In this interview, Cedars‑Sinai Vice Dean Bruce Gewartz talks with Dr. Stephan Targan, a pioneering gastroenterologist who has led the medical GI division for 28 years. Dr. Targan recounts his Los Angeles upbringing, education at Johns Hopkins, and a series of fellowships in infectious disease, immunology and gastroenterology that positioned him at the intersection of genetics, microbiome, and immune research. He explains that inflammatory bowel disease (IBD) is a multifactorial disorder driven by genetic predisposition, the gut micro‑environment (bacteria, viruses, fungi), and lifestyle factors, noting its historic description in the early 20th century and its rapid global emergence as diets westernize. The conversation shifts to therapeutic breakthroughs: the advent of biologic agents, a move toward earlier and more aggressive treatment, and the development of algorithmic, precision‑medicine approaches that match patients to specific drugs. Dr. Targan describes how disease classifications are blurring, with IBD now viewed as a spectrum rather than strictly Crohn’s versus ulcerative colitis. Looking ahead, he foresees therapies that target the microbiome and personalized prevention strategies based on genetic and environmental markers, aiming to halt disease progression and reduce cancer risk. He also highlights the importance of patient support networks, the role of social media, and the persistent socioeconomic barriers to accessing high‑cost biologics, urging payers to recognize the cost‑effectiveness of early, adequate treatment.
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Hello, I'm Bruce Gewartz, Vice Dean for Academic Affairs and Chief of Surgery at Cedars-Sinai, and today I'm pleased to have as our guest Steph Targan. Steph is truly an international leader in gastroenterology and inflammatory bowel disease. The longtime head of our medical GI department and a great colleague and friend. Steph, welcome.
Thank you.
Steph, you know, we're very interested in you as an individual. I wonder if you could tell us a little bit about where you grew up and where you went to school and how you ended up and got interested in gastroenterology.
Well, I actually grew up here in Los Angeles, went to schools here. In fact, graduated from Fairfax High School. Up the street, and then went back east to Baltimore to Johns Hopkins where I did undergraduate there as well as medical school. And after that, came right back here to Los Angeles, did my internship and residency at Harbor General. Then at the same time I went into the Air Force, actually did an IB, infectious disease fellowship there. Came to UCLA for the GI program, did a GI fellowship, and then stayed on and did a fellowship in immunology. So I've done a lot of things and got interested in GI actually as a high school student where I did research in the chief of GI at UCLA at the time's laboratory who was down at Harbor General. And just got, you know, just inspired by that in that sense and know that was I wanted to do was when I actually grew up.
And how long have you been at Cedars-Sinai now?
I've been at Cedars-Sinai 28 years, which, uh, it's hard to believe.
Yeah, well, time goes fast when you're having fun. How did you get interested in the topic of inflammatory bowel disease?
Well, it's, it's interesting. It was really, um, you know, I, I, because I worked with the head of GI at that particular point in time for when I was in high school I always had an interest in GI, but when I went down to Harbor General and did an infectious disease fellowship, my mentor at that time sat down and we went over and decided what I wanted to do. And I, you know, I wanted to do GI. And at that time, inflammatory bowel disease was at its infancy and it just seemed like nobody knew anything about this. And so given what I like to do, that's how I began to get interested. And then, At that time, we laid out the rest of my fellowships, which was gonna be immunology, GI, and infectious diseases, which today, looking back, is very interesting. It's exactly where the interface is of everything that's going on.
[Speaker] So I know that inflammatory bowel disease is a very broad and variegated problem. Is there, how would you describe the cause of it? I mean, what's the primary mechanism if there is one, and what might be some of the causes of inflammatory bowel disease?
Well, it's a— I'm glad you said diseases because it's a very set of complex processes and pathophysiology that arise in different types of patients with this. And it's really the interface between genetic predisposition, the microenvironment, which are the bacteria, virus, and fungi that are in the gut, and the environment, things that would manipulate those things and those interactions. So it's not a single cause in my mind. It's— there are several different components that lead to it in different kinds of patients.
