Paul Jaminet on the Perfect Health Diet, Carbs, and Cancer Research

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Katie: Hello, and welcome to “The Wellness Mama Podcast.” I’m Katie from wellnessmama.com and wellnesse.com. That’s wellness with an E on the end. It’s my completely non-toxic personal care line. This episode is with someone I’m very excited to talk to. I’m here with Paul Jaminet, and I cannot believe honestly that I have not had him on this podcast up until now. He was a very strong early influence of mine with his work around the “Perfect Health Diet” that we talk about today. He was also largely influential to people like Chris Kresser and Mark Sisson and has been in the nutrition and health world for many, many years. And we talk a lot about that, but we also go deep on his current project with his wife, Shou-Ching, that has really promising potential for cancer. And he explains just how that is and what makes it different in this episode.

But if you are not familiar with Paul, I would guess many of you are, he’s currently the founder and president of Angiex, which is the biopharmaceutical company that is developing these novel therapies for solid cancers. And the results so far are absolutely astounding. It’s built on discoveries made by his wife and co-founder, Shou-Ching, and they have a new class of drug we talk about today. I know that normally I am not the biggest proponent of pharmaceuticals. And I actually invested in this company because I think it’s potential and how it works in such a less toxic way. And works well in combination with natural therapies is really, really important. Again, something that we all know is an increasing problem.

Paul was MIT-educated in both physics and philosophy, went on to get a doctorate PhD in physics. He was an astrophysicist at Harvard Smithsonian Center for Astrophysics before becoming an entrepreneur and getting into the natural health world after some of his own health problems. And he’s combined his expertise in entrepreneurship and natural health with his wife’s research in molecular biology. And that’s what’s spearheading this new company. So this is a novel treatment that I hope you will never need if you’re listening to this or that none of your loved ones will ever need. But statistically, many of us at some point in our lives or our loved ones may encounter cancer. So I wanted to get him on today to talk about a very wide-ranging number of topics from diet and natural health, circadian biology, and then transitioning into these novel cancer treatments. And without further ado, let’s jump into this fascinating episode.

Katie: Paul, welcome to the podcast.

Paul: Oh, hi, Katie. It’s great to be with you.

Katie: It’s so exciting to talk to you. I have admired your work for so many years, and actually can’t believe we haven’t gotten to have this conversation before now. But we’re getting close to 500 episodes and I love that we now have such a big community here to share you with today. You are an expert in so many different topics. I’m going to try to keep it to just a couple of those today. A lot of listeners, I would guess, are already familiar with you. But for those who aren’t, I first found out about you through your work with “The Perfect Health Diet.” So I’d love to start there.

And specifically, I’ve heard you say that natural approaches to health can obviously have a big impact. I’ve talked about that here. And that most people can add as much as 20 years to their lifespan through basically, diet and lifestyle approaches. I know this is kind of the basis of the Perfect Health Diet. So, if you don’t mind, let’s start there, and just kind of give us an overview of what “The Perfect Health Diet” is.

Paul: Yeah, yeah. So, it’s basically an implement of Paleo. So, Paleo, I would just say is the approach to eating where you eat natural whole foods. And, you know, so, the idea is things that could have been hunted and gathered are, you know, going to be our natural diet. And things that get constructed in chemistry laboratories and assembled out of, you know, different purified molecules are not likely to be nourishing.

You know, and so when I first came across that concept about 2003, in the writings of Art De Vany, it was very persuasive to me. And I was interested in solving some personal health problems at the time, so I gave it a try. And, now, Art De Vany’s diet was very low carb, and I ran into some problems on it. So, I ran into some nutritional deficiencies, and so I thought, “Well, it’s not good enough just to eat natural whole foods. You need a balanced diet, where you’re getting all the nutrients you need. And it would be a good service to the world to figure out, you know, exactly how much do you need of each nutrient, and what would be the right Paleo diet, the right natural whole foods diet that gives you everything you need.” And I didn’t quite realize at the time it would take me seven years to figure that out. But I started working on it, and that became “The Perfect Health Diet.”

So, the reason for the name is just describing the aspiration we think you should have, that there’s no one magic bullet for health. You fix one thing, you know, you just go low carb and your health will be fixed. No, there are many, many things you need to optimize simultaneously in order to really fix your health or optimize your health. And so, in order to do that, you have to be aiming for perfection. You have to be aiming high in order to achieve, you know, very good. Which is, you know, what most of us want.

You know, so once I realized that you had to optimize many, many things and, you know, started researching and putting them all together, and the more I learned as I fixed my own health, then I started thinking, “Oh, I should be sharing this with friends and relatives and helping them,” and started doing that. And I kept learning, and then I thought, “Oh, I should start a blog.” And then, “Oh, we’ve learned enough. We should really share this, write a book, and then start a health retreat.” So I just kept kind of growing. And, you know, we were never quite as big as, you know, say, Mark Sisson or yourself now. But, you know, I’d say we were one of the most influential blogs in that period in Paleo.

And so, of course, I more or less suspended the blog, and the retreat, and other things in 2015, when my wife and I started a company to create therapy for cancer, called Angiex. And so, that’s what I’ve been working on the last six years. But Perfect Health Diet, it’s going to come back at some point, and as well, our retreats and other things, and lifestyle advice. You know, and we’ll seek to integrate it with medicine, to help people figure out how can you use natural approaches plus medicine and healthcare to really get the best life that you can.

