Oby Ukadike: Happy holidays, ThinkResearchers. We hope that you are enjoying some time away from the office. We here at Harvard Catalyst are out of the office for a couple weeks, and the next three episodes will be a compilation of some of our favorite clips from the past seven years of episodes. We look forward to reconnecting in 2023.

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From the campus of Harvard Medical School, this is ThinkResearch, a podcast devoted to the stories behind clinical research. I'm Oby, your host. ThinkResearch is brought to you by Harvard Catalyst, Harvard University's Clinical and Translational Science Center, and by NCATS, the National Center for Advancing Translational Sciences.

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This first compilation of past episodes will cover stories of unusual and unconventional paths to academia and/or research. First up, we dig back into the archives to one of our very first episodes of ThinkResearch. We sat down with Dr. Charles Deutsch to talk about his path to academia.

We want to jump right in and find out how you made your way to academia. How did you find your way to Harvard, and how did you settle into your niche?

Charles Deutsch: I had an unusual path to Harvard, and I think I made an unusual niche while I'm here. It's been 22, 23 years that I've been here. And as I think about it, I think about when I was first in school in the '60s and '70s. Erik Erikson was a very influential social thinker and psychologist.

And he would talk about triple bookkeeping and the fact that you're born into a body with a certain biology and genetics. And then you're born into a family, and that family has certain characteristics. And then you're born in an era and in a place that is different from other places and eras. And all of that has influence over what course your life takes.

So for me, I can trace how some of that worked out. I was an outlier in my family. I grew up in Brooklyn and was born the year Jackie Robinson integrated baseball. And that was a sort of-- there weren't any people in Brooklyn who weren't Brooklyn Dodger fans, and that meant a certain thing around social justice.

I lived through the '60s and '70s. The year I graduated, 1968, was the year, of course, of the assassinations of Martin Luther King and Bobby Kennedy. It was a highly political time. I spent a year in New Haven during the time that Bobby Seale, one of the Black Panther leaders, was on trial for murder there.

So there were just a lot of events in my time and place that colored my subsequent path. And I remember, as a kid in Brooklyn, thinking, oh, it would be great to be an academic. I remember thinking I wanted to do American studies.

And when I got to Yale, it was largely around staying out of the draft another year during the Vietnam War. But I thought, well, Yale has the best American studies department, and I want to do American studies.

And by the time I got there-- and I had this completely idealistic view of what an academic is. I mean, I now know that academics work constantly to get things published and grants funded. But back then, in my head, an academic was somebody with leather on their elbows who just could actually go around reading and thinking and teaching. And I thought, well, that would be great.

But by the time I got to Yale, the tumult of the world convinced me that there's no sitting back, that there's no point in studying when what seems to be needed is some action. So yeah, I think I was really a creature of my time and place in a lot of ways.

Oby Ukadike: Early in your career, you worked with a program called CASPAR. Can you tell us about that program, how it started, its evolution, and what it meant for you at the time?

Charles Deutsch: So CASPAR stood for the Cambridge and Somerville Program for Alcoholism Rehabilitation. And they had detox centers and halfway houses in Cambridge and Somerville, and had made some ties to the stellar psychiatrists at Cambridge Hospital.

And then, at some point, they got a grant from the National Institute on Alcohol Abuse and Alcoholism to try to prove that they could prevent alcohol abuse by having a school-based curriculum. And because they knew my work, I got hired into that program.

And we started to both train teachers to teach about alcohol-- these were the days when you could actually talk about responsible decision making, even for kids, and talk about how one learns to become a responsible drinker, as most drinkers are. And so we started to do that work, working on a curriculum.

And what strikes me in retrospect about that is how much happens by accident. Or if not by accident, how much you have to keep your eyes and ears open and see where doors have opened and opportunities have been provided that need to be followed up.

