Latest / Voices of Otolaryngology / The 1-in-10 Mindset: Grit, Reinvention, and Seeing Cancer in Real Time

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The 1-in-10 Mindset: Grit, Reinvention, and Seeing Cancer in Real Time · Voices of Otolaryngology

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Welcome to the Voices of Otolaryngology podcast series, where we spotlight
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diverse perspectives and insights within the field of otolaryngology.
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I'm your host, Rahul Shah.
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Let's jump into it.
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Welcome to the Voices of Otolaryngology.
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Super excited to be with a new friend of mine, Doctor Eben Rosenthal.
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Eben, welcome.
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Well. Welcome to you.
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Thank you so much for having me.
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Yeah, well, thank you for inviting me to visit Vanderbilt. Wow.
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I was blown away.
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Congratulations on what you've built there.
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Well. Thank you.
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We loved having you.
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Your energy.
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You have revitalized our interest.
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And I think what the Academy can do for us.
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And I love that.
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Well thank you. That's super kind.
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And maybe we'll talk about
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two of your faculty members who joined us on the leadership journey.
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But let's hear about yourself.
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So you're in Vanderbilt, but you're a michigander.
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Right. Or am I wrong?
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How did a guy like you end up in Nashville?
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Yeah. So?
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So I grew up in Ann Arbor and then did my residency.
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Well, medical school residency there, and then went and went to fellowship
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at Oregon with Mark Wax, doing free flaps and boarded in facial plastics
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before going to University of Alabama, where I did
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a lot of free flaps over the course of 14 years.
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That was incredibly formative clinically for me as I,
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you know, really learned the nuances of reconstruction
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in a very busy practice
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and and very grateful to all of the patients
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that I had the privilege of taking care of their as well as my
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my supportive colleagues at University of Alabama when I went.
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So then what happened?
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How did we get from Alabama to Nashville?
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So then I, I went to Stanford to be
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the Medical Director of the cancer center, which was a really unique opportunity.
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It presented me with the opportunity to learn hospital management.
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Essentially, it was a relatively corporate structure that managed the clinics,
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and the dean and the medical school actually managed the
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they actually managed the research and education enterprise.
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So being on the hospital side, I learned a lot about how
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hospitals are run, large academic centers are run.
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And kind of the diffusion or the complexity of the decision
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making within our current academic systems.
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You're not getting me to Nashville.
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And then you ended up from Stanford to Nashville.
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And then and then this chair job came open and it was literally
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like the most fun I came, I visited the faculty were all amazing.
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And they they wanted, I think, somebody much like me, it was a great fit.
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And it has been such a pleasure to be here every day, working with
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incredibly talented faculty and people that really,
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you know, are clinically excellent and completely devoted.
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I've been super excited about
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the culture of surgeon scientists that we have here.
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We have, I think, honestly, you know, a large group of surgeon scientists
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that we integrate into the
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the very fabric of kind of our clinical and educational mission,
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which has just been, you know, an incredible privilege for me.
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I'm struck.
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You and I spend a lot of our time mentoring folks,
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and I want you to reflect on something I wrote down here.
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And I probably missed some.
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University of Michigan, Oregon Health Sciences, Alabama, Stanford, Vanderbilt,
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five of the premier institutions probably in the world.
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You must have had a growth mindset.
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You knew what you were doing moving around.
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How do you mentor people and talk about that?
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Some people in academics stay in one institution and grow up there.
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You've said it yourself.
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You intentionally at Stanford learned
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organizational dynamics and thinking,
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which probably positioned you perfectly for what you've achieved at Vanderbilt.
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Talk a little bit about that and how you mentor folks.
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Yeah, that's a that's a great point.
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I do think that having an opportunity to work on a hospital side, I can speak to
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my my experience being mentored as well as mentoring.
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I think being mentored, I think is being willing to really say, I know,
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I don't know about this and what putting yourself
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in a vulnerable position so that you can accept
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the kind of wisdom that comes from people who are very different than you.
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And I, again, in that context, I was working with, you know, hospital,
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you know, leadership that had very traditional MBA
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type training, GE type training.
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My, my joy in mentoring people has primarily
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been in the initially in the residents and medical students.
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I really enjoyed having residents and medical students in my lab -
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that opportunity to work with bright young people who are eager and interested
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in the kind of basic discovery, and those that had curiosity
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and enthusiasm are so much fun to discuss those topics.
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I think the, you know,
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I think the mentoring that I have really enjoyed
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is that that occurs over time, that you work with somebody intensely
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for one, 4 or 5 years, and then you kind of see them throughout
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their career and communicate with them, and that's been incredibly rewarding
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to see them be successful and to feel
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like you have something still to offer them.