You know, we’re very committed to it, and very excited by what it achieved. And we had our Perfect Health retreat, it was kind of structured like a clinical trial, where you come to our retreat and we control everything for a week. You know, we control your food, your schedule, how you exercise, how you live. And everybody who came had significant health improvements. And we kept, you know, learning through the retreat how to improve things. And, ultimately, our goal would be to use that to, you know, ultimately do real trials of natural health interventions, and prove what works and prove what’s optimal.

So, you know, I think it was a very fulfilling thing for both my wife and I, so, my wife Shou-Ching was a partner in this, and was very fulfilling to help people improve their health, and to keep learning, and to improve our own health. So, you know, it was exciting and fun. And, you know, we look forward to getting back to it.

Katie: I know you’ve definitely had an influence on me. And you mentioned Mark Sisson. I know you’ve influenced him as well, from conversations I had with him, and people like Chris Kresser, I feel like you were very influential, especially in the early movement, of understanding that. And I loved how early on, you acknowledged that personalization component. Like you said, there wasn’t a prescriptive exact one-size-fits-all, that you might find a piece that can be helpful in solving one thing, but that the true answers lie in that discovering your own perfect health diet. And you were one of the first voices I came across that really talked about that and integrated a lot of these lifestyle factors that are so much more broadly talked about now, thankfully.

And just to note, I think it’s really fascinating, personally, that you are educated in both physics and philosophy, and even have a PhD in astrophysics, which has been a fun research topic for me recently. But that to say, just, you are extremely well-educated and have a high proficiency in research. And I love that you applied this to nutrition as well. I think a lot of us in this world got here because of personal health struggles, and if you’re comfortable sharing, can you just kind of walk us through what your health journey was?

Paul: Yeah. So, well, I had what turned out to be chronic infections. And still a little mysterious exactly what they were. But, you know, doctors couldn’t diagnose them and the treatments they gave me kept, you know, kind of backfiring, making things worse. You know, so, for example, in my 20s, you know, I had chronic bad acne and rosacea. And a doctor prescribed, of course, Minocycline for it, an antibiotic, that I took for a year. And that just made my health much, much worse.

And, you know, so, I was a runner. I could run, you know, I had a pretty good clip when I started the Minocycline, and my running just kept getting slower and slower. And I kept feeling worse and worse over the course of the year, and, you know, my rosacea got worse. And, you know, it seems stupid now that I stuck with the antibiotics for a whole year. But, you know, when you don’t know what to do, you know, you tend to follow your doctor’s advice or…

So, anyway, following that course of antibiotics, I just knew things weren’t right. You know, I didn’t feel good. It was not only that I couldn’t exercise well, my running was slow, you know, physically, I didn’t feel good. But also, I started noticing cognitive effects and memory loss. My memory wasn’t working. But maybe one of the most significant ones was in terms of mood. You know, I had always been happy. And then over the course of the year of those antibiotics, I stopped being happy. I became internally irritable. You know, all the time, I was just incapable of feeling happiness. And I knew that, you know, this wasn’t natural, this wasn’t me, and this wasn’t right, so I didn’t express it. And in fact, when I told my wife later that I felt irritable all the time, she was surprised, because I wasn’t expressing it. You know, because I knew it would be inappropriate to do it.

But that gave me a little bit of understanding of some of the mental health issues that, you know, a lot of these health issues can really affect cognition and mood. And it can be very chronic, and the doctors can be completely ignorant. And, you know, nothing may show up in standard blood tests. And, you know, so, you know, I would periodically say, “Oh, you know, I should try something to fix this.” And, you know, I tried various things, you know, but nothing ever worked. Nothing ever seemed to have an impact until I tried the Paleo diet. And that had a big impact, both good and bad, so…

But it was the first thing that had an impact. So, you know, some things got better, some things got worse. But at least I had found, you know, the right lever to impact my health. And so I said, “All right, now I’m on the right track, and now I just have to improve this and, you know, figure out how to get the good without the bad.” And, you know, so that was a great breakthrough for me, and had a big influence on my life. And, you know, so I’m grateful to Art De Vany, especially, for introducing me to this.

Katie: And I feel like your research and your work is so timely right now, even though I know you mentioned this was something that you started many, many years ago. There’s so much debate right now about low carb, and keto, and carnivore, and there’s a lot of popularity of those going on. And I feel like you were one of the early voices that was so good at illuminating, “Yes, Paleo, but, it’s not this quite so black and white as we think it is.” And I know that you are a big proponent of white rice, for instance, and whereas some traditional Paleo groups would exclude white rice. But I’ve read some of your work talking about the importance of carbohydrates, and I think with all the women listening, this is a really important piece to touch on. So, if you don’t mind kind of explain how you came to that, and why you feel that piece is important.

