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- [00:01]
A
It's on.
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B
Hi, everyone. From New York magazine and the Vox Media podcast network. This is on with Kara Swisher. And I'm Kara Swisher. When it comes to the science of living longer, there's so much garbage out there that it's easy to miss some of the truly remarkable things that are happening with scientific advancement around longevity. In this episode of our Hacking Longevity series, we'll go deep into the science behind some of the most promising medical developments happening right now, specifically when it comes to fighting pancreatic cancer. We'll speak with the leading researcher in that fight, Dr. Vinod Balashandran of the Memorial Sloan Kettering Cancer Center. But first, the bigger picture. I'm joined by Dr. Eric Verden, the President and CEO of the Buck Institute for Research on Aging in Novato, California. The Buck Institute was the first research center of its kind, and it's at the forefront of what's going on in the field. Dr. Verden has a medical background, of course. He also has an entrepreneurial take that I wish more doctors shared. I think it's really interesting to talk to all the various big names in this. Some of them are more scientific than others, and those are the ones I'm sticking with. But it's really important to understand all the differing viewpoints of where this is going, and that's what's necessary to moving forward, to have disagreement and then move forward with actual scientific facts and, of course, measurements. It's a smart and interesting conversation, so stick around. Support for this show comes from Kohler Health. The body sends you answers to important questions every day. How's your digestion? Are you drinking enough water? But most of us don't know how to interpret them. For over 150 years, Kohler has redefined innovation and craftsmanship in the bathroom. Now Kohler Health is reimagining its role in personal health with Dakota. Dakota is an attachment that fits discreetly on your toilet. Learn more@kohlerhealth.com and use the code karaoneyear for a free annual app membership. When you purchase Dakota,
- [02:23]
A
It is on.
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B
Dr. Eric Verdon, thank you for coming on on.
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A
Thank you for having me.
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B
So you're at the forefront of some of the most interesting ideas in this field. So the first question, what is something about aging that would surprise the average person and what people get wrong about aging?
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A
Wow, that's a big question.
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B
It is.
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A
What would surprise people is how much control you actually have over the way you're going to age at the end of your life. You know, many of Us live through life sort of hoping for the best. Flying blind, mostly. This is the state of medicine today. And I think there's what I call a revolution happening in a way that we're finding out that the way you live can have an absolutely dramatic impact on how you're going to spend the later years of your life. And in some way, that's the message I've been trying to spread, because I think it's an incredibly optimistic and positive message versus a fatalistic sort of, you know, my parents didn't live very old. Well, I might as well have another cigarette.
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B
Right, right. So what. What do people get wrong, would you say, is that idea that you have to be sort of a decrepit person no matter what happens, like, it's just the way it's inevitable kind of thing?
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A
Yeah. Sort of a very fatalistic view of their own aging. What they get wrong also is the. The intensity of what needs to be done to actually get maximum benefits. And I tell people that, as a very simple example, that walking 15 minutes every morning and every night is going to have a dramatic effect on everything in terms of how you age. Most people are not aware of this. They think, well, I have to eat perfectly, I have to sleep. I have to do everything perfectly. My approach has been everything that you do will help, especially at the early stages.
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B
So you're studying aging itself. What does it mean to study aging as a disease is that that's how you look at it. Explain that for people who don't understand what you're doing.
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A
And this is not something that everybody agrees on. I do not like the idea of calling aging a disease itself because it has a lot of implications. One very simple one is that if we start doing this, it means Everybody at age 25 is now disabled. I think aging is a normal process, but there are many different ways of aging. And the thing to know is that rather than calling it a disease, I call it a risk factor. It's the major risk factor for a whole series of conditions that your audience will be familiar with. Heart attack, stroke, type 2 diabetes, macular degeneration, hip fractures. The list goes on and on.
- [05:15]
B
Can I interject? How did you come to see aging itself as the root? Talk about how you got there about
- [05:21]
A
25 years ago, 30 years ago, 1995, for most part, a whole series of discoveries pointed to the fact that aging was really much more strongly regulated than we had imagined before this. People thought aging is just something that happens. What we discovered is that there were really critical genes that changed the rate of aging. So we can make a single mutation in a small animal and really dramatically double its life expectancy. That really changed the whole way of thinking of aging as something fatalistic that we could not control. That was random to something that's actually pretty strictly regulated. And this regulation implied the fact that if we could find drugs or interventions that targeted these regulatory points, we could really change the rate of aging. And when we started doing this, what we found is we could make animals live longer. So all of this work was done in small animal models, System mice and so on, but the animals not only lived longer, but they lived much healthier. That was really something that surprised us. And so they generated something called the geroscience hypothesis. I want to step back for one second.
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B
Sure.
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A
The idea that we live today about double the time that we lived 150 years ago. So, you know, 1850, we lived until around 40. Right now it's around 80. Most of the western world. But it has come with an incredible burden of chronic disease. When I ask people who wants to live to 100, very few hands will rise because people envision a future disease. What we have found in animal models is that if we tinker with these aging pathways, these mechanisms that regulate aging, we make the animal live longer, but they also live much healthier without the
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B
onset of these chronic diseases that happen, Right?
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A
Yes. And so they behave, in many ways, much more like the centenarians today. And centenarians not only live longer, they live much healthier. Your typical centenarians will live until 95 in good health, and then we'll have five years of a compressed morbidity.
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B
The things you're doing at the buck institute, Explain for people what you do. And it's the verdant lab at the buck institute. You've been particularly studying the connection between aging and immunology. Talk a little bit about that and the connection.
