In this episode of "On the Edge of Breakthrough: Voices of Cancer Research," Monty Pal, M.D., F.A.S.C.O., welcomes Marcel van den Brink, M.D., Ph.D., President of City of Hope Los Angeles and City of Hope National Medical Center, Chief Physician Executive and the Deana and Steve Campbell Physician Executive Distinguished Chair.
From mentorship and team science to the intersection of clinical care, innovation and personal resilience, this episode offers a candid look at the experiences and values driving one of cancer research’s most impactful leaders.
Together, they trace Dr. van den Brink’s remarkable journey from his early medical training in Holland — including formative mentorship under pioneering immunologists — to pivotal experiences that brought him to the U.S. and shaped his career as a physician-scientist. Van den Brink reflects on the challenges of navigating academic systems, the grit required during demanding residency years and the turning points that led him to leadership roles at premier cancer centers.
The conversation highlights Dr. van den Brink’s groundbreaking scientific contributions, including discoveries that have advanced understanding of T cell biology, the thymus, immune recovery and the microbiome’s role in transplant outcomes. He discusses his philosophy of fostering open, collaborative research environments and the importance of rethinking traditional academic models to empower the next generation of scientists.
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Full Transcript
Dr. Monty Pal:
I'm Dr. Monty Pal from City of Hope, and this is on the edge of Breakthrough Voices of Cancer research. Each episode, we bring you the minds behind the science, the stories behind the data, and the breakthroughs that could change everything. Let's dive in. Welcome back, everyone. It's a real honor for me today to have Dr. Marcel van den Brink in the chair with me here for this podcast. Dr. van den Brink is our president and really creating a lot of our scientific direction here at City of Hope. Welcome to the program, Marcel.
Dr. Marcel van den Brink:
Thank you very much, and please call me only by my first name. Okay. That is how I like to, um, interact with everybody.
Dr. Monty Pal:
Appreciate that, appreciate that. You know, we always start this podcast with the origin story, right? Where your interest in cancer research began. Um, and you've had an upbringing outside of the us. I'm just so curious how, uh, all roads took you towards cancer immunology.
Dr. Marcel van den Brink:
So, where do I start? I was born in Holland, um, and when I went to medical school, um, I worked with a legendary scientist there. Uh, he should have gotten the Nobel Prize for the discovery of, um, HLA. I sat down with him and, and was wondering what kind of research is really interesting, do you think? Uh, he said, you know, there's this very interesting work going on at the moment within the US that has to do with L cells, lymphocy activated killer cells, and it seems to be a therapy for cancer. And there was, at that point, only one or two articles in that field. So he said, I want you to work on that. Now, the big problem was there was nobody really in my hometown and in our, uh, university who was working on that subject. So for one year I tried to make something going, and then the same guy organized a annual, uh, conference.
Well, this is the weirdest conference that you can think of. It happens on two old Dutch sailing boats. Everybody, um, has to stay on that boat, even if you know that the walls are very, very thin, and there are people next door, uh, snoring, and you won't be able to get any sleep. You still have to, and, and I hope that this won't get cut. Um, a lot of alcohol, <laugh>. One of my, one of my major jobs was to schlep all of the alcohol into the boats. And some of the scientists were, were just nonstop, uh, drinking, but that had no impact on the quality of the science. For some reason, that format worked very, very well, and he was able to get the best scientists from all over the world to come. So he said, for this year, you are gonna organize that conference apart from schlepping all of the alcohol. And, uh, it's gonna be about L cells and immunotherapy, which at that point, nobody was really studying it. That is where I'm, uh, connected with a scientist from, uh, Pittsburgh. That is why I went for the first time to the us and that is where I started to develop my early interest in a field that basically at that point was mostly laughed at something that had been a, a theory since 1905 or something like that, but has never really paid off.
Dr. Monty Pal:
And may I res for a second. What a brilliant way to hold an audience captive, right? You're on a ship. We, we worry so much at our meetings about people driving in, driving out, and not really networking. I mean, I imagine a lot of na late nights on the boat talking science.
Dr. Marcel van den Brink:
It was absolutely fantastic. It is a format that worked and that when I organized, uh, workshops, et cetera, and I just actually did one at Ash, we, that half of it is about the actual content of all of the talks. The other half is about bringing scientists, uh, together and making sure that they can, uh, connect and can talk the most interesting data science happens outside of the talks.
Dr. Monty Pal:
Indeed, absolutely. All the water cooler conversations and so forth. Right. I, I've gotta agree with you there. Yeah. So you had this experience in Pittsburgh at, at what point did you start thinking, okay, I'm gonna transition my career to the us? How did that come about?
Dr. Marcel van den Brink:
Yeah, so this is a story. So I go back very often to Europe, and my story is, I still feel that Europe is not ready to provide the resources, the culture, the climate. For a physician scientist who want to spend a serious part of their time doing wet lab or dry lab science in Europe, it is still a system where, well, you have to be a, a clinician, you have to clock your clinic hours and so on. And then maybe you can spend every day a few hours doing some kind of science.
Dr. Monty Pal:
So it's more of a hobby there than anything else.
Dr. Marcel van den Brink:
Uh, whereas within the us, as you well know, you can be a true wet lab, dry lab scientist and spend most of your time doing science. That's the only way to be really as successful. So I keep on sending this message to all of the people in Europe. My personal story is I came back from, uh, Pittsburgh. I met with my chairman of medicine in Holland, um, Al Laden, which is the, uh, college where I went to, and I sat down with him all gung-ho like, you know, this was fantastic, and this is so great to do wet lab science. I would like to specialize in, um, oncology. I would like to, as quickly as possible, be able to do some research again. Um, and I would like to develop as a, a physician scientist. There was a long pause, and then he basically told me, no, no, and no.
