The science of aging is far more exciting than the topic might first seem. Imagine maintaining your peak function for longer in life. Imagine damaging a part of your body and having that part completely regenerated to a state of full function. The potential for this is real, it might be realized in the near future, and it may come from major advances in the field of stem cell research. In a previous episode of humanOS Radio, I spoke with Dr. Aubrey de Grey about the current state of anti-aging research. One subject that came up was the role of stem cells in aging. Today we’re diving deeper into this important topic. So, what are stem cells anyway?
To grasp what stem cells are, think about the fertilization of a new human being. During this process, a sperm cell and an egg cell come together to form a zygote, a cell with the genetic blueprint for the development of an entire person. All of this person’s subsequent cells can be traced back to this cell. As a zygote develops, different genes in different cells are turned on and off, resulting in cell specialization (differentiation). Such specialization occurs in response to signals in cells’ environments (niches).
Not all cells become fully specialized, however, and stem cells retain the ability to become different types of cells (red blood cells, neurons, and so on). Stem cells aren’t uniform though, differing in what they are suited to becoming. Indeed, there are stem cells in many tissues (like heart muscles, skeletal muscles, and even the brain) that function as reservoirs of regenerative potential in times of need.
Over time, these stem cells are depleted, and they do not remain perfectly untarnished. This raises questions about the roles of these cells in the viability of tissues succumbing to the wear and tear of ageing. Sure enough, some researchers have proposed a stem cell hypothesis of aging, positing that biological age (as opposed to chronological age) is partly a function of the how changes in stem cells influence our bodies’ regenerative capacities.
In this episode of humanOS Radio, I speak with Dr. Mike West, CEO of AgeX Therapeutics. AgeX is a subsidiary of BioTime that is focused on the development and commercialization of novel therapeutics targeting human aging. Dr. West has been on the Board of Directors at BioTime since 2002 and is now co-CEO of this company too. Were this not enough, he is a Director of Asterias Biotherapeutics, another of BioTime’s subsidiary companies.
Dr. West’s current work builds on several decades of experience in biotechnology research. After graduating with a PhD in the biology of cellular aging from Baylor College of Medicine in 1989, he founded Geron in 1990. At Geron, Dr. West coordinated the first collaborative effort to isolate human embryonic stem cells for use in regenerative medicine. Geron also did research on telomerase, working with Thomas Cech (winner of the 1989 Nobel Prize in Chemistry) to clone a part of the telomerase enzyme. And Cech wasn’t the only of Dr. West’s decorated recruits, for Geron’s Scientific and Clinical Advisory Board included three (!) Nobel Laureates including James Watson, co-discoverer of the structure of DNA.
Dr. West’s work in this space continued as he transitioned to a role as CEO, President, and Chief Scientific Officer of Advanced Cell Technology (now the Astellas Institute for Regenerative Medicine), where he dedicated his time to developing cutting-edge human stem cell technologies for use in regenerative medicine.
That’s quite a strong résumé.
In this episode, I discuss a variety of important questions with Dr. West, including:
- The distinction between progenitor cells and stem cells.
- What goes wrong with stem cells during senescence.
- Current clinical uses of stem cell therapies.
- What Dr. West’s team is working on at AgeX.
- The future of stem cell therapies.
Tune in below to find out more!
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Dan prepared for and conducted the interview, Greg wrote the first draft of this blog post, Dan edited the draft, and Dr. West continues to do the hard work!
Mike West - 00:06: Babies are always born young. Why? How do those cells escape again, and then why is it that the cells in our body just age in a few decades, whereas those cells left no dead ancestors in the wake.
Kendall Kendrick - 00:19: HumanOS, learn, master, achieve.
Dan Pardi - 00:34: All right. Dr. Mike West thank you for joining me at humanOS radio. I'd like to begin with a quote from the increasingly aging scientist [Aubrey Dugray 00:00:41] who has been a guest on this show before. He said, "You've occupied a pivotal role in the anti-aging world as by far the most effective advocate for true anti-aging research within the private sector."
00:51: Today, I'd love to talk to you about your journey, the companies you lead, mostly the company AGEX, and the future of aging sciences. So to begin, you founded the biotech company GENERON in 1990. This is one of the first biotech companies in the aging space. Why did you start that company? What does it do?
Mike West - 01:08: You know I started it because I wanted to make a difference on aging in our lifetime and thinking about really strategically how that would be done. You have to be strategic don't you if you're going to change how we age in our lifetime. Of course, this was back ... I don't know, 1979 or so. I was sober about this. I mean, we knew precious little about aging. We'd have a really steep learning curve. I had reasons to believe that there was something to be learned, just looking at how aging works in nature, but still we had molecular biology back then. You know, the cut and splice DNA technology was just coming onboard right then. You know, we really didn't know very much at all really about aging, and so you had to be strategic. Part of my strategic thinking was getting a PhD, you could have an academic lab and if you worked really hard and wrote a lot of grants, maybe you'd have 10 or 20 people in your lab.
Dan Pardi - 02:04: Mm-hmm (affirmative).
Mike West - 02:04: But I thought if you did biotech and you could do it successfully, you could potentially have hundreds of people working on these projects, and simple math - 10 times the number of people. How fast a lot of the science can be implemented is really driven by headcount.
Dan Pardi - 02:20: I have to just acknowledge your bravery at the time because being one of the first true pioneers in the science of the aging process of the human body probably was not an easy task -
Mike West - 02:31: You're right about that.
Dan Pardi - 02:31: Because I think aging was relicated to that of fiction and woo, so it was probably an interesting terrain to navigate at that time to get people to take it seriously.
Mike West - 02:42: I won't name names, but I'll paint a little vignette here. One day I was talking to one of the professors during my graduate training. Again thinking strategically, I said okay we were studying the aging of human cells. The fastest, best way to get at human aging is to study human biology, and then well you can't really study humans and put them in a test tube, so cells cultured in a dish. Human cells age. They have this phenomenom known as the Hayflick Phenomenon where they age in the laboratory dish.
03:11: So, I was talking to this professor and I said, "All right. Let's get my arms around this problem. What we want to do is understand the molecular mechanisms that cause human cells to stop proliferating after a certain number of times. Once we figured that out, [inaudible 00:03:29] driven by genes or something, find ways of modifying those genes to slow or maybe even expand the lifespan of cells. Then figure out how that could be translated into a therapeutic that could be applied to humans in the context of aging." I thought that was very logical, and I looked up at his face and the look of horror on this professor's face ... I wished I had a little handheld camera back in those days and took a picture of it.