So one of the consequences of the work we were doing was that we had recruited some peer educators, high school kids. And mostly, we had the same limited sense of what kids could do. And we thought, we need some kids around so we can test some of the activities that we were developing with teachers on these kids and find out if we were using the right words. I mean, that was as primitive, really, as our understanding was of how you use beneficiaries in developing a program.

And so we had this group of peer educators, and one summer, the Department of Labor funded a jobs program for kids in Somerville. And they mandated that the kids should have five hours or six hours of counseling, or like, an hour a week for the six-week period of their employment. And this was several hundred kids, and the counselors were going to be these college students who didn't know the kids-- it was just this silly idea.

And the head of the program was somebody I worked with. And she said, instead of that, let's bring them in and have them do three two-hour workshops. And let's have them do one on alcohol.

And so we had these hundreds of kids who were going to troop into our office in Somerville. And we had to turn to our peer educators and say, can you do a two-hour workshop? We designed a workshop for them to deal with these kids.

And we discovered very quickly that there were kids in the workshop who our kids could recognize as coming from alcoholic families. And they could recognize them easily because they were from alcoholic families. We didn't know that at the time. There was only one kid who was actively dealing with her parental alcoholism, and the others were hiding it, like most kids will.

But they could recognize the kids who were struggling with this because we were talking about how most people drink alcohol and drink it responsibly, and all they had ever experienced was abuse. So we started to understand that, while we wanted to reach all kids through their teachers, there were certain kids who we needed to reach really badly.

And we needed to reach them with interventions that might actually help them think about what they'd lived through differently. Because this was a very important piece of it that you find in Piaget and you find a lot of places, which is, it's not really what the circumstances are. It's how the kid understands the circumstances.

If anybody's explaining that this is not your fault, that there's nothing you can do to stop the drinking, that you still have to live your life and find your pleasure, there are certain things that enable a kid to reframe what's happening so that they don't blame themselves and they don't respond in the same kind of negative ways. And by negative ways, I include trying to be perfect at everything.

And we were able to develop a program where we had kids just working with other kids who had grown up in alcoholic families. And structured psychoeducational groups-- what would now be called cognitive behavioral therapy type groups-- for kids from alcoholic families has one part of what our program was.

And coming out of that, I realized that it needed to be written up. And so I did a book called Broken Bottles, Broken Dreams. And it was expressly intended for people who work with kids-- teachers and nurses and probation officers and social workers and other kids who have friends.

And I was fortunate. It got very wide circulation. It was odd having that early in my career, that kind of success. I mean, people would write to me and tell me how the book had changed their lives and everything.

And it was very fulfilling. My whole career has been largely focused on how people who aren't public health people, aren't even health people, may not even be professionals themselves, are actually really, really important change agents for health. And that settings like schools, and other settings that are not primarily designed to be about health, are really about health. That's been a big focus for me, both domestically and globally.

And by the way, we pay a lot of lip service to the notion that we can learn from what's going on in other parts of the world, and not just that they can learn from what we've already done here. But it's really true.

And we're often not that good at making sure that we translate going in both directions. Because there are some great things that we're starting to learn from going on in less developed countries.

Oby Ukadike: How did you get involved with Harvard Catalyst?

Charles Deutsch: I'm not exactly sure how I got to Catalyst. Karen Emmons was the dean for research at the School of Public Health. And she knew me, and she knew my work. And she knew that I had been involved, in my time at Harvard, in a variety of interfaculty initiatives. So I knew my way around the labyrinth that is Harvard.

But she knew that I had done a lot of work at the community level. I was just coming off of spending more than 10 years developing a center for the support of peer education in South Africa as part of the response to HIV/AIDS there. So she knew that I could live in both the academic and the community worlds.

And she was bringing more of a public health T4 emphasis to Catalyst, and so she brought me with her. We started working on how Catalyst could be more involved in improving population health.

For me, this was really just a way of saying, look, what the big research institutions like Harvard-- with all the resources they have, is the most that we can expect of those institutions that they do little projects in the community, the kinds of typical projects that get done when people talk about community engaged research?