Um, right. None of that fit within to the Dutch training system and so on. And to really punish me, uh, lighten, thought that it was a good way to teach people about the basics, how to become a doctor by going to a local rural hospital. So here I am, um, I'm gonna be sent to Gua from the Gua cheese. Um, so here I am in Gua in a very, uh, conservative Calvinist town trying to learn something about medicine, hating every hour of what I was doing there, and knew I need to get the hell out of here as quickly as possible. <laugh>, um, um, in those days, actually, I think it's still like that you had to be able somewhere to do the, um, exams, the entry exams to be able to study here. Um, I'm not sure if they're still called the U-S-M-L-E,
Dr. Monty Pal:
But still the same. Yeah,
Dr. Marcel van den Brink:
Something like that. Um, the only way for me to do that was to go to London. So I took a few days off. I had hardly studied. I went to London, and, um, I barely passed these tests. And then my lucky break was that, um, it was only one school that wanted to interview me, duke. And there was this amazing, uh, physician scientist there who saw something in me. And, um, he called immediately and said, let him into the Duke Residency program,
Dr. Monty Pal:
And this
Dr. Marcel van den Brink:
Is a, and that was my tier
Dr. Monty Pal:
Residency program, right? It's
Dr. Marcel van den Brink:
No joke. And nobody else was interested in interviewing me. It was my only break. I was there with all the other people doing their interviews, like, which other schools are you looking at? Yeah, none. This is it, huh. And that was my lucky break. And, um, at that point, I went to Duke. I had no idea where that school was. I didn't realize that I was now suddenly in the deep south. It was a quite a culture change, although Pittsburgh was already interesting. Um, and Duke was a fantastic program, and it's something that has stuck with me. What I learned there, it's a concept that I might have mentioned in other talks with you also, what they taught you is what this patient needs is a doctor. And what was meant by that is that practicing medicine as a way, like, well, I have a checklist. I have a consultants and I sort of organize a little bit that, that other people do. Whatever needs to be done is not the right concept. The concept is it's about how you as the doctor, control the care and are there for every aspect of the care of your patients. And they were very good at, uh, teaching us that. And as you well know, I'm sure you have similar thoughts if you sometimes see, uh, trainees having a sign out sheet that they're basically updating all day to hand it on to the next person.
Dr. Pal:
I remember that.
Dr. Marcel van den Brink:
Yeah. That, that's not really how we should be practicing medicine. So I liked my Duke training very, very much. I learned
Dr. Monty Pal:
A lot. It's such an important time, isn't it? Those residency years. I absolutely, I remember it was actually when I finished internship at a bad timing that they started introducing the 80 hour work week. But I have to tell you, I wouldn't replace it for anything being in the hospital for a hundred plus hours a week. It really, it really grounds you a little bit, doesn't it?
Dr. Marcel van den Brink:
But there's one aspect to it, because I'm actually worried the way that I'm talking now. I often say we shouldn't, right? Because I'm talking a little bit like the good old days mm-hmm <affirmative>. And we had to work so hard, and that is how it's done. On the other hand, uh, those hours were madness. I still know having been up for 36 hours, uh, straight and trying to finish a note and just dozing off and waking up with my pen scribbling, et cetera, <laugh>. Um, and it is a concept that I've told many people now who are in similar leadership roles as I am now, don't let your judgment about what we need to do now, be, uh, come from your personal experience, right? Because
Dr. Pal:
Hmm.
Dr. Marcel van den Brink:
Um, because we had to work so hard. Therefore, residents now should work also 80 or 90 hours. No, that's not the right way of thinking. Try to think about what didn't you like, what was actually wrong about the training? We can talk about a research also where we have similar kinds of, uh, uh, problems. Don't use as an argument to justify what we're doing now, because I had to do it, and therefore, you have to do it.
Dr. Monty Pal:
I think that's a terrific leadership pearl. You know, I, I think it's oftentimes underutilized, perhaps that we often do have this sort of experiential leak into the way that we, you know, sort of inform our own dogmas around these types of things. I'm curious, was, was Duke more of a pit stop for you? Because I believe after that you went to Beth Israel Yeah. For fellowship training, or did you kind of get your hands, what was some research at Duke as well?
Dr. Marcel van den Brink:
No, it was only, uh, clinical. Um, but as I said already, it was hardcore. Um, it was difficult for me because I still know the first weeks, um, US medicine, uh, thrives on acronyms, <laugh>, and I would read these notes and I didn't have a clue what anything meant.
Dr. Monty Pal:
Right?
Dr. Marcel van den Brink:
Right. It was CAD with mi and it's, it just went on and on and on.
Dr. Pal:
That's
Dr. Monty Pal:
Gotta be tough.
Dr. Pal:
<laugh>, that's gotta be really
Dr. Marcel van den Brink:
Tough. I needed a big dictionary to try to decode all of the acronyms. Um, no, that was really purely a clinical, um, and at that point, I knew that for my fellowship, I wanted to find a fellowship where I would have access to labs.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
So that's why I thought, oh, Harvard, I've heard of it, and they might have some labs, so that's good. So I didn't even care that much about the clinical program there. If it would be bi or if it would be Deaconess because it was still, uh, separated or Mass General, or Brigham or whatever. I just wanted to get into the Harvard, uh, system, and they promised me that at that point I could go to any lab.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
Um, so my lab was actually at the Farber where I worked.
Dr. Monty Pal:
And tell us about that experience.
Dr. Marcel van den Brink:
So that experience was good and bad. And this goes again to this point. Don't propagate what you've seen during your own, uh, training. So, um, what I liked very much about my BI training before it was the bi deaconess, is that, um, for instance, the nursing was exceptional. I worked with a lot of docs who were both, um, in private practice. So they would go to local hospitals for part of their time, and were working with a bi. So you got a very nice blend of guys who were just very good doctors, but also had the culture of putting patients on the study, on the trial, et cetera, et cetera. Okay. So that was good. The nursing care, as I said, already was exceptional. I, I've hardly ever seen anything at that level. Then when I went to, into a lab at the Farber, um, I was literally told, you can't talk with the postdocs next door. Right? So, no kidding. What I faced there was this old culture where all of the labs, even within an organization, are, uh, competing with each other. As, you know, both John Carton and I, I understand you spoke earlier with him, we believe very strongly that, uh, collaboration is critical. Um, some of my colleagues from other organizations use phrases like, one of my most critical, uh, goals is that I make sure that my postdocs talk with the postdocs of the other labs. I believe very strongly in that.
Dr. Pal:
Hmm.
Dr. Marcel van den Brink:
Um, another thing, certainly now at this stage where I am now, is that it's not so much about my brain coming up with some new thoughts and new things that we can do, but foster help the folks in my lab to be a creative, trust them to come up with some innovative, uh, thoughts.