03:56: He looked at me like I was a fricken maniac, bonkers. He kind of gulped, and he said, "Well, Mike. At least you've got a good imagination." That was the world of aging research in the 80s. There was an immense skepticism that we would ever understand the aging of human cells, let alone human aging. That has changed dramatically but, you're right, it took a lot of courage to try to raise capital and build a company in the face of that immense skepticism.
Dan Pardi - 04:30: It has been promised for a very long time and, I think, not only just the challenge of understanding aging as it's happening but then also, as you're saying, just the environment at the time. If you were in that field, you're sort of a charlatan.
Mike West - 04:43: More than kind of. I had one professor when I was in school say, "You know, Mike, I thought of this too, of getting into the field of aging research because it's just so interesting." Scientists love to explore, be pioneers, turn over new rocks, find new things, you know? A person [inaudible 00:05:01] just eats that up, they love that. He was saying, "Boy you know, I would have liked to have done that, but I asked my graduate advisor about it, and he said 'well, if you want to ruin your career ... .'"
05:09: t was perceived as fringe science. Why? I don't know because any reasonable person could have looked and seen their premature aging syndromes where people grow old in their mid-teens. Clearly, there's biology at work here to be found.
Dan Pardi - 05:27: So speaking about ruining your career, you're now leading how many companies? Geron, Bio Time, AGEX.
Mike West - 05:35: I don't have any involvement in Geron anymore, and Geron drifted away from its focus on aging not long after I left.
05:42: Currently, I'm co-CEO of Bio Time, which is sort of the hub of the wheel here, the parent corporation. It's a public company.
05:51: Then, I'm running a new spin out of Bio Time called AGEX Therapeutics, and we plan to have that, AGEX, public here this year in 2018. Its focused 100% on aging and aging therapeutics.
Dan Pardi - 06:08: Specifically, you're going to be looking at, or are looking at, stem cells as part of this. I'd love to get an introduction to stem cells because I think they're coming into the awareness of the general public. There are more conversations on this. People that have huge audiences, like [Joe Rogan 00:06:22] have had people on, and those shows are very popular.
06:25: So, maybe we could talk about what are stem cells. What are the different types of stem cells that are being researched for intervention in humans? To just get an overview so people have a better understanding of that before we look at what you guys do.
Mike West - 06:38: Let me both explain what the stem cells thing is about, how it relates to aging, but also dispel some really significant myths about them. Lets see if I can do all of that in a quick manner here.
06:50: So, why would an aging researcher get involved in stem cells? The reason is really simple. It's like a detective story. It's like a Sherlock Holmes mystery novel. You try to figure out instead of the murderer, you try to find out the force behind human mortality. What's killing all humans? What's the agent of the crime?
07:08: One of the trails I followed in that detective story was a very profound one, I think, which is we're made of cells of course. I think people don't really appreciate what that really means. Our bodies are comprised of billions of living entities called cells. All these cells are alive in a very true sense.
(07:30): You can free them of the body, and they can live. We think we originally evolved from these single cell, kind of like pond water animals, but the glued together in the case of humans. Now, as I alluded to earlier, you can free them from the body and grow them in the dish, but they age. They replicate a certain number of times, and then stop. Very reproducible. It's called the Hayflick limit.
07:52: It occurred to me that there had to be an exception. There is a lineage of cells that connect the generations, of course. This is reproductive biology here. A sperm and egg get together and make one cell that then divides and makes a body, but it also makes the lineage that makes another sperm and egg cell that connects together and makes another human. That process goes on forever and, indeed, the cells in our body are the result of a like domino cascade of cells that have been doing this for billions of years and escaped aging.
08:29: All these things we think cause aging, DNA damage, cosmic rays, or free radicals, or whatever it may be, it doesn't affect those cells and that they continue to make humans. Babies are always born young. Why? How do those cells escape aging? Then, why is it that the cells in our body just age in a few decades, whereas those cells left no dead ancestors in their wake? That is the question that I pursued.
08:54: So, we learned some of the mechanisms behind that cellular immortality, but one would predict that if we could capture the cells right after the egg is fertilized by sperm ... so like if you do in-vitro fertilization. You take the sperm and egg and put them together in the dish and you make a fertilized egg cell, this cell will divide and divide. After a few doublings, those ... they're called pre-embryos or pre-implantation embryos. They're little clusters of cells that have not yet formed any of the cells of the body. We predicted if you could capture those cells, you would have what are called embryonic stem cells, and in the mouse, you can turn them into a mouse. It's really cool.
09:36: What occurred to me was they would still have that replicative immortality of the reproductive lineage of cells. They would not age, and anything you made from them would be young and we could make any of the cells from the human body from them. What we could do from a biotech standpoint is make sort of a parts supply store for the human body, making young heart muscle, young nerve cells, or bone cells, or cartilage cells, or whatever, and we could do that on a truly industrial scale. Something that medicine has never been able to do in the whole history of medicine. Right now, if you have heart failure, you might have to try to find a heart transplant because there's no way of injecting new heart cells into the heart.
10:21: That was the vision. It came to be called regenerative medicine, and the myth part of this is that those are called stem cells because they branch out like a tree. You know, making one cell type becomes many hundreds of cell types like the branches of a tree. Well, there's a lot of myths in regard to the ethics, so people perceive it as unethical. I strongly disagree.
10:41: Secondly, without naming names, a lot of snake oil, charlatan type folks have gone out there saying, "You've heard of stem cells. Well, we have them now and what they offer people are treatments today that have not gone through FDA regulatory approval." There are so many of these, it's hard to judge and say one statement about them all, but they may well be very unsafe and they may not work because they've never been demonstrated by any proper clinical trials in most cases.
11:13: Someone just sent me the cover of a newspaper here recently all about stem cells. It said "stem cell," as though there was one cell, and I knew that this was all this [science term 00:11:25] borrowed from President Trump. That's part of the mythology of this. It's tough for people to sort through.
Dan Pardi - 11:31: I'll do a little synthesis here. Some cells in our body stay young, so when we produce new generations of humans, they're young when they begin. When a sperm and egg come together in a blastocystis form, which is many different cells, it has not yet undergone this process of cellular differentiation, so that these fundamental building blocks of cells turn into liver or heart or brain tissue, but rather they have the potential to become all these different types of cells.
12:01: Talk specifically about how do different cells know ... what are the signals that they are given? They're all somewhat the same. What are the signals to become a heart tissue or muscle tissue? What is that process?
Mike West - 12:13: Probably the simplistic way of thinking about it, it's sort of like ... you've seen these cascades of dominoes.
Dan Pardi - 12:20: Yeah.
Mike West - 12:20: I've spent many hours to line up all these dominoes and see them all fall down in just a matter of 30 seconds or something.
Dan Pardi - 12:27: Those are great.