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A
Yeah. So first, the Buck institute was founded in 1999 on the heel of these discoveries that we talked about With a generous gift from Mrs. Beryl Buck. Today we have about 300 employees working on all different aspects of aging and trying to really. To do two things. One, understand the basic biology of aging, because we've made huge progress, but there are still really big questions that we don't fully understand, but also, importantly, trying to bring all of this knowledge to humans, because that's. Obviously, that's the goal, is to make all of us live longer, better. But we've been a clinical center. We have clinical trials going on pretty much half of our faculty is focused on really bringing all this knowledge to humans. And so this will happen pretty quickly. Within the next five years, I would say, we will have some of the first interventions for humans. So the VERDIN lab itself. So I have a dual role. I am sort of CEO of the organization, I lead it, but also have my own lab. And I focus on understanding the role of the immune system. The immune system seems to be one of the few organs, along with the central nervous system, that play a dominant role in aging. And so there's evidence, for example, that if you. If you have a lesion only in the immune system, this will cause aging in the whole organism. And this is true also for the central nervous system. The other thing is aging in the immune system, I think, has not received the attention that it requires. And this was highlighted during the pandemic where your age, for example, was the major risk factor from dying from COVID It's also the major risk factor from dying from influenza, the flu, from rsv, respiratory sensitivity of virus. It's also the immune system is a critical system that controls how you respond to cancer. So there's a whole series of aspects linked to aging that are controlled by the immune system. What I like personally as a model system to study is that it's readily accessible. We can draw blood from your arm, and within an hour, we can really enumerate all the different cells. We can figure out what is the state of your immune aging. It's a system that we can intervene on by the same way, we can take cells out, we can modify it, we can put them back.
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B
Now, one of the things you've also focused on there, the issues around supplements, is something I covered a little bit in the series, but not a lot. And some doctors think they're a waste of time and money. You don't dismiss them at all. You sell some supplements, like the juvenescence metabolic switch. Talk a little bit about why there's a lack of scientific consensus in this area. Because I. I suspected somewhere in the middle in terms of there's a lot of influencers selling nonsensical stuff. And then there's some good stuff, a vitamin D, a vitamin K, for example. Talk a little bit about this because I think one of the things that the one question I've been asked by most people after the series was, what about supplements? And I was like, well, it's complicated. Let me.
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A
Yes.
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B
Don't buy it from Dr. Nobody. Like, please don't like Dr. Dr. Instagram. Don't buy it from Dr. Instagram, but go ahead.
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A
I could not agree more. And I've been called sometimes the grumpy man of longevity medicine because of the stance that I've taken, which is somewhat conservative, but probably a lot more open to the idea that most physicians would be. I went to medical school and I was told most supplements don't do anything. I disagree with this. So first, there's a whole world of what I call Instagram medicine.
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B
Yeah, it used to be Dr. Google, now it's Instagram medicine.
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A
And so, you know, quite often you will find these influencers making big pronouncements on science that they've never been close to and promoting products for which they are being paid. And many of these products have some kind of relationship to aging from laboratory studies and so on. None of them to this day have been proven in humans. No.
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B
Yeah.
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A
So that doesn't mean that I'm not taking any supplements. I do take supplements. Quite a few, actually. I do take them in a way that is based on some of the data that I have seen and what I think is promising or not. So we live right now in this sort of nether world where we have the supplements that have been documented to have big effects sometimes in animal models, and then we have humans where the barrier is much harder. So I advise people to, you know, there are some supplements that most people should take. As you mentioned, Vitamin D, most of us are deficient. Vitamin B12, quite a few of us are deficient. Omega Omega fatty acids. We know that the western diet is quite low in omega fatty acids in comparison, for example, to Japanese. Creatine is another supplement that really came out of the sports world and seems to have really big effects. Protein supplementation in some cases. This would be my essential list. Magnesium helps a lot of people as well, so that would be my essential list. Then beyond this, there's a whole series of additional supplements that have shown promising results in animal models. And this is where it really depends on your sense and your risk taking. My approach has been to introduce them one at a time and then to follow my numbers. And if I see. If I see a positive picture, I tend to continue.
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B
Give me an example of that.
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A
I'll give you an example of one that has been very controversial. Nad.
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B
I was going to ask you about that.
- [13:41]
A
Yeah. So NAD is a key molecule in metabolism. I spent many years studying it. There is some evidence that NAD levels can decrease in many tissues, although there was just a paper came out this past week saying it doesn't decrease in blood. There's Some evidence it decreases in several tissues. And so the idea has been, since it is so critical and it decreases during aging, why not try to bring it back to a normal level? And so two supplements have emerged out of these studies called NMN and nr, nicotinamide, mononucleotide, nicotinamide, ribozide. And they do restore in animal models and AD levels. And in animal models, they show very strong effect in my lab, in many labs actually. And so that has led to a whole industry of companies selling NR and nmn. And here's the downside. Many of the clinical studies that have been done in humans have really not shown very significant beneficial effect. And so right now we live in this nether world where people don't know what to do. Should I continue? Should I not? In my lab, for example, we've done some work trying to understand why do NAD levels decrease in the first place. What we found is that there's a molecule called CD38 which increases during aging. And this molecule, CD38, churns through NAD. So based on that data, I would say that the proper approach, the problem would be to block CD38. And we have some novel drugs that are doing this rather than pouring water more in.
- [15:20]
B
Let's go through some others then, because there really are out there like rapamycin. Had a moment, especially off label use of it. Talk a little bit about that.