Paul: Yeah. So, well, we came to our ideas by many directions. So, actually, if you read our book, it’s written as more of a scientific book, more than just, like, a popular diet book, where we try to walk people through our own scientific reasoning where we tried to figure things out. So, the first section of the book has some, you know, like, clues, you know, as to what’s the optimal diet. So, for instance, one of the clues is the composition of breast milk, you know, which must be the optimal diet for infants. And, you know, that doesn’t guarantee that the same thing would be the optimal diet for adults, but it certainly gives us a lot of clues. And if you have a theory about the optimal diet for a human being which doesn’t match up with breast milk for an infant, you know, then you have a bad theory.

So, you know, just things like that. And, you know, so we had a bunch of… You know, our first section, I think, had half a dozen different evolutionary thoughts, including, you know, breast milk must be optimized by evolution for infant health. And, you know, similar, you know, “How can we reason from evolution?” So that was one of the, you know, core Paleo ideas, “How can we reason from evolution to the optimal diet?”

And then, the other major angle was, “We want to optimize nutrition.” There’s all this evidence about, you know, what nutrients do cells need, what nutrients do animals need, do humans need, you know, very large literature, that we tried to synthesize to find the optimal amount of each nutrient. And there’s, like, 16 known nutrients that are essential for humans. And if you estimate the optimal amount of each one, and then find a mix of natural whole foods that gives you that optimum, you know, then you should have a really good-quality diet. And it’s kind of hard to get to that optimum if you’re a carnivore, or if you’re eating a tremendous amount of oil in order to assure that you’re in ketosis all the time. It’s actually much easier if you’re…

And, you know, if you think of our evolutionary environment, our paleolithic ancestors, they would’ve had a hard time getting, you know, pure oil in enough quantities or, you know, meat would’ve been intermittent. And, you know, so breast milk is about 40% carbohydrate. You know, so it’s definitely… You know, I’m not saying that infants should not have any carbohydrate. And our cells do need carbohydrate. You know, most of the proteins in our body are glycosylated, so they have glucose on them. All of the fats in our body have a glycogen backbone that holds the fatty acids together. You know, so there’s actually quite a bit of carbohydrate in the body. And we need it in order to maintain our tissues.

You know, so, just from, kind of, first principles, it’s not likely to be the right thing to not eat any carbohydrate. Actually, I think it’s pretty good to… You know, your body is constantly consuming these macronutrients. You know, its destroying fats, carbohydrates, and protein. And it’s probably a pretty good idea to eat something similar to what the body’s consuming, and that’s going to put the least stress on the body. You know, whereas if you eat in a different way, then your body has to try to make up for it by converting one macronutrient into another. You know, like maybe convert protein to glucose or something like that. And that may not always achieve optimal results.

So, you know, that was kind of the strategy we were led to. And, you know, so our basic paradigm is, “You should try to eat in a way that delivers to your body all the nutrients that it wants to consume, and just match those,” and that’s kind of our prejudice. And then maybe in some health conditions, you might want to vary from that, like, toward ketosis in certain conditions, where that may be therapeutic. But understand that that’s kind of a therapeutic intervention. It’s kind of similar to putting a drug into your body, rather than, you know, just trying to nourish it.

Katie: And is there a thyroid-specific component to carbohydrate consumption that you can go into? I know there’s been talk recently of too low carb for too long seems to be potentially harmful or at least stressful to the thyroid at some point.

Paul: Yeah. I think there’s definitely potential for that, by multiple channels. So, you know, certainly, thyroid hormone regulates consumption of glucose. You know, so if you’re really minimizing glucose, then you’re pushing that thyroid needle, you know, away from center to, like, you’re pegging it at one end, to really minimize glucose usage and maximize the conversion of protein to glucose. And so that’s kind of… You know, it’s not the state… It’s something that in our ancestral environment, you know, people would get into that occasionally. You know, but I don’t think they were spending all their time there. So we’re not necessarily well-adapted to having the thyroid, you know, at that, you know, kind of pegged at that extreme setting.

And then, another aspect of this is the thyroid gland, that’s actually very sensitive. It’s easily injured. And that’s because the iodine and, you know, thyroid hormone and the enzymes that carry it, they’re very energetic. And, you know, so one of the first places you’ll get oxidative stress or inflammatory injuries is often the thyroid gland. And if you’re very low carb, you may not be maintaining gut integrity that well, and you’ll tend to get, you know, things coming into your body from the gut, and you’ll tend to get inflammation. And, usually, gut issues, one of the first places you’ll see them is hypothyroidism. You’ll start to get injuries in the thyroid, inflammatory injuries. And, you know, so, and the gut definitely needs carbohydrate in order to maintain its barrier integrity and generate the mucus that protects the cells from everything that’s going on in the gut. And, yeah. So, I think, you know, it is risky for the thyroid to be too low-carb, especially for a very long time.

Katie: And you also mentioned that low carb or ketosis is a possible interventional approach, but thinking of it more in, like, a therapeutic sense, versus a diet that one would follow long term. It seems like to me, if we look at the evolutionary idea of food consumption, there seemed to be an element of cycling, that not all foods were available at all times, and we would’ve eaten, obviously, what we had access to at that point. Do you find that that’s a helpful concept to understand? And if so, how do you kind of categorize that cycling?