Mike West - 12:27: It's kind of like that. The egg fertilizes the sperm and you make a bunch of the cluster of these unformed cells, which are the equivalent of the embryonic stem cell. Then if the embryo implants into a uterus, which only happens about half the time, then you start a pregnancy. That's really where the individual human life begins, and the cascade starts. The cells ... one gene gets turned on, which turns on ten other genes that turn on ten other genes each and, like a cascade, they begin to form. As you said, it's called differentiation.
13:03: So this unformed cell starts to say:
13:05: "Oh, I'm going to become a nerve cell,"
13:06: "Oh, I'm going to become a nerve cell in the eye, in the retina."
13:10: "Oh, I'm going to become a rod or a cone."
13:13: And they make these decisions based on these genes, like switches get turned on and off in the DNA. In most cases, those decisions to become something, a skin cell or a bone cell or a blood cell, is a one- way process. Normally, they become a nerve cell, and that's what they are to the end of life.
13:35: The amazing thing is we've now learned how plastic that phenomenon is. We can actually profoundly change the fate of cells, even the mortality of cells.
Dan Pardi - 13:46: The other part that you mentioned that I did mention in my previous summary is that once cells differentiate and they become, let's say, heart tissue, I think we're increasingly learning that some cells of the body that we thought previously could not generate new cells, like in the brain, we know that we can generate some new nerve tissue. But like in the heart, once you have a myocyte and that becomes damaged, we have to do a heart transplant, instead of just growing new healthy cells in place of the damaged ones.
14:14: This here seems to be where figuring out a mechanism to utilize the understanding and techniques of stem cell differentiation in a full human being where we could somehow replace some or all of those damaged cells with new tissues, that would be a major boon for society. Is that specifically the type of work you and your team are looking at is looking at how to target stem cell knowledge to replace damaged tissue in the body?
Mike West - 14:40: You know, as I said, that's what came to be called regenerative medicine. The term was coined referring to what we're talking about right now. Now there are regenerative medicine skin creams and everything else, but that's what the term was originally designed to define. We've just really begun this revolution.
15:00: One of our sister companies, [Esterious 00:15:04], has a clinical trial underway for treating patients with spinal cord injury by injecting embryonic stem cells derived from cells for those patients. That trial has been doing quite well. We're injecting cells into the retina, so we've turned them into very young retinal cells for the aging retina. You get blindness. It's called age-related macular degeneration, and we're treating patients for that. Again, seeing some very promising results today.
15:32: There's a handful of other trials around the world, but there's literally hundreds of applications here. Making skin for burn patients, making cartilage for arthritis, Parkinson's disease, heart muscle as you mentioned. There's hundred of different kinds of cells in the body, and this will change medicine long-term forever. The hope is that one day you will never see a patient in need of some transplant or some replaced cells, bone marrow transplant or whatever it may be.
16:02: But that was really just the thought bombs that went off here in the last 20, 30 years. That was just one of them. Probably the next one I would point to would be there was this guy named Keith Campbell over in Scotland, in Edinburgh, at this animal research institute called the Roslin Institute. He tried this wild-eyed experiment. Remember how we were saying cells, once they differentiate, become brain or whatever, and they don't change. Keith tried something that he'd actually had to do an experiment kind of lying about what he was really intending to do. Of course, everyone thought he was bonkers, to use his own words.
16:43: Instead of a heart cell, he took a breast epithelial cell. These are the cells that make milk in the mammary gland in the breast tissue. There was a reason for doing that. They were culturing those cells for a reason, and he took that cell and put it into an egg cell, as though it were a sperm. Then he took the resulting cell, and put it into the uterus of a mama sheep, and got a baby lamb. Because it was made from breast tissue, they named her after Dolly Parton, and called her Dolly.
17:14: That experiment was a thought bomb because almost no one on the planet, maybe not the planet, other than Keith Campbell believed that kind of aging ... the aging with differentiation that occurs during development, was reversible. He did believe it was reversible, and changed the world forever.
17:34: That became what we call re-programming. It's like saying you have a floppy disc, the old floppy discs. You know, you stick them in the computer and you reformat them or reformat your hard drive, whatever. It showed that cells were completely plastic in that effect, and it really begged the question "Is the aging of human cells that plastic? Could you actually reverse the aging of human cells using the egg cell as a time machine, carry the cell back in time?" [crosstalk 00:18:07]. It is and it can be. Human cells can be reversed.
Dan Pardi - 18:10: So instead of just replacing cells that have aged because it has all the genetic information there, if you create the right environment, you could reverse them and turn them potentially into a whole different type of cell.
Mike West - 18:22: Most people heard about the stem cell thing. Like I said, there are myths. They don't understand what the real excitement about is that these [pleuracone 00:18:30] cells, as we call them, they [inaudible 00:18:33] eggs and can make young cells of any kind. But very few people have heard that the aging of human cells is entirely reversible.
18:41: The way we learned that was through some really ethically-challenging experiments that I led years ago at a company called Advanced Cell Technology. We actually did human cloning experiments, but not intended to make babies, but just this is a time machine for cells. That was around the year 2001.
19:03: That evolved over time into more sophisticated technologies where we no longer used cloning, but accomplished the same thing by a more sophisticated understanding of how cell aging can be reversed. That opened the door from taking a cell from 120-year-old person back in time to the cells they were born from. I think we pretty convincingly demonstrated that we could make young cells of any kind that you had 120 years previously, and they would be identical to the cells you had back then. To replace cells in the body, like fixing up an old antique car, the difference being that they would be your own cells, not cells of a different DNA type.
Dan Pardi - 19:49: I interviewed Mike and Irene [Convoy 00:19:51] from UC Berkeley awhile ago. They did the parabiosis studies, some of the first that were sewing an old mouse to a young mouse. They found that once the capillaries formed between the two mice, there's two things that happened.
Dan Pardi - 20:03: ... Once the capillaries formed between the two mouse, there's two things that happened. The younger mouse was made older and the older mouse was made younger. And they were then thinking, well what's going on? Is it their young factors that are going into the old mouse? Is it a dilution of old factors? But, one thing they're identifying essentially the microenvironment of these cells that are preventing stem cells from differentiating, that we have that are still young in our body that have the potential to become new tissue but just are stymied by inflammatory markers, et cetera. And so it makes me think that this pluripotentcy of if you can affect the microenvironment, it sounds like that would be one of the key factors to affect the age of differentiated cells. Is that what your focus is on?