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A
So rapamycin is not a supplement. That's an important distinction. It's a real medicine. Rapamycin targets a protein called mtor, mechanistic target of rapamycin. And MTOR is a critical protein in metabolism and in aging. The data in animal models says that rapamycin is the strongest molecule that we have in an experimental setting to increase lifespan. It's been tested in multiple species, all the way from yeast to mice to fruit flies, everywhere. It increases lifespan and the health span. What's interesting also is that rapamycin is already an approved drug in humans. It's used actually to immunosuppress patients who receive a transplant. What the field has proposed and what a number of people have jumped on is the idea, well, let's take rapamycin at low dose and take a bet, because it is a bet. We don't have the clinical trials that demonstrate that it is actually working. Those trials should be done and will be done. What we don't know is the proper dose. Obviously you don't want to get and use it at a level which is immunosuppressive because that's going to have a Whole series other bad complications. But maybe at lower dose you're going to get some benefit. I have taken it and so have a number of people.
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B
Yeah.
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A
Many of us have stopped.
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B
Stopped, that's correct, yes.
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A
And I tell you the reason why I stopped personally is that I could not see any difference in any of my numbers. The fact that I stopped doesn't mean anything by itself. The fact that Brian Johnson stop doesn't mean anything either. But I think what we need again
- [17:18]
B
here, gold standard clinical trial, which I was arguing with Brian about, I'm like, why don't you just do the trials like you can talk about it all you want. Another thing that I've noticed is a lot of biological age tests. By the way, my source scores came out excellent, but I find a lot of them are a waste of money too. Again, another these things, Brian does them a bunch of people and I'm like, they don't really say a lot. How do you feel about them?
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A
They say, I think probably a lot, that we don't know how to interpret them. So.
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B
Yeah, that's a very good way of putting it.
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A
Yeah. I think we are in discovery mode right now. So every week there's another of these clocks being discovered. The biggest group is the so called epigenetic clocks. Steve Horvath was the one who did it first. There's probably 50 or 60 of them different. If you send one blood sample to many of those. I did this, my number came back from 40 to 68.
- [18:11]
B
Mine too, mine too. All different.
- [18:14]
A
Of course. I like the company that tells me I'm 40 and if I only done one test and it had been that one, I could be sort of deluding myself that I'm 40 years old. So the way I look at them is that they are incredible tools. They will be important in the future, but they are right now experimental tools.
- [18:32]
B
Let's go through a few more. Cellular rejuvenation,
- [18:36]
A
very exciting area of biology. Late 90s, early 2000, a colleague of mine when I was at the Gladstone Institute at ucsf, Shinya Yamanaka, discovered a few factors called the Yamanaka factors that were able to take a somatic cell, so skin cells, nerve cells, brain cells, and bring it back to what we call a pluripotent stem cell. That is a cell that has the potential to become a whole organism. So this showed incredible plasticity of a process that we thought was irreversible. So our vision before was that when you are muscle cells, you're stuck being a muscle cell forever. It showed the idea that you could actually bring it back all the way now, there's something that happens when we are born is that we're not being as old as our parents were. Every time a baby gets born, there's a resetting at zero, which when you think about it, it is in some ways remarkable because this has been going on for billions of years. So what a colleague put these two observations together and said, what about if we would use the Yamanaka factor to bring you back a little bit closer to being a baby, would that actually make you younger? And so they introduced the Yamanaka factor in mice. And lo and behold, they were able to show that these mice were rejuvenated. They seem to be living younger. And so this led to the creation of a whole series of new laboratories and companies. ALTOS is probably the most visible one that are exploring the possibility of testing these Yamalaka factors or a variation of them to actually do what we call reprogramming.
- [20:22]
B
So a couple more longevity escape velocity. Explain for people what this is.
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A
Yeah, so over the last 150 years, we've gained two years every decade, two years of extra lifespan. So now let's just imagine for an instant that every decade we would gain not two years, but 10 years. That would mean our science would go as fast as we are aging. If we were able to gain 10 years every decade, then, you know, 10 years will pass and we would get another 10 years. This is the road to immortality. That's the way this is being presented.
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B
Presented. How do you feel about this?
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A
I've said that if you're looking for immortality, don't come to the longevity field. Join the church. And there is no disrespect to religion. It's just these are different spaces. I think as a scientist, we should never talk about immortality. It's just not, I don't know, frankly, if it's desirable. I think a long healthy life definitely is. And even I'm open to the idea of much, much longer healthy life. But when we talk about immortality, for me, we talk about first something for which we have absolutely no evidence. I know that the concept of longevity escape velocity is cute. It just. It just visual helps you to visualize how this might happen. Now, one thing that I always bring up as a counter argument to this whole immortality point of view is that this seems to be a very hard limit at about 115 for human to live. Now, it doesn't mean that we will never be able to change it. But I haven't heard anyone Bring sort of an argument of how we are going to be able to do this last one.
- [22:12]
B
And then I have some big picture things to finish up on fasting. This is one I believe you personally do. This is one I wish I could do. I never seem to be able to pull it off, but I do. These have, these are very clearly proven scientific benefits from fasting. Although I'm so tired of listening to tech people talk to me about it obsessively. And that's a different thing that's just shortening my life by wasting my time. But talk a little bit about it because this is an area that sort of became a trend and then fell out of trend in a weird way.
- [22:43]
A
Yeah, I'll tell you how it started. One of the oldest and most robust way to increase lifespan in almost every animal species that it's been tested in is calorie restriction. So decreasing calorie input. So here comes fasting, which is sort of a minimized version of calorie restriction. So there are many ways to do fasting that would induce the same response. I favor a concept that's been advanced by my friend and colleague Satchinanda Panda, which is called a time restricted eating. So most of us are eating for 16 hours in the day and fasting for eight hours while we sleep. The whole idea is to get as close possible to the invert which is eating in an eight hour window and fasting for 16. Now again, we started the interview by this whole idea that, you know, people have sort of absolutist versions of everything. If you, if you're doing 16, 8 today, eating for 16 hours and you decrease this to 12, you would already do yourself some good. So I tell you know, and I'd be curious to hear what has been your difficulty of trying this.