Dr. Monty Pal:
You know, I even see that in the physical structure of your lab, you know? Mm-hmm <affirmative>. I often like to walk through the Beckman building. I often meet with Rob Jenk, who I'm sure we'll talk about in just a moment, uh, over there. And, and the structure is such that, you know, there's really no separation, physical separation anymore between labs. Right. It's all just one sort of continuum. And you might have the T-cell lab interacting with the microbiome lab, and it's all blended, right?
Dr. Marcel van den Brink:
Yeah. Um, no, that is absolute what we wanted on that floor also. Right? Rob, Rob has his own lab. We have no problem sharing instruments, sharing space, um, uh, et cetera, because we have a similar, uh, philosophy. Um, I still know from the opening ceremony of the Parker Institute, which at one point I was a member of the final slide was and collaborate like hell.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
And that is very much a slogan that I believe in both, uh, clinically, but certainly, uh, research wise, right? We, we are too much in our silos. And again, John and I have very similar thoughts. We need to foster a collaboration also by changing the way that we look at an academic, uh, career. Right? We drive scientists into being solo artists. 'cause it's about your first author paper, your last author paper. It's about your grant, your NIH grants. If we put more value into a collaborative papers, grants, et cetera, we can change the whole culture. So we've been thinking about a new academic model. We're still working on that. We're working with Stacy Gray and with others. Um, on that, I think we're making a progress, and we very much let that be driven by our, uh, juniors, junior faculty, uh, trainees, postdocs, et cetera. Let them tell us what kind of future they want and what kind of academic model they want. It's pretty obvious that they don't want this same kind of, uh, competitive solo artist world that we grew up in.
Dr. Monty Pal:
I love that idea. So, getting feedback from our juniors, no, I took over as Vice Chair of Academic Affairs, uh, for medical oncology about a year and a half ago. I've, I've loved the role. I agree with you. I think the mindset has changed. Um, you know, this whole phenomenon of just striving for the podium and the podium only, you know, is very different. And I think that's a healthy change of the culture. Indeed. Um, you know, but getting back to your experience at the Farber, you know, you, you did bench based research over there. You were in the clinics and so forth, you know, and it was after your time over there that you transitioned over to Memorial and had this, you know, very storied, you know, almost 25 year career over there. What was it that influenced that transition?
Dr. Marcel van den Brink:
That's actually an interesting story. So, um, certainly as, um, as a little boy from Holland, I thought, wow, they're gonna offer me a lap at Harvard. I made it. This is fantastic. I was happy as a clam or whatever. Um, so then I got a phone call from, uh, Sloan Kettering if I was interested maybe in looking at a job there. And I told them, um, no, I don't think so, because I just said that I would stay here at Harvard. So I put down the phone, I will never forget, but a colleague of mine, a fellow a postdoc, overheard me making that phone call and said immediately that was wrong.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
And she was very forceful, you're gonna call back now and you're gonna look. Um, so I did that, and then I realized that that was actually a much better offer, that I liked my colleagues there, and that it was an amazing cancer center and
Dr. Monty Pal:
Space, resources, all that stuff. Better
Dr. Marcel van den Brink:
As well. Resources, far, much better. Um, I mean, still very, very small. I had an interesting start there.
Dr. Monty Pal:
I, I've gotta say, I mean, irrespective of, you know, earning this o on visa and having this amazing sort of, you know, uh, startup package at memorial's, still hard, right? Starting up a lab and getting a research program going. Tell us about those early days. I think it's really insightful for some of our junior investigators to hear how you went about doing it.
Dr. Marcel van den Brink:
No, I think it is for everybody incredibly tough. I hardly know any junior faculty members who haven't had sleepless nights and, um, anxiety, and am I gonna make it? Part of what I did actually at the ASH meeting was, again, meeting with some of my former mentees, and in some cases, giving them guidance, giving them courage, giving them hope, hopefully
Dr. Pal:
<laugh> Yeah.
Dr. Marcel van den Brink:
They will get through these first difficult years where you're fighting for your first NIH grant fighting for your first paper that is meaningful, et cetera. Um, no, those, uh, startup years are, uh, very, very, uh, stressful.
Dr. Monty Pal:
And I know a lot about the van den Brink lab now, but when the van den Brink lab was at its inception, right? Mm-hmm <affirmative>. What was the focus back then, and, and how did that sort of winding pathway come to the thymus and the microbiome and so forth?
Dr. Marcel van den Brink:
Yeah. So I knew that I wanted to do some work that was linked of course, to bone marrow transplantation, because that was my clinical focus. Uh, but I also knew I want to do something that, um, is not a crowded area. Right? I'm sure that you've heard many, many times that if you pick a topic for your lab, you wanna pick something that is not so crowded where other people aren't working, uh, already. And of course, the famous phrase, you want to go where the puck is going, right?
Dr. Pal:
Yeah.
Dr. Marcel van den Brink:
And Gretzky, um, so what I thought then is one of the major problems in allogeneic bone marrow transplantation is that the pace by which the T cells come back, right? The T-cell reconstitution, we don't have any therapies. We don't have anything for it, right? That's why these patients live for two years, like eight patients, basically, very vulnerable, and so on and so on. So that's what I picked as my initial subject matter. Um, actually, one of the first things that I was focused on was trying to develop a therapy for it. And the therapy that we picked, I still think it's the best therapy, is, um, recombinant IL seven.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
I'm not sure how much you know about that cytokine No, please tell me. But that is a cytokine that basically from start to finish, from the earliest precursor of a T-cell all the way up to a mature T-cell is a constant growth factor. It upregulates, bcl, uh, BCL two, right? Mm-hmm <affirmative>. But these T cells don't die that quickly, and so on and so on. Um, and I was able to figure out where the patent was for IL seven was sitting with, uh, Sanofi, a French company. They hadn't done anything with it. And I was sort of poking around like, is anybody working on it? So finally we found a scientist there who was just splitting off to set up his own company. Long story short, this was, what was it, 2000? We're now 25 years later, IL seven continues to be a very promising drug with low toxicity efficacy at low doses tested in 400, 500, uh, patients from different kinds. So we have eight patients, end stage liver disease, cancer patients, and so on. Everywhere meets its mark meets its, uh, targets, but has been completely mismanaged by biotech companies and big pharma, and therefore still is not available for our patients, although it clearly works. So what I learned from that is, first of all, that I had no clue, certainly when I started, how to actually develop a drug. And that is a whole field on its own
Dr. Monty Pal:
<laugh>. Sure.