Mike West - 20:42: Well, it's very similar to what you described in that when nature hands you this amazing holiday present and you open it up and like, "Holy cow, we could make," The pluripotent cells allows us to make human cells of any kind, that's just an amazing gift to mankind. Then, to have on top of that, the ability to transport disposable cells. I mean, you pull a hair out of your head and get living cells. And take a living cell from a patient and take it back in time and make the young heart muscle they had when they were born [inaudible 00:21:15] of economic and humanitarian benefit to mankind. Just an amazing thing. But it doesn't stop there. What you described was, like with those parabiosis experiments, you know, who would want to hook - if you're old, if you're an elderly person that's not doing well, who would want to sew your body to-
Dan Pardi - 21:36: To a millennial?
Mike West - 21:37: To your grandson, but you know, that's obviously not a cool thing to do.
Dan Pardi - 21:41: Well-
Mike West - 21:41: [inaudible 00:21:42] that there are people trying to do similar things, right?
Dan Pardi - 21:44: Right. The blood.
Mike West - 21:46: Reminds you of a vampire movie.
Dan Pardi - 21:46: Mm-hmm (affirmative).
Mike West - 21:47: And I think, by the way, some of that was the concept of those old vampire stories. But what science would do with that immediately and that's indeed what's happened in both these fields, parabiosis and what I just described about cloning, is to say, okay, but what in the blood of the young animal is making the old animal younger? So we don't have to sew the bodies together and do all that sort of thing. And the same thing, rather than doing this therapeutic cloning thing and trying to find human egg cells and do the cloning thing, what is it in the egg cell that does this? And that's what we call in science, reductionism. Reducing it down, boiling it down, what's the bare minimum number of molecules it takes to do the same thing? 'Cause you don't need all that other stuff. And that's what science does and routinely does and does quite effectively.
22:37: And so what we've done now in recent years - and it's really the basis of age factors you just described, is identified factors that reverse the aging of cells. And these factors - we call it induced tissue regeneration, because ... We could have called it reduced, you know, age reversal for that matter. But, what our goal is, is not to transport cells all the way back to these unformed cells. If we did, if I gave you a pill and I said to you, "By the way, the good news is this will profoundly reverse the aging of all the cells in your body back to the very beginning of life." You might be tempted to take the pill. But then if I told you, "By the way, it would reverse the differentiation of all the cells in your body so you'll be this puddle of unformed cells but boy, they'll be real young!" I think then you would say, "Oh, I don't think I want that pill."
Dan Pardi - 23:29: I don't want to be a 180 pound blastocyst.
Mike West - 23:32: Yeah, you don't want to be a blastocyst again, Benjamin Button or something. So what we've done again, trying to reduce things down to the bare minimum. What we're interested in doing at Ajax is finding these factors that can take the cells in the body back in time to reverse aging but only back in time to what we call the Weismann barrier. The Weismann barrier, named after August Weismann, a scientist in the 1800s who was the first to recognize that there's something that occurs after our body's formed that prevents cells from replicating forever but also prevents the tissue from regenerating, repairing itself. If you have a heart attack, your heart can't grow back. If you cut your skin, it doesn't really grow back, it scars over. Everything in the body scars. If you have a stroke, you have kind of a scar tissue in the brain, it doesn't grow back.
Dan Pardi - 24:23: Yeah.
Mike West - 24:24: But what we believe is, some of these animals that can do that, like the Mexican Salamander, you lob off a piece of its heart, it grows back, you cut it's leg off, it actually grows back.
Dan Pardi - 24:36: Yeah.
Mike West - 24:36: That that can be induced in humans by taking these cells way back in time in this way back machine but not back to the puddle of unformed cells. Just back to a regenerative state. And the thing that's really got us jazzed about this is we believe that these pathways are the same pathways that have, or downstream are [inaudible 00:24:58] things you probably had on your show before. Things like people working on mTOR and CER2 and growth hormone and all these sorts of things. These are the same pathways that are modified by what we call induced tissue regeneration.
Dan Pardi - 25:12: Mmm.
Mike West - 25:13: And so we're really excited about this and it's really the culmination of I don't even want to think how many decades now of R&D trying to get at a very ambitious program, you know, to profoundly impact the central biology of human aging itself.
Dan Pardi - 25:28: So I want to understand this with more clarity. Would your technology target, for example, scar tissue and reverse it back to healthy function cells? Or would it just try to avoid the scar tissue and just create more healthy new cells that would replace that scar tissue? What would that look like in the case of a stroke or a heart attack?
Mike West - 25:47: Right now, we see that it takes a few weeks to take cells back in time.
Dan Pardi - 25:53: Weeks? Wow.
Mike West - 25:55: Yeah, weeks. Yeah. So, it's not instantaneous, we're working on that. These are the early days, we haven't perfected the formulation of these things. We don't know how fast we can make it happen. But the good news is, in the case of stroke, you have weeks, it takes weeks in fact for the brain to regenerate and it takes weeks for scar tissue to form. So, that would work in the case of the brain.
Dan Pardi - 26:16: Yeah.
Mike West - 26:16: In case of like skin wound or burn, if you already have a scar from a burn or a wound or whatever, my best understanding is that this technology would not make the scar go away. But I don't know that for sure. But the thought is, is that if you had a fresh wound or fresh burn, it could be very effective at allowing tissue to regenerate normally without scar formation.
Dan Pardi - 26:38: So my instinct here is that the initial application would be reactive but the long term would be preventative. So reactive would be the issue occurs and we intervene at the right time interval to encourage a better outcome. So not scaring or scarred but plus additional function. But then, long term hopefully you could not have to wait for a problem to occur but you could prevent it from occurring all together?
Mike West - 27:02: I was in a hotel in Houston, Texas and Houston has got the Texas Medical Center, it's where I did my PhD.
Dan Pardi - 27:08: Mmm.
Mike West - 27:09: And Michael DeBakey was there, famous heart transplant heart surgeon. He handed me my Diploma, in fact. And there in this hotel wall, was a big picture of Michael DeBakey and it said, "Can you imagine a world where there was no heart transplantation?" And I said out loud, I think, "Yeah, I can." And that's the world we're trying to create. So-
Dan Pardi - 27:28: Yeah.
Mike West - 27:29: Our belief is that if we can take a cell all the way back to the beginning of life, taking it back to this regenerative state is less miraculous. The human body has that capability, it's just it gets lost. It's when we're first forming the body has that ability. It is a property of human biology.
Dan Pardi - 27:46: Mm-hmm (affirmative).
Mike West - 27:46: As is cell immortality, by the way, as we said at the beginning of our talk. And so, allowing us in our adult form of our life where as older people, to turn back on molecular processes that allow tissues to regrow after they're damaged, would forever change medicine. And it shouldn't be seen so miraculous because again, some animals can do it, we once did it, we just lose it as a part of normal development and aging. And we have very strong evidence at this point that this is where medicine's headed. So, good news for many people, I think a basis of hope. But then to be sober about this, these are the early days of R&D and it will take years to implement and perform clinical trials and to make these things available to patients.
