Welcome to Stem talk. Stem talk. Stem bangkok. Stem, pot stem talk. Welcome to Stem talk. Where we introduce you to fascinating people who passionately inhabit the scientific and technical frontiers of our society. Hello? I am David Lame and I'm stepping in today to help host today's episode of Stem talk. Joining me is the main man behind the curtain, Doctor Ken Ford. I c's director and Chairman of the double secret selection committee that selects all of the guests who
appear on the stem talk show. Hello, David. Great to be here. For regular listeners of Stem talk, you may recall that David was our guest guns Stem talk episode 69. David is a physical medicine and rehabilitation physician who allows a pensacola practice just a few blocks from I. Where we're sitting now. His practice focuses on
lifestyle and performance medicine. He is also a visiting research scientist here at I. Thank you, Ken for inviting me today to c host the interview with Doctor Charles Sir, and a good friend of mine who has a harvard professor best known for his discovery of specialized per resolution mediator, Sp are molecules that can activate natural resolution of inflammation and help to avoid anti inflammatory drugs. The discovery of Sp has been described as spur a paradigm shift in understanding of
inflammation and human disease. Charles has the Simon Gel professor of Anesthesia at Harvard Medical School, and the director of the center of experimental therapeutics and fusion injury at B him and Women's hospital. He is also a c director of the B Research Institute. Before we get to our interview with Charles, we have some housekeeping to take care of.
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Charles, I understand you were born in Brooklyn, and that your father was a French Lebanese, and your mother was italian and both were born in New York City as a youth You were quite passionate about music. You learned to play the vibrant phone in junior high school and became so accomplished that you played professionally for about a year before going to college. How did you end up as a scientist rather than a musician?
Well, I felt that I still feel today that I could help many more people via science than I ever could in playing music. Although, I have to say that I still love playing and I feel very comfortable behind the vibes and It's like second major to me. What kind of vi phone did you play? I have a must if that's what you mean. Yeah. Yeah. An m 55. Mh. And those are known as the 1 night because you could travel around with them. But someday, I will get the gold set of fives, which is the studio set.
Still looking forward to that. There used to be guy up in the Boston area. I don't know if he's still up there, Gary Burton. Oh, draw 1 of my heroes. Yeah. He was... I was in the music business in the early seventies, and we used to book him, and he he was a very talented person. 4 mall pro. Yes. I I like to replace some carry burton tunes. He was dean of Berkeley, as you know for some time. And a fantastic musician, and he comes from the genre of big band.
And but his quart at work and the recordings he did with Chi korea just phenomenal. Right. No there was a period when he he was really amazing you was... He was experienced and skilled and still youthful at 1 point, you know, and it it was wonderful time with Chick korea and others, he's he's etched into my memory. Oh, yeah. I would always turn to play with my group when I was in school. 1 of his tunes called c journey. Yes. And fantastic.
You know, you mentioned that you had always liked science and had done well in science in school, which doesn't surprise me What was it about science that you particularly enjoyed? You said that you felt you could do more good in science for more people than in music, but but, you know, was there a particular thing about studying science that you really mostly enjoyed?
I really enjoy the rigor and objectivity and the ability to test hypothesis do experiments, doing experiments is, yeah, nothing more fun than that. After you were a professional musician, you you went to the state University of New York at Stone Brook. Yeah. I was lucky. Yeah. Eddie and you studied biochemistry and amino history there? Biochemistry was my major and chemistry. The his chemistry side came
in my research project. I was really fortunate to work with very good I in the Department of pathology. Yeah. So... And for people in terms of the audience and understanding, this is something that's used to diagnose cancer and predict treatment responses and likely prognosis of the disease. In terms of your your switch from, you know, musician to biomedical science, was there anything that carried over in terms of the music side that you felt carried into the scientific side.
Yes. That's an interesting point. Yeah. Many things that I learned in music translate to science. For example, if you really wanted to play well, you had to study and practice your scales and you did this routinely all musicians do. And it's like learning a language and in science, the same is true. You need to learn the language and study and practice every day.
Makes sense? Does for sure. So after earning your bachelor's degree, 1 of your professors convinced you to head off to York University for your master's and Phd and also you worked in the lab of Gerald Wi at Woods home marine biological laboratory. This all seems like a must been a major move. In your development. Can you talk about that experience and how it all came about? Well, Ken, this was would set me on my path, and I was very, very fortunate. So I'll describe this in a
nutshell. I was very enthusiastic as an undergraduate. I took graduate school courses. As an undergraduate. And 1 of the courses was in the bio physics of membranes, and we used as a comp in in reading text Gerald Weiss book that he put together called cell membranes, which was a, a group of articles that were at the scientific American level that were published in hospital practice.
