Eric Nestler

January 27, 2021

Daniel interviews Eric Nestler for this episode of Science et al. The Dean for Academic Affairs and Director of the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai in New York, Eric studies drug addiction and depression, and has co-authored 4 books, one of which Daniel used to learn pharmacology. The two discuss how neuroscience and psychotherapy interact, potentially.

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00:10Hello and welcome to Science et al
00:12podcast about everything science
00:13sponsored by the Yale School of Medicine.
00:15I'm your host Daniel Barron and
00:17in this episode I'm speaking
00:19with Doctor Eric Nestler.
00:21Eric is the Dean for academic and
00:23scientific affairs and the director
00:24of the Friedman Brain Institute,
00:26the Icon School of Medicine at Mount Sinai,
00:28NY. Eric uses molecular tools to
00:31study drug addiction and depression,
00:33and is a Co author of four books,
00:35one of which I used to learn pharmacology
00:38and more than 650 peer reviewed articles.
00:41He also serves as principal
00:42investigator on 6 NIH grants.
00:44He is a busy guy.
00:46I decided to reach out to Eric
00:48after discussing his 1990 article.
00:50The case of double supervision
00:52with a few friends of the Owl Shop,
00:54New Haven Institution.
00:55Erkeln I completed psychiatry
00:57residency in the same program
00:59and his article demonstrates how
01:02psychotherapy wasn't then and remains
01:04somewhat less than data driven at
01:06the time Eric articulates in the
01:09article that he felt neuroscience
01:11was going to hopefully quickly
01:13revolutionized this concern.
01:14And yet so far it hasn't.
01:18And this is a feeling and also a
01:20hope that I've shared as a trainee Ann.
01:23Now as a young clinical
01:24neuro scientist myself,
01:25I really enjoyed meeting with
01:27Eric and discussing how his views
01:29have changed or not 30 years
01:31after he published this piece.
01:33What struck me most about Eric was
01:35his candor and gentle demeanor.
01:37And he explains how he was disappointed
01:39that neuroscience hadn't progressed
01:41as much as he had hoped when he was
01:43a resident or young faculty member,
01:46and we discussed his multiple high
01:48level leadership roles and how he.
01:50How he tried to promote innovation
01:52while still respecting and
01:54supporting institutional tradition?
01:55The entire hour with Eric was
01:57lovely and I should mention that
01:59hanging on his office wall,
02:01he had his old Texas license plate.
02:03This is from his time as chair
02:05at the Department of Psychiatry
02:06at you T Southwestern in Dallas,
02:08which is where
02:09I was born, Texas. Eric is
02:12a mammoth of a scientist, thinker,
02:14and person, and I hope you enjoyed
02:16our conversation as much as I did.
02:18So here we go, Eric Nestler.
02:35What was it that excited you about the
02:38molecular approach to mental illness?
02:39'cause it seemed like. That
02:42wasn't really mainstream. Not at
02:44all. In fact, psychiatry at that point,
02:46and we're talking about the early 1980s.
02:50Was divided. I would say into
02:53three general categories that
02:55were very well represented in
02:58the Yale Psychiatry Department.
03:01One was a focus on earlier
03:04Psycho analytical approaches.
03:05A second was the realization that more
03:09practical approaches in community and
03:12hospital psychiatry were needed to
03:14take care of chronically ill patients.
03:18And the third was a neuroscience
03:20approach which was basically focused
03:22on the range of medications that
03:25had been discovered by serendipity.
03:27To help people with mental
03:29illness when so you mentioned the
03:32Community approach, yeah, so how?
03:34I don't recall when the
03:36deinstitutionalization happened?
03:36Yeah, but I feel like it wasn't that long
03:40before, you know, it occurred in concert,
03:43in concert with the introduction
03:45of medications so that it occurs
03:48largely in the 1960s. As these.
03:52New classes of antipsychotic
03:54drugs and anti depressant drugs
03:56and lithium were introduced.
03:58And it made it possible for people who
04:02are chronically severely chronically
04:04ill in asylums to be improved,
04:06and then they were discharged to what
04:09was supposed to be a large community
04:12mental health effort which really
04:14only partly materialized in the
04:17ensuing decades. And something
04:19interesting about that. So you would have
04:22seen some of those patients.
04:24So yeah, absolutely yeah.
04:26And so the neuroscience and psychiatry
04:28in the early 1980s was extremely
04:31narrowly focused on neurotransmitters.
04:33So serotonin for depression and
04:35dopamine for psychosis and there
04:38was really little else going on.
04:40So you're absolutely right in that.
04:42What appealed to me about psychiatry
04:45was the opportunity to weave in what
04:48was being taught to me in medical school
04:51at the time as molecular medicine.
04:54We would now call it Precision
04:56Medicine into the field of psychiatry.
04:59And in fact, my colleagues and I were.
05:03Brash and unrealistic enough
05:06to imagine that when I joined,
05:10the faculty at Yale in 1987.
05:15In creating the Laboratory of
05:18Molecular Psychiatry that.
05:21By bringing the tools of molecular
05:23biology to psychiatry that we would
05:25fundamentally advance diagnosis
05:27and treatment of mental illness
05:29within five or ten years.
05:30Here we are 30 years later and
05:32have not seen those advances.