So from my understanding as a simple surgeon, inflammatory bowel disease was first described in the '30s and '40s in New York City. Is that correct?
Well, if you were really from Europe and England, it was really at the turn of the century, the first description, if you will, of both ulcerative colitis and Crohn's disease that became named because the gentleman who observed it in New York, but that they occurred at that time. But it was really recognized right in the '30s.
And are there— you mentioned genetic predispositions. I think initially, perhaps because of where it was first described, it was thought to be more common in Jewish people. Is that still the case?
No, it's gone beyond that. At that time, I think it was first recognized in what it came out in, in that regard, but it's all ethnic backgrounds will get it. And it's interesting, the genetic background in each of those that are associated with the diseases tend to be, there's some overlaps, but there's some unique aspects of it that occur in each of those different ethnic backgrounds.
Are there lineages and peoples that do not get inflammatory bowel disease?
Well, yeah, it's, it's, there are people, for instance, the old hygiene theory of this that live in, out in the rural parts of Africa. It's very uncommon. And it's not just because of the black background in Africa. But the rest of the world, it's all emerging now. So no part of that was the old. The new is it's all emerging and every country that didn't get it, for instance, never was in Asia for a long time, it's now emerging. And it's thought to be as people westernize and westernize diet, which impacts the micro and macro environment of everything, it's now emerging everywhere.
Now, I know there've been many changes in diagnosis and treatment of inflammatory bowel disease, many of which you've had a very fundamental role in. But what do you think over the last decade have been the biggest changes in treatment of inflammatory bowel disease?
I think that the two things are the emerging of new treatments that are the so-called biologic treatments that affect it. But it's also a more aggressive treatment approach. So making sure people are treated earlier and more aggressively in the onset of their disease, knowing who's going to become more aggressive by various means, and then putting therapies to those individuals. And what's now emerging in the latter part of this is sort of menus of therapies, combinations of therapies, And now I think IBD has been the leader in this outside oncology, really precision medicine approaches to know which of these subset of patients respond to what kinds of medications.
So it sounds to me like you're almost describing like in cancer, an algorithm of treatment. And how do you determine which treatment algorithm to initiate? Is it based on specific measures of inflammation? Or is it based on just, I hesitate to say, trial and error to see how the patients do?
Well, I think it's right between those kinds of things at this point in time. So the first thing that came out, the first biologic that came out, a lot of people that were moderately and severe got treated with that without any knowledge of there was people that weren't responding. So at this time, the precision approach is attempting to do what you've just said in the end. Predefined the individuals that are going to do best with which kind of therapy. But now there's, uh, you know, uh, it's more of, um, uh, algorithms that people have put together based on experience and trials and, and, and how to do, but it's just emerging as far as unraveling that, uh, and making it more, more, uh, direct and specific.
And, uh, have you seen a tremendous change in, I know the mortality from the disease isn't very high, but the morbidity is quite high. Have you seen changes in various indices of morbidity with the new treatments?
Yeah, so it's amazing that with the biologics that have come along, we're seeing, you know, fewer people that go into the hospital. And when they get in the hospital, more people responding to these biologics that can be very potent, and their onset of action is very much quicker.
So if you were to look down the road, I know you and your group have made many great strides in using biologics in particular in the treatment of these patients. If you were to look down the road for another 10 years, what do you think would be new about treatment? What do you see the most promising additional treatments?
I think the most promising additional treatments, again, I think are dealing uniquely with, again, parsing out the individuals that are going to respond to that. I think there are new therapies that affect the inflammation directly, but what's coming along and what's emerging is unraveling of the bacteria and the microbes that are in your gut and how they impact that host and all of that. But then how the host that has genetic abnormalities and therefore abnormal things that affect the whole environment that's in the microbes. And I think in the next 10 years that is gonna be unraveled enough to now have menus that aren't just drugs treating the inflammation, but then manipulating those things as well.