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And I think my my range of experiences
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between basic research, clinical trials, clinical activity
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in the hospital leadership has really provided me
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an opportunity where I feel like I can provide some help
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to most junior faculty and residents that I work with.
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It is not easy.
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And we'll talk about your research,
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which is the topic of what I wanted to focus on today in a couple of minutes.
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It is not easy to move labs, to move research, to move clinical trials.
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You have taken perhaps the hard path.
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It's easy to sit at one institution.
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Everybody knows you.
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Your trials are there, your labs are there.
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Talk to us a little bit about it. Every every step of the way.
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You're lifting people, moving your rebuilding teams, right?
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You're creating 4 or 5 Super Bowl winning teams.
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It's not easy. Talk a little bit about that.
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You know that's a really I mean that's really insightful.
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It is incredibly difficult to reestablish particularly because
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we part of my research is manufacturing
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drugs for human administration.
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And that is incredibly complicated and working.
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And then I think you're exactly right.
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I think working with the teams, the
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the thing, though, is that the teams really change every couple of years.
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You know, the nature of research
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in a medical lab is that folks are often there
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for one to three years at a time, and there are very few
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that are long term folks that you work with.
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And having said
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that, I mean, moving and reorienting the IRB
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and getting the trial started and all that is, it's a two year process.
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And I think honestly, at the same time, the moving
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your interaction with a whole new set of people bring a whole new set of ideas.
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And I could have never done what I have done without the different
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opportunities that UAB provided me, that Stanford totally different,
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totally different set of resources and ideas
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that encountered at Stanford compared to Vanderbilt.
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And it's not better or worse.
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It's just very different people who have very different perspectives
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on what direction you should be going with the research. So.
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Amazing point that I never had considered.
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I only looked at it as saying, hey, this guy lifts his life
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from Alabama, moves to Stanford, moves to Vandy.
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Riff on the point that you made, which I think is exceptional.
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Every time you do that, yes, there difficulties,
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but you get a different innovation ecosystem, different thinking,
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which obviously for you, based in hindsight on the success
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you've had, might have elevated your research or changed it a bit.
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Can you build on that for researchers that are listening here?
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I can't believe I'm I'm 51 years old, 20 years in academics.
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I've actually never heard that.
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And it rings true
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because there's a reason you left and you got something out of it.
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Yeah.
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So I think, for example, you know, University of Alabama was a
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it was a smaller cancer center, but it was incredibly dedicated
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to its scientists, particularly its physician scientists.
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And so it it really provided me with opportunity.
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And the people there was very much a
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I like to describe it a little bit as
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not is doing a lot of it
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by force of will, by pulling together
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a team that was very willing and going to Stanford,
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the environment, the tools there were so amazing.
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And for example, I had the privilege of working with the scientists
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that developed the code to the Codex sort of multiplexing protein.
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And our post, my postdoc was shared kind of between Gary Nolan's lab and mine.
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And so here was this, like brand new technology
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that you're using it with a very person that kind of developed it,
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and it created an enormous amount of data that I never would have
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even known was possible without without that kind of interaction.
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And then coming to Vanderbilt, the the clinical trial team
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and the team make enrolling patients incredibly easy.
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My partners, you know, Kyle Mannion and Sarah Rohde and all those and you know,
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they're just amazing and helping me to to really enroll patients.
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So that that's different.
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They were we work as a single team almost.
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Whereas and the other thing is the radio chemistry facility here is amazing
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and I'm very dependent.
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And we developed we just published it in Nature Protocols this month,
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a completely new way to manufacture
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fluorescently labeled antibodies, which can be used for a variety of reasons.
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But that technique, which is I didn't even know existed, was possible
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only by coming here
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and interacting very closely with the radiochemistry facility. So
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yeah, each place has provided
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I mean, I gave you just examples, but many, many techniques
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that I have picked up along the way and have allowed me to
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to continue to do the research,
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I think at a much higher level than if I had stayed at one place.
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Awesome, awesome.
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A story I really want to get into your research.
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I'm planning to learn about it, but.
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But I have to deviate.
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I lived in a world of mixed metaphors, so let me say a mixed metaphor.
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Then you just interpret it.
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Is it almost like the field of dreams?
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If you build it, they will come.
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But the other side of the Field of Dreams was you have to have
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the vision and understand that everything's not perfect.
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When you are looking from OHSU to Alabama
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to Stanford to Vandy, were you looking for the Field of dreams?
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Did you have the confidence slash arrogance
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fortitude ability to know - you know give me some structure and I'll build it?
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Were you out there networking or was it a little bit of both?
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I mean yes, there's some serendipity, but I have a feeling with the five successes
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you've had at five different institutions, you're the commonality.
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Yeah, well thank you.
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I definitely did not like,
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I think as a resident, I was not a particularly good resident.
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So there was that.
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I'm not sure I did well there, but you can ask Greg Wolfe about that.
