In this episode, we visit with Charles Mobbs, Class of 1974. He’s a professor and researcher at Mt. Sinai Medical Center in New York and he’ll talk about his work on obesity and on aging, why he chose MIT and how a theater class at Keystone changed his life.
Cobra Radio — Guest: Charles Mobbs ’74
HOST: Welcome to Cobra Radio, where we meet the people who make Keystone School such a special place. I'm your host, Edmund Tijerina. In this episode, we visit with Charles Mobbs, class of 1974. He's a professor and researcher at Icahn School of Medicine at Mount Sinai in New York, and he'll talk about his work studying obesity and aging, why he chose MIT, and how a theater class at Keystone changed his life. Enjoy.
HOST: Charles, welcome to Cobra Radio.
CHARLES: Thank you. Glad to be here.
HOST: Now, you are a professor and a researcher over at Mount Sinai Medical School, and your specialties are neuroscience, geriatrics, and obesity. Let me ask you to talk for a moment about your work.
CHARLES: Okay, so basically, I knew I wanted to be a scientist from about the second grade. I'd gone through all the books in the mobile library near my house — I started with the cowboy books and read them all, which was fun, but then I'd read them all. So then the next shelf over was books for elementary-school-age kids about science, and I said, okay. There was a book called The Sun, the Moon, and the Stars — I thought it sounded kind of interesting. By the way, I was a late reader because I was very ill as a child — I had asthma, and I didn't go to kindergarten. So in first grade, everybody else was reading better than I was; I couldn't read at all. But once I learned to read, boy, you couldn't stop me. I read The Sun, the Moon, and the Stars, and that was it — that's what got me started. Then I read all the science books and loved them, then all the science fiction books and loved them, and I knew I wanted to be a scientist when I grew up. That always stayed true. So then I went to Keystone — I'm happy to discuss that, what a lucky break that was for me — and then I went to MIT, which was where all the nerds wanted to go; in the science fiction books, all they talk about is MIT, they never talk about Harvard. So I went to MIT. But in my senior year, I had to decide — everything was interesting to me, but I had to figure out what I wanted to do for graduate work, which is probably what I'd do for the rest of my life. So I read a lot, including Time Enough for Love by Robert Heinlein, which is about aging. I decided that aging and age-related diseases are the main load on the health system and the main cause of health-related misery — since antibiotics were discovered, most other things stopped being a problem, but age-related disease still was. So I decided to focus on that. A lot of people, including Richard Doll, a famous cancer researcher, wrote an article called 'There Is No Such Thing as Aging.' Most gerontologists studying aging would say, well, there's no single process. Doll's view was that it's just the second law of thermodynamics — nothing very mysterious about it, it just takes a long time for these impairments to develop through entropy, and there's nothing in common between, say, cancer, his specialty, and Alzheimer's — totally different diseases with nothing in common. But I was a romantic — I am a romantic — and I look for the big picture, so I thought there was something bigger going on. One of my reasons was this: dietary restriction — formerly called caloric restriction, but I'll explain in a minute why it's not necessarily about calories — delays all age-related diseases in every animal ever examined, including diseases that are genetically engineered into them. Dietary restriction still delays those diseases, and for something like Alzheimer's, it would probably eliminate it altogether. I thought, that'd be a cool thing to understand, and the next step would be to put it in a pill and make a difference. My main personality trait is that I'm curious, and I could have done any kind of research — even philosophy — and had fun, but I wanted to do something that was fun and made the world a better place. I thought I could have the biggest practical effect by studying aging. To my satisfaction, we've discovered how dietary restriction produces these amazing effects, and now we're in the phase of putting it into a pill. We have several drugs now that seem to mimic the protective effects of dietary restriction, and we're developing those.
HOST: Now, what is the difference between caloric restriction and dietary restriction?
