The 3 DAILY HABITS That Destroy Your Health & DECREASE Lifespan! | Bob Hariri

What we put in our bodies impacts our health, our lifespan, our mental state. We live in a world where there are so many choices. The vast majority of choices are not great choices. People will often take the the path of least resistance and they'll get the fastest, most available food for their for their day. In many cases, what they're doing is they're poisoning themselves. Dr. Bob Hariri, welcome to the show. Tom, good to see you and it's it's a privilege to be here in your beautiful beautiful studio. Thank you, man. I'm excited to have you. I want to know what are three things that people do daily that shorten their lifespan. First and foremost, I think inactivity and a um a dependence on technology for for physical activities is damaging. Uh you got to Dependence on techno technology, what do you mean? Even even depending on uh motorized vehicles to drive to get three blocks to the store to pick up a gallon of milk. Um people need to be more physically active. They need to uh to to build and maintain their muscle mass. That's one of the most actionable things we can do to maintain our health and there's fundamental biological reasons for that we can talk about, but that to me is one of the principal principal factors that if you just pay attention can impact your your lifespan. All right, so lack of activity. Right. Diet, what else? So everybody the the go-to is diet, right? The go-to is diet. be fighting words. I couldn't agree with you more. I'm going to come at you at the end of this. I couldn't agree with you more. I was saving it for number three, but but let's let's leave it at number two. So there's no doubt what we put in our bodies impacts our health, our lifespan, our mental state, you name it. The problem is we we live in a world where there are so many choices and the vast majority of choices are not great choices. People will often take the the path of least resistance and they'll get the fastest, most available food for their for their day. And in many cases, what they're doing is they're poisoning themselves. Um how do you feel about people that say a calorie's a calorie? Doesn't matter. I don't believe that at all. Um there's a very big difference between a a calorie of protein versus a calorie of fat versus a calorie of carbohydrates. We know that, and we know that what you want to do is you want to provide yourself not just with energy, but you want to provide yourself with building blocks. The building blocks are essential to the repair and regenerative process, which is what I'm very focused on. You can't build new cells and new tissues and new organs unless you have the components that are necessary, and those components um for the most part are found in proteins. Fats are very very good because the byproduct of fat digestion gives you some of those building blocks. But we also have to take into consideration that many of the things we eat have um have pro-inflammatory elements to them. And at the end of the day, controlling inflammation and um uh and and controlling the exposure your body has to the toxic nature of things like raw sugars clearly has a big impact. The reason you and I first became friends was how thrilled I was what you were doing at Quest building these really fantastic products that were delicious, satisfied those cravings, but provided you with the building blocks I'm just talking about. Um so so clearly nutrition is something that that people uh unless they pay attention to it, may in fact be doing themselves harm rather than rather than benefit. a rule of thumb on diet? Like you have 30 seconds to explain to somebody what to either do or not do if they care about longevity specifically. Well, you know, somebody who's who's always always been plagued by a tendency to become overweight because of you know it less than than ideal activity and the wrong diet. I've decided that that I'm going to I'm going to focus on one thing that I know I can measure and I'm going to use that as my metric to follow. And so for me it's blood sugar. And we all know and I think it's increasingly recognized that blood sugar is is linked to metabolic inefficiency that exposes our entire system Inefficiency, why inefficiency? So What's happening? So I eat a carbohydrate, for those who don't know, I eat a carbohydrate, doesn't matter if it's a carrot or it's a bread, whatever, some portion of that is going to break down into glucose. That's what we're talking about when we say blood sugar cuz a lot of people think as long as it doesn't say sugar on the pack that it's not going to be a problem. Now carrots was probably a terrible example because so much of that's blunted by fiber, but you're eating carbohydrates, they're going to end up in your bloodstream as glucose. But why does that cause metabolic inefficiency? The easier it is for what you ingest to become that free circulating glucose, the easier that is, the less efficient it is for you for your for your system. What I mean by that is if your body has to go through a digestive process to turn the carbohydrate in a carrot into an absorbable form of glucose, that's better than if you get raw glucose just as a as a sugary coating on a product. Because if I have to work to get that glucose out of the product into my system, that's better. Is it better because it's slower or is it better because it there's just less of it? Well, it's better because it's slower and because you're you're actually utilizing energy to do that digestive process, you're actually balancing the the the asymmetry between availability of glucose, the raw availability, and the usability of glucose. I What I mean by that is I would rather you um you have to work a little bit to get the glucose out of a product than to just have an infusion of raw glucose into your bloodstream. And why does glucose cause so much inflammation? You know, um I think in part because as the food industry evolved, um it was about quantity, not quality. And the sugar plantations recognized it's real easy to grow sugarcane and grow other raw sources of glucose, molasses, etc., etc., and to put these into products in as simple a form as possible so that the process of making the product was easier and less expensive. That That means that your exposure to these sugars is much, much higher than under under by normal biological circumstances. If we were If we were back, you know, 2,000 years and we were foraging for food or growing our own food, the effort used to produce that helps burn some of this raw raw glucose that we're absorbing. The inefficiency in my mind is all about you don't you don't want to fill your system with glucose you didn't pay for. And you didn't pay for energetically. And that may not be the best description, but I just think about it. You're If you have to run before you get to the restaurant and order your meal, that's probably better for you. Going in, so we've got two things: not enough activity, a poor diet, a pro-inflammatory diet. Those are going to be problematic. Pro-inflammatory and the quick example would be high blood sugar diets. So, anything that's spiking your blood sugar consistently. What's one more thing? So, third thing to me um really relates to something else we put into our bodies, which is the medicines, the supplements, and the other things that um we think are benefiting us, but might might in fact uh not really be be all that useful. Everybody I know takes some form of supplement either either in a pill form, a capsule form, in a powder form. We have to consider how how that product got to be in the format we're ingesting. supplements altogether? No, no, I don't. But I avoid, for example, as much as possible the the gelatin-encapsulated supplements. People don't recognize that gelatin has to go through a process of being broken down, digested, in order to release the the contents. I remember a situation where a where a a gentleman who was very health-conscious was ingesting a tremendous number of supplements a day, actually developed an obstruction in his intestinal system from gelatin. What? Yeah. Yeah. So, so lot of supplements. It's a lot of supplements. And And by the way, it's not uncommon for people to take 20, 30, 40 capsules a day. Dude, there's people that take even more than that, which is crazy. I try not to supplement anything. Now, are you only So, you're worried about quality of supplementation versus supplementation itself. Is it just the gelatin, or are there other things that people are ingesting? Like, what are typical ones that mess with people? I think that if you don't look at all of the components of what you put in your body, um some of the other ingredients, they may be binding agents, they may be excipients that improve the solubility of the product. Any of those things that you're putting in your body, although they're a minor ingredient of the supplement, they do over time have an effect. And so, you have to pay attention to this. You know, like like you and I were just talking about uh the the concept of whole food, whole, real, natural, unadulterated forms of food helps avoid some of those added ingredients you don't need. And you may get your 1,000 mg of vitamin C, but if the vitamin C tablet you take is bound together by an algae-based or gelatin-based component, you have to consider that's going in your body as well. Mhm. When you think about aging, and people doing things that are decreasing their life, is it are we doing things that are Like I think a lot about methylation of the DNA, right? So you've got People have heard me talk about this a lot, but for people that are hearing this for the first time. So in every cell you've got the DNA, which is the program that tells your cells what to do. Right. But over time, there's little misreads, mistakes in the replication, and you've got these little things, which I never remember what they're called, but they run along and they like mark like this part should be read for this cell. This is a liver cell, so only this part of the DNA should be exposed and should be read. And as that begins to get confused and the bookmarks get put in the wrong place, the cell starts to dedifferentiate. And as we dedifferentiate, we age. One, did I capture that idea correctly? And then two, as you think about people doing things that shorten their life, is that effective what what they're doing? They're doing things that cause the the wrapping of the DNA to be wrapped or marked poorly, or is it something else entirely? So you're hitting on a on a topic that's near and dear to my heart. And I May I expand on it a little bit? Please. Educate me, cuz I know it like just enough to be dangerous, but Yeah, take me to the deep water. like I primed this entire conversation. Every cell in our body can be thought of as a computer. A computer that has in the nucleus all of the biological software, which drives the processes that provide all the synthetic products of the cell, proteins, peptides, etc. Um and also drives the the sequence of events necessary for that cell to continue to perform its function, whether it's a liver cell or a heart cell or a brain cell. That software can get corrupted. It gets corrupted through normal processes as well as abnormal processes. That in effect means the software doesn't get read properly. Give me an example of an abnormal process. A mutation induced by a virus. One of the ways that viruses actually create the symptoms is they begin to destroy your cells by taking over the machinery in the cell, actually damaging damaging that cell's ability to replicate normally. Unfortunately, our immune system will come in and clean that out. And fortunately, not all your cells necessarily are affected. So, viruses can cause these mutations and abnormalities. Um exposure to radiation, ionizing radiation can obviously do that. Um and then there's and then there's evidence that chemicals we ingest, maybe some of the things we've been talking about. Some of those chemicals might in fact either either stimulate or or prolong the the the what we call the epigenetic changes to our DNA, which affects the performance of the cell. So, so just to get back to what you were sort of alluding to, if our software, in order to run properly, has to be uncorrupted. Anything