and they did things the old way. It was very academic but also exceptionally great surgically. I had that notion of neurosurgery, but it is not like that everywhere. Thus, part of it was culture; it was hard to replicate the culture at the University of Washington. The other part of it was brain cancer. Surgery cannot cure brain cancer like glioblastoma. One of the preeminent neurosurgeons in the past was Walter Dandy, one of the students of Harvey Cushing. In the 50s, he showed that even if you cut out the entire half of the brain where the tumor was, it would still come back on the other side. He showed 70 years ago that surgery was never going to be a cure for glioblastoma. I realized that rather than spending my time doing surgery which any other talented neurosurgeon could do, I wanted to focus on a different approach based on developing new therapeutics for brain cancer like glioblastoma. My chairman at Cedars-Sinai, Dr. Keith Black, wrote a book called Brain Surgeon, which was published my first year there. In the middle of that book, which I read four months after I started my residency, there is a quote that says that in the end, it will be the science, not the scalpel, that will win the war against this beast known as glioblastoma. At that moment, something snapped in my head: I was going to quit residency because I had an idea for a treatment, and I was going to try to make it happen. It was actually pretty ironic that my own chairman’s quote was what finally convinced me to quit.
What is the goal of your company OncoSynergy? What is OncoSynergy doing right now to advance that goal and ultimately reach it?
Surgery is not a cure, and, in the past 30 years, there have been no real improvements in outcomes for brain cancer patients. The goal of OncoSynergy is to meaningfully improve patient outcomes, period. We are doing it by developing unique approaches and ones that we feel can potentially lead to a cure. We are doing this by being very adaptable with our strategy. Cancer is very adaptable, which is why it is hard to treat. The moment you treat it with something, it immediately changes and evolves. Because we are a small startup, we can also do the same. Initially, I had an idea for a single drug agent, but then we realized that we could get a lot more synergy by combining with certain therapies like immunotherapy. Our early data revealed some absolutely fantastic results. Currently, we have multiple different programs in the company right now, and they are all based on the concept of inhibiting the fundamental molecular pathways that drive drug resistance in cancer. We have identified several drug candidates like OS2966, which targets the CD29 receptor. CD29 receptors are the dominant adhesion receptors in the body and are responsible for cell adhesion mediated drug resistance (CAM-DR). CAM-DR appears to be a very fundamental driver of therapy resistance in cancer. Basically, what researchers have shown is that cancer cells hijack CD29 to drive CAM-DR and survive virtually every type of cancer treatment from chemo to radiation to immunotherapy to targeted therapy. Nobody before has been able to target CD29 or CAM-DR successfully; we are the first. We will also be the first to dose patients with a CD29-targeting therapeutic compound with our first trial starting next year. The original concept for the company came to me as a post-doctorate in 2008, and now more than 10 years later, it is gratifying that it will potentially be helping patients in 2019.
Where do you see cancer treatment in the next 10-20 years? The next 50-100 years?
Cancer is now becoming the primary ceiling for longevity, even outpacing cardiovascular disease. I think that it will be really key to focus our efforts towards treatment and, even more so, prevention. In the next 10-20 years, I think that we will see some really striking results with immunotherapies. I feel like some tumors will be curable with immunotherapies in certain combinations especially, we feel, with our approach. I think in the next 10-20 years that we will see some curative approaches for cancer, and we hope that brain cancer is among those. Each cancer has a different ability to adapt, so it will be a matter of determining the best therapeutic combination to treat each cancer. For the next 50-100 years, because we will be able to treat these cancers more easily, more people will be surviving longer. I think there will be a greater focus on prevention and detection of malignancies. That is at least my optimistic view of the future. In the next few decades, we can start curing some of these cancers, and in the next century, we can start preventing them. Of course, lifestyle plays a major role for many cancers so there are things we all can do today to change the numbers.
What is the biggest challenge that you have faced in your career thus far?
Quitting neurosurgery, for sure. It had been my dream since I was 19 when I switched to psychology and started working towards becoming an academic neurosurgeon. Then, I quit after 15 years of training. I did the PhD specifically for neurosurgery since all my mentors recommended I do it, and I am glad they did so. I went to the University of Virginia for med school because all my mentors trained there under the legendary Dr. John A. Jane, who was only two generations removed from Harvey Cushing himself and was the editor of the Journal of Neurosurgery. After that, I deferred my residency, even after getting my MD/PhD, to do a 3-year postdoctoral fellowship at Oxford, which was an amazing experience and where I got some of the initial inspiration for my therapeutic approach. But to go through all that in order to become the best academic neurosurgeon in the world before, all of a sudden, stopping to do something very different was definitely the hardest decision of my life. However, I’ve realized my vision of improving outcomes for
cancer patients is better served in my current role.
What motivates you to work endlessly long hours for your company and pour both your everything you have into it?
It is sort of the same thing that made me a good doctor: I give a f—. It is about the patients. My wife and I have also been patients, my wife more seriously, so we have seen it from both sides. I forgot where I heard this quote, but I remember it from my college days. Somebody said that happiness is using your skills and expertise in a meaningful activity, and what activity could be more meaningful than saving and improving lives. That is what it comes down to. This quality is sort of innate, and not everyone who goes into medicine has that, unfortunately. It’s not about keeping up with the Joneses, it’s about giving back, serving others, and paying it forward.
Do you have any “words of wisdom” or inspiration for teenagers like myself and my peers who want to go into the medical field?
The economics of medicine is no longer as favorable as they once were since medical school is significantly more expensive than when I started. It puts a lot of undue pressure on graduates. Even if some of these folks decide they do not want to pursue it anymore, they are coming out with $300,000 in debt, so they are not going to have much flexibility, especially if they have started a family. Thus, make sure that you are going in for the right reasons. You really have to love it. One of the best things you can do is to go out there and DO. Go volunteer in a hospital and interact with patients. If you like it, then you probably are cut out for it. If you counting down the clock and complaining all the time, then you might want to look into something else. Of course, you can have varied experiences. I volunteered at two locations: the Harborview Medical Center and the University Hospital. They were both very different experiences, but both were especially rewarding and confirmed for me that I wanted to spend my life advancing medicine.
Carbonell. Brain Surgery Dropout Instagram Page. Instagram, www.instagram.com/brainsurgerydropout/. Accessed 26 Dec. 2018.
—. Dr. Shawn Carbonell. University of Virginia, news.virginia.edu/content/you-cant-cure-glioblastomas-scalpel-discovery-leads-career-shift. Accessed 26 Dec. 2018.
—. Short Whitecoat from Medical School. Instagram, www.instagram.com/p/BlecCK7AaZg/. Accessed 26 Dec. 2018.
—. Thousands of Newly Filled Vials of OS2966. Instagram, www.instagram.com/p/BmMt2vjAkoG/. Accessed 26 Dec. 2018.
—. Volunteering at Harborview Medical Center. Instagram, www.instagram.com/p/BrInUDkBE5j/. Accessed 26 Dec. 2018.
Why Medicine. EDU Advisor, eduadvisor.my/wp-content/uploads/2016/10/Medicine-Why.png. Accessed 26 Dec. 2018.
Zghool, Hamzeh. The Father of Neurosurgery – the Great Dr. Harvey Cushing. Pinterest, i.pinimg.com/originals/c3/98/58/c398581b7c90b963e5e8fec3a0547909.jpg. Accessed 26 Dec. 2018.