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B
For example, probably the presence of food, the ability availability is the problem for most people. Right?
- [24:02]
A
No, I agree, it just, I, I, you know, my approach has been to do this progressively. If you, if you're eating for 16 hours, decrease it to 14 for, for a month and then decrease it to 12 for a month, then decrease it to 10 and eventually soon enough you, you'll be able to do it. There are issues, women have a totally different response to fasting depending on where they are in their menstrual cycle. So this is something always to consider. There are also alternative ways of fasting, by the way. There are many sort of traditions that have these fasting periods. You know, think about Lent, think about
- [24:43]
B
grandma.
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A
Yeah, exactly. So this is not something that we Even that we've.
- [24:48]
B
No, not at all. No, no. My son's doing the. No eating after dark. Although I'm like, summer. What do you do in the summer? Like, yes, but it's actually. He's lost a lot of weight doing it. That's how he's doing it. Let me finish up by talking sort of the bigger picture, as we've been talking. One of the things that's very. There's a lot of noise around longevity science and especially now with, as you noted, the charlatanism online. A lot of it, some of it good, some of it junk, but loud and noisy. And of course, as part of the series, I've been doing a lot of reporting on. The people who are most obsessed with it have been the people I recovering for years, a lot of the tech billionaires who were also involved in AI and various things like that. As you said, you've been called the grumpy cause you're so conservative with this stuff. I'd love to contrast the pushing towards this and at the same time with all this incredible scientific promise. No question, that's one of the things that's been the biggest takeaway. But is it okay if it starts as a narcissistic pursuit rather than something that's for all of us? How do you shift it to all of us, to the wider population, which is where you really want to see longevity increases?
- [26:00]
A
I'm really glad you're bringing this up because first we do receive money from billionaires. And I have nothing against the idea. I actually find it admirable that they give their money. And I, you know, there's a number of people, especially in Europe, have conflated these sort of narcissistic billionaire and their desire to live forever. And there's, you know, I read these articles and they make me mad because I think they don't reflect the reality. The billionaires that are giving money, I think are doing it, of course, out of self interest. There's nothing wrong with this. But they're doing it also of a long tradition of philanthropy that exists in the us so there's nothing intrinsically evil about, you know, Sergey Brin and all of the others, you know, giving money to longevity research.
- [26:49]
B
No, not at all.
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A
That being said, it also creates a problem for us because it creates this perception that we are only about increasing longevity for rich people.
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B
Rich people, right.
- [27:00]
A
And this is compounded by the fact that many of the longevity clinics that are opening today are actually catering to a small group of people, elite, wealthy clientele this is again, this is nothing new. When Elon Musk built the first Tesla, it cost $150,000, you know, and eventually he built a mass market car that cost $35,000. And so it will go for longevity medicine, which is a whole new discipline that we're building. This is really something that people misunderstand in terms of my intent when it comes to humans. It's nice to talk about longevity, escape velocity, but it should not obscure the fact that we have a lot of work that we can do today to make people live healthier longer now. And so this is really where I feel the passion that the longevity field should not only be about extreme longevity, it should also be about health. Span.
- [27:54]
B
My last question is a bit of a curve ball from the last one. I know you're a racing fan, auto racing, there's a model on your shelf. I see. And I know you actually drive some of these race cars. Life's work is about extending human life. Talk about why you do this.
- [28:10]
A
Yes. First, racing itself is a dangerous sport, but it is also, many of us have an image of it that's colored by what racing was in the 70s and 80s where every year two pilots would die in a Formula One championship. It's still a dangerous sport, but it's not more dangerous than diving or, you know, I have a number of friends who are road biking who get hit by cars. So it is, it's amateur racing. And when the time comes to really, you know, make a pass that is going to hurt your friend or your car, I think we all think about it. Personally, I thrive in these moments when I'm right at the edge where the focus and the concentration needs to be absolute. You get into these flow states. Racing also for most people do not appreciate, is an extremely physical sport. So for me it's a, it's a motivation for to staying in shape. And frankly, the community of, of people that I race with is incredible. So it meets actually many of the ingredients that I tell people. Yeah. So physical sport, community, something new. Cognition, excitement. So these are all the things, you know, I'm going to race this weekend, by the way, in a Mini Cooper and this big race with about 30 mini Coopers, which is going to be total of fun.
- [29:36]
B
Where is that?
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A
That's at Sonoma Raceway.
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B
Oh, wow.
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A
This whole weekend, the Velocity Invitational is an amazing event. It's the largest sort of a vintage racing event.
- [29:46]
B
That's a great, that's a great racetrack up there in Sonoma.
- [29:50]
A
Absolutely.
- [29:51]
B
It's really fun. I'm just teasing you on this because I think it's great. I think it's great to do things like that to have a hobby. Anyway, I really appreciate it, Eric.
- [29:59]
A
Thank you, Kara.