that corrupts the software, just like the software on your computer, if it gets corrupted, your program doesn't run properly. That same process occurs in our cells. And and if you think about the nucleus result is where the software resides, and the cytoplasm of the cell, the body of the cell, is where the processing takes place. And if you think of the surface of the cell as the keyboard, then that that kind of model of the cell as a computer means that what's the best way to protect yourself is to keep your master boot disk stored away somewhere so that it can't be damaged as a way of protecting the integrity of that software as early in life as possible in the event you need to reboot your system. One of the things that I want to answer today is if stem cells are as amazing as you would have me believe, why don't I see super soldiers running around? Why don't 100-year-olds look 25? But before we get to that, I want to just want to prime the audience that that's one of the places we're going to go, but I really want to understand how the cell operates. So, I've got the nucleus, all the DNA is jammed in there. I've got the cytoplasm, is that what we called it? Right. Uh how is it doing the processing? Like the more I can envision this, the more I'll be able to remember it. So, I have maybe a slight understanding of the way that DNA is read, Right. but I don't understand how the processing is happening in the cytoplasm. What what's actually going on? Not metaphor, what's actually happening? So, the DNA has a partner in in cellular processes called RNA. Mhm. That's what's in the cytoplasm? So, RNA transit between the nucleus and the cytoplasm. And they are little things that move around. They're little nucleic acids. They're They're little pieces of nucleic acid that copy the corresponding sequence from the DNA. But can they move? Oh, absolutely. They They traffic around the cell. They actually move through pores in the nuclear membrane. they like if I was looking at them for people watching, you can see my hand. For people listening, I'm like doing a crawling motion. Like how how do they actually ambulate? Is that the word? They don't traffic by their own motion. What they do is they move sort of through Brownian motion. They float. What the hell is Brownian motion? want to get into into into chemistry. it though. So, there's Are they They're not just sloshing around. They must have like They're doing something willfully. Now I know I'm getting into metaphor cuz obviously they're not they don't have a nervous system or anything like that. But like if I was looking at them under a microscope, I would see them move, right? So you can see RNAs Yep. These little molecules of ribonucleic acid my DNA. That first the way the RNA is created is that they they actually come up to the DNA itself and they create a corresponding sequence to that DNA that's now And they're just grabbing that [ __ ] out of the out of the floaty stuff, right? They're CTGA. They're just grabbing those letters and going C C T T G G, right? That's right. They have a they have a correspondence so that the the sequence of DNA is written onto the RNA. The RNA then traffics from the nucleus into the cytoplasm and it attaches to parts of the cell cytoplasm called ribosomes and those ribosomes are the are the place in which the RNA is is translated into protein. Okay? where the cell's going to split? So no, that's So you we're talking about two different things. We're talking about protein synthesis from your that's that's encoded in your DNA. The the the the So the DNA says create this protein. Exactly. Exactly. So the genes for a specific protein up getting out of the cytoplasm or does it? It does. So So the ribosome allows the mRNA, the messenger RNA. So the first step is you transcribe the message from the DNA to the RNA. Yeah. Then the RNA traffics transits into the cytoplasm with the copy of that protein. with the with the recipe. Okay. Think of it as a It just has the recipe. It doesn't actually have the protein. Doesn't have the protein yet. Got it. So I now have the recipe. So I wrote down on recipe. Then Now I go into the cytoplasm. That's right. Then this this this little molecule that constitutes the ribosome allows for that messenger RNA to be translated into a sequence of amino acids. Mhm. Okay? And if you ever watch the process, it's it's a fascinating process. It looks very mechanical. And the translation of the message from the gene in the in the DNA says make this particular protein. Make Make growth hormone. The growth hormone recipe, which is encoded in the DNA and transcribed to the mRNA and then translated to the protein in the in the cytoplasm, takes place on a piece of the cell called the endoplasmic reticulum. This is a little to guess that. Well, this is a little organelle. And by the way, it's a good name for your next dog. Reticulum. Organelle Organelle's a good name, too. But but once once you translate into the sequence of amino acids and you now have a length of amino acids that constitute a a protein, Mhm. the protein then gets packaged in part of the cell, an organelle called the Golgi apparatus. And the Golgi apparatus puts layers of cell membrane around this this this new protein. That protein then gets connected to the cell membrane itself, where it can be expelled into the into the extracellular space. That's how proteins go from recipe to design to production to secretion. Okay. And so now once it's outside of the cell, it's going to I assume it's made locally. So muscle cells are going to make the protein that I need to affix to the muscle in order to make it bigger, repair damage, whatever the case may be. How does it go from you're now free my child to being used in the way that it's intended? So, that that's the beauty of biology, okay? So, um the system is designed to read and express genes that are necessary for certain functions. And we don't fully understand the process by which those genes are turned on and turned off, but there is a series of signaling events that calls upon the production. So, for example, while you're growing, the need for growth hormone actually commands the expression of those proteins that then get produced and then secreted, and they now influence the cells around them, and in some cases even remotely by transiting through the bloodstream to go and affect cells in the rest of the body. That's called the paracrine effect, okay? And then the autocrine effect, where where your single cell may drive functions in cells all around it as well as as distant to that. Okay, so this [ __ ] is insanely complicated. Very complicated. I've said this probably a dozen times on the show. If you want to believe in God, look inside the cell. This stuff is so crazy and complicated, it is unbelievable. But all right, cool. So, that was an amazing walk-through. I actually want to now look at this under a microscope to see what it actually looks like. Well, the beauty is I'm going to send you some remarkable videos where where artists have actually created computerized graphic representations of this process, and when you actually see it, you'll say, "How could that possibly have been designed?" It is so intricate, and it is so elegant. Um literally, some of the molecules necessary for reading and writing the DNA, walk These molecules walk you you you you had that little description. Ambulate. They literally walk across the DNA, the chromatin. Yeah, what are are called? A polymerases, DNA polymerases. Um it's it's it's amazing, remarkable stuff. And and and believe me, I'm a surgeon, so this is probably way above my pay grade, but the um the fact is, we recognize that every cell is a synthetic factory that produces products encoded in the DNA, and those products are necessary not just for the function of that cell, but for the function and and and integrity of the cells around it, and to influence cells even far away, other parts of the body. Okay, so knowing that your specialty is stem cells, so what is it that stem cells are doing in that process? So for people that don't know, the brief history of stem cells is that they can become anything. So when we're first developing in the placenta, in fact, tell people cuz this is a very fascinating take on the placenta. Walk people through your the sort of early insight that you had that made you think, "Mm, placentas aren't what people think they are." If you're ready to level up, all you need to do is take the steps with the curriculum and community that's going to get you there. Enroll right now in Impact Theory University. 50 courses, 100 hours of content, and live sessions with me every week where you can get any question answered. Act now and get my exclusive live workshop, Make Any Goal Stick. Click the link and change your life. You know, back at back in the early part of my professional medical career, my entire focus uh was on the treatment of head and spinal cord injury. I was um uh I was I was Did it seem futile at the time? Well, it was it was very depressing. When you started, that had to be just like, "Oh, sorry, you got hit in the head, you're done." What made you think you could be helpful? Well, you know, maybe it was a little bit of optimism combined with um uh with fearlessness, the fact that it the outcomes were so bad after traumatic brain injury, we couldn't do much worse. Mm. Um I tried to as a as an engineer by training, I tried to break it down to the root cause of why people do badly after traumatic brain injuries. And my partner at the time was a brilliant neurosurgeon up here at Stanford now, Jam Ghajar. We we built a laboratory where we studied these processes. And we rec- brains have you poked around on? Too many to remember. Living? Yeah. Yeah. Person's alive and you're done. And and and virtually all of them a [ __ ] ever. And virtually all of them were the victims of some traumatic event where where we knew that if we could control the post-traumatic inflammatory process, so that the immune system response becomes the bigger problem? There's no doubt. Everything associated with the health, wellness, uh repairability, and recoverability in our body is driven by the immune system. The immune system is designed to um interrogate, to make sure things are working properly, and then respond when they're not. And so in the case of a traumatic brain injury, the mechanical insult to your brain disrupts, even at the cellular level, the integrity of those living cells. Uh and we showed this. We actually We actually create You You would have loved this. Tom, we actually created a a model in the laboratory to to replicate what happens in a car accident by creating a a water-filled piston that was percussed by a hammer, and the shock wave was transmitted through this connection into an experimental brain in order to compress the brain the way it does when it hit when the when the head hits a windshield. Okay? And what we found was that that that perturbation of the cell released factors which stimulated and and and recruited cells from the inflammation the inflammatory system from the immune system to come in and release factors, which disrupted the blood-brain barrier and caused brain swelling. Uh and affected the the the integrity of the cerebrovascular system, the blood supply to the brain. What people were dying from after traumatic brain injury was was unchecked brain swelling. Now, what happens if you bang your arm in the car door when you're leaving tonight? It's going to hurt and it's going to swell up. Yep. Fortunately, for most of our body, the swelling is is can occur without encroaching upon any of the anatomic structures. But not the brain. The brain is encased in a in a rigid skull, which means that as the pressure builds because of swelling, what what happens? Either the brain gets squeezed out of the skull, and that actually happens. It's called a herniation. Oh, god. Where does it go? Well, you remember you have this hole at the bottom of your skull called the foramen magnum. That's where your brain connects to your spinal cord. Believe it or not, your brain can be squeezed out through that little tiny hole. Yeah. Yeah. That's horrifying. Not not a good thing. shrink back, or is that like once it's there, it is all over? If you've progressed to that point, it's pretty pretty