Dan Pardi - 28:33: It exists in nature, it exists in us and we just, with greater understanding of those mechanisms and new technology to figure out how to implement the right way and with time to test and ensure safety, this could really be a possibility.
Mike West - 28:49: And let's add another thing. What is so exciting about current medical research is not what we just talked about. Although those things are pretty exciting. If I can go back in a time machine to that old graduate advisor and say, "Look what we did." That would be a lot of fun because what we already have seen happen in sciences would have been seen as miraculous just a few decades ago. But, what is maybe even more miraculous is the power of modern medical research. If I explained how, you know how we have this dialogue in the news media about the intelligence agencies monitoring emails and cyber communications and all of this, some people thinking they're communicating in confidence and they're not and all this, big brother's up there watching all your emails? Well, in a similar way, because of modern DNA sequencing technologies, we can read the entire genome of a person in one day now and under $1000 dollars.
Dan Pardi - 29:43: Mm-hmm (affirmative).
Mike West - 29:44: And we can read the emails within the cell. What are those? So, the DNA is the blueprint of life and then coded off from that DNA are RNAs, like messenger RNAs. And those are sort of the emails that get sent off to tell the cell what to make and how to behave and so on. And we can now read all of the emails of all the cells in the body, all the messenger RNAs, using this modern sequencing technology and do it for $300. And the amount of information that gives us, scientists are drowning in information, research that would have taken ... What we can do in one day for $300 dollars, would have taken us 1000 years and many millions of dollars-
Dan Pardi - 30:29: Yeah.
Mike West - 30:29: Just, you know, 20, 30 years ago.
Dan Pardi - 30:31: If we just didn't make progress and worked at the pace that 30 years ago had. If we just kept that, it would take 1000 years.
Mike West - 30:37: Right.
Dan Pardi - 30:37: Yeah.
Mike West - 30:38: So when I set off to work on aging, you know, back in the '80s. I had thoughts as to the kind of progress we could make using modern DNA technology. But I couldn't have foreseen the speed at which we could gather information. Now, really we're actually leaning a bit on computers and artificial intelligence-
Dan Pardi - 30:55: Yeah.
Mike West - 30:55: Too, with a lot of this because we just recently published a study where we were looking deep within cells, it was deep sequencing and thousands of different samples and the human mind couldn't possibly wrap itself around so much data and we used super computer algorithms and artificial intelligence to help us out. So, I mean-
Dan Pardi - 31:15: Yeah.
Mike West - 31:15: That should really be encouraging to your listeners that medical problems like cancer and others that were considered just, you know, not in your lifetime solvable, now there's immense hope in the medical research community 'cause of this unprecedented and really, unanticipated power has been put in our hands to decipher these riddles that have haunted mankind for so long. You know, what causes cancer? Why do some cancers go away in some patients? You know, what's the basis, what's the molecular causes of Alzheimer's disease? You know-
Dan Pardi - 31:46: Yeah.
Mike West - 31:46: These were deemed riddles for the whole history of mankind. In the lifetime of many now listening and many now living will see these things very much understood and in as much as it's within our power, a new path for treatment.
Dan Pardi - 31:59: I interviewed Ira Pastor, CEO of Bioquark who are looking to create what they call combinatorial biologics which is looking at the oocyte moieties and what factors can direct cells - as we are discussing, in certain directions and if we can understand the different species that have greater regenerative capabilities than us and what those factors are and then can we kind of transport that into knowledge in the human? But, in that conversation, I asked him if they're gonna be using machine learning and AI and the answer was absolutely yes and you know, whenever you're just dealing with things that have a combinatorial factor to the, whether it's just many different items that are taking part in the process. Then let's say it takes ten years for some of the things that we're talking about to come to fruition, like an understanding about how to completely end cancer, 75 to 90% of that might happen within the last six months of the ten year period but there's just this absolutely skyrocketing once we have the AI and computers doing analysis and crunching on it at a speed that is just [inaudible 00:33:00] unimaginable.
Mike West - 33:02: And all this is absolutely true, beyond dispute. But the implications to our society could be so profound. We have this baby boom tsunami coming our way, which I'm sure you've talked about-
Dan Pardi - 33:15: Yeah.
Mike West - 33:15: On your podcast. And it's gonna cost our nation trillions of dollars that we don't have budgeted. It's gonna be like a natural tsunami, it's gonna be disastrous 'cause we're just not prepared. But, what I'm telling you is that science and medicine have new understandings in our hands here that we can turn into therapies that would reduce costs because so many of the costs of aging are these chronic diseases where the body cannot repair itself, so you have chronic pain, chronic degeneration, you have to get a plastic or metal hip put in or whatever and it's expensive. And surgery's expensive, the rehabilitation's expensive and so on. Or blindness, you need help around the house, the shopping, it's just nuking our economy while these therapies could dramatically cut cost because if vision was just restored naturally, you wouldn't have to have someone shop for you, you could have an independent lifestyle.
34:04: And so what's really important is that we do some planning as a nation in terms of policy directives and there's none. We have almost none. There's a lot of talk about cutting drug costs but I've never seen anybody come to the scientific community and say, you know, could we cut costs by getting rid of, abolishing-
Dan Pardi - 34:23: It's a whole different model.
Mike West - 34:24: There's a lot of skepticism that would be the case but I can tell you, smallpox. Smallpox was a devastating disease, caused a lot of suffering and cost. It costs us nothing now because it's gone.
Dan Pardi - 34:35: Yeah.
Mike West - 34:36: And how is it gone? Science and technology. We made vaccines. It's gone. Medical innovation can cut costs and so if any of your listeners have any influence on government policy in the U.S. or in other countries around the world, some smart planning here to use this, what the scientific community is saying is we've got really incredibly powerful new technologies to solve these problems, now is the time in the history of our country to invest in this because by investing millions or billions, we could save trillions.
Dan Pardi - 35:06: With every, pretty much every person that I've had on the show discussing something relating to aging, there is this exasperation of the paltry amount of NAH funding that goes to the National Institute of Aging. I think it's 4% of the total budget and yet, if we understand these mechanisms of aging, it's almost like aging is doing a disservice. If you called it like, chronic disease prevention or something, they would maybe get on to the consciousness of-
Mike West - 35:30: National crisis tsunami prevention maybe?
Dan Pardi - 35:33: Yeah, yeah. Something like that.
Mike West - 35:35: But now, you say this paltry amount that goes to the National Institute of Aging, but the budget in the National [inaudible 00:35:38] Aging, a paltry percent. It used to be 3%-
Dan Pardi - 35:43: Mmm.