And don't mistake me. Clearly, academia and academic research produces major important benefit. People dive deep into their disciplines and advance our knowledge, and so on. But when it comes to actually applying what we already know to what we do in complex communities, in a way that can be coordinated and sustained and produce results, you can't Mickey Mouse it. It's bigger than that.

And institutions as big as Harvard need to make a more concerted effort. So coming to Catalyst gave me an opportunity to try to work on a grander scale in terms of what Harvard's contribution could be.

And we started working intensively with the Mass Department of Public Health because our reasoning was that department, more than any other, is responsible for the health of the 6 million plus people in the commonwealth. And that there was a lot that Harvard could do, bringing its own strengths and its own sustainable resources to improving how the Department of Public Health can do its job.

And that's especially true in terms of research capacity, evaluation capacity, the use of all this data that is now out there that's being collected but not necessarily linked and not necessarily used. The Departments of Public Health across the country don't have sufficient capacity, sufficient resources to analyze the data that they collect and to then use it to evaluate their own policies and programs, or to know what to try next.

Numbers tell a story. They don't tell the whole story. And a lot of times, they can mislead us because we can look at the numbers, and we can think we know how to explain why we got the numbers we got, but we're not always right. Especially to the extent that the people whose lives those numbers are trying to describe, in some respect and some small aspect of their lives, are people we don't know very well and who are not like us.

So the whole benefit of mixed methods is that it gets behind the numbers and enables us to learn more from the numbers than we would if we just look at the numbers. I think people who've been trained quantitatively sometimes have trouble understanding that qualitative research, that doing interviews and doing focus groups and doing observations because it's a small number of people is as scientific. And part of what we teach in mixed methods is why that's true.

And so there's just, by now, lots and lots of examples of the ways in which mixed methods amplifies both the qualitative and quantitative, that they derive strength from being mixed with and integrated with each other. And it is now something that the federal funders require, and that's a good thing. It enables us to hear the voices of the people behind the numbers, and really often, that's quite illuminating.

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Oby Ukadike: Next, we talk to Dr. Alex Lin about how you go from thinking you would be a DJ to becoming a radiologist and director of the Center for Clinical Spectroscopy at Brigham and Women's Hospital.

Hello, Dr. Lin, and welcome to the show.

Alex Lin: Thank you very much for having me.

Oby Ukadike: Can you tell us how you got started in your field and a little bit about your background?

Alex Lin: Sure. I was very, very lucky to land, right off my undergraduate studies, in the field of magnetic resonance spectroscopy, which is a method by which you measure chemistry in the brain and other parts of the body for use for clinical diagnosis.

And I think, certainly, as an undergraduate, I was a bit shortsighted in my ways. And coming out of Caltech, I had decided-- talk about shortsightedness-- that a career as a DJ would be my career of choice. My parents were obviously very displeased (LAUGHS) at that notion.

And basically, I remember we had done some gigs that month, but weren't doing as well as we should have. And I remember calling my parents and saying, I need a little extra money for rent. Can you spot me some?

And they said, well, if you don't get yourself a real job by the end of this month, you're coming home to live in New Jersey. And I was living in LA at the time. That was just something that was unfathomable to me.

And it's remarkable. That night, I received the call from a friend of mine who said, hey, I'm going off to UCLA to do my PhD. There's an opening in this company called Huntington Medical Research Institutes that's affiliated with Caltech and USC. Would you like to come check it out? And I was like, yeah, sure. I got to get a job, right?

So I remember sitting in that meeting, meeting Brian Ross, who's, it turns out-- I mean, I had no idea at the time-- is one of the world leaders in MR spectroscopy. He basically developed-- he's won awards for his work in his field.

And he showed me those cases where you can use spectroscopy to diagnose cancer without having to do any surgery. You could use spectroscopy to predict outcome in these patients after traumatic brain injury. And that really just blew my mind. I had no idea that chemistry could be used in this way.