Paul: Yeah. I guess I’d take kind of a middle ground in that I think most of our evolution probably occurred in the tropics, where the environment is pretty stable over the course of the year, so there wasn’t, you know, maybe, a huge amount of cycling. There weren’t a lot of people living at northern latitudes ancestrally, where you had the very severe winters. Although, that was certainly, you know, I think, significant for our evolution. And there was definitely gene flow from Neanderthals and other ancestors of ours, who were living at northern latitudes, and subject to a lot of cyclical variation. And there’s been recent… You know, of course, a lot of people living at northern latitudes for the last 10,000 years, and experiencing cyclicality. But, you know, definitely, there would be things like periods of poor food availability. So, you know, periods of involuntary fasting and then periods of abundance, you know, like at harvest time. And, you know, so, definitely, there was variability.

To me, I think, you know, one of the ways we can use that is for diagnosis. It’s, you know, how you respond to a ketogenic diet can be very informative about what’s going on in your body. So, for some people, a ketogenic diet will make your health problems worse. For some, they’ll make them better. And, kind of, you know, if you do everything perfectly, then, you know, you may not get a lot of information about your health conditions. You know, they’ll be kind of minimized. But if you go off and do something extreme, then, you know, you may see very big effects. And, you know, so I think that was how I evolved to using the ketogenic diet, after experience with the guests at our health retreat and helping a lot of people by email over the years, that its greatest value was in diagnosis. And, you know, if they tried it and you saw what happened, then that would often give you clues about what was going on. But then you could find other means to actually fix the issues. But it was very educational.

And, you know, so, the ketogenic diet, you know, it can have a lot of effects. It can be anti-inflammatory, it can affect cognition in certain ways. It can also be pro-inflammatory. It can, you know, if you have certain gut dysbiosis, it can carry, you know, fragments of the microbes into your body and cause inflammation. You know, so you can get a lot of information about what’s going on in someone by how they respond to it.

Katie: That makes sense. And I feel like this is going to be a segue into, I want to make sure we talk about the cancer side as well. But you’ve also written in the past quite a bit about circadian biology and its importance as part of a lifestyle approach. And I think there is, thankfully, more information about this available now. But I just got back from a biohacking event, and it really struck me how funny it was that there was all this really expensive equipment, which I think, there can be a time and a place for those things, certainly. But somebody posted a great graphic that I really resonated with that said, you know, “The best nootropic sleep, the best antidepressant sleep, the best biohack sleep.” Like, and I think we sometimes can ignore the obvious in pursuit of these more fascinating biohacking tools.

But you were, I feel like, one of the first sources I came across that really broke down the importance of circadian biology for health. And I’ve now come to believe very much that that’s one of the most important, if not the most important factor, that if you have that part off, you’re going to have struggles across the board. But can you just kind of give some overview of the importance of circadian biology, and some ways we can optimize that?

Paul: Yeah, yeah. So, you know, like I said, the motivation for our approach to health was that, you know, we believe you need to aim for perfection, you need to try to fix everything. You know, you don’t know what the key factors and the key causes are that are causing your health problems, but everything you can fix makes an improvement, and it helps clarify the other things, and makes it easier to diagnose them. And so, lifestyle, you know, we know that has an impact. We know exercise has an impact, sleep has an impact. And so, after I felt like we’d optimized diet pretty well, the next logical thing was to think about how to optimize lifestyle. And one of the things I noticed was, you know, the lifestyle interventions that improve health, they’re all impacting circadian zeitgebers, the time-givers to our circadian rhythm systems.

And then, the more I looked into the literatures, yeah, you know, the amount of this intervention that is good for you is the amount that entrains your circadian rhythms. Like the amount of exercise that’s good for you is just the amount, you know, the classic 10,000 steps, or, you know, 20, 30 minutes of moderate intensity exercise, like jogging. You know, that’s what you need to entrain your circadian rhythms to tell your body it’s daytime. And once you’ve achieved that, you know, you’ve achieved all the health benefits, and you don’t really get any more health benefits from doing more exercise that day. And of course, the next day, then you’ll get benefits from more exercise. And, you know, so that was… And also, the timing mattered. You know, so exercise in the evening isn’t beneficial, but exercise in the morning or midday is highly beneficial. You know, so, why is that, unless it’s through circadian rhythms that we’re getting the benefits?

And then from, you know, a kind of a theoretical biology perspective, so, I have a class at our health retreats on why circadian rhythms are so important. So, it’s kind of like, you know, in a computer, your computer chip has a clock, and the clock keeps all of the millions of transistors on the computer chip coordinated. And our bodies need that clock as well, to keep all of our cells and our molecules coordinated. And, you know, if you didn’t have that clock, the analogy I use in our health retreat, if you imagine two movers trying to move a sofa, and the sofa is too heavy. If you don’t have a mover at each end, then it’s going to fall, and, you know, if one mover tried to move it, either he couldn’t move it or he would scratch the floor, because the other end would be dragging. You know, so you need the two movers together, and they have to be moving in the same direction, or else you don’t move it successfully.

And so, our cells are like that. They have to collaborate, they have to work together. But, unlike movers, they can’t talk to each other, you know, they can’t write letters. You know, they need some kind of signal that tells them, “All right, this is the time to lift your side of the sofa, and this is the time to set it down.” And it’s our circadian rhythms which send that signal. And that’s how the various cells of the body stay coordinated. And if we don’t have that coordination, then nothing works right. It’s, the sofa doesn’t get moved.