Mike West - 35:44: I don't know what it is today. They spent on the biology of aging.
Dan Pardi - 35:47: Mmm.
Mike West - 35:47: You know, the [inaudible 00:35:47] of aging. Most of it's spent on, you know, what kind of carpet to put in their nursing home. And-
Dan Pardi - 35:52: Right.
Mike West - 35:52: Or all the social things, which, you know, are ... I don't mean to demean those, those are-
Dan Pardi - 35:57: Yeah.
Mike West - 35:58: Helpful but what would really be helpful is to invent a world where people could have an increased health span-
Dan Pardi - 36:05: Yeah.
Mike West - 36:05: But live free of chronic, debilitating diseases and maybe even extend the human life span. That's usually not considered the goal of most aging research today, you know-
Dan Pardi - 36:15: Yeah.
Mike West - 36:16: It's [inaudible 00:36:16] to allow us to live healthy longer. Well, how can I summarize it? We know how to do it. We knew how to go to the moon in the early 1960s. I'm sure that's why President Kennedy said, "We'll do it in a decade." Scientists could assure him that we knew how to get there. We gotta do some engineering, it's gonna take a budget and a lot of people.
Dan Pardi - 36:34: Yeah.
Mike West - 36:34: And that's exactly where we are today in aging research. We know how to dramatically improve aging, even maybe the unimaginable-
Dan Pardi - 36:42: Yep.
Mike West - 36:43: Maybe delay aging. And we know how to get there but the small entrepreneurial efforts like what we're doing is not sufficient. We really need to ramp this up at a higher level and it would be great if governments planned for this and helped with financial institutes of health and so on.
Dan Pardi - 37:00: Yeah, it seems like because of the culture of just the way the world works today, that these things that we could take action on now to advance things so that we're equivalent of landing on the moon ten years from now, it's gonna just drag out. It could drag out 30 years and yet, we're gonna have this inefficiency of all the spending towards symptom management and appropriate rug placement and you know, if you will, in the nursing homes. Where we could be just addressing the fundamental nature of what's causing the chronic disease and all age related symptoms, I guess, much more directly.
37:33: So, my opinion is that once the world is able to see one clear win from aging science, then there's gonna be a lot of momentum that builds. What do you think that first win is? What's the nearest term win in the aging field?
Mike West - 37:50: You know, I don't know. Years ago, a colleague of mine, Saul Kent, who's founded the Life Extension Foundation, you know? And been an advocate of cryonics, you know? Freezing-
Dan Pardi - 37:57: Mm-hmm (affirmative).
Mike West - 37:57: People when they die. Saul is a very clever man and he always predicted that there would be - this is before the term tipping point, you know? But he always-
Dan Pardi - 38:06: Yeah.
Mike West - 38:06: He was very vocal, he said, "This is the biggest idea in the history of mankind." Which-
Dan Pardi - 38:11: Yeah.
Mike West - 38:11: Is hard to argue against. And he said there's gonna be a tipping point, but he didn't use those terms, a time when all of a sudden it all changes and people realize this and it's gonna be dramatic. And I always listened to him, 'cause he used to say it a lot.
Dan Pardi - 38:26: Mm-hmm (affirmative).
Mike West - 38:27: And I thought it was an interesting idea. It's hard to imagine why science fiction writers like Gene Roddenberry and others never seemed to work this into their stories, you know, when they envisioned a future a few hundred years from now, that everyone's still aging the same way and so on.
Dan Pardi - 38:41: Mm-hmm (affirmative).
Mike West - 38:42: But you're right. In that future, clearly society's gonna look back on us and think we're a bunch of barbarians.
Dan Pardi - 38:49: Yeah.
Mike West - 38:49: Why did they just bury their loved ones or daughters and their moms and dads and they just found that okay, you know?
Dan Pardi - 38:55: Yeah.
Mike West - 38:55: Why wouldn't they mobilize? Why did they find that acceptable? We're gonna have a change, a sea change here. What will trigger it? I don't know. There's clearly momentum building. As we started our conversation, when I entered the field back in the early '80s, it was a desert. There was no one who thought about this. Now it's very much different, now there are scientific journals devoted to this field, many new scientific papers coming out, lot of excitement building, a lot of science building. This will translate into public understanding. Will there be one trigger? Perhaps, there are animal experiments underlay. Most of these are behind the scenes, you're not hearing about them. To see can we genetically engineer profound longevity into animals?
Dan Pardi - 39:38: Yep.
Mike West - 39:39: Some of those might get published. But then people will say, "Oh, it's an animal, you know, that's not a human." On the cell therapy side, we're transplanting these young cells into the retina of old people.
Dan Pardi - 39:47: Mm-hmm (affirmative).
Mike West - 39:48: And the program's on track, we're seeing what we expected to see at this point. Some of that may be a sea change but your guess is as good as mine, I'm a terrible fortune teller.
Dan Pardi - 39:56: Well one thing that I think is really savvy of you and also might be that bridge between the way the world works
Mike West - 40:03: And also might be that bridge between the way the world works now by addressing symptoms of chronic disease that occur with aging, mostly, and age-initiated technologies ... so things around stem cells ... that can meet at addressing symptoms. The one that I'm particularly thinking of, which I think is really smart, is AgeX, that one, so looking to help with type 2 diabetes by increasing stores of brown fat.
40:25: Just for the listener, we have white adipose tissue on our bodies, which we now know is an exocrine gland that releases lots of different hormones, but we used to think it was just this inert substance that stored energy. Brown adipose tissue, we used to think only children had it, but it is a metabolically active tissue. It's brown, because it's loaded with mitochondria. What's so interesting about brown fat is that it converts calories that we eat into heat, and it's a very interesting way to actually handle blood glucose regulation. It's taking in blood glucosin; it's turning it into heat, so it's a great way to manage it.
40:56: I'm looking at brown fat from different applications related to sleep. Interesting, but we don't have to get into those. Tell us about your work there. There's a couple of different programs that you have. How far along is this one?
Dan Pardi - 41:05: Yeah, so it's one of the lead programs in AgeX-
Mike West - 41:08: That's right.
Dan Pardi - 41:10: It really should be renamed, I think. It's called brown fat, but it's really like anti-fat [crosstalk 00:41:15]. Normal fat stores calories; it disposes of them.
Mike West - 41:20: It's like a furnace, as you said, to generate heat in the body. We have a lot of it when we're young and lose it precipitously with age. This is really a new understanding. It's amazing, really. We've been, in medicine, dissecting bodies and studying the body for ... going back to the Greeks. How in the world medicine overlooked this tissue until just the last decade is just bizarre, but there you have it.