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But but I think, you know, and then as a fellow I didn't match
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as a fellow, I scrambled to get the spot
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with with Mark Wax.
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And what a scramble, man.
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I do that seven days a week and twice on Sunday.
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I mean, jeez, Louise, you trained with terrific people.
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So that's let's let's actually go on that because people and I wrote this down,
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I actually wrote this down in life is not easy.
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You know, people look at you and say,
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oh, here's this endowed professor at Vanderbilt doing groundbreaking research.
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He's had an easy path.
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But but tell us a little bit about that.
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So you didn't match and you said, you know what,
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I'm going to hustle out there and do what I want.
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You ended up being board certified.
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You know, a master class head a neck surgeon.
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What is the message to those out there?
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We've all had our struggles, but people look at you and I think, oh, it's so easy.
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Yeah, well, I think, you know, a couple of things.
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I think it's really hard to be to, to move in a dual professional couple.
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I think a lot of our residents now are married to other doctors,
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and if both of them pursue an academic career,
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it can be that in and of itself is just you.
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You narrow your choices down dramatically,
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and so the flexibility to be to to redo it.
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And I did hear a phrase recently, I really like that.
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If you're a trailing spouse, you often need to reinvent your career.
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And that's a little bit what happened when I went to Stanford
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was that my wife was being offered and was was given the chair of surgery there.
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And Lloyd Minor, to his credit, recognized that
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I was really interested in a growth opportunity.
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And as a result, he he, you know, was willing to to to push
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for my hiring by the cancer center to be in that role.
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And that just was a, you know, phenomenal experience.
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And I never would have had that without the trust of
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Lloyd Minor and his and the cancer team there.
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And so, you know, so I, you know, I was board
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certified as a facial plastic
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surgeon, had spent all of my time doing research and cancer and so on.
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But so it was, you know, it was a bit of a change.
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And when I did that, I literally, no offense, stopped
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going to all the ENT meetings and went to all of the ASCO and,
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and you know, ACR like because I felt like
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I had to invest heavily in that in that field and learn about it.
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So rather than sort of trying to pick it up by osmosis or taking a formal course,
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I felt that the best way to your point earlier about networking
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and developing a presence in that region, it was to go to contemporary meetings,
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meet people, try to get presentations on the podium through abstracts and so on.
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And so really and then and then in the scientific,
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I've had to change what I do scientifically.
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And when I do that, I go to meet, I go to a meeting,
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a contemporary meeting on that topic and try to take notes
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and act like a student and, you know, learn about.
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And I've done and I've done a lot that haven't work.
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And in other words, I went there, I did it, and I realized this is not for me.
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And so, for example, the new technologies
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today around immunotherapy, I've never been an immunologist.
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But geez, if you're going to be doing science
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and head and neck cancer now, at least have to know a fair bit.
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So I have to invest in that, or I have invested in that over
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the past couple of years.
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I'm swearing to myself, I've got to get to your research
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because I'm dying to learn it.
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But but you keep bringing up these interesting points.
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I love what you said about Go All In.
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I am a trailing spouse to my wife,
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is a director at the FDA, and we'll leave it at that.
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This is a public we can chat about it offline.
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And when I took this job, I went all in.
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I come out to visit folks, private practice, academics,
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I attend society meetings.
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I attend policy and advocacy.
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Can you build on that a little bit?
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I think it's exceptional
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that someone of your caliber goes out there with a student mindset
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at a immunotherapy meeting in Europe to say, I'm learning
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you're not going there to to go around and do touristy stuff.
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It's fascinating.
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Can you just reflect back, maybe on the last 3 or 4 years and some moments?
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And I do this all the time,
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but I think it's more credible when you say you are still learning.
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People think like, oh, Doctor Rosenthal, he just walks in all day.
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He knows all the answers.
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Well, I mean, I do, you know, I think if you
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if you remember what Bo Schembechler said way back in the day,
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he was a he's an old Michigan coach when I was in a growing up in Ann Arbor.
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And he said, “when you're through improving your through.” And I
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and I really bring that to heart. And I like
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what you say about going all in, like, if you're going to take on a job.
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And so I think there are two ways to look at that.
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One is is as a outward reflection
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and in your job, the outward presentation is critical
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for you to present the face of the Academy.
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And I'm just saying here, but for me, in the last
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when I first got here, it was much more internal facing.
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I was I was very focused on getting to know the individual faculty,
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understanding their needs, and trying my best
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to reorient the clinical enterprise to be successful for the next ten years.
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So it's very interesting at different times in our life what we do.
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And so when I moved to to to Stanford, I didn't write a grant for two years.
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I focused entirely on the like you said, all in,
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how do I develop a quality framework for the cancer center?
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How do what are the commonalities
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amongst service line delivery and continuity of care that we have to do?