- [30:03]
B
We'll be back in a minute. Support for this show comes from Kohler Health. What if the most routine part of your morning could give you valuable insights about your health? Kohler defined the modern bathroom. It's where your daily routine already happens. Now it's bringing health tracking into that same space. That means automatic insights into your hydration, gut health and irregularities that often signal a flare up. How Kohler Health's Dakota slips seamlessly onto your toilet and passively captures your everyday biometrics without any manual logging. You'll see hydration and digestion patterns and even be alerted about the presence of blood in the Kohler Health app, giving you a clearer picture of your internal health and helping you build habits that truly work for your body. I'm very excited, actually. I have a lot of these things like the Oura ring and an apple watch and things like that. And it's actually something used in other countries and so far I just installed into it. It was super easy to put up. Now I'm really eager to find out how healthy I am and figuring out ways I can make changes for my health based on the information I learned. So learn more@kohlerhealth.com and use the code KARA one year for a free annual membership to the Kohler Health app when you purchase Dakota. Doctors and scientists are making truly remarkable progress against aging and disease. And we're going to go deep on one of the most promising areas of research right now, fighting pancreatic cancer. Researchers have really upended our understanding of how to treat pancreatic cancers. And one of the ways they're testing is using vaccines to treat cancers that have already developed. It's early days, but it has all the hallmarks of a huge breakthrough. I think one of the things that's been exciting is to see all the excitement around these MRNA technology solutions for pancreatic cancer when there's been such a backlash against vaccine among the general populace. But most people understand that this is a game changer and I just have paid a lot of attention to this. I've known a lot of people who have died of pancreatic cancer or lung cancer or cancers that are much harder to treat, even as they've made strides in other cancers such as breast cancer and colon cancer, which is amazing. One of the people leading the work is my next guest, Dr. Vinod Balashandran. He runs the Olian center for cancer vaccines at Memorial Sloan Kettering cancer center. He's a surgeon and a scientist, which is a rare combination. He has taken an unusual and very promising approach to his work. Vinod, thank you for coming on. On.
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C
Thanks for having me, Cara.
- [32:42]
B
All right. You're a surgeon, and you also run a lab. And for people who don't know, that's an incredibly rare combination, partly because the demands of even one of those are hard to manage. Explain how that happened.
- [32:52]
C
Sure. So the specific disease that I take care of is pancreatic cancer. And you may know pancreatic cancer is projected to become the second leading cause of cancer death in the United States next year. So more deaths from pancreatic cancer than many of the other common cancers, such as breast cancer, prostate cancer, ovarian cancer, melanoma, second only to lung. And part of the reason for this is because the current treatments that we have for this disease, which include surgery, chemotherapy, and radiation. Error, sort of still last generation, if you will, and the recent advances in oncology drugs, which there have been many, have not really impacted pancreatic cancer in a way that we would like. So when I started out as a junior faculty member to try to make a difference in cancer, which really has very high unmet need and patients really need help, I really wanted to spend time in the laboratory to be able to do this, as I felt this was probably where we would be able to make.
- [34:04]
B
Because, as you said, the treatments were so last generation, essentially.
- [34:08]
C
That's right. We think the most exponential advances here would come with scientific discoveries and application, and that really has to come from the lab.
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B
So explain why pancreatic and lung cancer. Also, I've known both the people who've had cancer who've had both those things have died of those things. I was thinking of Susan Wojcicki, who used to run YouTube and was an early Google executive, and then a friend of mine who died of pancreatic cancer. Everybody else seems to be okay, who's gotten cancer, which is. Explain why those are so vexing.
- [34:42]
C
Number one, it's very difficult to detect it early. So early detection, which has made significant progress in many other cancers, such as colon cancer, breast cancer. We don't have this for pancreatic cancer. And even when you detect it early, the treatments that we have are not as effective as other cancer types. So because of this, the mortality rate from pancreatic cancer, now at five years, still ranges on the order of approximately 90%.
- [35:17]
B
Yeah.
- [35:18]
C
So only about 10% of patients really survive long term.
- [35:21]
B
Long term. So your work on developing vaccines that will treat cancer is groundbreaking. It's something I remember talking to the German couple who had started some of the MRNA stuff around cancer, and it became a COVID vaccine. So most people know MRNA through Covid, but in fact it was aimed at cancer initially, as I recall. But I wanna get into the science of it. But first, provide some context for people who don't know how vaccines were targeted to do this.
- [35:47]
C
Vaccines, in short, perhaps you could describe them as the most impactful medicine in human history to improve health. And the way they work is by teaching the body to recognize what is foreign. So by delivering a small piece of a virus or a bacteria. So when or if they come, we already have a powerful immune system that knows that these agents are foreign and thereby can kill them. And these vaccines, the ones that we sort of commonly know about for influenza, Covid, others, these are given to healthy individuals to prevent future potential disease. Now, for cancer, this has been a significant challenge for many reasons. The first being that it's easier to teach our immune system to recognize, let's say, a virus or a bacteria as foreign, because this it already wants to do. That can't just derive from our own tissues, so they are in fact self. And our immune system is in fact hardwired to not recognize our own bodies as foreign. So to be able to teach the immune system to recognize specifically the portions of a cancer that are foreign compared to normal tissues is a fundamental scientific challenge. But in recent decades, we have made several significant breakthroughs in understanding how does the immune system recognize cancer as foreign, and how can we teach it to do this in a really effective way to make cancer vaccines? And this has really been quite exciting, right?
- [37:35]
B
So talk about the most common therapies right now for pancreatic cancer, right at the second, if you found out you got it, what would you go through? What would be the ways they would move through various therapies? And I know there's several that they
- [37:47]
C
do so in scenarios where the tumors are detected early, meaning sort of confined to the pancreas without any signs that spread outside the pancreas, the treatments include removal with surgery and usually chemotherapy afterwards to prevent it from coming back after surgery. In scenarios where the tumor is either not removable with surgery or has spread outside of the pancreas, the treatments include chemotherapy and or radiation. However, in recent years, there have been significant breakthroughs in using the more modern waves of oncology drugs to be able to target pancreatic cancer. Number One being immune therapy, which is sort of what we've been working on, vaccines, and a second being these targeted therapies, which sort of target the specific mutation that is found in pancreatic cancer using drugs. These are called the KRAS inhibitors. So I think even though our current treatments are still perhaps the last generation, there have been significant improvements in recent years.