Dr. Marcel van den Brink:
And that nobody should think that, oh, if I'm a physician scientist, I know something about a clinical, so if I have an interesting finding, I'm gonna develop it. No, there, there's a whole art to that. You really need experts, uh, for that. Um, and second that I don't want to give up on it, so we're still trying. Now, I've gone back to this kind of work now, uh, to come up with a way with a new formula for IL seven
Dr. Monty Pal:
Okay.
Dr. Marcel van den Brink:
To see if we can get it again into the clinic. It works.
Dr. Monty Pal:
Yeah. Well, you know, IL seven is, is something I'll keep an eye out for. Certainly indeed. I'll, uh, but I, I wanna hear more about IL 22 as well. Yeah. And that story, that's, that's a fascinating story. I wonder if you'll share that with our audience.
Dr. Marcel van den Brink:
Yeah, sure. Um, so as I said already, we were looking for a strategies that can, um, help, uh, with, um, overcoming the thic damage. So, so a little bit of background there. So the thymus is an organ where you make T cells, right? It's the only organ where you make T cells starts to, um, involute. So it starts to age already during your teenage years and is very vulnerable, very sensitive to pretty much every therapy that we use, chemotherapy, radiation, and so on. Um, so at one point in our studies to try to figure out how we can make thic function better, we thought we're gonna study natural rebound strategies of the, of the thymus.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
Little sidestep there. I still know when I did my boards exams at one point for oncology, I was told in one of these prep courses, there's a question that you might get asked. Uh, you treat, um, a 16-year-old or something like that for some germ cell tumor. Um, you are done with all of the treatments. You do your follow-up, uh, cat scans, and you see a rapidly growing mass in the anterior mediastinum. What do you do? A nu it B, more chemo C uh, cut it out. D don't do anything. It is a rapidly rebounding thymus.
Dr. Pal:
Okay. And
Dr. Marcel van den Brink:
That's the answer.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
So this is something that we know in patients can happen also, and in mouse models, when you would also, so that really got us going. Like we wanna understand what are the, what are the cell types, the pathways that actually do that in that context, by studying that in a very, uh, sequential way, we found that there was, at that point, a new type of cell innate lymphoid cells that at that point when we started to work on that was a new category of cells that people are looking at. Um, and there was an innate lymphoid cell type three, uh, that seemed to be very relevant for the rebound of the thymus. Long story short, when we analyzed, how does that cell do it? We stumbled on IL 22. Um, and that turned out to be a very interesting growth factor for, um, epithelial cells.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
At the same time, we were still doing some studies in a graft versus host also, and in the crypt of the gut, right? Where you have stem cells also epithelial, uh, stem cells, um, we noticed that there's also, there innate lymphoid cells going that are making IL 22. So in parallel, we were studying how IL 22 can happen, can be functional for the rebound of a damaged crypt, damaged gut, and a damaged, uh, sinus. The only place where we could get it into a trial was for the gut. And it was an early treatment trial for gut graft versus host.
Dr. Pal:
Got it.
Dr. Marcel van den Brink:
It's actually a positive trial, the initial trial. But again, for some reason, that is the fate of everything that I worked on, the biotech company that did it, uh, fizzled, and now it's still just hanging there somewhere. So I'm looking at two areas where we have positive data, and I've not been able to really get it to the next study. And maybe you can help me, maybe afterwards you can teach me how that's done, because I know that you were super successful with
Dr. Monty Pal:
That <laugh>. I don't know about that.
Dr. Marcel van den Brink:
I seven IL 22, help me.
Dr. Monty Pal:
I I, I would love to talk about clin dev. I mean, it's, it's a complicated space indeed. No, but, but you, you just sort of alluded to this, right? This continuum between the thymus, it's, it's funny, I'll tell you, uh, my connection to the thymus, I'm coaching my kids science Olympiad right now. Right. And, uh, my son and daughter are both doing anatomy. And the question that pops up there, not, not nearly as hard as your board's question, right? Is, you know, what, you know, endocrine gland disappears over the course of time, and it's the thymus and it, it just makes it so fascinating to me that you thought to look at this disappearing glandular structure, right? To really inform, you know, how the immune system might be reconstituted. So am I right in saying, you know, suppress IL two, then perhaps suppress this rebound effect and, you know, GVHD in the process? Or what is, what is the underlying principle
Dr. Marcel van den Brink:
There? So IL two's role is very complicated.
Dr. Monty Pal:
Uh, 22, excuse me, ill,
Dr. Marcel van den Brink:
But IL 22 is definitely relevant mm-hmm <affirmative>. And, um, what we actually saw is that cimic rebound is worse in the context of a graft versus host. And we saw that the cells damage during a graft versus host, right. By those allo activated T cells that are causing a graft versus host one of their target cells is IL C3.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
So in that way, during graft versus host within the gut, you see much lower levels of the ILC threes and IL 22. Hence you have that permanent damage almost
Dr. Pal:
Got
Dr. Marcel van den Brink:
It to decrypt. And if you think about it, the problem with graft versus host, if you don't immediately cure it, right? With high dose of steroids or whatever, you can fairly quickly get trapped in a situation that your biggest problem is no longer that you have lo activated T cells or whatever, but you have permanent damage to the epithelial, uh, structures. Got it. Right. Okay. And, and what you then need at that point is still something to, uh, suppress, uh, T cells, but you need a second line of therapy to, uh, regenerate the damaged, uh, damaged gut. Got it. Or the damaged thymus.
Dr. Monty Pal:
You've so elegantly taken us from the thymus up here, you know, to the gut down here. So, so let's talk about the microbiome. It was hard for me not to just jump in right. With that from the get go. 'cause obviously that's a, a mutual interest of ours. But I mean, you've been at this for a lot longer than I have. What was it initially that made you think, well, gosh, let's look at gut bacteria in their relationship to all these phenomena, or was it that simple?