far along. But Woof. But here's the interesting thing. The brain as an anatomical structure has brain tissue. Mhm. It has blood vessels. And it has fluid. The fluid is called cerebrospinal fluid. If you think about you have three things in a box, you need the brain tissue and you need the blood. Right? If you squeeze the blood out, you get a stroke. Right. The fluid that's in there, there's the cerebrospinal fluid, if you can get that out, you can make room for the brain to swell a little bit. Mhm. Okay? So, what we actually were very focused on early on is control of intracranial pressure. That was a plumbing problem. By draining that fluid. By just getting a catheter into that system and draining that fluid. You know, with with my partner and our team, we actually looked at at at device strategies to help doctors in the acute environment control that pressure. Okay, I'm going to walk through this is so fascinating my audience will have to forgive if they don't care but this is really interesting to me. Okay, so you're in an ER somebody you just got in a car accident they have battered their head they come in presumably unconscious and do you cut their head open? Like what are you doing it cuz I if let's say I don't understand the fluid part I would think you got to take the top off the head and just let the brain swell. That was old fashioned. So believe it or not if you go back historically in the management of traumatic brain injury and uncontrollable brain swelling one of the strategies was to do a a craniotomy craniectomy removing the skull and allowing the brain to swell out and in some cases actually removing part of the brain. Okay. Okay, okay. That seems really bad. Well, it's a it's a it's a last ditch effort to make enough room so that the rest of the brain can potentially be salvaged. Wow. It doesn't always work that way and you can imagine you know, removing a significant portion of brain tissue has significant consequences. Yeah. How long can you leave a brain exposed like that? Well, you know, again it it depends upon the surgical environment and and the surgical skill set and so on. Um in some cases surgeons will remove the part of the skull and just cover the scalp back over in order to give time for the swelling to subside but you know Pardon me? An hour? It it it all depends on the situation it depends upon the the extent of the injury to begin with it it it depends upon the the underlying inflammatory state of the individual but suffice it to say that's not the ideal way to manage that problem. unideal. So, you know, as I mentioned my my partner that I worked with Jam Ghajar, we we were very fascinated by the fact that you have an acute window of opportunity to address this brain swelling. Could you do it by getting a a proper drainage system into that fluid compartment of the brain and controlling pressure by relieving fluid? So, there's a specific place that that's happening? So, the fluids in your brain circulate around the outside of the brain. Got it. And there's a system within the brain called the ventricular system. And the ventricular system are cavities. They're open spaces where the cerebral spinal fluid circulates. So, if you can get a catheter in there and you can remove the fluid, you actually can get a some control over the pressure. But it's complicated, right? You know, the old saying is that if you if you relieve the pressure too too rapidly, you may actually exacerbate the problem and cause more brain swelling than than than existed before. That's surprising, but okay. So, the bottom bottom line is that that technology to control brain pressure, control intracranial pressure, has impacted the management of traumatic brain injury considerably, but the generation that has evolved since then, because this this is work we did in the '80s, since then is to mostly look at ways to control the inflammatory process. And and and and by the way, there are some relatively straightforward approaches that appear to work. Hypothermia, you know, cooling tissues off actually helps control things like like swelling. Uh and then also using using certain um methods to reduce the metabolic demands of the brain will reduce the need for blood flow. How do you do that? Well, you've heard of induced comas. Yes. Okay. So, if you if you have a patient who You're basically just trying to shut the brain off. You're basically lowering the demand for blood supply. And by lowering demand for blood supply, you lower intracranial blood volume. If you lower intracranial blood volume along with intracranial pressure control by draining that fluid, cerebrospinal fluid, you can potentially manage this wave of swelling that occurs. And you want to get to a point where where swelling starts to decline, you can restore blood flow, and you you haven't damaged the brain so much that it can't recover. That was, you know, kind of the the the fundamental strategy behind all of this. Taking it a couple of steps forward, we now we now work in a in a world where there are tools to use to control inflammation. Some of those tools are pharmacologic tools, or biologic tools. There are even methods uh that are mechanical that are being developed. You know, methods that use certain pressure differentials and so on. All that being said, I'm at the point in my life I'm more concerned about, "Okay, after all these acute events, what can I do to restore function in these patients?" Uh And now I assume we're loop back to stem cells. Thank you. So, here's I'm bitter about stem cells. So, I don't know if this is just it's still early days or what, but I want to see 100-year-olds go backwards to looking like 25-year-olds. And I I know Tony's story, it's amazing, but like do you think that there there is going to be progress in understanding of like the the So, let me back up. I'm going to make a hypothesis. Here's how I look at it. Stem cells can become anything, but stem cells are not the only part of what's going on inside the placenta, which we actually didn't even get to that part I derailed you. Uh so, we're going to have to walk through, okay, what was your insight around the stem cell? And then why my hypothesis is going to be that that what you're about to describe there, what's happening in the placenta, is so [ __ ] complicated that injecting someone with stem cells is like 5% of that milieu. And that we would have to get into sequencing different like chemistry and signals and all kinds of stuff if we really want to have radical transformation. But give us that first insight, and this time I will try to stay on task as you explain uh why it isn't what people originally thought. You're hitting upon some really um important opportunities to distinguish what we think the history was and what it really was. For for decades now biologists, scientists, and and clinical people have recognized that since we all start from a single cell and that single cell has all of the information and all of the ability to produce every mature specialized cell type of our body and do it at such scale that from a single cell in your lifetime tens of trillions of cells are produced. Um what is the the fundamental the fundamental unit, if you will, that's responsible for that level of differentiation, specialization, um scale, and integrity. If you think about it, right? Every cell in our body, Tom originated from a cell that originated in the placenta. So you know, Peter Diamandis and I we I think you and I Peter probably sat around talking about that the placenta is nature's 3D printer. It prints the the newborn baby. In doing so, it deposits cells that will take up residence and give give off progeny that will populate that developing human being for the rest of their lifetime. If you think about that, right? From one cell to tens of trillions of cells in our lifetime, how perfect does all of that information resident in the cell have to be? And how perfect have those systems have to be in order to support that level of expansion and differentiation and propagation? So, I was fascinated by that because I said, "Well, you know, couldn't every disease and every illness and every injury in our body be addressed simply by replacing the damaged or diseased cells?" And if you if you can do that, what would what tool would you need to do that? So, when stem cells first emerged in the scientific literature, um I was fascinated by the possibility that I could use them to restore the functions that are lost after a bad brain injury. The problem is what was the tool that I would use? Where would I get it from? Could I produce it to a to a form that the the average clinical community could utilize? Because let's face it, it's one thing to do work in a laboratory and and to have have discoveries and and develop some interesting theories that you test in the on the on the at the at the bench, it's a whole another ballgame putting it in the hands of a clinician to use to treat hundreds or thousands of patients in their professional career. That's why the industry of pharmaceuticals has grown to where it is because what the pharmaceutical industry does is it puts tools in the hands of clinicians. You know, if you go back a couple hundred years, doctors had to make their own medicines, right? So, so if you think of cells as a medicine as a biological medicine, I had to figure out a place to get them. Where could you source these cells? And what would you have to do to turn those cells into a product that was of the quality, the consistency, the reliability, and the scalability and economics to fit our health care system? So, if you go back 25 30 years when most of the work around stem cells was being done on stem cells derived from human embryos that were discarded. Uh or Hugely controversial. Very controversial and by the way, aside from the moral and ethical debate around the use of embryos, consider that at the stage of an embryo's development where you isolate the cells, which is the blastocyst stage, it's very early in development. Although the embryo might look normal, only four out of only one out of four, one out of five embryos that reach the blastocyst stage ever go on to form a full healthy newborn. Most of them spontaneously dissolute sometime after that blastocyst stage Because the body detects a problem? Exactly. Because nature detects that the underlying quality of that embryo isn't good enough to make it all the way through. And it turns out that the most common reason for those early early pregnancies from not continuing is that there's a fundamental defect in the genetic material of the developing embryo. So, let me explain that. As you know, we we are produced by an egg and a sperm which are which have half the the DNA content of a full cell because when they recombine, they create the full content of DNA. Which means that the cells that that are that are used, the egg and the sperm, are produced by a process called meiosis. Meiosis is different than mitosis. Mitosis is a cell makes an extra copy of its DNA and then splits. Meiosis is when a cell splits its DNA apart into two half It's two half portions of pasta. Okay? All right? You know, when I go to an Italian restaurant, sometimes I want the bolognese, sometimes I want the carbonara. It's really nice when you can get half and half. That's sort of what happens in the cell after meiosis. The cells that are that make up the sperm or the egg are produced by tearing apart the the chromosomes. When those chromosomes are torn apart, there are often mechanical defects. Both things are called uh deletions, translocations, trisomies, tetrasomies, all of the aberrant copies of your DNA that may be present in a in a blastocyst, but not capable of going all the way to a full preg full complete pregnancy, is the reason why embryos are probably not the best source of cells, because you don't know how what how good their quality is early on. Very interesting. So, so many of these things are dysfunctional anyway going there, even if it wasn't a moral and ethical problem, still not a good idea. That's right. I made the commitment to one fundamental principle, which was if you make it through a full-term pregnancy and there's a healthy product of that pregnancy, healthy newborn, that's gone through nature's quality control process. Mhm. Right? And so, if that's