05:34But that was the idea at the
05:37time, right? And I think this is
05:39where it kind of leaves in nicely
05:42with kind of my own brash thinking
05:44in my own research career, right?
05:47As I think every young researcher imagines,
05:49yeah, like I'm going to.
05:51Tackle a problem set and figure it
05:54out and you know 10 years later can
05:58dust off your jacket or something.
06:00So this is this is very soon
06:03we just add one further point to that
06:07is that. Even though in the early 1980s
06:11when I was finishing medical school.
06:15And starting psychiatry residency.
06:17My professors in oncology and immunology
06:20were presenting this vision of
06:23molecular medicine precision medicine.
06:25It really has taken the four
06:29decades since that time.
06:32To achieve. The goals,
06:34so we are now beginning.
06:36Also 30 years ago 35 years ago
06:38my professor said we're going to
06:40cut out a person's tumor or going
06:42to characterize it molecularly.
06:45This is before RNA sequencing and everything,
06:47but they were using older methods to
06:50profile molecular constituents of itself.
06:53We're going to identify the networks
06:55of proteins that are important.
06:57Make antibodies to the key protein,
06:59and that's going to be a treatment
07:01for that person's cancer.
07:03Well, it's taken 40 years,
07:05so I don't feel too badly that in retrospect,
07:08that psychiatry has lagged
07:10because psychiatry.
07:11The brain and psychiatry are orders
07:13of magnitude more complicated
07:15than a cancer cell, right?
07:17You
07:17know, I completely agree and
07:19understand and empathize with that.
07:21I would like to understand a
07:24little bit how this goal of yours.
07:26You know to be able to profile and
07:29diagnose and treat on a molecular basis,
07:32how was that received at the time?
07:36In psychiatry, specifically
07:37in. So I think I was seen as a probably
07:41a curiosity by much of the Department.
07:44I was very much a provoca tour.
07:47The article you cited in the
07:49case of double supervision,
07:51which we could come back to if you'd like,
07:55was very provocative to my
07:57psycho analytical colleagues.
07:58Something that did cash by any
08:00article, and you know,
08:02you being a provoca tour didn't
08:04come through. There's a.
08:06Sentence in here I wanted to ask
08:08you about that if you disagreed.
08:10If a resident trainee, I'm assuming
08:12herself disagreed with his supervisor.
08:14They assumed that it was a
08:16reflection of your personal problems
08:17or level in training my beef at
08:19the time, and I'm not close enough to
08:22this to know whether it's still relevant.
08:25Is that? Psychotherapy was
08:28presented to me. As a practice.
08:34That almost held religious certainty
08:36on the parts of my supervisors who were
08:39teaching me how to do psychotherapy,
08:41and I reacted against that.
08:43You could sense that religious as well.
08:46Of course, cousin when I disagreed with them
08:49and my fellow residents disagreed with them.
08:52We were not only told we were wrong,
08:55but we were interpreted at for
08:57having personal weaknesses,
08:58for even disagreeing with them.
09:00So that didn't make sense.
09:02Obviously, you know, if there's a.
09:04Medical treatment the
09:05psychotherapy works and it does,
09:07and it's a medical treatment.
09:09Then it should be subjected to the same
09:11rules of practice and proof that every
09:14other medical treatment is subjected to.
09:16And so that's why you know
09:18we were pushing back a bit.
09:20So what was your other point about?
09:24I was curious how you combined your
09:26interest about time,
09:27so actually it was very painful and
09:30it's remained painful over 30 years.
09:33In that it really, in my view,
09:36is not possible to combine
09:39the two worlds yet,
09:41and that I've spent 30 years now
09:43on the faculty teaching psychiatry
09:46residents the basics of neuroscience.
09:49And I am very sensitive to the fact that.
09:55Everyone, the vast majority,
09:58virtually everyone's lifetime.
10:00Course of patient treatment.
10:04Does not have to intersect any fact
10:06of neuroscience or molecular biology,
10:09and that's a sad statement of the
10:11reality of the field of psychiatry.
10:14But I think it helps to be honest about that,
10:18right?
10:18Well, do you
10:19view like at the time?
10:21I could imagine you formulating?
10:24A patient's condition.
10:25I mean, you mentioned
10:27serotonin and dopamine, right?
10:28So at that time it was clear
10:30that these medications affected
10:32dopamine and serotonin like
10:34anti psychotics in your presence
10:36and so was there a conversation
10:39even while you were resident
10:41over the meaning of Depression,
10:43BS and. So I
10:44think that that.
10:46Those conversations definitely
10:47occurred when I was a resident and
10:50they continue today and I feel perhaps
10:53that one of the contributions I've
10:55made over the years was pushing the
10:58field to taking a more sophisticated
11:01view of the brain and what it means
11:04to act on the serotonin system.
11:06Just take an anti depressant for example.
11:09When I was a resident we were really
11:12taught by the field of psychiatry that
11:15anti depressants boost serotonin levels.
11:18And that.
11:19Undoes a person's depression,
11:22almost as if.
11:23A person who's depressed can
11:26pull up to the gas pump,
11:28have a pump put in their brains,
11:31and squirt in serotonin,
11:33and I really feel that the
11:35vast majority of the field of
11:38psychiatry viewed anti depressant
11:40action in that way at the time,
11:42despite the fact that at that
11:44very point in time we knew that
11:47there were several collections of
11:49serotonin nerve cells in the brain.