CHARLES: Yeah — okay, so this phenomenon was first discovered in rats in the 1930s by McKay and colleagues. They expected that reducing caloric intake would shorten lifespan — that's what you'd assume — but this was a golden age of nutritional studies, so they decided to check it out. Much to their shock, if you reduce the number of calories the rats consume, they actually live longer, and they don't develop the diseases of aging. In rats, mice, and almost all species really, if you look at the oldest members when they die, they almost all have some kind of cancer — that's not necessarily why they died, but they have it — except for the dietary-restricted animals. So for a long time, this was assumed to be due to caloric restriction, because they were simply reducing the number of calories the animals ate, and there were good reasons to believe that. But we now know there are many ways to achieve the same protective effects without actually reducing caloric intake. One of the most famous examples — something some people are trying in their own lives — is intermittent fasting. In that case, you eat every other day. We can do this easily in mice: we take away their food for one day, and the next day we give them as much as they want. And when they can eat as much as they want, they'll eat twice as much — it's true for people too. So in the long term, they're eating the same total number of calories, and yet that intermittent feeding schedule still increases lifespan and still delays age-related disease. So it's not the total number of calories. There are many different ways to implement this. In C. elegans, the model organism we mainly use to study aging — which has a lot of advantages — there are about a dozen different canonical ways to do dietary restriction that extend lifespan and delay age-related disease, and most of them don't even involve caloric restriction. That's why I say 'dietary restriction.'
HOST: Got it. And now you've been able to take the benefits of dietary restriction and basically put them in pills — you've created a company, and you're trying to get these to market. Tell us a little more about that.
CHARLES: Okay, great — so there's something called the Valley of Death in drug discovery. What that means is you can get a drug to a certain point where it looks very promising, but then the FDA requires certain studies in animals to find out things like what the optimum dose is for protectiveness, and, for that matter, what the lethal dose is — because almost all drugs become lethal at a high enough dose, and the FDA wants to know how far off the effective dose is from the lethal dose. These are kind of boring studies, but the FDA requires them for good reason. So how do you fund them? They can be pretty expensive. The NIH generally doesn't fund those kinds of studies, because it's mainly interested in basic research, and drug companies generally won't fund them for a compound that isn't already theirs. So the only way to really get over the Valley of Death is to start a company. Why does that work? First, the NIH, the NSF, and a lot of government organizations have specific funds set aside to help companies — including small biotech startups — get over the Valley of Death, so they'll fund those kinds of studies. Investors will also often fund them, because you give them a share of equity in return. Alzheimer's disease is the main thing we focus on right now, along with stroke — we think our drugs will work for age-related diseases generally, especially neurological disease, but the way the FDA works, understandably, is one disease at a time. Those Alzheimer's studies in mice, which is the best model we have, are really expensive, but it's a ten-billion-dollar market — it's the most expensive disease there is, with stroke a close second, and there are essentially no effective treatments right now. So investors realize this is a great opportunity, but the only way to make that happen is to give them equity, so you have to have a company. That's why we started the company. It's been quite a ride, I can tell you — something a basic researcher like myself very rarely does. But I'm not like most basic researchers, to be honest — I always planned for my work to have a direct impact on human health, and most of my colleagues think their job is to do the basic research and that it's the drug companies' job to develop the drugs from there. And frankly, that's not happening. So that's why we started the company. It's been an adventure, but it's been fun in its way. As a Keystonian, I never shied away from a challenge — quite the contrary — and that's why I am where I am today.
HOST: And the drugs your company — I believe it's called Gilga-Med — is making, those are geared toward aging. Is the company also going to look at drugs geared toward obesity?