where I'm harvesting my cells to develop a cellular medicine, at least at least I eliminated the potential problems that may have been carried through by using the wrong cell source. That's the way That's the way I looked at it. Makes sense. There's another insight that I've heard you talk about before, which goes to your point about the placenta being the 3D printer, but if people don't understand like if they're lost at the level of analogy, they'll miss something really cool. So, your you were thinking about the placenta and the embryo and you're like, well, they should grow at the same rate. But you looked at it and they don't. The placenta blows up huge, massive resources go to the placenta and then the embryo develops. That's interesting, cuz then you start thinking of okay, the placenta's making all these stem cells and it the stem cells in effect and I know that this probably is not biologically accurate, but now this helps me picture why the placenta becomes so important. If it is a stem cell factory, A, stem cells are already coming quote-unquote from the outside. So, there's this thing, the placenta, creating the stem cells and basically sending them over to the fetus, then the fetus is going to grow. That would give me the okay, well, then if I already know that it can get this injection, air quotes, from the placenta, then it might work later down the road. But, it obviously has a way bigger impact in the placenta. So, again, stealing your own story from you, spina bifida, the skin doesn't close for whatever reason, it's going to have horrible consequences if left unchecked. But, you can actually do surgery on the fetus, which is already insane. All you have to do is close the skin and they will grow up normal. And PS, they won't have a scar on their back, which is crazy. You had surgery, you have no scar. Right. But, if you do that to a 1-year-old, presumably they would have a scar. And certainly do a 6-year-old. I love it, Tom, because it means that all the time we spent together, you're paying more attention to me than I'm paying attention, which is fabulous. But, but So, here's the here's what really intrigued me. So, first and foremost, um uh when my when my oldest daughter was in utero and I ran down from the surgical ICU where I was covering to go and look at the first trimester ultrasound and I saw that she was a peanut-sized embryo, but the placenta was already this developed organ and getting bigger, it dawned on me that as an engineer, for it to be bigger when I thought from my early medical school training that the placenta was a vascular interface between the developing fetus and the maternal system, they'd grow at the same rate. system. Right. Right. a loving way to say mother, yeah. I'm trying to be as politically correct as possible. But, I was I was fascinated by the by the fact that um this to me indicated that the placenta was the governor of embryogenesis and fetogenesis. Actually finishing the production of that newborn, okay? Now, if that was the case, why? Um and it just seemed to me obvious since the the net change in in cellular mass of a developing embryo to fetus is enormous, where does all that cellular mass come from? Some of it develops de novo in the developing embryo and fetus, but some has to come in there from this organ. That was my thesis. And so I started to look at the placenta and found that in this complicated organ was basically the anatomy of a bioreactor. It was basically a cultivation and and cellular propagation environment. It was a it was a it was a nursery for developing cells. And since those cells had access to a circulatory system that could gain access to the developing fetus, some of them were clearly trafficking in and out of the fetus. And so I came up with this concept that well, the placenta is basically nature's stem cell factory. And if it's nature's stem cell factory and we throw away in the world 150 million of these a year is that maybe the best place to find cells for the emerging field of cellular medicine? That was, you know, that was the crazy idea, you know, the crazy epiphany that I had looking at my my daughter's first trimester ultrasound. Fast forward, we did the work to show that in fact the placenta is a an environment for the propagation and expansion of these stem cells and their ultimate trafficking into the developing fetus, but after the fetus is separated at birth, when you cut that umbilical cord and the and the newborn baby is no longer connected to the placenta and that placenta comes out is there any way of harvesting some of these surplus cells from the organ? And that's what we based all of our efforts in our company on 20 some odd years ago. And and knock wood, we were we were fortunate that not only was it an ideal source of these cells, but I could develop systems to procure these leftovers. I could I could create what I call a procurement network where in partnership with obstetric practices and birthing hospitals and expectant parents, we could we could ethically, morally, legally, and under high quality control, collect these organs that would normally just wind up in the wastebasket. They'd wind up in the biohazardous waste material. And by the way, hospitals have to pay to get rid of them. I could recover these, bring them to the laboratory, extract the cells we need, and use those to produce the cellular medicines we were all dreaming of. Wow. At the at the genesis of this of this industry, that's what was really our driving our driving force. So, why don't I look 25 then? Well, first of all, you look amazing. That's very generous. But uh At 25, I do not look. Well, I got to tell you something. Since the last time I saw you, you look more youthful and and clearly clearly like you're you're working using this gym very effectively. Very kind. So, here here's where we are. Cellular medicine is a therapeutic platform, therapeutic technology, which goes through the same process of review, a demonstration of safety and efficacy, and then ultimately approval by our Food and Drug Administration that other therapeutic products go through. As you can imagine, the modern FDA was designed to evaluate, test, and and and approve traditional therapeutics. Those are chemicals, discrete chemicals, Mhm. and biologic products. saying that they're just slowing you down and like in reality, if you could just go crazy, like we really would have that kind of regeneration? Like I I have dude, I am the ignorant one at this table, but I I have a feeling that there is sequencing maybe not the right word, but something like that, where there's a whole bunch of things, whole bunch of contextual cues that the placenta has or sends out that cause stem cells to have the massive impact that they have that maybe not impossible to replicate, but is decades in the future as we like learn all the like nuances or no, you think this is really a slow down just from testing and approval. So, you know, the FDA and other regulatory bodies throughout the world have a very very tough job on their hands. Um considering all of the theoretical technologies and then and then reduced to practice technologies that are looking to gain approval for broad clinical use, you have to ensure that your your your exposing you're using the right lens on those technologies to ensure safety first and foremost. And then you have to you have to link that safe product to to to clear expectation of clinical of clinically meaningful benefit. Okay? What's often used the term is efficacy. Now, discriminating between safety and efficacy is one is one thing. The other is, do you have the right metrics to use to determine whether something is clinically meaningful as a cellular medicine versus a biologic product versus a chemical? Because remember, if I put a chemical in your body and the chemical is going to block an enzyme, okay? There's a there's a there's a what we call a stoichiometry. There's a there's a mathematics. It's a word. It's a great word, too. I love that word. I I use it all the time. The stoichiometry of of of of will that will that particular product work, the chemical product, you can you can actually figure out you need so much of this chemical to block so much of this enzyme. That's how you come up with things like dose. Mhm. And that's how you come up with things like um interval or frequency of dosing. That's pharmacokinetics, okay? That pharmacokinetic analysis is what guides the whether or not you give somebody 5 g of aspirin or 80 mg of aspirin, okay? Okay. This is all going to answer the punchline to why I don't look 25? Yes. Okay. I'm working towards it. I'm working towards it. So, with cells, the industry and the regulatory community took some time to better understand how would we even measure Mhm. how would we even determine the pharmacokinetics of cellular products because they they you don't just administer them and then and then they have a discrete function and nothing else. A living cell a living cellular therapy is going to have many many different biological activities based upon the environment it's introduced into, Mhm. the the health state of the recipient, the chemical state, the milieu, etc. And so, being able to discriminate between biologically meaningful effects and biologically irrelevant effects had to be worked through. And so, I it it didn't surprise me that that those who have to ultimately give the seal of approval had to figure a lot of this out. Plus, if you if you go back 20 years, we still didn't even know which cells we were going to use for these products. What we tried to do at our company, Celularity, and ultimately at um uh um in in in in the the next generations of these of these corporate efforts is to first and foremost come up with a reliable platform of cellular source material that could meet this need in the industry. Show that we can manufacture products to scale, quality, and consistency that was going to fit the healthcare system. Identify the clinically meaningful effect in a disease. Mhm. Show that it's better than the alternatives, and then submit the data to get approvals. So, that's kind of the process you've got to take. Now, why why aren't these products available to make us look 25 right now? It's because the current the current standard by which we get these products approved are first to show that they're useful in unmet medical needs. So, reading through this uh are you saying that you really have the faith that once this we're able to get it through the system, it really is going to be that impactful? Or, do you think we're at the beginning of a longer journey where we have to figure out, okay, you give them the stem cell, but then you hit them with this other thing, and then this other thing, and those three things together have the massive effect? I think we're we're we're approaching a threshold, a watershed event where approval, FDA and other regulatory approval of cellular medicines in a discrete clinical area, and I think that the first area is going to be a limited condition where there aren't a lot of good alternative because that's where the the regulatory community is most willing to be uh most risk tolerant, if you will. When that happens, and we begin to expand the safety database around those products, you're going to see an explosion in the number of additional approvals that will occur. And what And what what what what's really encouraging to me is I think we're really close to that happening. And so, the first approval of a cell therapy product in a really nasty disease like a cancer or an autoimmune disease that that destroys people's lives, following those approvals, you will see these products rapidly taken up and employed in in much more mainstream illnesses. Do you have to be careful how you answer this question because you're in a public company? Cuz I want to know like if I the guy that gave himself H. Pylori and then gave himself the antibiotic solution, like I want to know the answers to those questions. Like if I'm Do you know Ben Greenfield? Yes, sure. So, that [ __ ] injected stem cells everywhere. In his face, in his dick, like Right. literally everything. Right. And he was even saying like he thought it gave him an extra like quarter inch if I remember. I was like, "What?" Like people are going to abuse this, Ben