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And here I'd been out of the otology world for a while.
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I had been out of, you know, rhinology.
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So I really spent a fair amount of time trying to work,
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you know, visit the physicians in our practice
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where they are, visit the, you know, the regional physicians
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in their location understand what their practice is like
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so that when we talk over the years, I have a good impression
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of of what their what their day to day life is like.
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Awesome.
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Awesome insights.
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I'm reflecting on my career and the successes have come
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from going all in as Chief Quality Safety Officer.
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Even during my MBA,
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I remember I didn't
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I intentionally did not write a manuscript during those two years
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because I thought of it as an opportunity cost.
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How often will I get to learn accounting versus there's always another
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20 manuscripts literally to write.
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Yeah, you have to kind of
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think of it in phases and that and I think as when you're,
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you know, 19, you can probably switch and do things all the time.
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But I think as you get into your 40s, it's a little easier, you know.
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And there's a, you know, there's a couple really good books about that.
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The one is Strength to Strength, and it talks about intelligence
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changes over age and how you can I think it's by Arthur Brooks.
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And and essentially it helps you think through like, okay,
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I'm different today than I was at 55 or whatever.
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And then you, you know, advance.
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You kind of understand a little bit about you're not unique.
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It's that this is the way that you are best going to learn.
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Awesome insights.
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You have a huge faculty, I presume.
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I'm learning from this talk.
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We share a lot of philosophies amongst ourselves going all in.
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We see a lot of junior faculty have 17 things not going all in, even associate
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professors, even professors, because maybe they're fear not to go all in.
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Talk a little bit about that.
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The trajectory you've built on Dr.
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Netterville,
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literally standing on the shoulders of giants - and his predecessor.
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Have you taken that all in approach with some of your faculty?
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I think and and again, there is some trying
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not to put my view of what a career
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looks like onto onto somebody else.
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In other words, I've had a rich academic career that I
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that just has always been my goal has always been a passion of mine.
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But there are some folks that are clearly really,
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you know, great clinicians, and that's all they really want to do.
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They just want to be great clinicians.
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They take it incredibly seriously.
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They're, you know, incredibly responsive to their patients and things like that.
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So I think of an academic center like this as having lots of different phenotypes.
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And you need everybody.
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You can't do it with one group or the other.
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It's a mix.
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And so and I think the residents that you're training
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need to see that they need to see these are the different paths that I could take.
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And I'm not sure if I'm answering your question,
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but I do think that that the process that, that, that residents
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that you want to show to residents is that there's not one model of
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I think there used to be like
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a surgeon scientist was in the lab and then they were in the operating room.
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But that's not that's just not the case.
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There's just everything in between now.
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And going all in means that you find what that passion is,
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and then you realize that there are certain times when you may
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or may not be able to do it, and it’s cyclical.
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I think, you know, when the kids are really young,
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it can be exceptionally challenging to to focus on other things
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sometimes, or if there's medical issues within the family.
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I honestly think that that you just have to kind of understand
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that there are times for one thing
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and then times for another, but you really have to whatever it is,
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you really have to invest in being the best.
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We have got to get to your research.
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So if you see my eyes roving and hands clicking, I was checking Amazon.
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You are exactly right: “From Strength to Strength”, Arthur Brooks 2022.
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For our colleagues that are listening and and Doctor Rosenthal recommends
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that book.
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I also went to PubMed to see her several hundred articles,
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and I don't have the bandwidth to throw it into open evidence
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to summarize for me, but for our just just give us a summary,
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give us an elevator pitch of your whole career.
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You know your reason.
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And I'm kidding, I'm being facetious, but you know,
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and then then we're going to go into bits and piece of pieces of it.
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What has been your scientific contribution?
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The thing you're most proud of: the scientific inquiry, your research?
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You mentioned a little bit about it.
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Cancer, head and neck drug development.
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But I'll give it to you.
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So, you know, it's really interesting.
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When I, when I went in, I had worked in the lab multiple times
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before in my, you know, college,
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you know, medical school, etc.
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until I was a resident that I went in the lab with this guy who did in vitro
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experiments, Stephen Weiss.
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And he was he was he was diseased, practically
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with his intensity for the question, the scientific question.
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And he would sleep in the lab for days on end.
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He would come out and like, you know, question you.
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And one of the best things he ever said to me was I said I showed him experiment.
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Hey, it didn't work.
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And he goes, well, why didn't you do this?
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And he says, why did I say I did exactly what you told me to do?
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And he goes, I don't care what I told you to do,
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just do the experiment like it should be run.
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So what he's saying is, is you have to think through the problem.
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And as soon as I really got that part that it was on me.
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I really love doing it.
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But anyway, so I worked in vitro.
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I went to UAB, I worked in animals on tumor cell invasion.