You know, so that was kind of the key insight. And then I could work back from that and understand the scientific literature better, you know, so then work back from what are the known circadian zeitgebers, and then how do you optimize them, you know, what lifestyle choices should you make to optimize them? And I think we ended up with very powerful lifestyle advice, which had a big impact and was very helpful to our retreat guests.

Katie: And I know there’s so much more that you have available in resources, so I’ll make sure your book and a lot of your work is linked in the show notes for you guys who want to go deeper. I certainly recommend it. And like I said, I think this is a great segue into another area of expertise for you, and the top-of-mind one right now, which is cancer research. And I know there’s been a lot of press around the idea of cancer as a metabolic disease, at least, in part. And, unfortunately, the other side of this equation is when some of these factors are not optimized, we tend to see more diseases like cancer.

I hope this is okay to say, but this is also somewhat of a personal quest for you. I believe you lost your mother to cancer when you were pretty young. But I would love to hear you maybe tell a little bit of that story and what led to this research if you’re comfortable, and also talk about what’s going on at Angiex, because I’m personally so excited for the really cutting-edge research you guys are doing.

Paul: Yeah, yeah. So, yes. So, I did lose my mother to cancer. She was diagnosed with cancer while she was pregnant with me. She was only 22 years old at the time, and she died when I was 10, at age 33. But actually, what led to Angiex was I married my wife Shou-Ching, and she is a molecular biologist and cancer researcher. And actually, on our first date, I had an intuition. I had a thought that this woman can cure cancer, but she needs your help to do it. And for whatever reason, you know, I felt that that was a true thought. And we did end up getting married, and I just kind of followed along with her career, chipping in, helping where I could, and, you know, thinking about, “All right, how is she going to cure cancer, you know, and how is she going to need my help?” And it kind of became clear that at some point, you know, she did make a bunch of breakthroughs. And then at some point, it just couldn’t be progressed any further in academia, and we’d have to start a company. And so that was what I was good at. Kind of my area of expertise, entrepreneurship.

And so, we ended up doing that in 2015. So, we launched Angiex, and it’s been, you know, a tremendous experience. So, we had a good seed investor. Peter Thiel is famous for founding PayPal, being the first investor in Facebook, and has invested in a lot of companies, and was the first investor in Angiex. And we’ve been able to build it successfully, and we have a lead drug which is extremely exciting, which gives curative results in every animal model that we’ve tested it in, in one dose. So, we safely completely eradicate the cancer.

And, you know, so, very exciting drugs. It’s always more difficult to cure human cancers than to cure mouse cancers, but we’re very excited. And so we think it’s going to save many, many lives, and it will be entering the clinic early next year. So, we’ve finalized the drug. It’s being manufactured right now. And so we’re very, very excited about that.

Also starting to think about subsequent drugs. So, if this one doesn’t cure cancer, then how are we going to achieve it? But it’s a very exciting time for Angiex. And it’s been a lot of fun. You know, I think we’ve been blessed as a company with divine assistance. You know, I’ve been in and around startups for more than 25 years. And I would say Angiex has had kind of the smoothest course forward, even though we’re doing maybe one of the most challenging things a business can do, and starting with very few advantages.

You know, so, if you think of… You know, we have three founders. One was an 80-year-old academic who was retiring, and my wife, who was, you know, foreign born, born in Asia, PhD in Australia, you know, not really well-known in the U.S., pursuing research that nobody else was doing, she couldn’t get grants to research it in academia, and, you know, me, a diet book author.

And Shou-Ching had previously done a collaboration with Pfizer for three years, and they had spent $10 million working on it and taking a good look, and then decided to give up. And they gave up largely for internal strategic reasons, which I don’t think made a lot of sense. But, you know, they have their strategic judgments, and they decided to get out of the type of drug that we were working on, which is called an antibody-drug conjugate. And so they just gave up on antibody-drug conjugates entirely. And, you know, so our drug kind of fell by the wayside, which was exciting to me because then, you know, we could start a company and make it.

And, you know, so we did. But, you know, that was kind of a… You know, on the one hand, it was an advantage, so we kind of learned a lot through Pfizer’s work. But it was also, you know, a challenge to the entrepreneur. You know, “If Pfizer spent $10 million looking on this and thought it wasn’t worth carrying forward, why are you, a diet book author, and a relatively junior academic, and an 80-year-old retiree, you know, why are you the people who are going to cure cancer, and prove Pfizer wrong?”

And, you know, so that was where we were starting. But we were able to build Angiex successfully, and now, you know, we have the best people in the world. You know, world…all-star team of, you know, great people in drug development, antibody-drug conjugates, and, you know, the best data anyone has ever seen. So, you know, it’s a tremendously exciting time.

Katie: Well, and certainly, I want to make sure I acknowledge Shou-Ching’s contribution across all of these things we’re talking about, because she also coauthored “Perfect Health Diet” with you. I would say, having a molecular biologist and a Harvard astrophysicist entrepreneur in the same house, I would pay to be a fly on the wall at your dinner-time conversations. But we share a friend and investor in Peter. And I know he believes very, very strongly in this work. I know I read through… I’m also an investor, in full transparency, in Angiex. It’s certainly the first pharmaceutical I’ve ever invested in or even considered investing in, because I was able to kind of delve into the research and ask questions.