Greenfield. Uh so, yes, I understand you have to be very thoughtful and careful about how you answer that. I'm very eager to uh probe off camera, perhaps. Okay, so this is fascinating. It's going somewhere very interesting. What do we have right now today? Like maybe using Tony's story as an example, like if we're really committed, we follow through with the therapy, like what kind of benefits right now today with what's approved can we get? So, you're asking a really interesting, challenging, and treacherous question. It's my favorite kind of question. And you're so good at it, Tom. The The truth of the matter is we are going to first first move approvals for cellular medicines in the worst diseases where we don't have really good therapeutic alternatives. And when we prove the utility there, Are you guys going like for COVID? So, so we we've actually we've actually we've actually pursued the treatment of various cancers. How would that work in the cell? Like I So, so that's where so that's where cellular medicine has evolved. We went from originally wanting to put stem cells as the as the primary product into different conditions like autoimmune diseases to now saying, "Well, if the stem cell can give rise to an immune cell that has biological activity like a natural killer cell that can be used to fight cancer, prevent you from from uh help treat viral infections." So, are you training the stem cell before injecting it in? Like, you're a killer cell now, go. That's a good way of looking at it. I Instead of using the word training, what I would say is we're we're specializing from a stem cell a discrete population of cells we know the activity of. Mhm. So, natural killer cells, which are a How do you do that? You have to give it a instruction? It has those instructions already pre-programmed. All you have to do is lead it down the path. you do that? Like, literally, no analogy, how do you do that? You do it with a with a cocktail of factors which under normal circumstances drive the specialization of your stem cells in your body to become a red blood cell or become a white blood cell or become a hair cell. We understand what those signals are. That's [ __ ] crazy. You may not understand this, but this is really interesting. Dude, this is bananas. I love this [ __ ] Like, we are at the we're beginning to live in the future. It feels like that. And Tom, listen, I spent I've devoted the last 25 years of my life to this. Um it's it's what I it's what I get up every day to pursue because I do believe like you that that we are on we are on the threshold of cellular medicine becoming the most logical, the most deployable, the most the most impactful way of treating disease because it's way nature treats disease. We know how often used to used to say that stem cells are nature's first aid kit. When you have an injury or disease, your body is signaling the compartments in your body that house these stem cells to send them to me. Um by the way, I'll tell you something fascinating you're going to love. Do you know that that a pregnant woman um who is injured, for example, a pregnant woman in a car accident where even the fetus might have some degree of injury. Do you know that there's evidence that stem cells from the placenta actually traffic into the mother and find their way into her injuries? Impact Theory University, one full year for only $997. And if you act now, you get to join my exclusive live 90-minute workshop called Make Any Goal Stick. The great news is I don't care if you were the highest achiever in the world in 2022 or if 2022 beat you down hard. 22 has been a brutal year for a lot of people, and that's why I'm going to be going live later this month to host a workshop on exactly what you need to do if you want to make any goal stick. Do not miss it. Dude, that that's how I know that a fetus is basically a parasite. Abs- Yeah. And it's like, "No, no, no, I can't have you dying on me because I need to exist, so I'm going to give you a little sum-sum to get you back in business." That's crazy. And I know the punchline about cancer as well that women can go into remission when they're pregnant. That's insane. So, sorry, I derailed this again. So, we about but I'll have to do but you used the term parasite. They're actually they're actually a saprophyte. They actually A saprophyte? term. So, a parasite would be if all the benefit was unidirectional. Yeah. Right? Yeah, fair. They actually benefit each other. Fair. And and you mentioned something which was one of the hallmarks of our work in autoimmune disease. We recognized early early early on that that certain women with autoimmune diseases, multiple sclerosis, Crohn's disease, and so on, would experience profound improvement in their symptoms during pregnancy. And you know, what's the reason? Some guys said, "Well, it's hormonal." But when you use hormones, it doesn't work. And some guys said, "Well, you know what? Maybe maybe the the same cells which are making the mother accept the placenta." So so So let's May May I tease this out a bit? Yeah, please. All right. You know, a a placenta is produced with the fetus from the fertilized egg and sperm. It is a unique individual with its unique geno- genomic and and and genotype, right? Which means the mother that carries it is not a perfect match for it. And should reject it. Should reject it, but she doesn't. She carries it for 9 months without any immune conflict that would terminate the pregnancy or damage her health. Right? Moms carrying the placenta and fetus aren't more subject to infectious diseases, things like that. Mhm. Well, consider this. In surrogate pregnancy, the mother's not even related to the fetus. the cells. It's crazy. She's not even That is more like a true parasite. Mhm. But the fetus coexists in the maternal system without that immunologic conflict. Now, we said, "Well, can we use that to our advantage?" So since we saw Really fast, I want to give people one anchor. So one of the things with MS, you get lesions in your brain. You've seen lesions be eradicated. That's crazy, okay? With that in mind of how dramatic, please continue. So and the best the best evidence of that was a a report in the New England Journal of Medicine probably 10 years ago. The study followed 300 women with multiple sclerosis who were pregnant. And they found an enormously high percentage. I think it was 80% of the women went into profound states of of remission. Where just like you said, the lesions in their brains improved, their symptoms improved. In fact, many women came out of pregnancy and they relapsed and they said, "You know what? I got to get pregnant again." Yeah, dude, I literally was thinking the same thing. I'd be like, I'd stay pregnant forever. Yeah. So, on the basis of that, we theorized, is it possible that the same cells from the placenta that permit cohabitation in a surrogate mom, Mhm. if we productize those and use those as a therapeutic, could we induce a state of remission? And in fact, we saw that. In fact, when we used placental cells, these are just pluripotent stem cells. These are versatile stem cells from the placenta. From any donor? From any donor. This is bananas. Because remember, once placenta is a one-size-fits-all cell, if you take those cells and put them into a into a patient with an autoimmune disease like Crohn's disease, we saw evidence of of really significant improvements in the patients' patients' disease. Since stem cells have DNA, they must. So, how on Earth can they be a universal donor? Cuz it should be like, a male cell is telling you to be male, a female cell is telling you to be female. Like, if I inject you with stem cells, does your hair color change? Like, what? I don't understand that. So, it it it it just turned out that the cells from the placenta, because of evolution's brilliance, Mhm. have the ability to um to to turn off any immune response against them and induce a state of tolerance. Do they stay around, though? They do. And when they split, how are they not like, if I gave my wife stem cells, how does she not start getting my cells populating in her brain, her liver, her kidney? Like And and if they did, you got to think about the stoichiometry of this, okay? If you're if you're 25 trillion cells and you get a million cells from your wife, think of the or vice versa, think of the tiny contribution of those cells to your overall your overall biology and genome, right? In other words In other words, it It's not like you're replacing your entire body with these new cells. You're just supplementing your body with these new cells. Do you have to keep topping them up then? So, I love it, Tom. This is exactly what I believe may in fact be a a method or a strategy to help um improve our health and biology during our lifetimes by simply giving us the benefit of an added set of instructions, okay? So, think about this for a second. You know what the term chimera means? Okay. So, you can actually create chimerism in an individual by delivering cells from a from an a donor, an unrelated donor, and those cells take up residence in you for a period of time. You now carry two sets of instructions, right? Yep. And And by the way, you we know from our friends in the in the microbiome world, you carry lots of instructions, not even not even human instructions. But these additional instructions that you carry in the cells that maybe make up 1 millionth of a percent of your total cell volume, they still respond to the same signals and factors in your body that you that you're exposed to. So, so let's say let's say you've got um you've got a susceptibility to develop Let me give you an actual example. HIV the the the the positive agent behind immunodeficiency of AIDS occurs because the virus gains access to the cells by docking to a molecule on your white blood cells, your lymphocytes called CCR5. Now, CCR5 is a molecule that in a percentage of the population just isn't expressed. They are natural what we call CCR5 knockouts. And interestingly, about 4% of the human population in the United States is naturally CCR5 negative. If you if you inject HIV into them, they do not get AIDS. What? Yes. Now, by the way, roughly 10% of the population in Europe is thought to be CCR5 negative because bubonic plague selected for them. That is Isn't that cool? so interesting. So, listen to this. If I if I can't get infected with HIV because of my cells not expressing that molecule, but I take some of my stem cells and put them in a patient who is HIV positive, who actually has CCR5 and has been infected and has developed a disease, we actually now know you can actually convert them to HIV negative. Holy [ __ ] You can You can take somebody 100% HIV negative? Yeah. And it's now being published. not eradicated then? So so all HIV does is it damages the integrity and the functionality of your immune system, right? That's why you get opportunistic infections and so on and so forth. If if I now give you give you cells that create your immune integrity, but resistant to HIV, you now can combat and battle HIV. And in fact, some of those cells will actually go and kill off the HIV infected cells. So So this is now being done and published on. And some of the pioneering work, in fact, at my alma mater, Cornell. Uh they actually showed the ability to convert an HIV patient from positive to negative doing this. Jesus. I thought I heard a headline like that, but I never that Do you think that'll become standard of care over some period of time? It's my dream. So so in fact, um many many years ago, almost 20 years ago, um I had a concept that I wanted to explore. One of the One of the motivations for creating cellularity was to was to look at the possibility that I could induce a state of super health by simply giving you more than one copy of DNA, different copy of DNA, and allow natural selection to upregulate those things that give you a health advantage. So, you know what hybrid vigor is. Hybrid vigor is mom and dad have two separate genetic makeups. The more distant they are from one another when they recombine, the offspring has certain biological advantages. That's hybrid vigor. Okay? It's It's why It's why every generation health improves. That's why sexual reproduction is the things. Exactly. Now, a hybrid vigor occurs between generations, right? If