What especially appealed to me was the kind of clinical translational aspect of it. At that time, as undergraduate, I didn't know better. I was just not satisfied, I guess, with the benchtop work that we were doing-- and again, being very shortsighted and not recognizing the value of it. I found that clinical applications was something that would be a more direct line into research. And that really fascinated me. It was the first time I got a chance to work with patients, and was hooked ever since.

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Oby Ukadike: Our conversation with Dr. Corrie Painter in the spring of 2017 was a story of a painful diagnosis that led to patient-driven research and communities of support.

Hello, Dr. Painter. Welcome to the show.

Corrie Painter: Thank you for having me.

Oby Ukadike: Thanks for being here. You focus extensively on cancer research. What is it that drew you to this area of study?

Corrie Painter: That's a great question. I was drawn to this area of study out of necessity. So I was trained as a biochemist, but then I was diagnosed with an incredibly rare and aggressive cancer right as I was supposed to graduate with a PhD in biomedical sciences.

And I was supposed to follow that up with a post-doc sitting ALS, all drawing on those biochemistry skills. But I decided that having this exceedingly rare cancer diagnosis, and as a scientist, knowing that there was no resources to guide any type of research toward this particular area mandated that I became a cancer researcher.

Oby Ukadike: Yeah, that's incredible.

Corrie Painter: I had my second surgery within two weeks of each other a week before I was supposed to walk at my own graduation. And because it was so close to my graduation, they still had my name on the back of the chair where I was supposed to sit.

And I had to delay graduating, and my PI was kind enough to let me stay as a graduate student for that next year. My prognosis was extremely poor, and we did not think that I would be alive to actually go back and sit in that chair, stand up, and walk and receive my diploma. That was almost seven years ago.

Oby Ukadike: Can you tell us more about your diagnosis and your experience?

Corrie Painter: Yeah. It was a Friday evening that I found a lump in my breast. So that left me the weekend to start Google searching lumps, breasts, and find everything I could out about breast cancer, which would be the natural inclination to a young woman who found a lump in their breast. And I was encouraged by some of the statistics, although now, in retrospect, knowing what I know now, there was a lot of false hope that was provided to me in those first initial searches.

When I finally went through the diagnostic process, it took about three months for them to come up with the word angiosarcoma. It is something I had never heard about. It's something that, when the first inkling of it came across in a cytology report from a fine-needle aspiration and I Google searched, I was absolutely devastated by because it had an incredibly poor prognosis.

It has a five-year survival rate of about 30%. The vast majority of people who are diagnosed with this disease already have advanced disease and typically have very poor outcomes.

At first, I went to PubMed as a scientist so that I could understand what research there was, what we knew about it, what are the molecular drivers. And because there's only about 300 people a year diagnosed with this disease, almost nothing was known. There was a couple retrospective studies where a major academic institute would look through its entire catalog of patients over the course of 40 years and dig up 19 or 20 patients that had had it.

And so very poor statistics, very little known, followed by case reports that said things like, sarcomas typically have a poor prognosis. Angiosarcoma has the worst. And all of those put together with the one study that really showed the largest cohort-- an extremely steep Kaplan-Meier curve, which looks at survivability over years-- made me have this sense of vertigo, looking down at that steep curve. And it was absolutely devastating, to say the least.

And at the same time that I was looking for information in the literature and I was looking for information in Google and finding almost nothing, I was also trying to connect with anybody else who had this disease. There was information that I had to have. And it wasn't just information. I had to have that human connection with anybody else who had survived the disease.

So I would Google search other people that were looking for the same thing, and I'd find them. And I would reach out to them, and they wouldn't respond. And I would Google search their name and find their obituary every single time. And every time that happened, it was devastating. It was like being diagnosed and being told you're going to die all over again.

And in a last-ditch attempt, I went into Facebook, and I found this very small support group with maybe eight or nine people. But each one of those were people that were living, they were alive, they knew more about this disease than the collective literature.