11:51Each collection of cells send projections to.
11:54Partly overlapping different other
11:57areas of the brain and spinal cord.
12:00That there were 14 serotonin receptors,
12:03an advance made by molecular
12:06biology in the mammalian brain
12:09that respond to serotonin.
12:11Each of which is signaled couple differently
12:14to post receptor signaling pathways.
12:16Each receptor expressed in a
12:18different array of neuronal and
12:20honorable cells in the brain within
12:23these circuits so that it really.
12:25And then finally the fact that
12:28simply boosting serotonin acutely,
12:29one can show in brain imaging.
12:32Again, not long after I joined the faculty.
12:36That anti depressants do boost overall
12:40serotonin synthesis in the brain.
12:43After a few days of exposure to the drug,
12:46why aren't the clinical anti
12:48depressant effects seen for several
12:50weeks or months? No clinical change,
12:52right? And so all of these facts
12:55forced the field to take a far more
12:58sophisticated view of how is it
13:00that an SSRI is actually producing
13:03an antidepressant effect now?
13:04In honesty, we still not really
13:07know the answer to that question,
13:10but at least we have heuristic models
13:13that are accurate in terms of the cells,
13:17the circuits and the time frame of the
13:20adaptations induced by the drugs that
13:23might mediate their therapeutic effects. So,
13:26so at the time. There was just
13:29this general serotonin hypothesis,
13:31and the dopaminergic hypothesis
13:34about these illnesses.
13:36When did you begin to sense that
13:38it was much more complex than that?
13:41It was out when you were
13:43a resident or it was when
13:45I was a resident and I had the
13:48wonderful opportunity to meet a
13:50few of my fellow residents around
13:52the country around the same time.
13:55I'll mention two people in particular,
13:57Steve ***** and Rob Malenka.
13:59Steve was at Harvard, Rob,
14:01but then at UCSF now at Stanford
14:04and we became very good friends and
14:06had a very shared experience with.
14:09Robin, I have PHD's in neuroscience.
14:12Steve had extensive neuroscience
14:14training otherwise and the three
14:16of us realized that there was a
14:19disconnect between the neuroscience
14:21that was available and that was
14:23that which was being incorporated
14:24within the field of psychiatry.
14:26So I feel that we and others
14:29helped bridge those two gaps.
14:31Were those conversations like like did
14:34you meet at a conference or we met
14:37at conferences?
14:38And you know part of it frankly,
14:41was kind of making fun of
14:44the lack of sophistication of
14:46some of our professors who's.
14:49Who's naivete about neuroscience and
14:53molecular biology was shocking to us.
14:58And being very provocative individuals,
15:00we reveled in that and but it also
15:04turned to serious conversations.
15:06And in fact so Steve ***** and
15:10I wrote a book in 1993 that grew
15:12out of these conversations that
15:15started during residency is called
15:18the molecular foundations of
15:20psychiatry that tried to layout for
15:24the field how a more sophisticated
15:27understanding of molecular biology.
15:29Andro Science could provide the
15:31underpinnings for psychiatry.
15:32Now we were naive ourselves because
15:34at the time we imagined that there
15:37might be that this the genetic basis
15:40of schizophrenia or autism or bipolar
15:42disorder would be very complicated.
15:44Thinking at the time.
15:46Maybe there would be 5 or 10 genes involved.
15:49Now we know there are many
15:52hundreds of genes involved,
15:53but how
15:54could you have known at that
15:57time without data, right?
15:58So I'm really curious what
16:01impact like this essay,
16:03or you know your conversations and
16:06you know you publishing this book.
16:08One of two books I believe that
16:11is on similar topics and relating
16:13neuroscience to psychiatry mean what
16:15sort of conversations did you have
16:19with psychiatric colleagues who maybe
16:21didn't share exactly your vision? Yeah,
16:24so I think that.
16:27Most people in the field were eager
16:30to incorporate new knowledge,
16:32and so you know,
16:33my provocative side can be overstated,
16:36because I really feel that I was.
16:40Fully embraced by the opinion
16:43leaders and power structure of the
16:47time an I was treated extremely
16:50well by leaders in the field.
16:53And I felt that.
16:56The papers that we wrote in the
16:59books that you mentioned were
17:01definitely welcomed within the field.
17:05I think at the same time there are always.
17:09People who remain old-fashioned
17:11an resistant to change.
17:14I think that's still is seen a bit
17:16today and I don't know if you still
17:18see that in your residency training.
17:21I was at a recent meeting of the American
17:24College of Neuropsychopharmacology.
17:27Where we talked about
17:30psychiatric residency training.
17:32And now I'm an old man and I
17:34stood up and basically gave a
17:36different perspective and said
17:38one of the problems that we have.
17:40In the field is attracting the best
17:43and brightest to psychiatry because.
17:46We can't provide a clear path of
17:49integrating molecular biology neuroscience
17:51with the clinical care of our patients.
17:53And my gosh,
17:55I thought I wasn't being provocative.
17:57I got so much pushback from people
18:01leaders in the field that I was for
18:03the heresy that I was speaking at.
18:06I believe I was speaking the truth,
18:09an reality particular part of that.