I gave you Oh my god, I know where you're going. If I gave you a dose of stem cells that had a completely new complement of DNA, this being tested? Finish the sentence. I Yeah, this is insane. concept was can I create chimeric vigor? Can I create a stable chimera that gave you the advantages of all the DNA in the world that was disease resistant, and let nature let natural selection let's put Darwin in the driver's seat, okay? And let natural selection upregulate those things that give you the highest quality of health. So, the theory of chimeric vigor is simply this. You have 23, 24,000 genes in your body that you're born with. What if I gave you access to to 10 different times the number of alleles at those different genes so that you could you could have at the advantages that every individual has but but you can't package in one individual. And so here's here's something that's really interesting. I believe, and it's one of the theories that that I again base my work on, that chimerism is in fact biologically sound. Chimerism occurs in for example, in animals that create litters. Like dogs that have five or six puppies in a litter. Each one of those puppies has a unique genome. But they ex- they are exchanging cells with each other and some of those cells will take up residence in the animal for their lifetime. So the animals become chimeras of one another. And as chimeras of one another, they have the advantage of more than one ge- one one more than one form of a gene to call upon in order to advance their health. And by the way, natural selection will always upregulate the trait that gives you a survival advantage. Dude, that's bananas. Is that being tested now? It's one of the things we're very excited about testing. And we and and again, you know, it's it's it goes it goes back to why over 25 years we've built the one of the largest libraries of newborn cells that are cryopreserved so that I can interrogate the genome of all of those donors. And eventually, I'm working with I'm working with some absolute rockstars in the field. Um one of my dear friends and one of the smartest people I've ever met, Jack Hidary, has a new company called Sandbox AQ. Sandbox is a quantum computing artificial intelligence expert expert company. And we've been talking for some time about using that type of technology to interrogate the library of donors, interrogate their genetics, and then use machine learning to pull out which donors give me the best traits to convert to this patient. And if I can give those to a patient who might have an underlying genetic predisposition to disease, can I counteract that? And so that's where I think the future of cellular medicine is. The future is coming up with the right mix of donors that allow allow Darwin natural selection, Darwinian natural selection, to to select for those traits that maximize and optimize your health and disease resistance. And and it's one of the things that turns me on. I mean, this is what gets me excited. Jesus. Yeah, that's very interesting. So go back to COVID for a second. So So let me give you So I I I know where you're going. Let me preempt you. Please. We talked before about the fact that from any stem cell in the placenta, I can produce any mature phenotype, any mature cell type, a brain cell, a heart cell, an immune cell. Now, we recognized another observation we made. We talked about the observation of um uh placentas being one-size-fits-all, universal donor cells, and all that. The other observation we made was that one out of every thousand pregnant women has some form of cancer during pregnancy. But the transmission of cancer from a mother to a developing fetus essentially is non-existent. It's so rare that the few few reports of it haven't even created a causal relationship. So the theory was The theory was that something is protecting Something was selected for in nature to protect the developing fetus from a threat like a like a a transferred disease from the mother, like a transferred cancer from the mother. Okay? Now, we went looking, what could possibly be behind that? And we found that the placenta has a population of immune cells called placental natural killer cells that are part of the innate immune system, which means that they don't have to be educated. They come out they come out punching. They're already primed to protect the developing fetus. And if you think about it, right? A human being devotes nine month months of reproductive energy to one offspring. Natural selection is going to do everything to keep that offspring viable to get the full term. So, to protect against cancer transmission threat, to protect against infectious disease threat, we theorized that this natural killer cell played a role. Because remember, when a baby is born, they're born with their innate immune system and a limited adaptive immune system because they haven't been exposed anything yet. In the window after birth, what's protecting that newborn from an infectious death? So, we started to test this hypothesis and found that the natural killer cell is pre-programmed to traffic to and destroy cells that express certain markers on their surface called stress antigens. A stress antigen is a flag. It's a flag the cell waves to say, "Hey, something's not good here. Kill me." Right? So, it turns out that stress antigens expressed on cancer cells, virally infected cells, and this is exciting, senescent cells. The same stress antigens make them the target for these NK cells. So, think of the NK cell as the cleanup cell. It's the seek and destroy cell that goes out, kills kills uh stress antigen expressing cancer cells, stress antigen infect expressing infected cells, stress antigen infecting old senescent cells. Now, we tested this hypothesis and it works. And so we currently are are using placental natural killer cells to treat cancer. We've used them to treat viral viral infections like COVID. And we're using them to treat age-related degenerative cells, senescent cells as well. So we believe that the placenta is the best source of immune cells that clean up bad stuff, help create an environment that promotes survival of the healthy cells, and is renewable, can be redosed, reutilized as you live your life because the threats you are exposed to in your life differ. It's COVID today. What's it's going to be 10 years from now? So that same mechanism that protects you today, we believe will be therapeutically useful to protect you in the future. Whoa. Okay, so we are we're able to train the stem cell. Nope, you didn't want me to use the word train. We are able to create the milieu so that it becomes the cell that we want it to become. Can we turn one into one of these killer cells? Absolutely. Or or do those have to come from the placenta? Or we now know what the chemical signals are to get it to become what you call it an NK? NK NK. NK. So I can I can convince, I'll use the word convince, I can convince a stem cell from the placenta to mature and specialize into virtually any phenotype mature cell we know of. In order to get them to become natural killer cells, we get to a state where we have the hematopoietic progenitor stem cell. That's the stem cell that matures from the original stem cell, but specializes to become red blood cells, white blood cells, and platelets. And when I get it to the point of making a white blood cell, I simply nudge it to become a natural killer cell. Now, I can mass-produce those natural killer cells, and I can administer them to you as a therapeutic as a one-size-fits-all therapeutic product. So, if you think about it, for a cell therapy product to be meaningful, you got to make it. You got to make it with such quality that it meets a high standard like a pharmaceutical. You got to You got to make sure that you can administer it safely, and you got to be able to do this without breaking the bank. So, there's no better place to find cells to do all this than the placenta. There's no better place. There's a There's This is a This is a raw material. This is the In my opinion, the most valuable biological raw material we know of. And And we've been We've been working on this for 25 years. We've built all the systems. We've procured cells and biomaterials from approaching 100,000 newborn donors in our in our history. And that's just the tip of the iceberg. So, here you've got a natural resource I call it nature's crude oil. And all we had to do is develop a refinery system. And by the way, aside from the cells we get from the placenta, we also harvest the structural biomaterials from the placenta, and we turn those into products. What does that do? So, um I think you may have seen I may have shown you from the placenta, we take the membranes which create the amniotic sac, and those membranes can be can be processed to remove the cells, but leave behind the three-dimensional architecture. I can then dehydrate it and sterilize it and put it on the shelf, and if a surgeon needs to replace a tissue and create a tissue repair template, they can use that product right off the shelf. I I take the structural materials and break them down into the component structural structural elements that are a couple of couple of microns in size and I can administer those to boost or augment your your your structure in order to allow the repair process to occur. So, let's look at a thing like a like a wound or a non-healing fracture. In the defect of the wound or the non-healing fracture I have cells that are dividing, but they need to stick to something. If I can give them something to stick to, what we call a template a a repair template we actually can can support the functional restoration of that tissue. And I could show you examples in burn patients. I could show you examples in patients with non-healing diabetic ulcers. I can show you examples in patients with uh um with defects from traumatic injuries where just the introduction of the structural material supports repair. Now, think about if I use that plus the cells, how how much you are basically mimicking nature's attempt to and you're augmenting nature's process of of repair. And that's what what cellularity in our technology is focused on, providing these very very biologically logical tools to augment repair, regeneration, and restoration of function. What's the state of the art with burns? I heard about the skin gun. Yeah. Yeah, like 6 years ago. Is that real? Absolutely. So, so Steve Badylak in Pittsburgh one of my one of my heroes. Brilliant brilliant by the way, I think he's an MD, DVM, PhD. He's got all He's got a lot of credentials. Lots of initials. He's got the longest business card in biotech. Um you know, Steve showed that that that you can spray some of these structural elements onto a defect and they will again set up a repair template, encourage the the arrival and that attachment of cells, and then the cells will start the process of rebuilding that tissue. Makes a lot of sense. You know, again, as an engineer, every every structure in our body, every every piece of our anatomy is a combination of structure and cells. It's like if you build a house, what do you put up first? The frame. Mhm. Right? The frame then supports the attachment of of the of the matrix components, the cells that ultimately create the living tissue, the functional tissue. So, if if your problem after a burn or after an injury is you're making cells, but you're not making matrix, then where do the cells stick to? And so, I you I often I often describe it this way. At the heart of a wound, a non-healing wound, you have a tremendous stimulus for cell division at the margins, right? At the margins of the open wound, the cells say, "Hey, wait a second. We're not This isn't a closed tissue. I need to make more cells to close the gap." When they make more cells, but there's no temp there's no matrix there, the cells just get dumped into the into the void and they become what's called exudate. An exudate is that liquidy kind of material that [ __ ] sort of material that is is is basically washes away over time and the defect doesn't close. But, if I put a template in there, if I put this structural material in there, and the cells can attach to that structure, they're happy. They start to divide, and when they get close enough, you know what the cells do? Mhm. They form