The other graduate school course that I took as an undergraduate was in cell cycle kinetics, and I really enjoyed mathematical modeling. And that professor, professor Edge encouraged me to to para and do something serious. So I was very fortunate to go to Nyu. And get a Nih pre doctor fellowship at the time, and I was in the first year, medical school class, and Gerald Wei came to give a lecture on the cell biology of le. And he had just returned from Paris. I remember this clearly.
He had this movie of Lucas chemo taxing, and I just thought that was so cool. So I went up to speak to him after class. He said, oh, come up to my office, and his office was in Bellevue Hospital and where his lab was department of Medicine. So I went up to see him and he said, Oh, what are you doing this summer? So I said I haven't made any plans yet. He goes could, because you're coming to woods, the marine biological laboratories at Woods. Wow. This was incredible.
What an opportunity. We worked on white luke... White blood cells, lu sites from dog fish. But the entire environment was really stimulating, and I had an opportunity to work that summer with Bank Samuel daughter, who was working with us in the lab. And then Samuel came at the end of the summer, we were really lucky. We won the mb award that year, and I presented on behalf of the lab that was fun. So He I asked me to tell him about what we were doing.
And I did and he looked at me and said, charles, when you finish there'll be a place for you in Stockholm. I said, wow. So I hadn't really thought about doing something like that, but it changed all my plans, and I decided yes. I'm going to stockholm on. I'll finish early. And I was really fortunate to continue a collaboration between the Wei lab and with Samuel and 2 of my publications with Samuel that were part of my thesis were cited and bank Samuel Nobel lecture.
I was very proud of that, and I'm still proud of that today. Yeah, that's amazing. And this kinda led you into the focus on ne membrane remodeling for your Phd. Is that right?
Yes. I was really fascinated with the process of ph and how these cells defend us by seeking out bacteria and foreign invaders and then quickly in matter of seconds and minutes, fa these organisms and then destroy them To do that, neutrophils have to very very rapidly remodel their membranes make new phospholipids to expand the surface area to be able to and inform a fa l vacuum that they then pour the armament in them that break down the bacteria and kill them and This is
very well known area of medicine and biology, and that process was discovered by Mitch K, and the late 18 hundreds, and and he received a Nobel prize in physiology medicine for that discovery and the innate immune response. Yeah. It's an it's incredible. And I I understand that after you earned your Phd, that at you you had mentioned the Caroline Institute. Is that where you met your your future wife? Yes. Samuel used to joke that said, oh, yeah. Trolley was
very productive. He even met his wife. I think care let's yes. We met on the cafeteria line during lunch 1 day, and my wife there was studying medicine and finishing up her medical degree at the time. It seems clear that you are quite fortunate and have been quite fortunate. To have a number of strong and ineffective mentors where you in school, 1 who stands out is Michael He bird a 2 time winner of the last girl award in medicine.
He stands out particularly because of the advice he gave you, I think and how to be a good scientist? What was his advice and what impacted did it have? Well, doctor He burke was really special. And he was an organic chemist by training, and someone in the Dean's office noticed that I had a background in chemistry and that like chemistry. And I remember very clearly this woman value cocoon. She said, oh, you should go up and Talk with Doctor He burke, He needs someone
to help him at this time. And I did and worked with doctor to Har park just he and I in this very small land. His career was at Columbia University, and he was the scientific grandfather of Bar Ben who also received a Nobel prize for his work on antigen antibody combining sites. So when they asked Doctor H, about what it took to become a good scientist, and he would always chat with me, and he said 2 things.
Charles, you have to work on something that you're passionate about because this will carry you through the difficult times. And second, write everything down write all your observations down in your notebook and carry a second notebook, that you can jot down your observations and notes because in those notes will be your discoveries and I tried to bring that message to all those that come to work with me and my research program costs. I found them to be
absolutely essential. And I should point out that Doctor Hard at that time, was 91 years old, and he lived to a hundred and 3, and I was the last person to work with him. So I was fortunate in so many ways. He also encouraged me to go to work with Gerald Weiss. That's incredible. And speaking of, you know, in terms of discoveries and amazing scientific progression in the nineties, you discover what became known as specialized pro resolution mediator. And most people don't realize, you know, that
there... There's even another pathway to the aspect of, inflammation that is active. And since that discovery, you pioneered a new field of research in the utility of Sp for all kinds of different diseases from chronic pain, rheumatoid arthritis, dental disease, macular degeneration, cardiovascular disease, depression, brain injury inflammation, conditions like arthritis. I mean, it's basically a necessary part of our body in terms of healing and repair at that nobody really knew existed before.
