Longer Life: What Does Science Say?

22:54So 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, Sachinanda 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 to 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 people have sort of absolutist versions of everything.

23:41If 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'd be curious to hear what has been your difficulty of trying this, for example.

23:55Kara Swisher:Probably the presence of food, the availability is the problem for most people. I agree. It just, you know, my approach has been to do this progressively. If you're eating for 16 hours, decrease it to 14 for a month and then decrease it to 12 for a month, then decrease it to 10. And eventually, soon enough, 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.

24:40You know, think about Lent. Think about, you know, many. Yes, they do. My grandmother. Yeah, exactly. So this is not something that we even, that we've really eaten. No, not at all.

24:48Kara Swisher:No, no. My son's doing the no eating after dark, although I'm like, summer. What do you do in the summer? Yes. 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 clear, 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 were covering for years.

25:25Kara Swisher:a lot of the tech billionaires who are also involved in AI and various things like that. As you said, you've been called the grumpy because you're so conservative with this stuff. I'd love you 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 the wider population, which is where you really want to see longevity increases. I'm really glad you're bringing this up because, first, we do receive money from billionaires.

26:06And I have nothing against the idea. I actually find it admirable that they give their money. And, you know, there's a number of people, especially in Europe, have conflated the 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, giving money to longevity research.

26:48No, not at all. 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.

26:59Kara Swisher:Rich people, right, exactly. And this is compounded by the fact that many of the longevity clinics that are opening today are actually catering to an 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. And 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 and longer now.

27:44And 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 healthspan.

27:53Kara Swisher:My last question is a bit of a curveball 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. 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 the 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.

28:35So it's amateur racing. And when the time comes to really 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 motivation for staying in shape. And frankly, the community of people that I race with is incredible. So it meets actually many of the ingredients that I tell people. So physical sport, community, cognition, excitement.

29:25So 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 fun. Where is that? That's at Sonoma Raceway. Oh, wow. This whole weekend, the Velocity Invitational is an amazing event. It's the largest sort of vintage racing event.

29:47Kara Swisher:That's a great racetrack up there in Sonoma. Absolutely. 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. Thank you, Cara.

30:02Kara Swisher:We'll be back in a minute.

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31:27Kara Swisher: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.

32:02Kara Swisher: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 Balachandran. He runs the Olean 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.

32:38Kara Swisher:Vinod, thank you for coming on on. Thanks for having me, Cara. 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. 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.

33:18And part of the reason for this is because the current treatments that we have for this disease, which include surgery, chemotherapy, and radiation are 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...

34:04Because as you said, the treatments were so last generation, essentially. 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.

34:17Kara Swisher:So explain why pancreatic and lung cancer also, and 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. Explain why those are so vexing. 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.

35:06So because of this, the mortality rate from pancreatic cancer now at five years still ranges on the order of approximately 90%.

35:17Kara Swisher:Yeah. So only about 10 % of patients really survive long-term. wrong 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 want to get into the science of it, but first provide some context for people who don't know how vaccines were targeted to do this. Vaccines, in short, perhaps you could describe them as the most impactful medicine in human history to improve health.

35:57And the way they work is by teaching the body to recognize what is for it. 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 it already wants to do that.

36:57Cancer is derived 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.

37:34Kara Swisher:Right. 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 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.

38:23However, 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.

39:03Kara Swisher:What are the drawbacks to most of these? Well, I mean, I think the central drawback here is we want drugs that work better. Yeah. They don't work. Yeah, they don't work. Yeah. We want things that work a lot better than this. We want to 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 effect cure, meaning although about 90 % of pancreatic cancer patients die with current treatments.

39:51Not 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? 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...

40:30Kara Swisher:You can facilitate it via vaccines. How could we teach other patients' immune system to recognize their cancer, just like it's happening in these rare survivors? And cancer researchers had traditionally not looked at it this way, correct? 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. This is a series about longevity, so it's also a series about aging itself.

41:07Kara Swisher:And 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? 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 incidence of pancreas cancer in the United States is also slowly increasing. Yes, it is. As is low cancer. 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...

41:59Kara Swisher:As the age range wafts down. That's right, because the population is going to continue to... Is there a reason why, or is there something that scientists are looking at as why that's the case? Yeah, the etiology, like why does it happen? Why do patients get pancreas cancer? And why is it increasing? Why is it increasing? Yeah, it's not clear. There's not one sort of magic bullet I think that would explain this. We'll be back in a minute.