So when I was a, a medical student and surgical resident, there was this tendency to have a sort of a, for lack of a better term, like a bimodal thought about inflammatory bowel disease, that you had Crohn's disease, regional enteritis that had small bowel manifestations, transmural manifestations versus ulcerative colitis that had more of a mucosal colonic manifestation. Are those sort of definitions being blurred now?
Yes. So we're trying our hardest to blur them because we think they're blurred based on what the underpinnings are, the the different kinds of expression of this disease, and they are being blurred. So what's thought to be ulcerative colitis turns out to be Crohn's from other markers that people would look at and vice versa. So it's sort of now rather than Crohn's, and you see emerging as IBD 1 through 10. I'm just making up that number, but that could cross those two different types of disease that were thought to be.
Do you think there will be some type of cure for inflammatory bowel disease or something sort of quasi-preventative once you can find the genetic and other demographic markers that lead to inflammatory bowel disease?
Yes, in fact, we here at Cedars and some other places are kind of leading the way understanding what are the early processes that one could measure that could lead up to the disease. What's the predispositions that occur which can be the genetics, but also the microenvironment and what's going on. And we're doing just that. The first thing we're gonna prevent is when they get the disease, prevent any progression, but also stepping back and then preventing, you know, moving forward. We think we'll do a better job in finding something that will prevent it than they did in type 1 diabetes, which they can mark it with a, you know, response to insulin, antibody response and so forth. But have yet been able to prevent it from occurring.
So from my general surgery experience way back, I remembered that after something like 10 years of activity of ulcerative colitis, there was a general feeling that the incidence of carcinoma went up high enough that removing all or part of the colon was the right thing to do. Has the treatment, the more aggressive treatment, modified that measure? In other words, are you keeping patients in somewhat control so the temporal indications for colectomy are reduced?
Absolutely. And so the goal is to, you know, turn off the inflammation completely because it's the inflammation, whatever type of it is, that causes the repetitive growth of the lining cells and that they have the opportunity to develop precancers. So now the incidence of cancer to the old time, which was 30% at, you know, 20 years. Therefore, as you say, let's take the colon out to prevent. We see much lower incidence and we stress with our patients, the goal here is to shut off your inflammation. And before it was to get it down and people could then go out and do it, but they still were active and now it's more aggressive. And yes, I've seen much less cancer coming along.
So, you know, in this day and age, social media and crowdsourcing is so prevalent. And from my understanding, there's an incredible network of patients with inflammatory bowel disease that provides support and other transfer of information to each other. How have you viewed that?
I think that's really important because it gets down to the essence of What are the patients feeling like, which we all try to do, not just do what we think scientifically is right for them because we can do things, but how are they feeling about that? And they have that. Support groups, as an example, the Crohn's and Colitis Foundation, which has really been the main group that have, you know, put out the accurate information on their website so people can use that. And I think it's critically important without a doubt. So the patient and how they're responding is equally, you know, as important as giving them the right medicine.
And I understand that, you know, we all know that there are very significant therapeutic and access issues that are based on socioeconomic indicators. Have you seen tremendous differences in the outcomes of patients based on socioeconomics in the United States?
Well, one has to, yes. There There can be, if they can get the medications, the answer is no, they all seem to respond that way. But there are some that have more aggressive kinds of disease. And it's not that they're not getting the medicine, it's the part of how their disease is. But the key is gonna be pain for these. And the key is now we know as an example, people that are getting a medicine and aren't responding fully, We know now that if you can increase the dose of the medicine, those people that respond fully shut off their inflammation. And so it's getting the payers, it's getting the, the government payment to recognize that that's important and that's really preventing them going to the hospital. That in very— is less costly in getting them into remission than not paying for the medication going up.
Yeah, an ounce of prevention versus a pound of cure.
Absolutely.
Well, Steph, thank you so much for really your life's work, which has really changed the outcome for patients with inflammatory bowel disease, as well as the many outstanding gastroenterologists and researchers that you've trained. And thank you very much for being here today.