Just gonna jump in here and tell you a little bit about that journey. And the journey that was still on. You're right in that when I was at the Carolyn Institute, we discovered the these new molecules and call them the lip because they will like interaction products, and I was convinced that there were regulatory mechanisms that we didn't know about to control the production and actions of the le and Samuel part of his Nobel citation is the discovery of the le.
And these are very potent molecules that control airway and smooth muscle constriction and they're important in asthma and in ana shock So my reasoning was very simple that there must be some other molecules produce that could count regulate these potent actions because why would the body molecules that could ultimately kill us. Because didn't make sense in evolution. And we already knew that platelets when they become activated, they make t boxing, that was another molecules that Samuel
discovered with Mats Hamburg at Car. They did the structure el liquidation, very elegant molecule, only 15 to 30 second half life in vivo. And this molecule propagate, platelet aggregation and is essential for clock formation. So there's another molecule that counteract interacts the actions of t called pros. Which was discovered by Sir John Veins group. It's also an ara acid product is made by the vascular and epithelium.
And pros the cyclone puts the brakes on the platelet aggregation response. So this already evidence that the physiology of counter regulation important in the small molecule lipid mediator. So when I came to Boston, we didn't yet know what the role of the were.
We needed to do a lot more investigations, physiological experiments and then we had a Eureka moment to the fellow who came to work with me from Barcelona Spain, John Cla, and I work together and found that when we take Aspirin, It was already known that Aspirin would block the production of t boxing and pros. And it's widely used as an inhibitor still today, and that was part of the Nobel citation for both Samuel and ci on vein. They shared price in 19 82 in physiology of medicine.
What we found is that Aspirin triggered lipid mediator, not only blocked frost the gland and in t production but it also triggered the bios of what we called aspirin triggered lip or, lip that were longer acting and a different chi this was really exciting, and I then to devoted our efforts to making my medics in stable analog of the aspirin triggered my toxins because we thought this was the stop signal.
For excessive le site recruitment and then worked for the next 10 years with Be Bios, sciences and shea Germany to advance an aspirin triggered lip my. Into clinical trials, and it worked fine. There were 4 phase 1 dosing trials and many, many preclinical models and animal models demonstrating that the mime that we made with Bro shea was very potent in reducing Gi inflammation and it was queued up to end enter trials for Ib and eventually Crohn's disease.
And this was really exciting but then there took over the sharing and decided that Ib d was not on their lists of things to do, and they dropped the program, which was so disappointing.
After having put in such a monumental effort, but we learned a lot during those studies And that's the knowledge of the aspirin triggered like toxins really opened the door to uncovering the resolve, which are also aspirin triggered lipid mediator, and that's why when the families of resolve in pro resolving mediator that are made during the resolution phase of inflammation. Became clear as we did the structural el
liquidation. I went back and classified all these molecules as specialized pro mediator, not because they're special, but but they have a specialized function to put the brakes on ne infiltration and stimulate macrophages to clear ap, the cells, particularly ap neutrophils, dose neutrophils that diet at the site of battle in inflammation. And this is a very important part of the pro resolution stimulation of clearance of inflammation.
So I know that's a bit of a long answer, but I hope it gives you a picture of how we wandered into the resolution phase. A That was a great answer. Thank you. According to scholar Gps, you've done more research in the field of inflammation than any other scientist. That's pretty remarkable. We will be talking a lot about Sp today, but I'd like to back up a little and set the stage and ask you about the research and the work you did that led to the discovery
previous to it. I suppose this journey of yours really kind of started, when you're in your post doc years at Karl and studying inflammation itself? What ent you about inflammation. I mean, we all know it's... It has many, many functions, acute and chronic. But could you talk to us a little bit about what really intrigued you about inflammation and and point to you in that direction? Yeah. Can, when I was a student when I first learned about the innate immune response.
And inflammation, I just felt that this was the keys to all of medicine and surgery and that we needed to understand how the body controls the acute inflammatory response, which is protective, control it from preventing collateral tissue damage and more inflammation.