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I eventually worked in mice
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on a fluorescently labeled therapeutic antibody for imaging cancer.
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Like, how do you see cancer?
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That became a fundamental question for 15 years of my career.
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How do you see cancer in the operating room? And
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the process of doing that
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meant that we had to label the antibody for human use.
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We had to administer it first in a series of first in human trials doing that.
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And that really taught me the clinical trials that taught me
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the FDA, how the FDA works, and then how to kind of manage
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this translational thing with with safety is the most important thing
25:46
in scientific discovery. Next.
25:48
So we were sort of the first in humans around 2013,
25:51
in the United States to do this.
25:53
And really my goal was not to develop an agent for commercial use.
25:58
There are many undergoing tests.
26:00
My my real issue, my real desire was to understand how it can be used,
26:06
like we had all thought it should be used one way,
26:08
but as soon as we got it into patients, we realized that imaging cancer.
26:12
It worked great, but it didn't work great the way we thought it would work great.
26:16
It worked great differently.
26:18
And so we basically spent, you know,
26:21
five, ten years putting out a series of papers
26:24
about how it
26:27
how it can be used to improve surgical decision making.
26:30
And then we have now we're now looking at the next step of that, which is
26:35
how do we identify tumor positive lymph nodes in real time in the operating room.
26:40
So so it's sort of transitioned to that.
26:46
I'm just reflecting.
26:47
That was an awesome summary.
26:48
I couldn't pull that out from the articles because, you know,
26:51
the articles go in depth, right, with certain hypotheses.
26:54
But I love the way you I would say kind of three steps.
26:57
I was also googling the gentleman you mentioned from Ann Arbor,
27:01
and I've heard several stories about that surgeon or that scientist,
27:05
and one of my mentors was mentees was with him too.
27:08
I've heard that. That's great. It was great.
27:10
I mean, just in the level of scientific rigor was just
27:14
I learned like, that is what scientific rigor is.
27:18
Talk to us about what you're doing currently:
27:22
identifying real time
27:24
intraoperative positive lymph nodes.
27:27
Right. I say that's a game changer.
27:29
That's a game changer. Where are we with that. Talk about it.
27:32
Yeah.
27:32
So, you know, if we think of it as like we
27:36
you know, we realized in doing the procedures
27:39
that the lymph nodes would light up, but they tended to light up
27:44
in a distribution suggesting
27:47
that it was a sentinel node type.
27:50
In other words, we would systemically administer the fluorescent agent.
27:55
It would then travel to the tumor and then travel
27:59
nonspecific to the lymph nodes.
28:02
So it's just like injecting directly in a set in the lymph node setting.
28:08
What makes sentinel lymph node
28:11
feasible is the radial label not the optical label.
28:16
So the radial label would get an image.
28:17
You know where to make your incision, you know how many lymph nodes there are.
28:20
And then you remove the lymph nodes and you go back
28:22
with the probe and identify that there is no radioactivity left.
28:27
So our initial studies were
28:30
using an antibody labeled with a
28:34
with a radial label that could be detected in the operating room.
28:39
Unfortunately the background was too high when we removed the positive nodes.
28:43
So we are now we just developed and got the IND for a peptide
28:49
that is smaller and is cleared from the system rapidly,
28:53
and should be more appropriate.
28:55
We are actively investigating how,
29:00
with my colleague Mike Topf, how to image a specimen
29:05
with a pet CT in the operating room so the patient gets FDG,
29:10
the tumor is removed, and then you get a pet CT of it - of the specimen itself.
29:15
And you can visualize the entire tumor and through the CT,
29:19
the distance between the tumor and your cut edge.
29:22
So it provides a circumferential real time or not quite real time,
29:27
but within the operating room within minutes, the full scan.
29:31
And it's like a just a sort of
29:34
tabletop type device that you just drop the specimen into.
29:38
And it provides a very, very high resolution image.
29:42
Thank you for that eloquent
29:45
explanation for a lay surgeon to understand.
29:49
And so I understand that your lab has to have the carriers.
29:53
So you're building the antibody, then you morph to a peptide.
29:58
Is that right? That's what your lab is doing behind the scenes.
30:00
You mean you and Doctor Topf
30:02
are thinking of these visualization ideas, but then you need a carrier.
30:05
So, I mean, you can imagine telling all your O.R.
30:10
team that you want to go now
30:11
- inject radioactive material and do a pet CT in the O.R..
30:15
So, I mean, the regulatory steps, I would say are the most challenging,
30:21
both from the from manufacturing something for human use locally.
30:27
It's is a challenge.
30:29
And then and the communication with the FDA is really important.
30:33
And then making sure it really means that you're responsible
30:36
for safety and the safety of those in the area.
30:40
And so the the radiation, we had to wear badges
30:44
and we had to go through this whole protocol.