- [39:04]
B
What are the drawbacks to most of these?
- [39:06]
C
Well, I mean, I think the central drawback here is we want drugs that work better.
- [39:15]
B
Yeah.
- [39:16]
C
Despite.
- [39:17]
B
Yeah.
- [39:17]
C
They don't work. Yeah, yeah. We want things that work a lot better than this. We want cure. You know, this is, of course, a word that oncologists use sparingly, but certainly this is what we would want to achieve. And it's interesting because the story of the vaccines for pancreatic cancer really emerged from the few patients that naturally sort of affect cure. Meaning. Although about 90% of pancreatic cancer patients die with current treatments, not everybody does. And There's a rare 10% that survive long term. So about a decade ago, we began studying these rare survivors of pancreas cancer, long term survivors to try to understand, well, how are they doing this and how could we replicate this in a therapy?
- [40:10]
B
Right.
- [40:11]
C
And what we learned is that these patients, we believe their immune systems are able to naturally recognize their cancers in a very potent way that allows these patients to survive so long. So this led us to this idea that if this is sort of happening in the best case scenario, you can
- [40:31]
B
facilitate it via vaccines.
- [40:33]
C
How could we teach other patients immune system to recognize their cancer just like it's happening in these rare survivors?
- [40:39]
B
Cancer researchers had traditionally not looked at it this way. Correct.
- [40:42]
C
Right. And also for immune therapy, I think pancreas cancer was considered perhaps one of the toughest cancers for immune therapy, which the vaccines would fall under this category. And perhaps there was also a question whether an immune therapy or a vaccine would ever be possible for a cancer like pancreas cancer.
- [41:04]
B
This is a series about longevity. So it's also a series about aging itself. And is. Is pancreatic cancer one of the diseases you're more likely to have the older you have? Or how does aging factor into how you approach the disease?
- [41:16]
C
Yeah, so it is a disease that is found or typically occurs in the age range of 60s to 70s. So it is not something that some would refer to as a young person cancer. But the, the incidence of pancreas cancer in the United States is also slowly increasing.
- [41:39]
B
Yes, it is, as it's lung cancer.
- [41:42]
C
Yeah. So I think it is a Significant national and global health challenge to be able to try to find effective drugs, medicines that can help treat and cure these patients of this really terrible.
- [41:59]
B
As the age, age range wafts down.
- [42:02]
C
That's right. Because the population is going to continue to.
- [42:05]
B
Is there a reason or is there something that scientists are looking at is why that's the case?
- [42:10]
C
Yeah, the etiology, like why does it happen? Why do you patients get pancreas cancer
- [42:16]
B
and why, why is it increasing?
- [42:18]
C
Why is it increasing? Yeah, it's not clear. There's not one sort of magic bullet, I think that would explain this.
- [42:29]
B
We'll be back in a minute.
- [42:32]
A
Foreign.
- [42:42]
B
Support for this show comes from Kohler Health. Everyone's looking for more information about their health. Watches, rings and monitors can give you a snapshot, but they don't always show the full picture. Meanwhile, what if you've been flushing away some of your most valuable data all along? You probably have. Cola has spent 150 years redesigning the bathroom. Now its new venture, Kohler Health is building on that expertise with its Dakota tracker. From fingerprint authenticated sessions to data privacy is designed into its features. Obviously it's very important. In this case, Dakota fits seamlessly onto your toilet and works discreetly in the background. The Kohler Health app then translates the signals your body is sending so you can see patterns in your gut health and hydration and get flagged when there's blood present. That's really important. I just installed it and it's going to be really interesting to see because I use a lot of these different things like these rings and watches and things like that. It's really important so you can make changes to your diet or whatever else you need to do. Once you learn this information, learn more@kohlerhealth.com and use the code CARA one year for a free annual membership to the Kohler Health app when you purchase Dakota. So let's walk through the research you're doing. There's something interesting about your approach as you described. You decide to focus on the outliers, the small percentage of people who do better from existing treatments. Talk about why you do that and what did you find in your hypothesis of how to replicate the success these patients had?
- [44:11]
C
Yeah, I think this goes back to one of the first questions that you asked about, you know, being a physician, scientist and how, how does that really help? I think this, this was something that I had encountered as a surgeon taking care of patients with pancreas cancer. You see these patients who come into your clinic that get the same Treatments as everyone else, but they survive long term. And it immediately strikes you as well. Why is that happening? Maybe we could try to understand what's happening in these patients. Because they're doing great. We want everyone to sort of do great just like them. And essentially fast forward after us studying a huge cohort of these rare survivors and comparing them to other patients who had pancreas cancer, but that didn't survive that long. What we found is that these patients, when they develop their tumors, their tumors are infiltrated by many more immune cells. So specifically a type of immune cell called a T cell, which protects the body against viruses and cancer. So these patients, tumors, they have about 12 times more t cells that show up in the tumor compared to other
- [45:27]
B
patients looking to attack the cancer.
- [45:30]
C
Exactly. So this led us to this question, oh, these T cells are seeing something. What are they seeing? Because if we can could find out how they are able to potentially recognize these patients cancer as foreign, maybe we can teach other patients T cells to recognize their cancers in a manner very similar.
- [45:48]
B
So what's the chief challenges in using vaccines to attack cancer cells?