CHARLES: Yes, that's a very perceptive question, and the answer is yes. Let me fill in some background. When I first decided to focus on how dietary restriction produces all these protective effects, one of my views is that you have to have a hypothesis to move forward. That's not generally thought to be a good idea by a lot of people, because they're afraid you'll try to prove your hypothesis rather than follow what's actually correct — but I'm a big fan of the history of science. I actually taught a course at MIT as an undergraduate on the history and philosophy of science, that's how much I'd learned about it and how important I thought it was. And in the history of science, you don't get out of bed if you don't have a hypothesis. So I had to think hard about what my hypothesis was for how dietary restriction was working. I figured it would probably have to be mediated by cells that were specialized to sense nutritional state — how else would it work? There's really only a small number of cells in the body whose job is to sense your nutritional state, and those are a small number of cells in the hypothalamus. I liked the hypothalamus for other reasons too, because that little part of the brain also controls all your neuroendocrine functions — reproductive function, thyroid hormone, growth hormone, glucocorticoids — all controlled by that small group of hypothalamic neurons. So I liked the idea of focusing on that.The reason I knew those neurons were important goes back to a strange discovery made around 1900, and this syndrome still exists today — usually in children, though sometimes adults. A child is doing fine, and suddenly becomes a voracious eater — their appetite increases dramatically, they become obese, and, depending on their age, they don't go through puberty, and then they die. Around 1900, when people started doing more autopsies, they found these children had tumors in a tiny part of the brain at the base of the skull, right above the pituitary, called the hypothalamus. So it appeared that neurons in the hypothalamus regulate energy balance, and the people who studied that were mainly interested in obesity. That was confirmed about twenty years later — you could induce obesity in basically any animal with a hypothalamic function by damaging those neurons. So my interest in those neurons was that they obviously have to sense nutritional state — that's their job, to control your metabolic state — which I thought was necessary for the protective effects of dietary restriction. But at the time I first started these studies, I didn't have a good handle on where I was going with this in terms of aging, so I was mainly focused on the obesity side, which, as you know, is one of the major health problems we face in the 21st century. We discovered a lot of things that I thought would turn out to be relevant to aging — how these neurons sense nutritional state, what the main output is that controls metabolic status, and so on. It was really fun, and that's primarily what I'm noted for. By the same token, my hypothesis had two parts — I thought it would be hypothalamic neurons, but then, what is the nutritional signal? The signal I focused on was glucose, for a lot of reasons. We discovered how these neurons detect glucose, and it turns out there's only one other type of cell in the body that can sense glucose the same way — pancreatic beta cells, which secrete insulin. We showed that hypothalamic neurons sense glucose by a very similar mechanism, just slightly different. So that became my basic hypothesis, and it's still my hypothesis today: dietary restriction works by reducing the glucose signal to those neurons, and the neurons in the hypothalamus then send out signals to the rest of the body that turn out to be highly protective. We also had to figure out how glucose is toxic — because glucose seems like a good thing, yet in diabetes it obviously becomes a bad thing — and we've worked that out too. So our work is primarily known for the obesity side, and hopefully the aging work will become more widely appreciated as well.
HOST: Is that kind of related to — forgive the layman's terms — the natural process where the brain tells your stomach, 'I'm full, I don't need to eat anymore'?
CHARLES: Oh yeah, definitely, it's related. To put it in a nutshell: when those neurons sense that glucose levels are low, as happens in dietary restriction, they send out a lot of different signals. One of those signals makes you hungry, makes you want to eat — so when glucose levels go up after you eat, that signal turns down. That part is very important for obesity, though not so important for how dietary restriction protects you. The other part of what these neurons do is a metabolic effect: when you have a lot of glucose, these neurons say, let's metabolize it, because glucose — the product of photosynthesis — is the main source of energy for all living things, and species have evolved to be very efficient in using it. But if you don't have enough glucose, which is what the glucose-sensing neurons detect, they send a different signal to the whole body: we don't have enough glucose, so we need to use an alternative fuel — either lipids from stored fat, or ketones, which I could discuss later. So it's exactly the same sensing process, but it's the second part — the metabolic effects of these neurons, reducing glucose metabolism — that's really how this extends lifespan. In that respect, it's kind of the opposite of diabetes.
HOST: So if these drugs turn out to be a big hit in the market, do you stand to make a ton of cash?