30:45
It turns out we're going to publish on it.
30:47
So nobody else has to go go through that.
30:50
But, but that's, that's the idea is to kind of
30:53
identify the, you know, the best method to do it.
30:56
And that was probably, you know, those are the sticking points, right.
31:00
Is like the approval process through the institution, through the FDA. And
31:07
that takes an enormous amount of time.
31:09
And and ultimately you're responsible for the safety of the patient.
31:12
So and I always worried about that when we were doing
31:15
these trials with the drug that we would we would significantly dent
31:21
the field by having an event with
31:25
there was attributable to an optical label..
31:30
When I meant carrier.
31:32
My ignorance I was thinking about through the blood.
31:36
How do you inject and carry it to the site?
31:38
But that that's probably a long, longer story.
31:41
I see.
31:41
No, no, it's just an antibody.
31:42
So it so the antibody is a therapeutic antibody.
31:45
So we use the text a map or a two map which binds EGFR.
31:49
So it's super.
31:51
It's so it I see. Yeah.
31:53
Yeah. The fluorescence alone is insufficient.
31:55
That's ICG an unveiled a carrier.
32:00
You know that's not specific.
32:02
What we do by labeling the antibody with a covalent bond to the philosophy
32:06
label the antibody is injected and binds to the tumor.
32:10
And it once it binds, it stays there.
32:15
That's awesome.
32:16
Gosh, it's so intense what you're doing when you say covalent bond
32:21
I think of my son's AP chemistry, what he is studying now.
32:24
So it's crazy how you how you put all this together.
32:26
When we talk about research, I have to ask this, and it's embarrassing.
32:30
We're 35 minutes into it.
32:32
I'm a big AI guy.
32:34
Is AI impacting your research?
32:37
I don't mean that crassly. Seriously.
32:38
It seems like what you and Doctor Toph are doing,
32:42
there's a lot of cognitive stuff going on, and it would
32:44
it would probably help you a little bit.
32:46
Does it or does it hinder you or is it all hype?
32:48
No, I mean, so it's a great question because
32:54
for for what I do,
32:57
the image analysis of the PetCT, of the protein multiply,
33:02
I mean, that is all machine learning and is,
33:06
you know, the cell segmentation at every step.
33:09
And I have to say,
33:11
I'm not like, I, I'm not the person that does it.
33:16
I'm the person that understands what it's telling me.
33:20
But the if you're going into a lab today and you're not
33:26
and you have to learn how to do coding and Python and, and
33:31
I mean, it's critical image
33:34
analysis that all of that requires some level
33:38
of using a program that is doing that.
33:43
Or, you know, very few people are developing their own specific
33:46
programs, but it's it's the fundamental.
33:51
I tell the folks that are coming to my lab,
33:53
they need to spend a couple, you know, a year
33:57
just investing in understanding how to use Matlab and how to use Python
34:02
and R, because you can't do research without them.
34:06
Yeah, I did coding in high school for fun.
34:11
I give those vibes and.
34:13
It’s the best. I mean, it's incredible.
34:15
It teaches you how to think, teaches you how to think.
34:18
It's brilliant.
34:19
Yeah, yeah, I want to play a game and we're going to play.
34:22
We're going to get two swings of the bat.
34:24
Have you heard of “High/Low/Buffalo”?
34:26
So it's like yeah you haven't. It's okay.
34:29
You're a normal guy.
34:30
This - I’m a funny guy.
34:31
So what is the “high” of something? What is the “low” of something?
34:34
And “buffalo”?
34:35
What's the unusual or weird kind of thing?
34:38
And I want to do it with your research.
34:40
What's been the high of your research?
34:42
The low of your research and the buffalo?
34:44
I think, you know, perhaps the buffalo would be
34:47
you've been working alongside luminaries that that might, you know, be
34:51
recognized with the highest honors of medicine.
34:53
But anyways, I'll let you do that.
34:54
What's been one of the highs of your research career over the last 30 years?
34:57
Low and Buffalo?
35:01
Honestly, I think I think getting
35:05
into the National Academy of Medicine was I mean, that's like an event.
35:10
Yeah, yeah.
35:11
I think discovery wise,
35:14
it has really been the privilege of defining,
35:17
I think, how back table imaging
35:22
can be used to identify closest margin.
35:27
It was just a, you know, a series of things that we started
35:32
seeing the technique and we just found that we couldn't use it
35:36
the way we thought we could.
35:37
And we, you know, we're very flexible about how we interpreted the data.
35:41
The buffalo, I think, was just the pure luck
35:45
that we labeled Cetuximab and it worked in humans.
35:48
Like - You know I go back now and just think,
35:54
you know, there were just so many people who told us it wouldn't work
35:57
and that there was no way and that there was too much drug going elsewhere.