For you, I know I’ve read through a lot of the science of it, but I know you’re also very good at explaining. I know this can be very science-y and high-level, but can you kind of walk us through, I know there’s some limitations, but as much as you’re able, the difference and kind of what sets this apart, and what makes it so exciting?

Paul: Yeah. So, we’re special because, A, we have very specific delivery to tumors. And we deliver in two places. We deliver it to the tumor cells and we deliver to the endothelial cells of the tumor blood vessels. And the special aspects of our delivery. First of all, we get delivery directly to the nucleus of all of those cells. And that’s unique. No other drug gets to go to the nucleus. So we have what’s called an antibody-drug conjugate. Our antibodies handle the delivery aspect. They get to the tumor, they get into the vascular endothelial cells and the tumor cells of the tumor, and into the nucleus of those cells, and then they drop off a chemotherapeutic payload. So we’re basically taking, you know, chemotherapy, the same kind of chemotherapies people take systemically, where they go to every cell in your body, and cause lots of sickness along with tackling the tumor, and we just deliver them very specifically to the tumor, into these two cell types. And those are the only cells we let them go to.

And, you know, so, the miraculous thing is we get this nuclear delivery. And we can get tremendous therapeutic margin, you know, meaning safety. The margin between where we’re effective at regressing the tumor and where we’re safe, to the rest of the body, because we’re so selective for the tumor, and because our drugs that do go to the tumor, and they go right to the nucleus, they have very high potency there. And then when they leave, they get excreted. So we’ve designed the chemotherapy so that it won’t go into any other cell of the body. So, all of that antibody delivery selectivity is preserved.

So we get that great delivery, and then we get our great potency. And we didn’t know we would be quite this potent, but we get curative results. And the reason is that the targeting of the vascular endothelium leads to the death of every tumor cell within the tumor, because all of the blood vessels within the tumor are killed, and all the cells lose their blood supply, and they basically starve and die. And the only tumor cells that escape that are those that invade or metastasize, to get away from the tumor. And it turns out that in order to invade or metastasize, tumor cells appear to need to turn on the mechanism that our antibodies exploit. So, our antibodies are like hobos hopping on a freight train, and the freight train is a freight train that supports vascular growth and supports invasion and metastasis. And if you don’t turn on this freight train, then the tumor cell can’t invade or metastasize. But if you do turn it on, then our drug will kill the tumor cell.

And so, what we found in these animal models is we kill every tumor cell that doesn’t invade or metastasize, we kill that through the vascular targeting. And everyone that does, we kill through direct tumor cell killing. And so as long as we can dose our antibodies high enough, we get curative results. And a lot of the work that we did was figuring out what we needed to do to be able to dose our antibodies high enough, and, you know, kind of tuning all the parameters of the drug, and so that we get these curative results in people. And, you know, so, we think we’ve done a really good job, and, you know, we can’t wait to see how it does.

Katie: Can you talk a little bit about kind of the specifics of the initial trials that you guys have seen? I know they’ve just been animal trials to this point. And what you, kind of, expect as a runway? Of course, things can always go in their own direction, but, like, what you guys are expecting to see at this point?

Paul: Yeah. So, what we’ll be doing next year is what’s called the dose escalation. So, the regulators make you start at a low dose, that you know is safe. And then you work your way up to higher doses, and with the goal of reaching efficacy before you reach a limit on safety. And with conventional drugs, typically, you don’t expect that they’ll be efficacious in one dose, you know, so you just raise the dose until it starts becoming unsafe. And then you say, “All right, well, dose just below that. And we’ll give a dose and we’ll let people recover from that dose. Then we’ll give another dose, and another dose, and another dose. And we’ll keep dosing until they can’t take it anymore.” And so that’s how it normally works.

In our case, you know, hopefully, we’ll get curative results in one dose, you know, like we do in animals. So, we’ll see. And so, we’re going to start… You know, we’ll probably treat our first patient potentially April next year. We should start seeing responses. So, we’re not necessarily expecting in the first few patients to get a response, because the dose will be so low. But it’ll be very safe at those doses. And then, you know, we should start seeing responses, you know, maybe around October next year. And so that’ll be very, very exciting. And we should know the ultimate dose that we’ll use to treat patients by the end of the year. You know, so, by December. And then once we know the right dose, you know, and then we can do what’s called an expansion and start treating more patients.

And so that’ll be very, very exciting. And we’ll probably start with pancreatic cancer, triple-negative breast cancer, and then quickly move on to ovarian cancer, liver cancer, lung cancer, stomach, esophageal, head and neck. You know, potentially cervical, renal, other cancers. So, we can treat all solid cancers, essentially. And, you know, we’ll see.