- [45:52]
C
One challenge is what we've been talking about here, which is, well, what do you put in it? Antigen, Meaning what do you encode in the vaccine that can allow the immune system to recognize, to take instructions? Yeah, the instructions, the code. So here what we found was in pancreas cancer. In fact, it is these red flags, these code, the codes really are derived from mutations. And this was a bit surprising to the community, I think, because pancreas cancer is a cancer which generally has very few of these mutations. So the thinking had been that, oh, it has too few mutations. Therefore, a vaccine perhaps may not be possible because there's just. No. There's no instructions there. So the immune system would not really be able to see pancreas cancer is foreign because the mutations just don't arise.
- [46:49]
B
But they are there.
- [46:50]
C
But they're there. Right. You just need to find the right ones. And then what we found was that these mutations were in fact individual to each person's cancer. So the instructions have to be different for each person, are different for each person's cancer. So this would require individualized vaccines. And this is where MRNA comes in. Because this is in 2017, well before the pandemic, we felt that the best technology for this rapid custom cancer vaccination in the clinic was to use rna.
- [47:21]
B
Yes, exactly. And M stands for messenger for people who don't know. So the idea among cancer doctors was this isn't a vaccine. Doesn't gonna work for this cancer, even if it worked for an infection, that this. This couldn't happen because there's no message to send, essentially.
- [47:39]
C
Right?
- [47:39]
B
Correct.
- [47:40]
C
Cancer vaccines are hard as it is. They haven't even worked for cancers where we know the immune system can recognize it really well, such as, for example, melanoma or lung. So why would it even work in pancreas cancer when it is the toughest of all cancers? We don't actually think the immune system can actually even see it as foreign. So this would be the last place that this is going to work.
- [48:06]
B
So explain for people who don't understand how a cancer vaccine is different from, say, a flu vaccine which is infectious, or an HPV vaccine to prevent cervical cancer, Explain the difference of what's happening there.
- [48:18]
C
I think this is a important point because we use the term vaccines for both infectious disease vaccines and cancer vaccines. But there are some important differences. Number one, for infectious disease vaccines for influenza, flu, Covid, these vaccines are given to patients who are healthy. So it is given to healthy people to prevent future disease. For cancer, nearly all cancer vaccines are given to patients who have cancer as a therapy versus a. Versus prophylactic.
- [48:59]
B
Prophylactic. So could you. Could you use it as a prophylactic? Could you put it into people so they. So the cancer doesn't develop ever?
- [49:07]
C
This would be the holy grail in the future that we're all sort of trying to work towards. We think to get there, we need to understand how to do it when.
- [49:17]
B
When you're going in, when you already have it.
- [49:19]
C
Right, right. And this will give us instructions on how to perhaps take it to prophylaxis.
- [49:23]
B
So could you explain the difference for people to understand how this vaccine works and specifically how MRNA technology comes into play?
- [49:31]
C
So what we had learned from our work is that these vaccines for pancreas cancer, we hypothesized, we thought that you would have to make them individually for each patient's tumor, because the instructions were individually in each patient's tumor. So the way in this clinical trial that we ran in pancreas cancer here at Sloan Kettering in New York is that we perform surgery to remove the tumors, and then within 72 hours, we ship the tumors to our colleagues in Germany, and they do the genetic analysis of the tumor. They find the instructions, and then they encode the instructions into messenger RNA or MRNA and make an individualized or bespoke vaccine that's specific to this person, specific for this individual.
- [50:23]
B
And it has to be. There aren't commonalities between These correct? Is that at this moment?
- [50:29]
C
Yes. Well, in this trial we tested it from a personalized fashion. There are other clinical trials that are also testing. The question that you're asking, meaning do you have to do this individualization. Right. We don't actually know the answer whether one is better than the other, but we will find out in upcoming years.
- [50:50]
B
So talk about the other tech that's being used and for example, what role AI is playing or anything else. What is the tech that is used in MRNA technology?
- [51:02]
C
So you were asking earlier about why, why is there so much excitement about mRNA? And I think one of one reason is, number one, when you have to do an individualized vaccine, you need a platform that can go from sequence to drug really fast. We're talking weeks. The MRNA technology allows us to go very, very quickly. So that's one advantage. And this is a contrast from other technologies that we have used in the past, which took much longer.
- [51:37]
B
But you have to cook essentially.
- [51:39]
C
Yeah. The second thing is that we think the technology is very potent, meaning not only can it make a fast vaccine, it makes a very, very strong immune response against cancers which have been historically considered really tough to make an immune response against, like pancreas cancer. So in our trial, what we found is that when we give these vaccines, it makes an enormous amount of T cells in the peripheral blood. And not only can you make a really strong immune response, cells last for, we think, perhaps even years to decades in patients.
- [52:23]
B
And you use AI, how? In this.
- [52:25]
C
Right. So the of the front end of it was where we do the genetic analysis and we find the red flags and we decide which red flags have to go into the instructions. This science is not fully matured yet. And this is where AI comes in, we think, because we think there are patterns of the best instructions for different cancer types, perhaps. So by learning more and more of what these patterns look like, we can then sort of go to an automated best case selection of the targets, hear the instructions and be able to make.
- [53:01]
B
And they would see things you wouldn't see as quickly, essentially. If at all. That's right, if at all. As you said, you've been running a trial of a small patient group, just 16 people, of an MRNA based pancreatic cancer vaccine that's showing promise. Back in April, Memorial Sloan Kettering announced that eight patients whose immune system responded to the vaccine, seven, nearly 90%, were still alive four to six years after the surgery. Talk about the significance of that. Because before there'd be an outlier, right? This is a lot of outliers all of a sudden. And what happens next in testing the treatment after that.