And that moment, where I stumbled upon that group started by my friend, Lauren Ryan, had changed the course of my life like I never could possibly have expected. It led to me being here today, talking about the Metastatic Breast Cancer Project and the Angiosarcoma Project. It changed the course of my scientific career, it changed the course of my family life, it changed my advocacy and everything else. Eight people never could have been more powerful.

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Oby Ukadike: Finally, we talked to Dr. Gupta about his unconventional career path that led to clinical radiology.

Welcome to the show, Dr. Gupta. We're glad to have you here.

Raj Gupta: Thank you.

Oby Ukadike: You have an unconventional career path. You have a PhD in computer science. You taught at USC and then spent some time working in research and development at GE. Could you describe your career path and what motivated you to decide to go to medical school?

Raj Gupta: Yeah, that's a long story, and it's a good question. So when I started and when I was doing my PhD, medicine and doctoring was not in the cards, or at least, I didn't think it was.

I was always interested in medicine, even back in India, when I was-- before I came to graduate school here. Even though I didn't have any background in medicine, I would-- there were friends of mine who were doing medical school at that time. And I would go to the hospital with them, sit down, do overnight calls with them, just observing them.

And then I came here, and I started working in chip technology doing VLSI design, Very-Large-Scale Integration. These are the chips that go into all computers, everything electronics. And then I started at USC doing the same kind of research-- how to test the chips, how to build systems using those integrated circuits.

And then I started working-- I moved from USC to General Electric with their corporate R&D division in upstate New York. And that's where I started diving a little bit deeper into medical technology because GE has a very large imaging technology subsidiary, GE Medical Systems. And I started doing projects with them. I started getting into computer vision. I did some projects with other parts of General Electric.

But the thing that solidified me and prompted me to go into medicine is my work with Medical Systems. For GE ASTRO, I had built a system which will monitor the Earth from satellites, take pictures taken from satellites, and put them into a 3D representation of the ground so that the pilots who are training can train in geospecific, realistic terrain.

And they had a very large flight simulation business in Daytona Beach. I went down there, I took my program, and I rendered it. And I got into this very large dome with the cockpit hanging in the middle. And I could fly in my own terrain, which I had created from satellites.

And then I came back to upstate New York. And my manager saw this, and he said, well, in Medical Systems, we have the same problem. I say, how so? He said, well, we have this X-ray machine that goes around a patient and take pictures of the patient from various angles. And those have to be stitched together, and you have to make a 3D representation of that.

I said, maybe I can use my program for doing calibration of this machine. So they sent me to France outside of Paris. The headquarters for GE Europe is near Versailles. And from there, they sent me to this smaller town called Nancy, where they were building a machine which was doing exactly that, taking X-ray images using an imager.

And so I tried my program, and it worked. And it looked pretty good. And so when I came back from GE France, I told my wife, I want to go to med school.

So my wife said, oh, no, no. You're old, you got two kids, we got a mortgage to pay. Forget about it. So then I sat on it for one year, and then I said, no, no, why don't I just take this MCAT exam? So she said, OK, OK, he's just taking an exam. Let's let him take an exam.

And so I took that exam. I did well. I applied and I interviewed at HMS at that time. And then I landed up at Cornell in upstate New York.

And I continued my work with GE. Along this time, I was doing sort of part-time work with GE because I had written a lot of software for them at that time. And one thing led to the other, and then here I am.

Oby Ukadike: Wow.

Raj Gupta: So that's sort of the career path. Somewhat unconventional--

Oby Ukadike: That's amazing.

Raj Gupta: --but yeah.

Oby Ukadike: So now you're a clinical radiologist.

Raj Gupta: That's correct.

Oby Ukadike: And you're also interested in research. How does your clinical work inform the research you're doing?

Raj Gupta: Very much so because I have-- because I came into radiology building systems, building imaging equipment and CT scanners, much of the research that I do currently is in that domain. And much of it is very closely aligned with what is needed in the clinic.