Dr. Marcel van den Brink:
No, as you know, right? And I wanna highlight those kind of stories also, because it's not that I was such a brilliant guy who knew like, oh, we're going to now study such and such. Now this was, um, serendipity again. Um, a Spanish postdoc, uh, started working with a colleague of mine, Eric Paer. He was the head of, um, ID at, um, MSK. This guy came with, you know, there are these new methods, you can sequence the gut flora and you can figure out what all these, uh, bacteria are. And I was looking at that and saw the first set of data that Eric in his lab generated and thought, this is really interesting, and why did I jump on it? Well, there is a history in allogeneic bone marrow transplantation where started in the 1970s or so, but in the 1980s, nineties, it was actually used clinically where they thought if you sterilize a patient, both skin and gut, put them literally into a bubble. That's what we did at the Brigham. Um, then, um, they will have a lower incidence of a graft versus host, right? So they thought all these bacteria in your gut, in the course of an allogeneic, uh, transplant where you're so vulnerable, that's bad
Dr. Pal:
Mm-hmm <affirmative>.
Dr. Marcel van den Brink:
Um, but there were also, uh, studies, uh, from mice also that demonstrated that the incidence of graft versus host would be lower. So it was both the infection risk and the graft versus host risk if you wipe out a bacteria. Um, so the initial studies in those days were positive, but then the follow up studies didn't really show it anymore. And of course, this is so complicated, right? Right. These patients had to literally live in a bubble setting, uh, that people gave up on it. But I knew that history. So I thought, Hey, this is a whole new way of looking in, much more detailed than they could ever do in the eighties or so because of these new sequencing methods. So that's why with Eric, with Eric Paer, we jumped on it. Um, and Rob Chang
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
Was, uh, my postdoc in those days. He was studying something completely different. And I said, I think you should do this project. Um, so he worked side by side with the Spanish postdoc and with other people within Eric's lab. And, and yeah, it was amazing. You know, this is the fun of science, right? Um, when I was a little kid, I would read these books about them, a discovery of something, the origins of Nile, the first person going to the North Pole or to the South Pole, or whatever. So this is amazing, right? This is, uh, seeing something for the first time, and that's what science still has, right? For the first time to analyze in a bone marrow transplantation patient, what happens with the gut. And what you find is amazing, and, uh, I'm sure you've seen some of the data, but
Dr. Pal:
Yeah.
Dr. Marcel van den Brink:
The changes in the gut flow during trans, you don't see that in any other setting. And you go from an Amazon rainforest, right? Like your normal flora looks like to sometimes either nothing or a single bacteria that has taken over the whole landscape of your gut.
Dr. Monty Pal:
Well, I remember a lecture that you gave here at City of Hope years before you arrived as our president. Um, it was here in the arduous auditorium. I think Steve Foreman might've invited you out and tell me if I'm correct about this. It was right around the time that your New England Journal paper had come out, right? Mm-hmm <affirmative>. Um, which I just wanted to, you know, sort of remind our audience is such an incredible feat, and it in my mind, speaks to the clinical practicality of some of the work that you were doing. Patients are in-house for these extended periods of time for bone marrow transplant. Right? You have, if I will, a captive audience, right? Yeah, exactly. You know, where you can continuously collect stool during the course of their hospitalization really without, uh, without much work on their part, right? I mean, it, it's less effort on the patient's participant stool specimens during that period of time. True. So brilliant utilization, I would say, of that particular resource. Um, you've already alluded to it to some extent, but tell us about some of the associations that you teased out between gut composition and GVHD in that New England Journal paper.
Dr. Marcel van den Brink:
Yeah. So the two major findings were, first of all, as I said already, you very quickly lose the diversity of, of your flora
Dr. Pal:
Mm-hmm <affirmative>.
Dr. Marcel van den Brink:
And it's really fun by multiple factors, right? Because the first thing that we thought, oh, it's probably the use of antibiotics, but it's much more than that. It's the change in diet, it's the chemotherapy, it is the radiation. Um, it's all of the other drugs, right? We had another paper couple of years later, which would basically demonstrate that every drug has some impact on gut flora. Sure. Right? And any a transplant patient at any given moment is getting six, seven different drugs for nausea, for pain, whatever. Um, so that was an eyeopener, that's a diversity mattered. And specifically, patients who have a greater loss of their diversity within their gut flow, which happens very quickly within a week or so, uh, have worse outcomes. The outcomes were first and most of all, lethal graft versus house. So it had direct impact on the overall outcomes of a transplant.
That was one. The other thing, and and I, um, mentioned that, um, already, is that in the change, in the loss of the, uh, diversity, there are certain, uh, bacteria that can start to dominate. And the one that does that more than anything else is enterococcus. And what was really fascinating in that paper, in the New England Journal, that we had, uh, patient data from four centers from all over the world, uh, Japanese data, German data, US data, et cetera, and in all cases, in all settings, it didn't matter where it was, it was enterococcus that would do that more than any other bacteria. Um, and that was, again, if that happened, if you reached a state of domination in your flora, your outcomes were, again, even worse, specifically increase in lethal graft versus host. So those were probably the two major findings. And then we had a whole bunch of, uh, follow up studies where we looked at the mechanisms by which enterococcus, that was actually a science paper, uh, how that happened, right? Why does it lead, uh, to worse the worst outcome? So it was a fascinating story, and as I said already, it was really a journey, like stuff that you had never thought of, right? I mean, I never thought about bacteria. Sure, yeah. I was studying, uh, T cells and K cells. That was my business.
Dr. Monty Pal:
Well, what an impressive feat. I remember thinking this when you just joined, um, us here at City of Hope, I mean, to publish in science at New England Journal of Medicine is really the, the translational physician's dream, isn't it? To, you know, really have that high level of, you know, sort of laboratory based validation that really does manifest in patient care, but getting to that side of patient care, where, where are we headed with the microbiome? I've always wanted to ask you this, right? I mean, you know, we talk about, you know, how the composition affects outcomes. Clearly at some point we wanna get towards addressing the microbiome with various therapies. Um, you've been involved in studies and developing programs around fecal microbiome transplant. You've also informed the direction of companies like SRIs Therapeutics and others, you know, that have been involved in crafting these live bacterial products. If you pull out your crystal ball here, Marcel, what, what do you think we're headed towards in terms of manipulating the microbiome in the future?
Dr. Marcel van den Brink:
Well, there are two things, I think, um, that are relevant for the whole future of that field. Before we go to, uh, therapies. I think we need to realize that changes within the gut flora really have impact.