- [53:38]
C
It was what we call a phase 1 clinical trial, where the purpose of the trial is really to understand whether the drug is safe, whether you can make it in time and deliver it to patients, and whether it does what we think it should do, which is make a good immune response. And it wasn't really specifically designed to understand whether the drug can make people live longer, because this requires what we call a randomized trial where some patients get the drug, some patients don't get the drug. However, in this trial, what we found was a sort of a stark dichotomy. Namely, if you made an immune response, most patients lived, and if you didn't make an immune response, most patients died. And it was perhaps very close to black and white as you might get in a trial. So I think that, like you said, was a bit striking to us in a very unexpected way, that perhaps these vaccines could be quite important in preventing pancreas cancers from coming back after surgery.
- [54:51]
B
Does this have implications of other cancers and is it if you can solve this one? I know every cancer is different. I'm aware of that. But why is this the cancer you wanted to make it to show the most vexing cancer of the treatment cancer, or does it have implications for the others?
- [55:08]
C
So our idea here was if we could crack the toughest here, perhaps this would provide a blueprint to crack the rest. And we're excited now to see that there's lots of clinical trials now using these concepts or testing these concepts. Breast cancer or many other cancer types. Right.
- [55:27]
B
You explain MRNA piece of this. But the technology itself is under attack. Health and Human Services Secretary RFK Jr. Recently pulled back a half a billion dollars in funding for MRNA vaccines. Talk a little bit about how well you're doing this groundbreaking technology which everyone's very excited about. You're operating in an environment that's been hostile to it. Now, it may not last. Look, these things have happened before, but it's not the greatest time to have these incredible breakthroughs at a time when the hostility towards even a basic flu vaccine is at an all time high.
- [56:02]
C
Yeah, I mean, I think the current moment that we are in, particularly for cancer vaccines, is a really, really exciting moment because perhaps we now know, after many decades of study, how to make an effective cancer vaccine for one of the toughest of cancers, pancreas cancer. And what that unlocks is, well, what other cancers could the technology be used more?
- [56:32]
B
Exactly.
- [56:33]
C
And for us to go there, we need broad scale Testing of these drugs in patients with more deadly cancers like pancreas cancer. And it's been exciting to see that. Actually the national cancer institute has launched a national cancer vaccine plan. This is a public private partnership to be able to develop a national cancer vaccine roadmap to allow and enable this testing.
- [57:03]
B
But what has happened on the government level, has this had an impact? A lot of MRNA researchers I talked to said it set us back decades in terms of different things. They were working. I was up at Johns Hopkins, I was at Penn, and all of them have the same. This government attack on MRNA technology has to stop at this, at this point. Because you're at the cusp of these breakthroughs, right?
- [57:28]
C
I mean, I think you're bringing up the point that, well, we want the government to be able to actually invest in it. Invest in it so that we can expand into broader testing. And it's been exciting to see that they are investing in it.
- [57:42]
B
Now, what would you like from the government more to do this? What would you. Or from private companies? Because other countries are also working on these things. China in particular, for example.
- [57:54]
C
It's essentially what we were just talking about, like what do we actually need at this moment in time. And I think what we really need is broad scale testing in clinical trials across the country to answer the questions of, well, what other cancers could be vaccine suited. These would all require, we think, not just the federal government, but we also need really cross sector support from all of the sectors, Public, private industry, philanthropy, academia, federal government. This is a moment where everyone has to come together to be able to try to really invest and tackle these questions as a collective team.
- [58:38]
B
So final question for you. You said once in an interview that you like solving problems that have a definitive answer. Math problems, physics problems. When you think about that, you're picking something that people did not think had a definitive answer. And you firmly believe that this is
- [58:53]
C
a solvable problem for pancreas cancer union. I think it is solvable, yes. And in fact, I think perhaps, maybe even in our lifetime we're going to see major solutions for this cancer, which would be a huge change. Because over the past five decades plus, we have not really seen much change. But change is, I think, upon us now.
- [59:20]
B
Absolutely. I'm going to ask you one actual final follow up question. 100 years from now, what is the treatment from you? Just, you're not going to be here, I'm not going to be here. Just be creative.
- [59:31]
C
Right now, one in three Americans will have cancer in their lifetime. And so it is a huge, huge national and global health crisis. But 100 years from now, I hope we will be in a society where their cancer does not exist.
- [59:47]
B
Yeah. Yeah, well, we'll see. We'll see about that. But that would be a great way to, to end it. Anyway, thank you so much, Vinod. I really appreciate it. And congratulations on these, these breakthroughs you've had. They're, they are exciting people. Very much so, which is great.
- [60:01]
C
Thank you, Kara, for having me.
- [60:03]
A
Foreign.
- [60:11]
B
Hunt Emma McNamara and Dave Shaw Nishat Kirwa is Vox Media's executive producer of podcasts. Our engineers are Jim Mackle and Steve Bone and our theme music is by Trackademics. If you're already following the show, you're about to achieve longevity escape velocity. If not, you're still stuck with the rest of us mortals. Go. Wherever you listen to podcasts, search for on with Kara Swisher and hit follow. Thanks for listening to on with Kara Swisher from Podium Media, New York Magazine, the Vox Media Podcast Network, and us. We'll be back on Monday. Thanks to Kohler Health for their support. We focus a lot on what we put in our bodies, but not nearly as much on what comes comes out. You get my point. Kohler Health is changing that with its Dakota Tracker, which turns your everyday bathroom habits into meaningful insights about your gut health, hydration, and even presence of blood without any manual logging. Over time, Kohler Health helps you build your baseline so you know what's normal for you and you can take action when something changes. Learn more@kohlerhealth.com and use the code CARA one year for a free annual membership on the Kohler Health app. When you purchase Dakota.