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43:53Kara Swisher: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? Yeah, I think this goes back to one of the first questions that you asked about being a physician scientist and how does that really help? I think 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.

44:32And 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.

45:19So these patients' tumors, they have about 12 times more T cells that show up in the tumor compared to other patients.

45:28Kara Swisher:Looking to attack the cancer. Exactly. So this led us to this question, oh, these T cells are seeing something. What are they seeing? because if we could find out how they are able to potentially recognize these patients' cancers foreign, maybe we can teach other patients' T cells to recognize their cancers in a manner very similar. So what's the chief challenges in using vaccines to attack cancer cells? 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.

46:06Yeah, the instructions, the code. So here, what we found was in pancreas cancer, in fact, it is these red flags, these codes, 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 no instructions there. So the immune system would not really be able to see pancreas cancer as foreign because the mutations don't arise.

46:48Kara Swisher:But they are there. 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 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. Yes, exactly. And mRNA, M stands for messenger, for people who don't know. So the idea among cancer doctors was, a vaccine isn't going to work for this cancer, even if it worked for an infection, that this couldn't happen because there's no message to send, essentially.

47:39Right. Correct. 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? Right. We don't actually think the immune system can actually even see it as foreign. Right. Exactly. This would be the last place that this is going to work.

48:05Kara Swisher: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. I think this is an 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.

48:55Versus a? Versus prevention. prophylactic.

48:59Kara Swisher:So could you use it as a prophylactic? Could you put it into people so the cancer doesn't develop ever? 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 you're going in with sick people. When you already have it. Right. And this will give us instructions on how to perhaps take it to prophylactic. So could you explain the difference for people to understand how this vaccine works and specifically how mRNA technology comes into play. 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 included individually in each patient's tumor.

49:49So 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 this spoke vaccine. That's specific to this person. Specific for this individual. And it has to be,

50:24Kara Swisher:there aren't commonalities between these, correct? Is that at this moment? 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. 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? So you were asking earlier about why is there so much excitement about mRNA?

51:08And I think 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.

51:36Kara Swisher:But you have to cook, essentially. 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, the cells last for, we think, perhaps even years to decades in patients. And you use AI how in this?

52:24Right. So 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 the precise vaccines.

53:01Kara Swisher: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?

53:37It was what we call a phase one 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. 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.

54:25And 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.

54:51Kara Swisher:Does this have implications of other cancers? And 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. 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. For breast cancer or colon cancers. Right. You explain mRNA piece of this, but the technology itself is under attack.

55:31Kara Swisher: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. 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 or one of the toughest of cancers, pancreas cancer.

56:24And what that unlocks is, well, what other cancers could the technology be used for. 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.

57:03Kara Swisher: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 on. 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 point because you're at the cusp of these breakthroughs. Right. 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 exciting to see that they are investing in it now.

57:42Kara Swisher: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. Yeah. It's essentially what we were just talking about. It's 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.

58:29This 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.

58:37Kara Swisher: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 a solvable problem. For pancreas cancer, you do. 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.

59:20Kara Swisher:Absolutely. I'm going to ask you one actual final question. A hundred years from now, what is the treatment? You're not going to be here. I'm not going to be here. Just be creative. 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 a hundred years from now, I hope we will be in a society where their cancer does not exist. Yeah. Yeah. Well, we'll see. We'll see about that. But that would be a great way to end it. Anyway, thank you so much, Vinod. I really appreciate it. And congratulations on these breakthroughs you've had.

59:57Kara Swisher:They are exciting people, very much so, which is great. Thank you, Cara, for having me.

1:00:09Kara Swisher:today's show was produced by tracy hunt emma mcnamara and dave shaw nishat kurwa 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 stuck with the rest of us mortals go wherever you listen a podcast search for On with Carol Swisher and hit follow. Thanks for listening to On with Carol Swisher from Podium Media, New York Magazine, the Vox Media Podcast Network, and us. We'll be back on Monday.

1:00:48Kara Swisher: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 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 at KohlerHealth.com and use the code CARA1YEAR for a free annual membership on the Kohler Health app when you purchase Dakota.