what are called tight junctional complexes. The cells at at connection points anchor to one another. And when they anchor to one another, they can actually contract and pull the wound closed. That's how wounds heal. So, all we're doing by taking these materials out of the leftover placenta is we're providing a an alternative to nature's attempt to close these defects by supporting it with a supplement. And the supplement is in the form of a structural material and or the cells. Are we at the point now where we could, if somebody had a scar, we could go in sort of create the wound again and lay the structural material down and eliminate the scar or we still a ways away from that? So, we're absolutely at this point. In fact, scar revision surgery, when someone has a has a an injury or a wound and it doesn't heal and they get these na- nasty um hypertrophic scars that look terrible, what surgeons do is they cut that scar out as cleanly as possible, doing as little damage to the underlying tissue as possible, and they hope that they can restore continuity and minimize the the the secondary, the next scar. Well, the best way to do this is to introduce components that the body would have to synthesize on its own in order to shorten the time for that process to occur. And so so we already know that these biomaterial products can help and we are certain that the cellular products, even the byproducts of these cells, can help support and encourage and augment and and and accelerate that repair process. That's crazy. So, you kind of melt in my brain a little bit with the uh chimera idea and being able to make somebody's I don't know if it's only the immune system or if it's anything, but to make them more robust by introducing the new cell types. And then um also I want to go back to you've got the stress flag that the cells are waving. How advanced is that process? Because theoretically, if you can swap out all of your senescent cells, that really would be where you're aging literally backwards. And so is there a tolerance? Like is there uh a point at which it's too many cells? Like going back to Lisa and I, so if you take my stem stem cells and you're putting them in her, you were saying, "Well, if she's 20 trillion cells or whatever and you inject 1 million, it's not a big deal." But what if it's 10 trillion? Like is there a point at which like it becomes an issue or no, we can just the more the merrier? You know, we're still working on the calculus of cell therapy, right? We know for example in in immunotherapy for cancer, where we're introducing a a an immune cell, that there's clearly there's clearly a calculus. You need so many immune cells to defeat so many cancer cells, right? There's no doubt about that. In regenerative applications, regenerative medicine, we're going to figure that out, too. But remember, if the cells I deliver to you in a million cell dose take up residence in your body and they themselves propagate and expand, maybe that million cells over the course of 6 months to a year turns out to be a billion cells. So the contribution to your overall biology will actually be be enhanced. Now, consider this for a second. The process of aging, okay, which you know, there's lots of theories behind it and so on. And we don't yet have great tools to figure out what your real biological age is. I've been convinced What do you think about the Horvath clock? that these clocks are really important. In fact, I was with Morgan Levine from Altos Laboratories uh maybe a week or two ago talking about this. There's no doubt in my mind that epigenetic changes that are accumulated in your lifetime can be thought of as a metric for the age of your of your the biological age of that cell. Now, we we still don't fully understand how much DNA methylation is too much. But, here's the bottom line. The closer you get to a newborn source of cells, the lower the amount of methylation that exists on the DNA. So, if I introduce that cell into an individual, by definition, I've put a younger cell into an older system. Now, now hear me out for a minute. If you say that we are we are the summation, we are the sigma of all of the all of the ages of the cells in our body, by the time we reach 40, 50, 60 years of age, the vast majority of our cells are going to have advanced age, biological age. And if I want to if I want to change that, I either have to pull out the really old cells or I have to introduce younger cells that change the sigma, right? If if the average is a function of the age of 5 billion cells out of 5 trillion cells, do the math. You can figure out how much you can affect your your overall biological age by looking at that that calculus. But, consider also that we're at a point now where you have to look not just at the DNA methylation as a marker of of the age of the cell, but you've got to look at things like telomere length. And you know, telomeres often at one time thought of as being a potential biological clock. Telomeres, which protect the ends of our chromatin and are are exhausted after repeated cell divisions because you literally degrade the telomere as you as you divide. The other thing to keep in mind is that your your your mitochondria age as well. So, any cell coming from an older donor, older source that has short telomeres, older mitochondria and lots of DNA methylation by definition ain't going to make you younger. Mhm. But, a cell from a newborn with long telomeres with with very very little if if any DNA methylation um and really young mitochondria that's what I want to put into my into my uh into my tank. So, stem cells if if I were to take my own skin cell or whatever, spin it into a stem cell and reinject it those are going to be aged cells. Yes. Okay, so they're still going to carry some of the methylation, the short telomeres. That's right. So, so that's that's I wondered about that. So, that's a that's a really good point because the the world has made great advances in induced pluripotent stem cells. What that means is and Yamanaka who won the Nobel Prize showed that you can take you can take a mature cell and you can you can coax it into becoming more stem-like with a with a series of factors, a cocktail we call it. The the reason for inducing pluripotency is because most adults don't have their own cells stored away from birth. Right? The problem is that everything that's done to induce pluripotency in in a mature cell is already resident in a cell found in a newborn. And so although I might be able to coax this cell into behaving like a stem cell it doesn't necessarily have the biological quality of a newborn stem cell. So, if you think about this, well, how do we get to that mature cell, that mature specialized cell? We get there by a series of of cell divisions and cell differentiations. When a cell goes from a stem cell to a mature cholinergic neuron, a specialized brain cell, every time it divides and specializes, those specializations are a series of gene silencing events. So, if you think about it, you have all this chromatin, okay, when in a in a in a in a stem cell, but if I want to if I want to become a a cholinergic neuron, I don't need 40, 50% of the genes to be expressed. And so, what nature does, in order to create a more efficient terminal phenotype, is it silences those genes. It literally takes the chromatin and kind of crumbles it up and keeps it out of access to these transcription factors. By doing that, you've created a cell that's very efficient at being a neuron, but not versatile. So, Yamanaka's work showed that you can take that cell and you can coax it back in to behaving like a stem cell, but you don't necessarily make it a younger cell. So, there's two different things, right? There's stemness and then there's and then there's young versus old. So, if you take placental stem cells, you can make them replicate? Oh, yeah. And they will stay young forever or do they age as they too. But if I have a supply of the young ones, if I have a supply of these ones which are young and uncorrupted, and I just keep introducing them into the system, what what what what effect will that have? So, you and I talked about this, I think, when we were like sitting around. It turns out that maybe 15 years ago, the theory that we age because we use up our stem cells drove me to a set of experiments where I collected the stem cells from the placenta of newborn rats. And I processed them and just the same way we did with our human cells and I cryopreserved them. I put them in a state of suspended animation, which means that they they're going to be the same 10 years later than they are today when I thaw them. When I took those cells and gave them back to the animals as they were aging Their own cells. Their own cells. When I gave them back as they were aging the cells that got the animals that got their cells back lived 40% longer Whoa. 40% longer than their littermates. Yeah. Whoa. Yeah. And and they were bigger and stronger and meaner, you know. That to me said, "Hey, one of the most obvious places to look here is can we create a biological state with enhanced youthfulness by simply averaging down the age by introducing these young cells into an aging aging subject?" a more potent effect if they were your stem cells? Right now, I don't think so because again, the placental cells are the universal donor. I think there are advantages to giving someone else's placental cells because you get that chimeric benefit. Yeah, that Okay, so huge impact in rats. Are we running any long-tail studies on aging, life extension, and stem cells? So, here's the dilemma we have. Um to the regulatory community and to and to a good part of the clinical community aging isn't a disease. Right? Aging is a process. Mhm. And and so it's very difficult to convince that community in all cases that an attempt to address aging as the indication is ain't the way to go. Because first of all, how long would the study have to be in humans? Yeah. You know, decades? You know, how are you going to show that you can slow aging? Are you going to start treating at 20 and look at them when they're 80? It's kind of tough, right? It's long. It's long and there's and no one's going to care about But no one's going to invest in that. Fair. Okay, but Very fair. What we our approach is to say, well, well, let's look at conditions that are a hallmark of aging. Mhm. One of those conditions you and I know about very well, sarcopenia. Age-related loss of muscle mass, sarcopenia, is in fact a a hallmark of age-related degenerative processes. If you say that can and and and you remember from our from our days developing strategies to block things like myostatin, that if you can and if you can um in in in essence um have a have a a known rate of decline in an organ or tissue, and in muscle, we estimate that after the age of about 25, average people lose 1 to 2% of their lean muscle mass every year. Whoa. Right? And by the way, you you've helped provide tools to address one of the reasons why we lose muscle, which is a protein defect, right? If you now say, okay, I'm going to administer something which is going to block or reverse the loss of lean muscle mass and maintain the integrity, quantity, and quality of muscle tissue into our advanced years, is that a tool we'd use to address aging? Mhm. And I argue that yeah, it would be. And so, we're we're deeply committed to exploring how placental newborn derived stem cells, administered to support the integrity and the health of our muscle tissue, might be one of the most actionable ways to address aging. And let me give you one one clinical reason why I believe that. Yeah. The Karolinska Institute, which is like the Mayo Clinic of Europe, they did a study where they followed 9,000 men for 25 years. Like a Framingham type study. Yeah. And they were looking to see whether they could correlate body mass index, BMI, to risk of risk of death and risk of risk of death from cancer, risk of all death, risk of death from cardiovascular disease. And the everyone assumed that of course BMI is going to definitely have a relationship. What they found was that BMI wasn't correlated. What was correlated to resistance to death and death from cancer and heart disease was was muscle mass. That's why BMI is dumb. BMI is very dumb. It doesn't differentiate between