18:11Did they consider heretical?
18:13They thought that
18:14there were tremendous advances
18:16in treatment of mental patients
18:19over the last 30 years.
18:21I really disagree with them.
18:25They felt that. Neuroscience does inform
18:29the clinical treatment of patients.
18:32Again, I disagree with them.
18:38I've sensed the same thing. I mean,
18:40I don't feel like that's radical,
18:42but I guess I'm here because I
18:45in essence agree with you. The
18:48field is not going to improve unless we
18:51recognize our own progress and limitations.
18:55So I'm really interested as as you know,
18:58I've mentioned before,
18:59young trainee and researcher how how
19:01do you navigate something like that?
19:03Like how do you as a.
19:07Physician scientist a clinical researcher.
19:12Try to marry those two.
19:15Worlds like a lot of your
19:17research on addiction on stress.
19:20You know the molecular approach.
19:22How do you bring those two
19:24together or try to bring those
19:26two together while realizing
19:29those limitations, right?
19:30So I think the critical ingredient
19:32is understanding what is possible and
19:35at the same time what the inherent
19:38limitations are with either approach.
19:40So I've talked about the limitations
19:43of clinical psychiatry today.
19:45But we should in to be honest and fair.
19:48We should also talk about the
19:51limitations in the research.
19:53And this is where being a physician
19:56scientist and having the combined training,
19:58I think is absolutely.
20:00Instrumental, if I were a PhD only.
20:04And I took the viewpoints that I did.
20:07I don't think anyone would
20:09have paid attention to me,
20:11but it because it was the cause that I did
20:14get complete clinical training in psychiatry.
20:17I did have a clinical practice small,
20:20but it was.
20:21I was active clinically
20:23and cared for patients.
20:25That I think it forced people to pay
20:27attention to the things that I was saying.
20:32At the opposite end of the spectrum.
20:35When I see basic scientists underestimate
20:37the complexity of mental illness
20:40there falling into the analogous trap.
20:43So as the editor or deputy
20:46editor of certain journals,
20:47I'll see papers submitted where
20:50an author says we induced
20:53depression in a mouse by doing X,
20:56we made a mouse schizophrenic by doing why?
21:00And you know, I laugh at what is that the
21:04lack of sophistication of the research,
21:07and so, just as psychiatrists need to
21:10pay attention to the sophistication
21:12of the science, the scientists,
21:15and the animal and cell models?
21:18The people who use animal and cell
21:21models need to pay attention to
21:23the complexity of mental illness
21:25and how it is impossible to capture
21:28depression or schizophrenia or mental.
21:30Any mental illness in in an animal,
21:33let alone a
21:34cell, sure. So I mean
21:37and so that means that one just needs to do.
21:41The best research possible and
21:45take it incremental steps.
21:47While at the same time by being
21:51incremental also being innovative
21:52and creative and trying to make
21:56the paradigm advances that are
21:58needed to achieve progress.
22:04So I'm imagining you in the
22:06early 90s as the young faculty
22:09member where you director of the
22:12Ribicoff Laboratory. At that,
22:14I became director of the Ribicoff
22:17Laboratories facilities in 1990,
22:19two 92 OK and so.
22:22You have this molecular enterprise.
22:25This clinical enterprise
22:26at the same time, and.
22:30How did you navigate?
22:34I couldn't call it how did
22:36you navigate the emotion of.
22:38Like wondering when those two
22:40would come together or like
22:42at what point did you realize
22:44this is a lot more complex
22:46than I thought as a resident,
22:49and I'm unsure that in the
22:51next 10 years, right?
22:52I'm going to pull
22:54this off. I think that hit me after I
22:56had been on the faculty about 10 years,
23:00so probably around the late 1990s or so
23:02it became clear to me as the genetics.
23:06Were appearing far more complicated
23:09and the nervous system appearing far
23:12more complicated that it was going
23:14to take a much longer period of time.
23:17The you know the challenges so around.
23:23The same time that I joined,
23:25the faculty was actually during my residency.
23:27There were the first reports of genetic of
23:30genes that confer risk for mental illness.
23:32So this was these were the Amish studies.
23:36One of which implicated the gene for
23:38tyrosine hydroxylase and bipolar disorder,
23:40and I remember saying to myself, well,
23:43either there's no need for Mycareer,
23:46they figured it out, done, got work done,
23:49but really in the back of my mind
23:52saying really,
23:53it just didn't make sense to me that the
23:56gene that encodes the enzyme that rate
23:59limiting for catecholamine biosynthesis,
24:01that that's where bipolar disorder
24:03comes from, is way too simple.
24:06And of course,
24:07that turned out to be my view mice.
24:10My skepticism turned out to be accurate.
24:12It's not even considered a risk factor today.
24:14Also, how did
24:15you maintain that skepticism
24:17of your of your field and also
24:19of your personal research while
24:20retaining your motivation as well?
24:22So this is something I tell
24:24all of my trainees that I think it's
24:26very important for each scientist to
24:28be successful to tell a story and to
24:31advocate for one's research findings.
24:32So you gotta get up.
24:34You were going to write papers,
24:36you gotta give research talks
24:37where you're telling a story.
24:39If you're a nihilistic.
24:41And saying it's hopeless.
24:42Well, that doesn't do anybody any good
24:45cisely the way that excellent work.