CHARLES: Yeah — what can I say. I'm listed as the main inventor on the patents, which by itself doesn't give you money, but in the case of Gilga-Med, since I founded it, I'm currently the only shareholder. That's going to change, hopefully quickly, when investors come in — the government doesn't ask for equity when it funds studies, but investors obviously do, so I'm not going to keep 100 percent. I'll allocate the equity in whatever way is most likely to lead to the maximum effect in terms of generating results and getting FDA approval. Well, for one thing, my wife won't let me not keep a certain amount of stock. And since this is a huge market, even if I only keep ten percent of the equity, that's still going to be a lot. But I really want to add — that is not why I started the company. I think that's why most 20-year-old guys start companies, because they want to make money, but maybe not even that — maybe it's just really cool, I don't know.But to jump ahead a little — Keystone would definitely be my main philanthropic destination. Who knows what will happen, but I can't think of a better way to use that money than to basically make Keystone free. I really want to, because Keystone saved my life. I grew up on the south side, a blue-collar family — barely that, honestly. Nobody in my family had ever gone to college. It was a pretty poor part of town, we didn't have any money, and I was only able to go to Keystone because they gave me a scholarship. That just saved my life — I never would have done any of these things if I hadn't gotten into Keystone. So it would be a great honor for me to be able to facilitate that kind of situation for someone else. Keystone already does an amazing job of letting people like me in, and they do fund people — I'd just like to make it even easier for others. That would be it for me, honestly — I have enough money. Although, despite the background you might expect from a Zoom call like this, I don't actually live on the 50th floor of a Billionaires' Row apartment — I wouldn't mind it, that's about the only thing I could think of to spend money on. I don't know what people use billions of dollars for, other than philanthropy. So yeah, I probably would make a lot of money at this point in my life, but my biggest hope would be philanthropy, and Keystone would be number one.
HOST: Let's focus on Keystone. When did you first come here?
CHARLES: I only went there for high school — I started my freshman year. The way it happened, I just can't imagine, I've been so lucky in my life. I lived on the south side, and Keystone was kind of a legend you'd hear about once in a while if you were a certain kind of nerdy kid. They announced at my junior high that Keystone was holding entrance tests to get in. I didn't really think it would be possible for me to go, because we didn't have the money for it, but I could never resist a challenge — that's a Keystone trait for you. So a couple of friends from junior high and I went to the testing, and amazingly, all three of us got in — which is really something, because there were only 20 people in that entering class, which is still a fairly large class for Keystone. So that's how I got started. Then there was a negotiation about the scholarship, and Keystone was very generous to me with it — that's what enabled me to go. Could I have gone sooner? I don't know, but I'm not going to second-guess anything, because it was just amazing, amazing in my life. I went there for all four years of high school, and it saved my life, like I said.
HOST: What were some of your favorite classes?
CHARLES: That's a great question. I was a science nerd, so I loved the science classes. At the time — probably nobody remembers Coach Eargle— but Coach Eargle was the biology teacher; we called him Coach Eargle because he'd previously been a coach for, I don't know, some kind of sports, I guess. But he taught biology at Keystone, and I just loved it — he was my charismatic leader, and he was very kind to me. This is hard to believe now, but back then the bells that signaled the change of classes weren't automated — somebody had to actually go ring the bell — and he asked me to do that. I was so flattered, because it felt like real responsibility, and I don't know exactly why he picked me, but I did it. I guess that was my job at Keystone, working off a little of my scholarship, maybe. But I loved all my classes — I loved every single one. Still, maybe a bit of a surprise is that in some ways the classes that influenced me the most were my speech and drama classes, taught by Mrs. Bathke. I'd always, in elementary school and junior high, participated in whatever kind of drama was available — whenever I saw an opportunity, I just took it — so I'd done a lot of theater before Keystone. But Mrs. Bathke created a theater curriculum at Keystone and directed the shows, and I think she basically did it for free — I don't think that was her official role; I believe she was really brought on as an English teacher primarily. Those classes may have made the biggest impact on my life, on how my life went, because I was going to be a scientist regardless, but it was because of Mrs. Bathke — and especially when she cast me as Romeo in Romeo and Juliet, opposite a girl I'd had a crush on since first grade — that I could never look back after that. Now, that's my third full-time job, doing theater in the New York City scene, which has a lot of professional-level fellow actors. So it's hard for me to say what my single favorite class was, but that really made a huge impact on how my life turned out — if I hadn't had that, I still would have been a scientist, but I doubt I would have done theater. So thank you, Mrs. Bathke — and Coach Eargle too, thank you, wherever you are up in heaven, I'm sure it's nice.
HOST: Any other extracurriculars besides theater? I assume you did science fair?