So for example, we have a system. Very routinely, I'll be working in the emergency room. We'll get patients who have had a hemorrhagic stroke, which is basically bleeding in the brain. And we will give them contrast to figure out where the bleeding is, where the aneurysm is, where the vessel, if there's a rupture of a vessel.

Then both things-- the hemorrhage as well as the iodine or the contrast that we give-- both are bright on the imaging that we-- on the conventional imaging. So we developed, for example, a method for distinguishing the two using the spectrum of iodine and blood. Because they are different, and so one can distinguish one from the other using something known as dual-energy CT.

And that is now routinely used in clinic. So much of the work that I do has foundation in engineering.

Oby Ukadike: So could we step back a second and talk, in the context of the example you're giving us about the contrast, what is the basic imaging process? What do people do, and then, how do you take and then read the image?

Raj Gupta: Yeah. So basically, what happens in the context of the specific clinical problem I described, a patient would have what is known as the worst headache of their life. They will describe it as, my god, it's 10 out of 10, and it started all of a sudden. They were brought to the emergency room.

In the emergency room, we do a computed tomography scan. So this is an X-ray based modality where we are doing the process that I just described. You have an X-ray source on one side, you have a detector on the other side, and the whole machine is spinning around the patient, acquiring pictures from multiple angles.

And the density of what the X-rays are going through is what is getting recorded in each one of these images. And then all this image set is then given to a computer. The computer then makes a slice-by-slice representation of that. So things that have a high density look the same.

So blood, because of the blood clots and so on, will have high density and will look bright. Iodine also has a high atomic number, will look bright. But they are slightly different under X-rays in terms of their spectral response. If we change the energy of the X-ray, they behave differently. And we use that property to distinguish the two.

Oby Ukadike: You just talked about tomography, and one of your areas of research is about computed tomography and strokes. Could you tell us how CT is used in treatment of strokes and what your research in this area is focused on?

Raj Gupta: Yeah. So CT is actually integral to stroke. It is the standard of care. So when a patient comes in with an acute stroke, either hemorrhagic or ischemic-- hemorrhagic means they have bleeding in their brain. ischemic means that a blood clot is blocking an artery in their brain, and then blood is not getting past that blockage.

In both cases, you will do a CT scan, a Computed Tomography scan, to number one, distinguish which kind of stroke it is-- whether it is a bleeding in the brain or is it oxygen not getting because the blood is not flowing. And once you distinguish that, depending on how far away they are from the start of their symptoms-- if they come within first 4 and 1/2 hours, we will-- and let's say it is a stroke where a blood clot has gone into the brain, is causing a blockage-- we'll give them a blood thinner or an agent that will dissolve the clot.

And we'll also do an angiogram, where we'll map out the vessels of the brain, again, using CT scan to figure out where the blockage is. And now, there has been, essentially, a revolution in stroke care. And that revolution centers around the fact that we now have the ability to put a small catheter through the groin, snake it all the way up to the aorta and then into the brain, and then pluck out that clot.

And it has been shown that, for a large number of patients who are selected using imaging, we can actually stop the progression of the stroke. And so that has now become the standard of care.

There was a recent study that was published in the New England Journal of Medicine called the DAWN study. And that says that, for appropriately selected patients, even if the patient comes up to 24 hours, there is a benefit for doing this.

But the bottom line is you have to pick the right patients. You can hurt the patients by opening the blockage. It is paradoxical that, in some patients, if you remove the blockage, you let all this high-pressure blood go into the part of the brain which is already infarcted, and you can have hemorrhage in that. So you can convert a stroke that was ischemic stroke into a hemorrhagic stroke, which is something you don't want to do.

However, for appropriately selected patients, in the last six months to a year, this has been a change in the way we treat stroke.

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Oby Ukadike: Thank you so much for joining us for this first compilation episode that is closing out 2022. Again, we hope you are enjoying your holiday break, and we'll see you soon in 2023.