And so the other thing we’re finding is that our drug activates the immune system against cancers very effectively. So, currently, the only curative drugs against cancer are drugs called checkpoint inhibitors which help to activate the immune system against the cancer. And they achieve curative results in about 5% of cancers. And we have the potential to increase that to 100%. So, you know, we basically potentiate checkpoint inhibitors against every cancer. So, it’s exciting. And, you know, so, the combinations, you know, so, if we don’t cure cancer as a monotherapy, we might cure it as a combination with other drugs. So…

Katie: I lost a close family member to pancreatic cancer, so it makes me really excited that you guys are seeing such incredible results in this, and I think another reason I was so excited to be able to invest, and why I never, again, never thought I would invest in a pharmaceutical drug, and was so excited to be able to do so, is knowing your background and Shou-Ching’s background in understanding all the other aspects of health as well. And I would guess a lot of people listening, many of us came into the world of natural health and maybe have a kind of perception of pharmaceutical drugs that’s negative. And I think that’s warranted in many cases. I think we’ve seen that play out in the medical industry quite a bit.

But I am curious to hear your take on more of an integrated approach to cancer, and this is why I was so excited that you guys were the ones advancing this. Maybe kind of high-level, what do you think of natural approaches versus pharmaceutical, and more aptly, what about them together?

Paul: Yeah, they should be integrated. So, definitely, circadian rhythm entrainment. Very, very important for cancer prevention and for activation of immunity against the cancers. And actually, you know, there are some cases of spontaneous remission of cancers. And almost invariably, the things that led to the cancer remitting is if somebody decided, “Oh, I’m going to quit my job and I’m going to go off and hike in the national parks for the rest of my life.” And, you know, so they spent three or four months, you know, hiking in the national park, so they’re living, you know, really, a Paleo lifestyle, and getting a lot of exercise and sunshine. And then they come back and their cancer is gone. And, you know, so, the circadian rhythm entrainment is very, very important.

We’ve had a lot of people on our diet with cancer have undergone chemotherapy and tolerated it extremely well. You know, so, definitely being well-nourished enables you to tolerate toxins and poisons much, much better. You know, you’ll detoxify them, excrete them, and, you know, do a lot better, and very likely live quite a bit longer. You know, so that’s been our experience with our readers who have reported their experiences with cancer.

Our drug, you know, it should work well for everyone. But, you know, I think the better you’re treating the normal parts of your body, you know, the better they’ll be able to deal with any cancer therapy. So, you know, I think, you know, we do need the drugs to get rid of the cancer, but you can assist that by promoting good immune function. So, your immune system is the one way that you have to try to cure the cancer. But then you can also protect the rest of your body from the cancer and the cancer drugs, and, you know, enable you to tolerate the cancer a little bit better.

Katie: It’s so exciting. I know, like I said, it’s high-level and somewhat science-y, but I’m really personally excited for what the future holds for this. I know it’s no secret, I would guess everyone listening has someone in their lives who has been affected by cancer at some point. And I love, like I said, that you guys bring the background knowledge of metabolic health into this amazing research knowledge. And I’m excited to be involved and to be kept up to date. We’ll have to do updates as things become more available and hopefully, as they get to market, and can help people really, really soon.

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And as we get to the end of the interview, a few questions I love to ask, and I’m so excited for your answers on. The first being, if there are any other kind of things people don’t know or understand about these areas of expertise that we’ve touched on?

Paul: Yeah. So, I mean, I guess what I would say, I’ve just been, in many ways kind of led through my life, you know, just trying to pursue… You know, I was a scientist. I still think of myself as a scientist. And I became an entrepreneur. You know, partly, that was because, you know, I was bored with other things and that seemed like the most, you know, exciting. You know, and once I did it in the 1990s, with an internet startup, I had a lot of fun. You know, it was, you know, the most exciting thing. And I think, of, you know, kind of, science and entrepreneurship similarly. You know, that in science, you know, it’s motivated by a love of truth. You’re seeking the truth and you’re trying to construct theories which are kind of networks of ideas, and, you know, make them all fit together and work really well together. And in entrepreneurship, it’s kind of the same thing except instead of loving ideas or truths, you’re loving people. And you’re trying to put networks of people together that really fit together well, and, you know, that are very fruitful.

And that’s been, you know, kind of, tremendous fun for me, you know, so I kind of always thought of myself as, you know, pursuing love, pursuing truth. And, you know, I guess that comes from religious faith. You know, kind of, a Christian upbringing and Christian faith. So, you know, we’re commanded to pursue love, pursue truth. And then, you know, so, if you’re pursuing it, I guess I’d say I’ve just kind of… You know, things have kind of fallen into my lap. You know, kind of, you know, my wife came to me, and it was just a matter of helping my wife, right? You know, so I haven’t necessarily done anything special except, you know, tried to consistently pursue truth through science. And, you know, putting together, you know, loving networks of people through entrepreneurship. And just, you know, tried to have the faith and the courage that if, you know, you pursue these things, that things will work out. And so far, at least, they have. You know, we haven’t been kicked out of our home and, you know, starving to death in the gutter yet, so…

Katie: I love that. That’s beautiful. And I have a note in my show notes that you read about 1,000 novels earlier in your life, which makes you one of probably the most well-read people I’ve ever talked to. But you’re not as much into novels now. But it goes to my next question which is, if there’s a book or a number of books that have had a really profound impact on your life? And if so, what they are and why?

Paul: Yeah. So, well, the Bible, certainly, and the gospels. So, you know, like I said, I am religious. And I’ve kind of, you know, tried to shape my life in a, you know, loving and truth-seeking way. And so, I’ve had regular recurrence to that and just compare my life challenges, life problems with commandments from Jesus, and trying to figure out what would be the right course. So, that was something.