CHARLES: Oh yeah, of course — I did science fair. I was also president of the class junior and senior year, so that was one of my main activities. I didn't do sports — that's the one thing I didn't do. I'd had asthma as a child and really couldn't do sports, though for some bizarre reason I did try out for the basketball team once — of course I didn't make it, thank God. But other than that, I did everything else that was available. Theater was my main preoccupation, but I was also president of the chess club — how nerdy can you get, right? And I was president of the math club too, not surprisingly, so my job there was mostly working out the logistics of getting our math competitors to competitions. There were people much better at math than me who won all the awards, but I played a small part by at least supplying the transportation. So between all of that, my days were pretty much filled up.
HOST: One tradition that's been big, as far as I know, for decades is Valentine's Day — was that a big thing when you were here?
CHARLES: Oh yeah, yeah, it was a big thing, so much fun. I'm not sure what exactly set it off, but people — anonymously — would put books in my locker about various aspects of romance and sex, and I'd read them like, whoa, this is a new world for me. But also, obviously, with the letters and notes and messages, it was really fun.
HOST: That's wonderful.
CHARLES: I have to elaborate slightly — look, I was a nerdy boy. As you can imagine, I didn't have much of a romantic life as a nerdy boy in elementary and junior high, but it was a totally different story in high school, because at Keystone, nerdy boys aren't so unappealing, I guess. So suddenly I had a fairly active romantic life in high school too. So that's another way Keystone saved my life.
HOST: What are some of your other favorite memories?
CHARLES: There are so many things — let me mention one that's a little poignant, but that's the way these things are. I mentioned I was president of the math club. This is a very personal story, but I'll lay it out. In the first week or two of class as a freshman, our algebra teacher mentioned that a certain boy had scored the highest ever on the [Keystone] entrance exam. The teacher told us his name — he was in eighth grade, I was in ninth. So I made it my business to go find this guy and introduce myself. He didn't know me from Adam, and I didn't know him either, but I just said, listen, man, you sound like the kind of guy I'd like to hang out with — which is kind of unusual between a ninth grader and an eighth grader. We were both very nerdy and, at the time, not particularly comfortable around girls, so we wound up spending a lot of time together. Then the next year — or maybe it was that same year — we went to a math contest in Andrews, Texas, up in the North Texas area, which has a famous math contest every year. I made it my business to charter the bus that was taking us, sit next to him on the ride, and arrange for us to be roommates for the contest. We chatted the whole way up — it's about four or five hours — and then we were roommates, and we spent most of the evening sitting in the bathroom, which had a mirror, just talking about all kinds of things and looking at each other in the mirror. The next day we did the math contest, and he won first place — I didn't even place. But after that, we were basically bonded for life. I'd thought I couldn't afford to go to MIT, but he told me I had to go, because he was going to go to MIT. That pushed me to call the financial aid office and say, look, I'd like to go, but I can't afford the package you're offering me right now — and they said, don't worry, we'll take care of it. And they did. That's why I went to MIT. So, after Keystone, that friendship was the second most important experience of my life, and I owe that to him, along with so many other things. Unfortunately, he recently passed away, which is a great tragedy for me, but I've stayed close with his family — I just had dinner a couple of nights ago with his widow, and we had a great evening reminiscing. I also made some other amazing friends at Keystone who are still very much part of my life today. I've said this many times: God bless Keystone and its teachers, but the most important thing to me about Keystone was my fellow students — that's where I learned the most and got the most out of it, because you can always read a book, and the teachers were great, but it was the students who were the real revelation. It was like, oh, there are people like me out there? How cool is that.
HOST: You'd be happy to know the MIT tradition is still very strong here — this year's graduating class, out of 30 students, has 3 going to MIT.
CHARLES: Wow, that's great. You know, it's funny — there was sort of an in-group of super-nerds, my friend I was just talking about and another friend, and he went to Harvard. We asked him, why are you going to Harvard? And he said, well, they have a lot of good stuff there. To my friends and me, it was like, why would anyone do that? Now I realize why people go to Harvard, but I'm delighted to hear three of you are going to MIT — that's really impressive. I was the only one in my class who went to MIT, and I think my friend was the only one in his class too. So three is great, I'm really delighted to hear it, and, as you can imagine, I stay in touch with the MIT crowd a lot too.
HOST: That's great — I'm delighted.
CHARLES: Yeah.