Dr. Pal:
Mm-hmm <affirmative>.
Dr. Marcel van den Brink:
Um, if we just put it within cancer on the efficacy and the toxicity of our therapies. And what I've been, um, arguing is that if we think about how we monitor what kind of correlative science we do for any clinical trial, um, there's an organ function test that we always do, right? We look at kidney function, cardiac function, pulmonary function, et cetera. Microbiome function as an organ should be part of that. And I would argue as a drug company, biotech, pharma, you wanna know that you want, just like you wanna know if impaired pulmonary function has impact on the outcome of whatever drug you're testing for, whatever,
Dr. Monty Pal:
Sure.
Dr. Marcel van den Brink:
You wanna know if that microbiome organ has impact on that, even if you don't have any way to, uh, manipulate it. Right? You often don't have that for pulmonary function also, but it is valuable data to really assess what are the problems with your therapy and what impacts on efficacy and toxicity. So that is the first thing that people start to understand that microbiome in many ways, through the stimulation of the innate system, through all of the metabolites, through what it does to the uptake of nutrients, et cetera, it has so much impact on so many cells, organs, et cetera. So that if you do a trial and you really wanna understand what your therapy is doing, you wanna know about that big organ with as many cells as you have in your whole body. So that's my first way of thinking, right? That, that, and that's also with Chen, um, why we wanna make it easy for people at City of Hope when they do a trial to build into the correlative science, access to stool sampling, biobanking, um, analysis, et cetera.
So that's one. Thinking about, uh, therapies, two ways of thinking. One is indeed directly having impacts on the, uh, composition of the flora. And you can do that, of course, with the fecal transplant, et cetera, with this company, a series. Uh, what we have done there is based upon our studies and studies by the company, we figured out that there was a, uh, constellation, a, a composition of, of an X number of, uh, bacteria that all in their own way could have positive impact on an allogeneic transplant. And then we had to figure out how you could turn that into a, a composition that is stable, that when you give it to a patient, that it will take, that it will, um, eng graft. So that's what we did, that was that serious, uh, product that we have tested now. And that is, I think, a very, uh, controlled way to put exactly the right flora in place for whatever purpose you have.
Right? In this case, we were very focused in the context of allogeneic transplant to prevent bloodstream, um, infections. So then, you know that there's a series of, uh, bacteria that are high risk for that. Um, escape is the acronym for that. Um, so that's what we specifically measured. And yes, we have positive signals there. So what you're really banking on then is that whatever you put into these patients creates colony resistance and maybe some other mechanisms by which it prevents sepsis and, uh, infections. So that's one way. The classic way, of course, which is now already being done for, uh, c diff, is a fecal transplant of normal healthy donor. Um, I don't know what a normal healthy stool is. So, but, um, it works. So that is definitely something where we can go forward. The one that I'm really excited about, and, uh, and you too, is, um, trying to go to diet as a drug.
Dr. Pal:
Yeah.
Dr. Marcel van den Brink:
Right? We all realize that diet has enormous impact on your health, right? Through all of the nutrients, right? That's the classic story that everybody knows. But realizing that changes in diet within 48 hours lead to changes in your flora. That's a whole other way of thinking about it. And then diet can be a drug to implement changes in the, uh, composition of microbiome. And that's another area that we really want to develop here, right? We want, we want to get diet monitoring to a whole new level. You and I both know that the way that we are doing it now, um, in normal clinical settings is lousy, right? I still know from all of my rounds when I was rounding on our, uh, transplant patients, right? Here, you have patients who are being monitored as if they are ICU patients, often twice daily blood counts, all kinds of imaging studies. We know every drug when we give it, you ask the nurse. So, uh, what did the patient eat? Oh, let me see. Uh, I see here something with half of a sandwich or something,
Dr. Pal:
Right?
Dr. Marcel van den Brink:
Okay. What kind of cent? I don't know,
Dr. Pal:
<laugh>.
Dr. Marcel van den Brink:
Um, so it, it is almost mind boggling that in all of the careful clinical data collection, right? We know of any, every episode of nausea and whatever, we don't collect what patients eat.
Dr. Monty Pal:
Such a great point. Yeah, indeed. Yeah. And
Dr. Marcel van den Brink:
So we wanna get that to a next level, and that's where we need partnership with nursing, with groups like your group, et cetera, to do better. We're just working on a new app actually, with, with ai, of course, um, uh, on the background to analyze data so we can get meaningful diet data, because that's the biggest problem in most cases. We have lousy diet data. Once we have that, then we can start really to analyze which diet changes have clinical impact, and then we can really use diet as a drug to change microbiome and clinical outcomes.
Dr. Monty Pal:
I love that. You know, I've been some great talks from Jenny Perus from your group and others that really sort of speak to some of the technologies. But before I get to that, you know, I've gotta ask you, I mean, things were just firing on all cylinders for you Memorial, you know, chairing the department over there and really having these terrific, that, you know, looked at the translational aspects of the microbiome, some great dietary studies as well. All the bases were really covered. It must have taken a really big pull to bring you over to City of Hope. Tell us about that transition now.
Dr. Marcel van den Brink:
So I had been eyeing City of Hope for a couple of years already. No kidding. Okay. And specifically, I mean, some of your most well-known people I knew Steve Rosen, Steve Foreman being, uh, certainly two of the people I had to mention. And those are, um, impressive people and impressive in two ways, of course, based upon all of the amazing science that they've done, the big clinical programs that they built. But specifically with somebody like Steve Foreman, there was something else. And that is culture.
Dr. Pal:
Mm-hmm <affirmative>.
Dr. Marcel van den Brink:
Um, right. All of us know, uh, that Steve Foreman is not just an exceptional, a clinician, an exceptional scientist, right, who is really innovative, but also that he cares very much about the culture, not just a compassion towards patients, but towards colleagues. And that really struck me as something amazing coming from Yeah. A hardcore East coast culture. Sure. Duke, Harvard, MSK, right? I mean, you got your gloves on in many cases, right? Um, and this was so amazing to watch this, and even now, right? I'm now a little bit more than two years here at a meeting that I just came from the ash meeting when, when people ask me, so, so how is it going? And what is different? That's the first thing that I mention. All the cancer centers have a very, uh, compassionate culture, how they treat patients, but they don't necessarily have the same level of a compassion, respect, uh, collegiality that we have here. It's incredibly, uh, important. A colleague of mine a couple of years back, gave me one of these 1 0 1 business books with a fantastic title. I hope it doesn't get X-rated or censored. The No <inaudible> rule. <laugh>, and I believe very strongly in that,
Dr. Pal:
Okay?