24:47How do you avoid an? I know
24:49it? Then I've known and I've known faculty
24:52have been nihilistic over the years,
24:54but you can do both.
24:55So you could present the research.
24:57This is what we found objectively.
25:00This is where we think this is
25:02what we think it's telling us.
25:04This is where we think it's bringing
25:06us and where the next steps can
25:09lead us while at the same time.
25:11Retaining some intellectual
25:13honesty and self reflection
25:15not to believe ones koolaid.
25:18And to keep in mind the limitations
25:21and challenges of the field,
25:23it's something that I feel I've
25:26been able to do and have really
25:29tried to encourage my trainees's
25:31call and colleagues to do as well.
25:36That one can tolerate that
25:38when you can make advances,
25:40but also see where they fit in in the
25:43big picture, right? How have your
25:46trainees in your colleagues
25:48responded differently to that?
25:49You could call even a stressor, the.
25:54There's this huge complexity of the
25:56brain and people are looking at a
25:58small facet thereof nowadays right
26:00in back then you know the tyrosine
26:03hydroxylase hypothesis, right?
26:04You know one was tempted and people
26:07were tempted to just kind of,
26:09you know, close up shop.
26:11After that, like you mentioned.
26:13And now the brain is understood to be
26:16so complex that one specific research
26:18endeavour is unlikely to unravel the.
26:21Picture, yeah,
26:22it it. You know, I've seen people get stuck
26:26at both opposite ends of the spectrum.
26:31There are some people as we just mentioned
26:33who are nihilistic and who just throw
26:36up their hands in exasperation and
26:38saying what I'm doing is, you know.
26:41Two insignificant it's spinning in the ocean.
26:44It's not worth it.
26:45I'm just going to quit and do something else,
26:48and I've seen people do that at
26:51the opposite end of the spectrum.
26:53I've seen people.
26:55Who present their research findings
26:57with no self reflection?
26:59And you know those are those people
27:01who tend to oversell what they're
27:03stating and their obnoxious.
27:07You know, I think the field gets it
27:10right in the middle and just has to deal
27:12with both from a training perspective.
27:15However, I think it's very tangible.
27:18To teach our young students and postdocs
27:22and residents had to get it just
27:25right somewhere in the middle. Well,
27:28so that maybe that brings us to
27:31the next stage in your career.
27:33So after you were at yell,
27:35you want to Dallas and you.
27:38Did you go there as chair of the divided?
27:41So that's so you had a much wider sphere
27:44of influence over that Department.
27:46Yes. And so. Having this.
27:52Call it dedication, motivation to
27:54your molecular science and then also
27:56your dedication of clinical practice.
27:58How did you balance the need for innovation
28:01and training in clinical practice with
28:04the reality of what was going on at
28:06the time in that institution? Yeah,
28:09so it was a tremendous opportunity for me.
28:12And at the same time a tremendous
28:14learning experience of what's possible
28:16and of what what one's limitations are.
28:19So I went. I moved to Dallas.
28:22At you T Southwestern,
28:23which I should say I was born in Dallas.
28:26Oh my gosh, what really went?
28:28Yes, the Texas trip.
28:31Yeah, which town in
28:32Dallas did you grow up in?
28:34So I only live there till I was too OK,
28:38yeah. And then I think we lived
28:40in Plano OK Time and then. So we live.
28:43There's a park cities very close to
28:46downtown and close to the Med School Med
28:49school that psychiatry Department at the
28:51Med School was led by Ken Altshuler.
28:53It was a very good Department,
28:55particularly strong clinically and the
28:57leading researchers were John Rush,
28:59an Madhukar Trivedi.
29:01Very much along the lines of efficacy
29:05research in antidepressant treatment.
29:09My goals in moving to the Department
29:11were to build a foundation of
29:13basic neuroscience and molecular
29:15biology while at the same time
29:17building the clinical programs.
29:19And I think, you know,
29:21we had tremendous success.
29:22We were able to move the Department,
29:25I think from something like 30
29:27fifth in the country in NIH funding,
29:29we broke it into the top 10 and NIH
29:33funding we were #9 at the time I left.
29:38We recruited a small army of basic
29:40neuroscience researchers and molecular
29:42biologists and also clinical researchers.
29:44'cause one of the goals was to try to
29:47build a program that integrated the
29:50basic science with the clinical science.
29:53The other thing that I did that I
29:56felt was very important and which
29:58was my learning curve.
30:00Was how under funded and under
30:03attended to mental health care was
30:06at you T Southwestern in general,
30:08and in Dallas overall,
30:10so that there was not sufficient
30:12psychiatric resources for the patient
30:15population Parkland Hospital,
30:16which you may know, is you fabulous?
30:19That's well,
30:20there's a brand new parking area,
30:23but also Parkland as the County
30:26Hospital is just a spectacular
30:28resource for the people who live in
30:31in Dallas County and surrounding areas.
30:34Um the.
30:38We doubled the size of the clinical
30:40service at Parkland Hospital and
30:43we did the same at Children's
30:45Hospital and other outside other
30:47general hospitals in the area and
30:50so we were able to dramatically
30:53expand clinical services,
30:54but it was at the time of
30:57building this Department when
31:00I realized that there was this.