HOST: Let me ask about your theater involvement in New York — I can't let that go. What do you do, where do you perform?
CHARLES: Yeah, that's a good question. I'd done theater pretty much my whole life, and I went to the University of Southern California for my PhD, so I lived in LA for a while. I was in a lot of movies as an extra there, but I found it kind of boring, so I came to New York. I didn't really know what I was going to do, so I took some classes — improvisational theater, for example, and some other things. But then a friend who'd also gone to MIT — I knew her through a mutual friend, we never actually met each other at MIT, though we'd both done theater there — she was in a theater group, and she was a little more aggressive than I was about it. The group was putting on a musical called 1776, and that musical, as you can imagine, requires a lot of men — and, as is usually the case, women are a lot more interested in doing theater than men are, so it's hard to cast something that needs 20 men. The word went out: call everybody you know who might be interested in theater. So she called me and asked if I'd be willing to audition.Now, I'd never done a musical — we couldn't do musicals at Keystone, we just didn't have the infrastructure — and I'd honestly thought musicals were kind of dumb, because the main one I grew up seeing was the movie Oklahoma!, which is definitely dumb. But I said, you know, typical Keystonian response: sure, let's do it. I'd never auditioned before and had no idea what I was doing, but I did it. I'd always been in choral groups — for example, while I was at Keystone I was in the San Antonio Boys Choir, and my poor mom, God bless her, was basically my full-time chauffeur, driving me everywhere, including getting up early on Saturday mornings to drive me across town to choir. So I'd always sung, but I'd never done musicals. Anyway, I guess in theatrical circles, if you're a man and even vaguely talented, you get cast in a leading role — I wasn't cast as the lead, but I got a substantial part in that group. It was fun, but I let it go for a while because I was doing my postdoc and had other things going on. The group's next show was Arsenic and Old Lace, and I didn't know much about it, so I wasn't going to audition — in hindsight, what was I thinking? The same young woman from MIT had also decided not to audition, because Arsenic and Old Lace is a straight play, not a musical, and musicals were her main thing. But neither of us showed up to the first night of auditions, so the director called each of us afterward and said she really wanted us to audition for the play. When a director calls you and asks personally, that's very flattering. I didn't know anything about the play, but she knew a lot about Arsenic and Old Lace — it's a famous movie starring Cary Grant — so she filled me in before each part of the audition. I ended up cast in the Cary Grant role, the romantic lead, and she was cast as my fiancée. That play involved a lot of kissing. Suffice it to say, that young lady is now my wife — we call it a 'showmance,' because that happens a lot in theater, though it almost never really lasts. Ours did. We've been working with that theater group for about 30 years now. We just did a show last weekend — our first in two years because of the pandemic — a musical revue. My wife is basically the president of the group now, and I do what I can to help keep it going. New York, as you know, is a magnet for people who want to do show business, so a lot of the people who audition for our cast are genuinely talented and want to be professionals. It's a real privilege to get to perform alongside such talented — at this point, much younger — people. So that's a big part of my life.
HOST: That is fantastic. I'll bring this to a close with one last question: what advice would you have for a young high school student getting ready to start at Keystone?
CHARLES: That's a great question. I'd say: take advantage of the opportunity, because it's amazing — don't ever say no. Anything that comes up, say yes, I'll do it. People make fun of me for that — they say, come on, you can't do all these crazy, weird things — and I say, you know what, some of them, most of them, are crazy and weird, but you never know what's going to pay off. Sure, learn as much as you can, but the social aspect of Keystone is actually the most important part — make friends, talk to people, go out to lunch and dinner with them, and realize these people are going to be your friends for life, honestly. Most of all, just take advantage, don't be shy. I'm famously always overcommitted — I've always been overcommitted, people think I'm nuts, and it does make me miserable sometimes, but I wouldn't do it any other way. So don't be shy — just do it. The Nike thing.
HOST: Fantastic. Well, Charles, thank you so much for spending time on Cobra Radio — we really appreciate all of your memories and your knowledge. It's just been absolutely fantastic.
CHARLES: I hope I've lived up to your expectations. It'll be really fun to see who listens to this and what they get out of it.
HOST: Wow, what a fun conversation. Join us next time on another edition of Cobra Radio.