41:44: A new understanding of this and obesity and type 2 diabetes and all of its downstream effects ... this predisposes you to coronary disease and lots of other complications, diabetic [inaudible 00:41:56] everything else, is an enormous problem. I've had critics say to me, "Mike, okay. Let's say that you transplant these cells into patients that are struggling with weight control or diabetes or whatever, but come on. We've got the cure. It's exercise and losing weight."
42:13: My response is, "It doesn't work. People can't manage their weight this way. They've been trying."
42:19: "We'll have a national campaign. We'll put ads on television."
42:24: My response to that is, "Look. Most people take a shower every day. I do. Look at yourself in the mirror, and there you go."
42:32: Everybody, every day, is looking at themselves, and I'm sure they're motivated, saying, "I need to take off those extra pounds."
42:41: They don't, and this is just a real challenge. We've evolved. I have a dog at home, and I have some meat. This dog is at my feet begging. Why? It just ate. We have an evolutionary instinct, when food's on the table, to eat it. This is ingrained in our brain. It's a very difficult thing to fast, to exercise, and to lose weight, and our nation's not doing it. The United States, in particular, we're known around the world as being an obese nation, and I think one of the most humanitarian things, maybe the smartest business move we could make, is to provide an easy fix for this problem. We hope that this product will be that.
Dan Pardi - 43:22: I have been fascinated in brown fat for a while now and looking at all the mechanisms, the triggers, and I do a cold shower in the morning to try to [crosstalk 00:43:33] stimulate it. I look at different supplements like cinnamaldehyde and dihydrocapsiate, and I think that those are ... The question of whether or not you can regenerate brown fat where there was ... Let's say you had some as a kid. You became an adult. There was very little. How much can you get back? If you could use stem cell therapy to implant a lot more brown fat than you had previously ...
43:53: One of the differences, for the listener, for people who ... You can have two people that basically eat the same amount of food, and one person will get fat. One person won't. The other one that ... Some thinking is that their ability to turn that into heat is a major determinant in that person's ability to stay lean and healthy. [crosstalk 00:44:10] We know that obesity, such a problem, associates with 50 to a hundred different comorbidities, things that are also going to reduce your health and your longevity. Like you said, simple solution. Yeah, there's a lot of other reasons to eat well and exercise; keep doing those, but why don't we make it easier for people?
Mike West - 44:26: Another way of looking at it, too, is when we're young, most people are like me. I was on the thin side and got self-conscious of that when I became a teenager. People [crosstalk 00:44:36], "Mike, you're skinny."
44:37: I thought, "Okay, I'll solve that," and I went out and bought these milkshakes at the local ice cream shop. Also, they added milkshake formulas to gain weight, and I just stoked up on that stuff. I said, "Okay, I'm going to put on 10, 20 pounds."
44:52: I couldn't do it. I was young, and most people when they're young, you can just eat like crazy and barely put on a pound. If I did that now, I'd completely blimp out. What's changed? What we believe is ... It's aging, but a big part of it is precipitous loss of brown fat. It's kind of like balances the scale, and as you pointed out, it burns a terrific amount of glucose and circulating lipids. It also, the loss of brown fat, is implicated in climbing triglyceride levels and cholesterol levels in your blood, because this tissue absorbs that out of the blood as well.
45:29: Yeah, it's a new approach to obesity and eventually type 2 diabetes, which is likely our target indication for a clinical trial, and there's lots of exciting things here. We've made over 200 different cell types of the human body a scalable format, and we had to look at them and say, "What is the greatest unmet need? Where do we have the best competitive edge?"
45:53: The long list of criteria, and brown fat came up near or at the top of the list.
Dan Pardi - 45:58: I think that's really smart, so how might this work? Would a person go into a clinic, get some other tissue biopsied? That tissue would then be turned into brown fat for that individual, then planted back into that person, and then monitored, or would you even need to have tissue from that individual?
Mike West - 46:15: Yes, as we said earlier in our conversation, that is actually possible, so you could take some disposable cell, a skin sample or a hair plucked from your head or whatever, and reprogram those cells, take them back in a time machine, make young, unformed [inaudible 00:46:29] stem cells, and then turn them in to brown fat or heart muscle or anything else. They'd be your own young cells again.
46:35: The challenge of that approach is not the science. It's a combination of the cost and the adoption by industry, and let me start with the latter. Companies like off-the-shelf stuff. Pills are, for the most part, off-the-shelf, so yeah, sinus infection or whatever, your doctor doesn't personalize it to you. He just gives you a prescription for the standard dose, and you get the same pills everyone else gets. Large pharmaceutical companies and biotech love off-the-shelf products as does the FDA. It makes it easy. You can do quality control, which is everything about drug development and therapeutics development. All is based on quality control. You have to manufacture a really uniform product that's safe and works. An off-the-shelf approach, where everything's the same for everyone makes that tremendously easier.
47:32: Making cells from a patient and doing it patient by patient is extremely challenging for all those reasons, and FDA is very cooperative and would allow such a trial, I'm sure and everything. The costs of getting such a product approval would be multiples an off-the-shelf product, and it would cost, therefore, more for the patients as well. What we're targeting are off-the-shelf cells that we believe can be injected into all patients. They won't be your own cells. We believe they'll be in grafted and provide the same benefit, but they will not be your cells. They won't be anybody's cells. It'd be the same DNA type for all people, so that's what we're doing. That's the approach we're taking.
Dan Pardi - 48:18: I'm also now seeing that with a lot of these therapies, there's probably going to be clinics that open up that are serving more high net worth individuals that can afford the higher costs, and some of that will be speculative and possibly dangerous. There are people that are going to want to take action [crosstalk 00:48:33] now.
Mike West - 48:34: I'm sure there will be, and then I can think of two scenarios that ... almost inevitable, because of people's profit motive, right? One is off-shore clinics that say, "We'll do it now, and it's expensive." Billionaires can afford it, and that'll be one. I wouldn't be surprised if it's happening right now.
48:49) The second is the copy cat, I'll just say, "snake oil" type people who will say, "We have brown fat skin cream," or whatever it will be. The best bet for all the listeners is to consult their physician and try to get really solid medical advice and not follow up on something just because they hear it in a podcast or read it in a magazine. Be careful, because with the aging population having over 70 percent of the financial assets of the United States. [inaudible 00:49:20] six million Americans are going to have the vast majority of savings. They're going to be manipulated by opportunists that see an opportunity to cash in on aging, so your listeners should be very skeptical and very cautious here. [crosstalk 00:49:33] Wonderful opportunities, but opportunities to do good and make the world a better place and then opportunities for people to take advantage of other people.