31:03Divide between the research and the
31:05clinical care that was impossible to join,
31:09at least at the present time.
31:13I'd like to learn more about that,
31:15so I've seen. You know,
31:18I obviously don't have the perspective
31:20that you do have any Department,
31:23but I've noticed even when interviewing
31:25for residency programs that different
31:27programs have different personalities,
31:29different affinity's to
31:31specific theories of treatment,
31:32one that comes to mind is for
31:35instance Washu in Saint Louis.
31:38They're very psychopharm oriented biology
31:40based, whereas other institutions.
31:43I mean, I think VL being more
31:46psychodynamically oriented and kind
31:48of the East Coast schools being more
31:51psychodynamic oriented generally.
31:52And so how you stepping in
31:55as a new person in Dallas?
31:58You know,
31:59very city with a lot of personality.
32:03What did you find in terms of
32:06kind of the general personality
32:08of the clinical teams like?
32:11Were they
32:12more it was? To be honest,
32:14it was a tremendously refreshing change.
32:17So when I was at Yale and I
32:20had been there a long time,
32:2327 years from undergrad undergrad,
32:25MD, PhD residency faculty,
32:27when I left the Yale Department
32:29of Psychiatry, I left a Department
32:32that I felt was fractured.
32:35Between those three focuses that
32:38I mentioned earlier, neuroscience,
32:41Community Hospital, community psychiatry,
32:43and psychodynamic psychiatry.
32:46And those three factions were at each
32:49others throats in the L Department,
32:52so that when something good happened to
32:55one rather than everyone else being happy.
32:59People were jealous and angry.
33:02And.
33:03Moving to Dallas and being part of
33:05a new Department was probably the
33:08most important psychotherapeutic
33:09event in my own lifetime.
33:11What do you mean by that?
33:14Because I realized that I was part.
33:17Of this disagreement and strife
33:20among different views of psychiatry,
33:22and when I got to Dallas,
33:25Ken Altshuler as the as my
33:27predecessor and other faculty there,
33:30made it very clear that it
33:33was unnecessary to disagree,
33:34and really that the challenge at hand
33:37was to make our patients better.
33:40And So what I found Dallas among the
33:44psychodynamically oriented faculty,
33:46the hospital and community.
33:50Psychiatrist psychiatrist was a tremendous.
33:54Welcoming to consider any approach that
33:57would help them get their patients better.
34:00He's very pragmatic,
34:01extremely pragmatic. So in fact,
34:03one of the things I did with Ken's help.
34:08Was to invite the Dallas Psycho Analytical
34:10Institute to basically join the Department.
34:13So here I was building basic
34:15neuroscience, microbiology,
34:16expanding hospital community psychiatry.
34:17the Dallas Psychoanalytical Institute
34:19was housed within my Department,
34:21just a floor under my office,
34:23and they were not beforehand.
34:25They were not.
34:26They were in the community and
34:29they and you know, they were part.
34:31They were affiliated with the Department,
34:34but not so tightly,
34:35and so we worked hard with our residency
34:38training director Paul Mole. And others.
34:41To provide an education for our residents
34:44that reflected that integration.
34:46And I felt that that was
34:49a really nice achievement.
34:51And so it really reflects very well on
34:54the psychiatric community in Dallas and UT
34:58Southwestern overall to be more flexible,
35:01more reasonable.
35:03More agile and nimble than a far
35:07superior Department at the time,
35:09which was at Yale.
35:11But it speaks to the value of being
35:14new and being on the frontier and
35:17being able to do things differently
35:21as opposed to being part of a several
35:24100 year old enterprise where things
35:27get stodgy and setting concrete.
35:32And you know,
35:33so my criticism of an old Department
35:36or let me phrase it more positively.
35:39The challenge for an old,
35:41established Department is to find
35:43a way to retain the innovation
35:46so that they can continue to.
35:49Adapt positively to all the new
35:52advances that are coming from the field.
35:57I feel like. You must be an extremely
36:02charismatic person to balance tradition,
36:05which is how a lot of people
36:08view their clinical practice,
36:10specially older clinicians with this
36:13innovative stance that you're promoting. You
36:16know I don't like to toot my own horn,
36:19but I think that the one thing that I can do.
36:24That I do do is respect.
36:27What other people are good at
36:29and recognize what I'm good at,
36:32so I would never put myself
36:34up as a model clinician.
36:36You know, I've had a limited
36:38clinical experience in Mycareer,
36:39and so it was easy when I
36:42moved to Dallas and I met.
36:45This army of outstanding clinicians
36:47to respect and admire and appreciate
36:50what they did and and I think
36:53that made it possible for them in
36:56turn to be extremely enthusiastic
36:58about this brave new world of
37:01molecular biology and neuroscience
37:03that I was exposing them
37:05to. So you fostered an environment of
37:08mutual respect, then an even when.
37:12I'm trying to understand that
37:14dynamic term or so I've sensed that.
37:19Some people feel threatened by
37:21novelty or by innovation in such a
37:25way that they become more entrenched
37:28in tradition and so especially given
37:31the limitations of your science,
37:33which largely still exists today,
37:36clinically mean marrying those two seems
37:39that it would have been very complex.
37:43Yeah, you know.
37:44So to your point,
37:46I would say you asked me
37:49earlier about the reactions to.