Dr. Marcel van den Brink:
Right. When, when, when we are, uh, recruiting people now we really check
Dr. Monty Pal:
<laugh>. That's great. You know, it, it really begs the question, right? You've been eyeing City of Hill from a distance for several years. You know, you're, you're excited about the culture. You are, you know, thrilled about the potential for the colleagues that you'd have over here and so forth. I mean, it really begs the question, you must have seen something at the institution that you could also potentially make better,
Dr. Marcel van den Brink:
I wouldn't say necessarily better, but use what was built already by these amazing people who he mentioned already, right? Mm-hmm <affirmative>. We didn't mention Micah Kuri, I think I did mention Robert Stone, but, but so many other, uh, folks. Uh, they put City of Hope on a journey and a very rapid one, uh, to go from being a local cancer center with good physicians, uh, caring physicians, great clinical outcomes, with a great Beckman Research Institute to suddenly exploding into this National Cancer Center. Um, so that was, for me, a fascinating aspect of City of Hope that it was on that journey. But there's something else that I actually realized even more once I came here, and that is the power of our clinical network, um, that was brilliant to connect with 35 community practices in the greater LA area, um, and to really make them part of City of Hope.
This is not from what I've seen at other organizations, that maybe another hospital or clinic can put up the shingle, right? Which you are connected with Anderson or whatever. No, no. These are really our doctors. We are connected with them. We help them in every possible way to, uh, to really bring the same high quality cancer care to these patients. That is amazing. For two reasons. First of all, uh, personally, I think it's fantastic that we bring our outstanding care to the communities that we are going to Antelope Valley, et cetera, and that that patients there can get the same high quality care. The second thing is, it really, uh, protects us also from the dangers that other cancer centers have, where, where other healthcare networks can block your pipeline of getting patients. We have this amazing opportunity to provide cancer care from the community to the super high-end, highly specialized allogeneic transplant, car cell therapy, and that robotic surgery, whatever, right? That whole spectrum we have here. And we're growing into a national cancer center that is amazing. And I wanted to be part of that and just do my little bit to, to continue that amazing journey that that's people, uh, before me. Yeah. It's already started.
Dr. Monty Pal:
Well, I, I have another tough question for you, and there's only tough questions on this podcast,
Dr. Marcel van den Brink:
By the way. Yeah. They're very tough. <laugh>. I'm, I'm sweating. Yeah,
Dr. Monty Pal:
<laugh>. Indeed. So you, you know, when I came to City of, this was 20 years ago, right? You could fit my entire department, medical oncology in a room that's the size of the studio that we're sitting in comfortably. Right? You know, 18 medical oncologists, I think at the time. Um, now we've grown to 10 times, literally 10 times that size and medical oncology alone. And I think our other departments have experienced similar, if not greater growth. You talked about culture earlier.
Dr. Pal:
Mm-hmm <affirmative>.
Dr. Monty Pal:
How do we keep that amazing culture alive with this very rapid expansion? It's gotta be something on your mind.
Dr. Marcel van den Brink:
That's a very good point. Um, we literally last week, um, set our goals, set our standards for the upcoming fiscal year, right. Our communication is incredibly important. And if you grow to a certain size like we are now, like you said, it's difficult and there's no doubt about it. It's one of the things that I find really difficult in my job, um, trying to, uh, communicate with as many staff and faculty as possible.
Dr. Monty Pal:
Well, if I can give you some feedback on the flight, I mean, I think you've done a masterful job at it in the sense that, you know, I feel like you're just so accessible. If I have a, you know, question for you, you know, or, you know, something I wanted to bring up off the flight. You've taken my calls on Sundays, late evenings, et cetera. And I, I think that we as faculty are incredibly grateful for that. It, it's really a, a big boost to us to be able to have leadership, uh, that's, that's as successful as you've been. So kudos on that.
Dr. Marcel van den Brink:
Well, that's very nice that you say that. Um, but of course you're doing that because you're sitting here next to me,
Dr. Monty Pal:
<laugh>. But, um, you know, turning the tides a little bit, we've talked a lot about work. Okay. But you actually alluded to this both in your discussion of your residency experience and also the experience of, you know, starting up a laboratory and so forth, uh, work life balance. Right? It's so critical, right? Uh, uh, I know from, you know, seeing a couple of your posts on online and so forth, you've got a ton of interests outside of medicine. I, I think I know what they are, but why don't you share 'em with us for the audience?
Dr. Marcel van den Brink:
Yeah. So, um, during med school, um, I realized I wanna do something to still stay fit
Dr. Pal:
Mm-hmm <affirmative>.
Dr. Marcel van den Brink:
And it was just when the running boom started and I thought, well, that's easy. You just buy some shoes and you go running. Um, so I kept on doing that, and then that's maybe my character. You want to challenge yourself.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
So you pick marathons, and I like marathon running because I'm not trying to beat anybody. I'm trying to beat myself. Yeah. That's the only person. Uh, so I stuck to that. Um, and I've lost count how many marathons I've done.
Dr. Monty Pal:
I was just gonna ask you. How many? 26 point twos or, uh, I don't know,
Dr. Marcel van den Brink:
40, 50, whatever,
Dr. Monty Pal:
40 or,
Dr. Marcel van den Brink:
Wow.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
And I still, I now travel less than I used to, but it's easy. You can put a pair of shoes in your, in your carry on a suitcase and you just go running. And, um, over the years, um, what used, or what started as basically something you did for health, for fitness has turned into mental health and mental fitness. And now for me, running, it's my moment of zen, my moment of introspection, thinking through it, it's incredibly healthy to have some wind blow from ear to ear through, through your head, and, um, um, relax a little bit and, and, and think about things. It is, it is now extremely important. If I don't do some kind of exercise every day, then I get antsy.
Dr. Monty Pal:
And is that what you're doing when you're writing? 'cause a lot of people listen to a podcast or music. Are you just sort of clearing the air a little bit?