Dan Pardi - 49:42: It's so true. Being a part of the ... let's call it the "biohacker" community, that is essentially people trying to figure out ways to optimize some part of their health. Either their healing process ... so I call them the "unsatisfied sick." They've gone through mainstream medicine and have really received only drugs to suppress symptoms ... to people that are performance optimizers or even aging optimizers or whatever that ... there's a lot of different categories. We're at this interesting place where evidence-based medicine moves slowly, and then it feels very outdated, oftentimes.
Mike West - 50:10: True.
Dan Pardi - 50:11: Then you've got this panoply of options, some of which have great potential, some of which are neutral and expensive ... You're just going to waste some time ... and some of them are dangerous. Maybe there's some cross-pollination there, too, where something that is very effective is also very dangerous. We just don't know enough yet.
Mike West - 50:25: Let me speak to that just briefly here, the dangerous part.
Dan Pardi - 50:28: Yeah, please.
Mike West - 50:28: When we're talking about free radical scavengers, vitamin E or C or whatever it may be, a lot of people heard the theories that we age because of free radicals. I had friends; you'd see them with a big pile of these pills, swallowing them after dinner. Yeah, it's called biohacking, right? You're taking science into your own hands. We now think that that actually might have hurt them more than helped them, but probably to a small extent. It probably wasn't terribly dangerous, although it might have had significant negative health impact.
50:57: I'm not a fan, myself, in my opinion, of growth hormone [crosstalk 00:51:02]. You see a lot of advertisements get growth hormone. In my opinion, it might make you look good in the near term, but I believe it accelerates aging. I think most gerontologists agree to that, but the technologies we've been talking about today, really profoundly reversing the aging itself by understanding the fundamental mechanisms behind the aging process, these processes are dangerously close, although not identical, to the processes involved in cancer. Right? Learning about what some of these agents are ... and patents are being filed. Many of them will be in the public domain. People can read about some of these factors and things and [crosstalk 00:51:42] saying, "I'm going to experiment on myself."
51:44: One should be careful, because the closer we get to modifying fundamental biology of aging, these are very powerful interventions, as you would imagine, and could have very powerful and negative consequences if administered in correctly. I would point to cancer being a major risk in that case, so just a word to the wise.
Dan Pardi - 52:05: Thank you for that, and I have two quick questions. Then I'll let you go. I've really appreciated all your input here, but one, do you see a future where stem cell therapy will be administered for system-wide improvement, instead of, again, trying to address specific tissue? I know that there are such things as IV stem cell therapy, so that's one question.
52:24: The other is around mitochondria, so while we have the ability to make cells younger, can you also do that to mitochondria? Does the reversal of a differentiated cell also reverse the aging that has taken place within the mitochondria in that cell, or is that something that needs to be solved as well?
Mike West - 52:42: Very sophisticated questions. On the mitochondria one first, the-
Dan Pardi - 52:45: Sure.
Mike West - 52:52: Some people believe that the mitochondria, of course, is the powerhouse of the cell in a sense, the battery of a cell, and some people believe that there's mutations that occur in the DNA of the mitochondria and that that's driving the aging of cells. I don't personally adhere to that hypothesis myself, but I do believe that there are age-related changes in mitochondria that are very reversible as part of this technology we're working on called ITR and does tissue regeneration or, as I said, could be induced age-regression. We should have named it that, because I believe there are multiple different states that the mitochondria can be in. One's a regenerative mode, and one's a non-regenerative mode. [crosstalk 00:53:24] regenerative mode is beneficial, and that is [inaudible 00:53:28].
53:29: Oh, then you asked about the systemic or whole-body administration of stem cells, and that should raise alarm bells in people's minds. The only cell that can reasonably be delivered to the whole body by injecting it, IV, into the circulation, are the blood-forming stem cells. [crosstalk 00:53:48] delivered that right way routinely. The concept of these cells that you can inject them and they .. I've heard them been called "ambulance cells." They rush to the scene of the crime and fix the problem, you know?
Dan Pardi - 54:00: Yeah.
Mike West - 54:03: I know a little bit about stem cells. I just don't believe that. I think it's kind of true for the blood cell, but I have almost no evidence for any other kind of cell. It has to be administered to the tissue, so if you had a heart attack, the cells need to be put in the heart. If you have arthritis, it would need to be put into the joint. Parkinson's Disease, the cells would need to be injected into the brain. If someone is looking at a local stem cell clinic and they say, "Oh, yeah. We take these cells, and we inject them in your blood," in my opinion, that's the basis to realize that you're being told a story.
Dan Pardi - 54:32: Yeah, so if things go perfectly, how soon do you think that one of your technologies could be in clinic?
Mike West - 54:38: We have multiple clinical trials now. For age-related macular degeneration, we have clinical trial sites in the United States. It started in Jerusalem, and spinal cord injury, we have multiple sites set up in the United States. We're about to begin a clinical trial, and our company [inaudible 00:54:55] making it a cancer vaccine, are getting this immortalizing gene called telomerase, which we didn't talk about much today.
55:03: Those are in clinical trials, and patients can look up some of those trial sites if they have friends or family with those problems. Approved products, while we're well within ... We're a public company, so we don't normally provide timelines unless we've officially announced them-
Dan Pardi - 55:20: Sure.
Mike West - 55:20: Any reasonable person would expect, if they're going to be approved by FDA, that they would be approved within the decade. That's an outside limit.
Dan Pardi - 55:27: Mike, thank you. I think being a pioneer as there is increasing appreciation of aging not being something that ... how to take care of older people so that they have a good life, but actually keeping us young, youthful, productive, happy, and functional much later into our lifespan. There's a lot more life in our years. There's going to be an increase in appreciation of that. There's going to be increasing appreciation of your work for being brave, for being smart, and for persisting so that you could navigate this tricky environment as the early stages. It's going to be popular soon, and a lot of people are going to be getting ... and it's getting there, but-
Mike West - 56:04: I wouldn't call it bravery. If you see a house on fire and there's a child in the window screaming for help, you run in. I don't know if it's bravery; it's just we've got a nation of people here that are asking for help. I think anybody in the scientific community thinks nothing of applying their life to that goal. [crosstalk 00:56:20] bravery. It's what any normal, decent person would do, but I appreciate all the intelligent dialogue.
Dan Pardi - 56:26: Thank you. Like you said, we didn't even talk about telomerase and all that, and I know you've done ... So much of your work in the past has been around that, so maybe in the future, we'll have a whole separate conversation about that.
Mike West - 56:35: Look forward to it.
Dan Pardi - 56:35: Thank you so much. Have a great day, Mike.
Kendall Kendrick - 56:38: Thanks for listening, and come visit us soon at humanOS.me.