36:01
And only 10% of the I there are just a lot of people like,
36:04
you're going to screw up the field if you do it.
36:06
And I mean, it just happened to work.
36:08
It's just so such dumb luck.
36:11
So you get an idea and it takes you two years, three years to get to the infusion.
36:17
And then we
36:18
had really good support from some of the industry.
36:21
So yeah.
36:23
The “low” is, every five years or maybe ten years,
36:27
there's a point where you're like not getting grants.
36:30
You don't have a good team in the lab, and you're just like, this is stupid.
36:34
I'm going to give this up. Why? Why don't I worry about my day job?
36:37
Like like it's just it seems futile that
36:40
you when you get the rejections from the grants you feel like,
36:44
or rejections from the papers, you're like, nobody gets this.
36:47
Or maybe I don't get it.
36:49
Maybe I'm just being, you know, pigheaded about it.
36:53
So and so it has been those periods where it's like,
36:58
this is not working, and I don't know what I'm doing.
37:01
And what I was doing doesn't work anymore.
37:04
So anyway, that that's the true low is when you just feel like
37:08
you can't you can't carry it on because you don't have a good idea.
37:12
You're not getting the funding.
37:13
You're not responding appropriately to to critiques.
37:18
This is a tricky question.
37:19
Try to do your best to answer it. No one's going to hold you to it.
37:22
I bet you we could calculate it, but it's not worth the time.
37:26
What has been your overall career success rate with grants?
37:30
And I'm going to talk a little bit so you can think it through.
37:33
So the denominator everything from a rookie resident all the way to
37:37
now where you are,
37:39
it's probably hundreds probably I don't know several several dozen.
37:42
And then the success rate I'm trying to get the percentage.
37:46
And when I talk to exceptional surgeon scientists like yourself,
37:49
what's striking to me is it is a very low success rate.
37:54
You're not you're not hitting 80, 90% at all, Eben,
37:57
you know, but but where is a ballpark about 1 in 5, one in 6 or 7?
38:03
So I do
38:04
like to I have this rule of one in tens.
38:07
Like it is.
38:08
I want to say it's 10% okay.
38:11
And honestly, the grants are 10%.
38:14
And I tell the students in the lab that when they're the, you know,
38:19
the residents, when they're working on this, that look, when you're in school
38:25
and you get an A, you know, you did the best.
38:28
You know, you did the best you could do.
38:31
If you, on the other hand,
38:34
in science, if you submit a paper and they get to give you an A
38:39
and they accept it without any revisions, you submitted it to the wrong journal.
38:45
You you're not aiming high enough.
38:46
If if every grant gets accepted, you're not asking for enough money,
38:51
or you're not applying for a long enough grant,
38:54
or one that's going to give you real feedback.
38:57
So, you know, honestly, you're
39:01
the way you view success has to be through the lens of
39:05
I have to fail consistently in order
39:08
to make sure that I'm aiming high enough.
39:12
So it completely flips.
39:14
Failure is just a natural and I think 1 in 10.
39:18
So for example, if you reach out to a colleague and say,
39:21
I've got a good idea, we could collaborate on this, that works out about 1 in 10.
39:27
Does that mean that you should never reach out?
39:29
No. It means that 1 in 10 will work out.
39:33
But when one works out, when you get one grant,
39:36
or you get one really good collaborator, you don't need a whole lot more.
39:40
That's like 15 years.
39:42
So the 1 in 10 is just understanding
39:45
that the failure is inherent in what you're doing.
39:48
But you don't need ten to work, you just need one.
39:52
So I think and that is just so hard to change as surgeons,
39:57
where we think that if you have a complication,
40:00
we naturally think, like, I screwed up, how can I do better?
40:03
And and it's and you have to have the same perspective for grants.
40:09
I you want to get that criticism.
40:11
You want to be rejected from a journal,
40:14
that you want to hear what they have to say,
40:16
and the higher journals that you apply to, the more rigorous the review
40:19
and the more valuable the comments, like if you submit to some journals,
40:24
it's like they'll take your APS money and they'll publish it.
40:28
Great.
40:28
But the comments are often trivial, and what you really want
40:32
is the person that's going to spend, you know, sit down.
40:35
Look through the supplementary data
40:37
and tell you that ten different reasons you're wrong.
40:40
Eben,
40:42
that is just mind opening for me.
40:45
If I had you as a mentor, man, I don't know what kind of career I would have had.
40:48
Holy smokes, that is such an awesome, awesome insight.
40:52
I love investing and I don't think of a hobby.
40:55
I think of it as is a passion.
40:57
And that's what venture capital is all about.
40:59
You have a 10% or 5% success rate, and if you're wrong, you're aiming too low.
41:06
You're in the wrong space. I could not have said it better.
41:08
I want everybody to listen to what you said.