Dr. Marcel van den Brink:
I have music. I, I've done a podcast a few times. Maybe I should sign up for this podcast instead. If
Dr. Monty Pal:
You don't mind. That'd be great. Yeah. Like, and subscribe.
Dr. Marcel van den Brink:
Okay. Um, but, um, I like to listen to music because it helps you with sort of a rhythm also how you, um, how you run. And, um, I don't listen to the words of the songs. It allows me to think about whatever I want to think. I, I, I write, I write grants when I'm, uh, when I'm running, I, uh, prepare some kinda speech, whatever. So that's one thing. The other thing is art. Um, almost every type of art, music, visual arts, et cetera, it's incredibly important. It's sort of a lifeline, uh, for me. So one of the things going back to a travel that many years ago I built in is, okay, you go to all of these cities all over the US and all over, uh, Europe. You stay in the same boring marriot or whatever
Dr. Pal:
Mm-hmm <affirmative>.
Dr. Marcel van den Brink:
Um, do you really wanna tell people I went to Paris and I stayed in the Marriott, I did my talk and I went back, no, come on.
Dr. Pal:
Mm-hmm <affirmative>.
Dr. Marcel van den Brink:
And take at least a few hours or so. So that's what I've built in to see the museum.
Dr. Pal:
Okay.
Dr. Marcel van den Brink:
So I've seen most of the museums, um, in the big cities in Europe and within the us, et cetera. And that gives me an enormous, uh, satisfaction.
Dr. Monty Pal:
And I've got to share with the audience too, that as it pertains to the arts. Right. You emailed me last night and told me that one of your, I saw your post paper bands is The Smashing Pumpkins, which happens to be for the audience. It's very first album that I ever bought. Siamese Dream 1993
Dr. Marcel van den Brink:
Dream. Yes. I still know it. We used to play it in our lap.
Dr. Monty Pal:
Yeah, no kidding. Oh my gosh.
Dr. Marcel van den Brink:
So text album. Um, no, I have a very broad, uh, broader taste. When I would write an NIH grant, I would put on, uh, b piano music. Okay. Which is not piano, by the way, because there was no piano in those days, uh, keyboards and music. Um, and I could really see it helped me with rational thinking, right? Because it's all structured with little fukes and little themes, and it, it comes back and it rolls over, et cetera. And it really helped my thinking. I grew up in the 1970s and I hated all of the music except for punk. So I was one of the first punks in, in Holland <laugh>. You're kidding. Yeah. I went to all the original bands, the s, sex Pistols, uh, Ramones, talking Hats, et cetera.
Dr. Monty Pal:
There you go. Awesome. Awesome. And, and, and you've also spoken in other forms about Yeah, just the importance of family, right? As it is important for each one of our faculty members, our, our nursing staff, et cetera, mean family is so critical. Maintaining that is vital. You, you've got two sons that I know you're very proud of. Tell us about them.
Dr. Marcel van den Brink:
Yeah. So, um, as you probably know, um, for doctors and busy physicians and scientists, um, it's difficult. And if you have a spouse who does the same thing as you do, then managing the household, and you're raising your family in New York to put an extra layer of stress, um, uh, on top of it, it's stressful. But, um, I think both my wife and I were able to find that balance. And, um, for me it was of course, much more than just raising a family. I always feel that that what I got back from it was also absolutely amazing. I mean, my most beautiful memories in life are reading for my sons, right? Um, my wife would always ask me, can you please stop reading now? They need to sleep. So, but, um, I mean, those are some of the most beautiful memories,
Dr. Monty Pal:
You know? And, and, and I've gotta ask you, I mean, just looking at your experience as a father, 'cause I, you know, I'm a father of an 11-year-old and a 13-year-old right now. What advice do you have for me and others like me, sort of coming up in academic medicine?
Dr. Marcel van den Brink:
Well, absolutely take time for your kids, right? Because, um, those, the, when, when they're still young, I mean, my goodness, it's so beautiful to, yeah. See kids growing up. So that's one. The second thing is, um, really think about giving them some freedom and making sure that they connect. I mean, for instance, for a New York, that was difficult with nature and with friends, social, social media, as you know, there are now countries where they're gonna ban it for kids below a certain age. And I think we need much more of that. We need a real discipline in, when it comes to gaming, social media, et cetera, we need to find a discipline and make sure that these kids still connect with the real world, with friends, with their surrounding, with nature and so on.
Dr. Monty Pal:
Yeah, it's, it's, it's so helpful to hear that, you know, as much as I think about phase one trials and microbiome, what's next in kidney cancer, I mean, my kids are always at the forefront, right? So this is, this is really, really valuable advice. You know, we always wrap up the podcast with, again, a tough question The title of this podcast is on the Edge of Breakthrough Voices of Cancer Research. What does on the edge of breakthrough mean to you, Marcel?
Dr. Marcel van den Brink:
Well, that's a very difficult one because I see so many areas within cancer where that is possible at the moment. Um, I grew up believing in, um, immunotherapy of cancer. I still think that there's a lot more to gain from that. Of course, in my own area, I hope that thymus biology, thous, uh, regeneration therapies will pay off. We have already data in my lab how we can improve outcomes for, for instance, checkpoint blockade. So, so that's where I'm very interested in. But there's another aspect, and that is, um, reaching patients and financial toxicity, if we can figure that out. I was just listening, not to a podcast, but NPR
Dr. Pal:
Mm-hmm <affirmative>.
Dr. Marcel van den Brink:
And they talked again about the fact that, um, I think the number one reason for bankruptcy is healthcare cost. Right. And that hasn't really changed. If anything, it is worse. So for me, a real breakthrough would be in this country specifically, if we can make healthcare more accessible and if it could reach more people. I think that would be, for me, the biggest breakthrough that that means more almost than another new therapy for a new cancer.
Dr. Monty Pal:
Brilliant. Right, because I mean, what, what's a good in having all these amazing therapies if, if they can't get to patients? Right. Indeed. Well, what a marvelous conversation. Marcel. I hope you'll come back on our podcast and chat with us. Happy to more Yeah. If you're still want me. Yeah, absolutely. Thanks again.
Dr. Marcel van den Brink:
Good. Thanks very
Dr. Monty Pal:
Much. Thanks for tuning in to On the Edge of Breakthrough. See you next time for more insights from the front lines of cancer research and care.