37:52The Laboratory of Molecular
37:53Psychiatry is a provocation within
37:55the yield Department of Psychiatry,
37:57the people who were probably
37:59most negative and threatened
38:00where the other neurobiologists.
38:02No kidding, not the hospital community.
38:04Psychiatrists are the psycho,
38:05an psychoanalyst.
38:06I think that they were as I said,
38:09so I mean as a curiosity or
38:11intrigued and interested,
38:12it was the neurobiologists because
38:14it was they I was referring to when
38:18I was saying you guys are not.
38:20Taking the full sophistication of
38:22what's available on neuroscience
38:24and applying it to questions
38:26relevant to psychiatry.
38:27I
38:28hadn't imagined that. So how do you?
38:30How do you navigate that
38:32conversation? That was probably
38:34one of the greatest points of.
38:36Article awkwardness and contention.
38:38In my early years on the faculty,
38:42not everybody was happy.
38:44After five years of me being a a
38:48provocative assistant professor and this
38:50is allowed Mountain at Yale Loudmouth,
38:53assistant professor for me to be named
38:56the director of the Ribicoff facilities.
39:00Not everybody.
39:01In the North, in
39:03there now, that's right.
39:04Not everybody was happy with
39:06that. So as chair, then you were able
39:08to both encourage the development
39:10of the neurobiology and then also
39:13help build the clinical practice,
39:15both quite significantly so you set the
39:18shift in funding was dramatic, as was
39:20the growth in clinical practice is yes.
39:23And so you were still very much.
39:26You know, the physician and
39:27the scientists building both.
39:29How did you?
39:30How do you do something like that?
39:33Did you get you had instant buy
39:35in from the community there?
39:37And then everyone kind of banded
39:39together in their respective parts.
39:41Or how did you avoid that fracturing
39:43of the Department that you said, you
39:46know? I don't know the answer to your
39:48question, but I can say in retrospect
39:50that I felt that there was very little
39:53resistance to doing just what you said.
39:56Whereas in contrast, I had spent 13
39:58years on the Yale Psychiatry faculty.
40:01And I was part of a tremendous
40:03degree of fractionation that was
40:05evident to me and many other people,
40:08so I don't know what was so different.
40:12Fast and not just it could be the newness.
40:15Dallas is a newer city,
40:17you T Southwestern as a newer school.
40:20The psychiatric community is smaller,
40:22less established.
40:22The faculty were newer.
40:24You know, there's this frontier
40:26spirit that is positive.
40:29So then your transition from Dallas
40:32back to East Coast you into New York.
40:36That was also another position of leadership.
40:39Yes, now you're a Dean of
40:42scientific affairs and Dean
40:44for academic and scientific affairs.
40:46Essentially Dean for research.
40:50And when I moved to Mount Sinai,
40:52I was director of the Friedman Brain
40:54Institute which was charged with bringing
40:56all neuroscience together on campus.
40:58So this is an ideal opportunity for me,
41:01which what?
41:02Is what appealed to me so much about
41:06it is that it was a platform where I
41:10could now at a bigger scale bridge.
41:14Basic neuroscience, neurology,
41:15psychiatry, neurosurgery.
41:16Now into these integrated
41:18research to clinical programs,
41:20the Mount Sinai Department of
41:23Psychiatry is an interesting.
41:25Entity in itself,
41:26within with along culture that
41:29Jive very well with this goal.
41:31So along time,
41:32chair of the Department is Ken Davis,
41:36who is now our CEO and can build the
41:39Mount Sinai Department of Psychiatry
41:41on a very strong biological model.
41:44So while you mentioned that many
41:46East Coast schools tend to be
41:49more psychodynamically oriented,
41:51that's not the case here at Mount Sinai.
41:54We have very strong clinical programs,
41:57very strong psychodynamic psychiatrists.
41:58But the heart and soul of the Department
42:02has been focused around the brain.
42:05So it's been a fabulous substrate for me.
42:08The funding that's available
42:10in New York City,
42:12through philanthropy and through
42:14Mount Sinai has been an order
42:18of magnitude greater even than
42:20what was available in Dallas.
42:23And has made it possible for us to sustain.
42:28I think an unprecedented degree of
42:31growth across our basic neuroscience,
42:35clinical neuroscience,
42:36and clinical treatment programs
42:39across the different departments.
42:41And I'm talking about 50
42:43new basic science faculty,
42:4550 new clinical science faculty,
42:47hundreds of new clinicians,
42:49and so on.
42:51And you mentioned something that was
42:54that kind of piqued my interest of
42:58how now you are able to have an even
43:01higher level view over neurosurgery,
43:03neurology and psychiatry.
43:05And I'm curious what differences you see or.
43:09If the you know specific
43:11to molecular neuroscience,
43:12whether you feel that that has been
43:15integrated in some way differently if
43:18through those medical door specialties,
43:20sure, and why
43:21that would be, yeah, you know,
43:24definitely to this day,
43:25the neuroscience per say,
43:27is far more integrated in neurology
43:29than the other two disciplines, least.
43:32So in psychiatry, by far.
43:35Our neurology residents meet weekly
43:38for lunch over lunch hour where
43:40there are brain scans on the board
43:43and discussions of jeans and.
43:45Protein aggregates contributing to
43:47neurodegenerative disorders, and so on,
43:49and that's the psychiatry resident lunches.