fat and muscle. The average bodybuilder, extreme athlete you find at the gym, is morbidly obese by those scales, right? Right? The truth of the matter is that that BMI ain't related to your your risk profile for certain things, but if you maintain your muscle mass and strength into your advanced years, 70s and 80s, Mhm. the report showed you had a lower risk of dying from cancer by 30 to 40%. cancer? I'm really scandalized by that. You You think Please. tell you why. Your muscle mass makes up in the average individual 50% of your wet body mass. Yeah. Which means it's the largest venous capacitance organ in your body. You have more volume of Venus blood in your muscle tissue than anywhere else, right? It's just a It's a lot of tissue and a lot of blood vessels. In your low-pressure Venus system is where the blood that the blood cells, the immune cells, and the stem cells that are traversing your system, they stick to the walls. They stick to the walls of those little low-pressure blood vessels. Why do they do that? Because they're sitting there waiting for signals to traffic into the system. What's one of the best things you can do uh in response to injury or illness? Exercise. Exercise helps mobilize those immune and stem the flu, I should work out? Absolutely. What? Absolutely. And by the way, 100 years of bed rest after MI and after surgery, why do you think we get patients up walking hours after their surgery? Hold on. Hold on. Hold on. Hold on. We have a Bilyeu family rule. If you're sick, you need to take the time off from the gym. Because you're going to wear yourself out, you're going to decline your immune system, you're going to stay sick longer. I I could pass a lie detector that that is 100% guaranteed true fact, and you're telling me that it's delusion on my part. In your household, that that may be one of the tenets, but I would say you need to test the opposite, which is that if you actually exercise, and if you actually Aren't you just running yourself down? No. Because look, if this works, the next time I'm sick, I'm going to [ __ ] hit the gym. to. You have to. You have to. Weird. Is this going to shorten the amount of time that I'm sick? Absolutely. Because I'd do anything to shorten the amount of time I'm sick. Remember, the immune cells that are going to protect you from that infectious illness, if if if some of them are sitting laying in wait in your in your muscle tissue, But isn't there such a thing as fatigue? Like you're just wearing yourself out. The reason you feel fatigue is that your immune system is is needs needs reinforcements to combat the illness. You know, like with COVID for example, some of the problems with COVID is that you have you have residual effects of of highly stimulated immune system localized that needs support. And and it's very very clear that even things like massage help mobilize immune cells and stem cells that take up residence in your muscle tissue. So, next time you're sick, give me a call, okay? Yeah. But I'm going to insist you go to the gym and work out. Work out work out work into a big sweat and and I guarantee you I guarantee you you will feel differently than you expected to feel. Hm. Man, that is one thing like Lisa and I have talked a lot about that cuz she is a a workout demon. Right. And she no matter what, sick, whatever, she wants to be in the gym and I'm always like, you are going to make yourself sick for longer. You're wearing yourself out, you're you know, taking your immune system down. That's crazy. Well, don't take it just for me. I want you to talk to any cardiac surgeon you know, any any surgeon that you know, and you ask them, "When you guys started 20, 30, 40 years ago, didn't you keep patients in bed after surgery? How come now you get them up walking immediately? How come you you increase are we talking? Oh, cardiac surgeries patients will be walking the night of their surgery. Whoa. Oh, yeah. Wow. So, there's By the way, and they they do it for lots of reasons. They do it in order to prevent stagnation of of of of your circulating blood. They want to make sure that you're that you're not developing clots in your small blood vessels and so on. But there's another big component of it which is that active muscle active muscle actually helps your immune function and helps initiate the process of repair and recovery. Hm. All right, if I'm injecting stem cells in the way that you're talking about to fight the loss of muscle mass, Am I going to just not lose the muscle mass or does this have an androgenic effect? Like if I am taking stem cells, obviously I still have to work out, but if I'm taking stem cells, would I add more muscle mass than I otherwise would? We have We have data from some of our clinical studies not in muscle loss, in other diseases, where the injection of of these stem cells into muscle tissue encourage both improved uh circulation in the muscle, actually actually allowed us we saw that collateral circulation was improving. Um and we saw improvements in muscle mass and function. Now, we are studying now. We have a current IND, an investigational new drug application on file to look at forms of muscle loss associated with inherited diseases and ultimately acquired diseases. I am extremely convinced that we will show that you can in fact augment um uh and and increase the quality and I believe the quantity of muscle tissue with the introduction of these stem cells into your muscle uh as as a therapeutic. Mhm. All right, that definitely starts to get interesting, especially with the correlation. I'd never heard that it's muscle mass is correlated to inversely correlated to incidence of cancer. That is really intriguing. Talk to me about genomics. Like what is the role of our genes play in this? Is this going to be able to combat that kind of thing or they're just totally unrelated? No, this listen, everything everything draws back to your underlying biological software and what that encodes for everything from the health and integrity of your stem cell population to how those stem cells function. There's no doubt about that. However, we already know that that you you may be born with a certain genome. That genome may in fact be affected by we talked about before epigenetic changes and so on. But consider that if you can actually boost or augment your genomic um uh capabilities with chimeric therapy or the introdu- introduction of a therapeutic product that even exists transiently in your body, like a cell therapy, that the more the more genetic alleles you have access to select from, the more likely you are to accommodate for any disease or illness. And that's again, that's that's that's the process of natural selection. Biology biology is driven towards whatever allows survival, right? It's it's one of the reasons why um uh you know, even even viruses, which are not living, need a host. And if the host isn't viable, the virus goes away. So, viruses that kill too fast don't stay in the don't stay in the environment too long, right? Um so, you know, it's a complicated it's a complicated um dance between the programming in your genes, the quality of the stem cells in your body, and the and the the diseases and the threats they have to address. And if you and if that balance is always shifted towards giving you the greatest optionality, genetic optionality, cellular optionality, you have the greatest probability of being able to survive. What do you think about fat in all of that? So, obviously keeping muscle mass high critically important, but fat is an organ as a as an organ that secretes hormones, like what what is that role? I do worry about that in terms of you can have all the muscle in the world, but if you also have a ton of fat, then you're going to be creating problems for yourself. You know, the reality is that the the experts in metabolism um will tell you that that um you need a certain degree of fat for normal biological and anatomical functions. You know, fat plays a lot more of a role than just storing uh storing energy. Fat also plays a role in in um in cushioning your organs and your tissues. In other words, believe it or not, you have fat around your organs and tissues that are there to provide shock shock uh suppression, okay? Um and and there's different types of fat that when stored it's harder to mobilize them in order to create energy, and in some cases that fat can actually wind up having you negative impacts on your anatomy and and so on. However, when you are operating at a maximum optimal lean muscle mass I guarantee you you'll have the best balance to the to your fat stores because that muscle mass helps control the level of fat that you develop. Right? I mean, you know, the the um you've heard about the uh uh the the what do they call it? They call it the the skinny fat, right? People who appear to be thin and in shape who actually if you actually look at them if you actually dissect them, you realize that they have very little muscle mass and and it's been replaced by by fatty tissue. That's actually age-related sarcopenia. There is a there is a balance there that that can be optimized if you opt if you focus on optimizing one system, which is the lean muscle mass. Very interesting. So, you have less concern, I'm putting words in your mouth, so correct me if I'm wrong, but you have less concern about somebody carrying too much fat if they've got the muscle to back it up, and in fact, there is such a thing as too little fat. Absolutely. I mean, we know that from the population of cachectic and anorexic patients, right? Well, so put the muscle back on the anorexic patient or a bodybuilder for that matter. They're getting down to, you know, 2-3% fat. Like, are they I doubt this has been studied, but are there If you've got a gaggle of muscle mass, but very little fat, are you Does your survivability start to go down? So, I don't want to I don't want to make any statements about how how long can you be in the true bodybuilder phenotype in your lifetime and still be healthy? Yeah. I don't I can't answer that, but I don't believe personally that the the the true competitive bodybuilder phenotype is a form that you can sustain your entire lifetime, okay? Look at You remember Jack LaLanne? Of course. Jack LaLanne was an incredibly fit guy. He wasn't 2% body fat. No, no, no. Right? He was more like the norm. I think that that the the quest to reduce body fat for the aesthetic purposes, okay? In temporary or transient use so supports the the objectives of that particular individual, but over a long sustained period of time, I think it's dangerous. All right. Obviously, you co-authored the amazing book Life Force. Where else can people find you? So, a couple of things. So, I'm really excited. You know, one of my important partners in in this whole quest is is is DLP, a company that that not only has deep interest in their business, but also in in advancing the state of health around the world. So, you know, we're very excited about about the success of the book, but we're also very excited about working with with one of our partners, DLP Capital, which is not only supportive of their of their business, but also using their business to to advance progress in our field. Um I'm very, very excited to be one of the speakers at their event in Puerto Rico, in San Juan, the 9th to the 12th of November. And for those folks who want to actually come and hear me, meet me, speak with me, uh or talk to other of my colleagues, we'd love them to go to dlpcapital.com. Under events, they can actually register for this program and they can join us. And I can tell you, having been at several of these, it's it's it's one remarkable assembly of of of of investors, health-conscious people, uh scientists, physicians. And I'm excited about being able to talk about what you and I have been talking about, as well as some additional things we're doing at at Cellularity and at and at um uh Fountain of Life, which as you know is our clinic operations. Love it. Yeah. Guys, if you haven't already, be sure to subscribe. And until next time, my friends, be legendary. Take care. Peace. If you want to live longer and feel younger, click right here to learn how to age backwards. So, we're reversing aging of the eye, that's not hard at all. But we can reverse the age of the liver and the skin.