41:10
We're like ten minutes past due, but I can't end yet.
41:13
I've got to.
41:14
I've got to go back to your luck point.
41:16
And I promise you, I know you've got research and clinical duties.
41:19
Go back to the luck.
41:21
You said we were lucky.
41:24
Nobody believed in it.
41:26
It took 2 to 3 years.
41:28
We had to ideate.
41:31
I don't call that luck, Eben, I call that grit.
41:33
You had conviction.
41:34
You had science.
41:35
You're being humble about it. But
41:39
I don't know, man.
41:40
Luck is me walking on the road and finding 100 bucks.
41:42
I think you you had some conviction and scientific belief
41:47
that something was there.
41:48
I give you luck being in the right place at the right time.
41:51
But I want to end with your grit.
41:53
I mean, I think that's that's the message of today.
41:55
You know, nothings come easy.
41:56
But, man, you're in the National Academy of Medicine.
41:59
You've obviously got it right.
42:01
I'll give you that as a mic drop.
42:02
You can end any way you want, Eben.
42:05
Rahul, this has been wonderful.
42:06
Thank you very much for giving me the privilege to reflect on
42:09
some of the things.
42:10
And I think that when I say lucky, I think, you know,
42:13
there is some preparation.
42:14
But what I didn't say was the ten times I was or nine times
42:19
that I was unlucky, that I spent two years and I did it.
42:23
And you know what?
42:25
Good idea.
42:26
I couldn't replicate the data. I didn't, you know.
42:28
So it is one of those things of like, luck
42:31
does kind of meet - and it takes it does take a level of grit
42:36
to like keep failing and recognize that that's one failure
42:40
and that you could just as easily succeed the next time.
42:44
I was getting chills thinking, here I was a young surgeon scientist as well,
42:48
and one of my professors once said, the coolest thing about research
42:52
is seeing a discovery that nobody has yet seen.
42:55
And tell me when that moment happened with this that we're talking about.
43:00
You probably saw the data, you saw something, nobody else saw it.
43:03
And you're like,
43:04
oh my God, just describe that because it's got to be the coolest feeling.
43:08
And it probably happened just a couple years ago.
43:11
Yeah.
43:11
So what what I want to say about that is, is that
43:18
that almost always occurs in a room
43:22
with other, with 1, 2, 3 other people,
43:26
and you're intensely discussing a topic and it.
43:30
Yeah.
43:30
And so and I like to say that there's no
43:34
great scientific idea that happens with me sitting in front of a computer
43:39
typing like, that's not where it comes from.
43:41
It comes from a whiteboard.
43:43
It comes from people kind of arguing or brainstorming or throwing out ideas
43:48
and the several events that's happened as we saw, you know, we administer
43:52
these drugs that are labeled and we can see where the drug binds.
43:57
And we found for the first time that just a couple years ago that we are
44:03
grossly overdosing antibodies to patients and causing these excess toxicities.
44:08
And we should not be dosing based on weight.
44:11
We should be dosing based on an antigen level.
44:15
Or there are ten different things we should do in an era
44:18
of precision medicine.
44:19
So we were in a room talking about that and realizing that we are that we could
44:25
physically see that the drug was overflowing
44:30
in the tumor, that it was nonspecific
44:32
everywhere, and it implied that people are getting way too much drug.
44:36
And so when we had that idea, we were like, wow, we could use this
44:40
at the FDA as the optimal biologic dosing program.
44:44
And boom, like, that's
44:47
that's a whole nother idea.
44:49
And that and again, that came from one person in the lab
44:53
going to a talk where they kind of talked about optimal biologic dosing.
44:56
Another person at the microscope looking at the microscope.
44:59
And it kind of comes together.
45:01
It's not it's not me kind of like going, you know, I wonder what I could do?
45:07
So I just find that so fun. And it is fun.
45:10
I mean, it's talking through it.
45:11
And 1 in 10 of those discussions won't drum up anything.
45:16
But every now and again it works.
45:20
So anyway, I'm really, really grateful, Rahul.
45:24
It is so much - so exciting to see the Academy doing,
45:29
finding so many things that are needed in our group and our specialty
45:34
in the huge variety that that is
45:38
part of our how we practice the demographics.
45:41
I mean, it's just it's wonderful to see the the excitement around
45:47
what the Academy is doing and what you're doing for the Academy.
45:50
Well, Doctor Rosenthal, thank you.
45:52
I've made a new friend.
45:53
I think I'm going to call you my contrarian friend, because today you've
45:57
looked at things
45:58
a little bit differently from me, and I think that's part of your success.
46:02
Much gratitude for you and for what you do for our academy.
46:05
Thank you, Doctor Rosenthal.
46:06
Thank you very much.
46:07
I really, really appreciate it.
46:10
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46:13
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46:18
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46:20
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