43:52It's unusual,
43:53have a brain scan on the board
43:56and unusual to talk about jeans.
43:59Partly because the science hasn't
44:02yet provided the information that is
44:05clinically relevant for the residents to
44:07take care of their patients of the day.
44:11Neurosurgery is also very
44:13focused on the brain. Obviously.
44:15You know from a more practical
44:19manipulating point of view of
44:21how one can go into the brain,
44:24dissect pathways,
44:25cells,
44:25circuits safely and with innovative
44:27devices and imaging equipment.
44:31And you're still use of
44:33an ongoing laboratory.
44:35I still have it in my basic science lab,
44:39which is amazing.
44:41So busy doing all these things,
44:44I'm curious how you guide your graduate
44:48students or postdocs and that sort
44:51of conversation you have to someone
44:54looking to have a clinical impact
44:57in a brain based disease specialty.
45:01What is that conversation like?
45:02So say I was a postdoc or grad
45:05student and I was like I want to do
45:07something that I have clinical impact.
45:09Kind of the way that you felt
45:11when you were a resident.
45:13How would that
45:14conversation go?
45:14Well, they would be twofold.
45:16One would be for the PHD's and the other
45:18would be for the physician scientist.
45:20The MD PHD's 'cause it would be
45:22different conversations for most of
45:24the graduate students and postdocs
45:25who were in my lap by joining my lab.
45:28They've already stated their interest
45:29in working in disease oriented research,
45:31doing basic research but within models.
45:33Of psychiatric neurologic diseases and
45:36what I think my lap can provide them is
45:40a good pathway or template and how they
45:44could fashion their careers as well.
45:48For MD PHD's,
45:49it's been more problematic for me,
45:51and I've thought a lot about this.
45:53I have tried.
45:54I've had probably over 20 MD PHD's
45:57in my lap over the last 30 years.
46:00And I have.
46:01I've thought I've tried to convince every
46:03single one of them to go into psychiatry.
46:06As of now,
46:07if my numbers are correct,
46:08I think only one has most have gone into
46:12neurology and a few in other disciplines,
46:14and I've thought about why that is.
46:17I think one of the reasons is that
46:20when my MD PhD students finish in
46:22the lab and go back to the clinic,
46:24they were all gung ho for psychiatry.
46:27And then they do their psychiatry
46:29clerkship and they realized that
46:31there's no science in the clinical
46:33psychiatry and where I was willing
46:35to make the leap and say that's OK,
46:38I can bring the science to psychiatry.
46:40That's an opportunity for me.
46:42For whatever reason,
46:43these individuals are not willing
46:45to make that leap.
46:46They want to join a discipline
46:48where the science is already there.
46:52What do you suppose the difference is?
46:54Just generally curious. I mean,
46:56obviously you're the guy who wrote the
46:58book about. Yeah, I don't know.
47:00We certainly see a good number
47:02of MD PHD's go into psychiatry.
47:05A bit more than went into
47:08psychiatry in my year, but frankly,
47:10nationally we don't see the army of
47:13MD PhD students who want to go into
47:17oncology or immunology, for example.
47:19It's a different level in those other fields.
47:23And I I don't know what that difference is,
47:26but we're continuing to say
47:28about the same number, choose it,
47:30but not the people in my lab.
47:32I think it's so.
47:33Then I have to take some of
47:35the responsibility myself.
47:37And then I thought, well, Gee,
47:39maybe there is something about the way
47:41that I've been presenting psychiatry,
47:43even though I love the field of psychiatry
47:45and I am ferociously loyal to it.
47:48While I am a loyal critic.
47:51Maybe the criticism that I've
47:53made of psychiatry has filtered
47:55into my students in a way that
47:57has turned them off to the field.
47:59So I've in the last 10 years since
48:01moving to Mount Sinai have been
48:03very conscious of that and tried
48:05to be a lot more positive with my
48:08students and muted my criticism.
48:09But to be honest,
48:11I haven't seen a change in their
48:13choice of psychiatry, so I don't know.
48:15Maybe they don't know why.
48:17Maybe they sense that in
48:18their clinical rotations.
48:31We hope you enjoyed that episode.
48:33Many thanks to Eric for being on the
48:36podcast and letting me take in little
48:38over an hour from his day. Such a
48:41busy fellow is a
48:42real treat to not only meet
48:44him in person, but also to
48:46essentially have fair game to
48:47pick his brain about whatever such
48:49a delightful guy, you can learn
48:51more about Eric in his work,
48:53obviously on Wikipedia.
48:54You can also check out his faculty
48:57profile page at Mount Sinai,
48:59or you can find his
49:01articles on Google Scholar.
49:03Just searching for Eric Nestler,
49:05Eric is also the author of
49:07multiple books on pharmacology,
49:09which are not exactly for the
49:11layman, but I found them
49:13immensely helpful when I've
49:15been studying my pharmacology. Thanks to
49:18the Yale School of
49:19Medicine for sponsoring the
49:20podcast to Adrian Brandenburger
49:22for producing the podcast and Ryan
49:23McEvoy for his help sound editing.
49:25A special thanks to you for listening again.
49:28My name is Daniel Baron and I've
49:30been your host and I'll see you
49:32next time here on science at all.