So, early in my career, early in my life, actually, as a teenager, I got interested in economics. And I really wanted to solve the problem of… I really felt like, you know, in the physical sciences, we made a transition from, like, alchemy to chemistry, astrology to astrophysics. From, you know, kind of pseudoscience to real science. And I felt like the social sciences had never achieved that, and that it would be, you know, kind of like a worthy enterprise to try to figure out how to do that. And so I got interested, as a teenager, in economics. And so the great influences on me in that were Friedrich Hayek. His writings, his papers, and books had a big influence on me by, you know, kind of posing the problem with economics in a very clear way. You know, so I knew exactly what the problem with existing economics was. But I didn’t know what the solution was until I came across the work of Ronald Coase, who won the Nobel prize about 1990. And that showed, I think, that the path to a solution and it gave me some ideas, you know, fruitful ideas. So it was kind of like, you know, my equivalent in economics of coming across, you know, Art De Vany and the Paleo diet.

And, you know, what he showed me is that in order to find the path forward, I really had to understand entrepreneurship. And wanting to understand entrepreneurship was a big part of my motivation for leaving academia and leaving physics, where I had a secure but boring job, in order to, you know, take a risky but interesting job in, you know, starting a software company.

And like I said, I just loved that, so that had a big impact. And I learned a lot. And I’ve thought of myself as an entrepreneur ever since. And then when I learned about Paleo, then I wasn’t afraid to say, “Oh, you know, I can write a book, start a health retreat, you know, do whatever. You know, the key thing is to figure out how to be healthy. You know, and that won’t be wasted energy. And if I can actually figure out how to make people healthy, then I can earn a living helping people to be healthy.” So, you know, I wasn’t, having some entrepreneurial experience, I wasn’t afraid to go pursue, and to go do the science of natural health.

You know, and then my wife was busy figuring out how to cure cancer. And, you know, so I was following along and, you know, so then I could say, “Oh, well. If you get to the point where the way forward is to start a company, then I’ll get a company started and we can raise money, and actually make a drug, and prove your ideas.”

And, you know, so that was the course of my life. And now I’ve forgotten what question I was trying to answer. But, you know, it was… You know, so I’ve just kind of… You know, it may have been something what books were influential? You know, so I was kind of following what I felt like were the commands, you know, to try and pursue love and truth. And, you know, just do it faithfully, and, you know, follow some ideas along the way. And definitely, all those novels I read, they were helpful in thinking about people, in thinking about myself, you know, what’s important. You know, I think one of the key things in life is just to figure out, you know, what is your life for? You know, we’re all trading 80 years of time for something. You know, and what do you want to trade your life for? You know, what’s the pearl of great price that you’re going to trade those 80 years for? And, you know, so, everyone has to make that trade. You’re not allowed to keep those 80 years and, you know, hang on to them. You have to spend them. And, you know, so it’s a question of what you’re going to spend them on.

And I guess I feel I’ve been blessed. I’ve been able to, you know, spend my years on things I enjoyed, that were a lot of fun and that were fulfilling. And, you know, so, if I had any advice from books that were… You know, and just, kind of pursue your interests, try to do what’s right, and have faith, have courage.

Katie: Well, on that, I think you might’ve already answered my last question intuitively. But any other parting advice for the listeners today? I’m grateful for you and for Shou-Ching and the work that you’re doing. But any parting advice for everyone today?

Paul: Yeah. I think I would say that’s, you know, kind of the lesson of my life is, you know, love truth, love people. I would say, you know, there are many ways to do that. You know, you can love truth by being a teacher in a kindergarten and, you know, teach kids how to tie their shoe laces. But, you know, and that’s a gift, and, you know, teaching is a way to pass along the truths that other people have learned.

For me, I felt like I was fairly talented, and so I had an obligation to try to pursue truth in the most difficult way, through science, and to pursue love in the more difficult way, you know? So you could learn to be a doctor and to, you know, treat people in the conventional way, you know, with existing knowledge. You know, and that’s the virtuous thing, much like teaching. But, you know, if you can discover an even better way to improve people’s health, that’s even better. So I’ve, you know, kind of felt like, you know, I was talented enough that I should pursue the most difficult paths. You know, if you’re going to do difficult things, then there’s a risk of failure, and you’re bound to be afraid, maybe terrified, you know? You know, so you need faith, you need courage. And so, you know, to me, those are the most important things.

Katie: I think that’s a perfect place to wrap up. I have so much hope and excitement for the work that you guys are doing. Thanks for explaining it today. Thank you for your time. And please tell Shou-Ching thank you and hi from us as well.

Paul: Yeah. I’m looking forward to coming back and telling you how our drug is doing.

Katie: You are always welcome. And thanks to all of you guys for listening. And speaking of time and a limited amount, for sharing your most valuable resource, your time, with us, and your energy and attention today, I know that we’re both so grateful that you were here, and I hope that you will join me again on the next episode of “The Wellness Mama Podcast.”

If you’re enjoying these interviews, would you please take two minutes to leave a rating or review on iTunes for me? Doing this helps more people to find the podcast, which means even more moms and families could benefit from the information. I really appreciate your time, and thanks as always for listening.



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