Yeah. So in in in simple terms, we kinda think of inflammation as getting rid of what's damaged, but also protecting what's healthy, and there's different ways that we would discuss inflammation acute versus chronic, the the symptoms for the... Kind for the audience. The symptoms of inflammation would be pain redness and swelling typically. Like you would get if you you know, got a rug burn, cut your skin, rolled an
ankle something simple. But I've heard you say that inflammation comes in many forms and that we have what you referred to as new villains of inflammation. And since we're talking a little bit about inflammation, can you kinda give us an overview of the different types of inflammation? That we might talk about? Sure. I've come to learn that each of the medical specialties thinks about inflammation differently. It means different things to different specialties.
An op thinks of inflammation in the eye very differently than a surgeon and who is themselves a inflammatory stimulus. From the first cut. Charles that's that's a great. I I just love that. I I have a surgeon the office 2 doors down for me here at I c, and I love that description. I think I'll describe him that way. Well, inflammation has been done since ancient times, the times of celsius.
Ancient physicians described as you put heat, redness, pain, swelling and then when Vi came along, it was the the the loss of function. So the different forms of inflammation that are common to most clinicians and the general public is acute inflammation, 1 that occurs rapidly acute and then chronic inflammation, ongoing persistent inflammation. That 1 may see in autoimmune diseases, for example. Or as we appreciate today, in neuro generative diseases.
Okay. So in the post genomic era, my view is that controlling inflammation is the frontier of medicine and surgery because most of the issues that we face in western societies are the result of excessive inflammation. And that's come to light. I would say only in the past 10 years or so was more and more cellular and molecular studies. People arrived at this conclusion that, oh, inflammation is set
at hand here. Okay. So it in our research, it was important for us to define very carefully what is known as the acute inflammatory response? This is a programmed repertoire of how white blood cells, specifically neutrophils leave the post capillary v and then arrive in tissues, various tissues in the body to defend that tissue.
When that process is excessive when there's an excessive swarming of neutrophils and neutrophils swarm in, and they move, they need chemical signals to smell like sharks moving to red blood cells, they swarm in. When this warming occurs to protect us from invaders or tissue damage. If it's too much collateral damage occurs, and that collateral damage, propagate
inflammation. I think of good example is in rheumatoid arthritis, when neutrophils swarm into the s, if they spill these enzymes that have you evolved to kill bacteria outside of the cell, if this incomplete ph if that membrane doesn't close and seal from the healthy tissue. The enzyme spill reactive oxygen species spill and this destroys the s with time and leads to spanish formation, which is takes the smooth surface and turns it into a s surface, and it leads to a lot of pain.
So in the textbooks of pathology is very clear that the acute inflammatory response had a resolution phase when the area is cleared and the tissues returned to homeostasis. That's what we focused on and asking what's going on in this resolution phase. It's self limited. Okay. Let's think about this for a second. Think of having a small pimple on your skin on the back of your hand. The white of the pimple,
the p, if you will. Those are the lucas sites that have sworn to protect us And if you leave that, pimple alone for a day or 2, it completely resolves. So what's going on there? The body has resolution signals to bring us back to homeostasis, and that's what we set our guns to understand and see if we could learn that process, learn about those molecules? Can we use those molecules to make better and more precise therapeutics, Mh. Better drugs.
So the villains that you mentioned in today's society turns out that ara acid, which controls the bios of pros, and, and it was well appreciated that the pros play important roles in initiating inflammation. All the signs we mentioned, heat, swelling, pain. These are all mediated by pros. Well, in the resolution phase when the lu infiltration reaches a maximum.
The resolution program kicks in, and that's where on serendipity comes in, and we found in mouse models that the precursor of the pro resolving signals, the chemical mediator that orchestrate resolution come from the omega 3 essential fatty acids. Essential because we do not meet Epa or Dha We need to take these in in our diet in our nutrition. And as you know, these are the major fatty acids that are present in marine oils.
And it had been known for quite some time that the marine oils could reduce inflammation but the mechanisms of how that occurred is argued about in literature and not very clear. So in a nutshell, what we learned is that the omega 3 fatty acids that we take in in our diet. In our daily nutrition set us up for self limited
resolution. We are challenged everyday hundreds and thousands of times, the alarm rings for our defense mechanisms are white blood cells to come out and protect us in tissue, and that's when we need to turn off that response and that's where nutrition plays in a a very important role in enabling us to have self limited inflammation and return to homeostasis. That's an excellent explanation. And I think it it really hit
all the big points. A key development in your research on inflammation turned out to be a trip to Asia where unfortunately, you developed a hole in your intestine. Now that had to be pretty traumatic and does not sound like a fun time. Can you tell us about this incident and it's aftermath, which I understand gave you a first handy experience and why controlling inflammation is important. Yeah. Okay. I was returning from Japan, and I thought that I had horrible jet lag.
But it turns out that I couldn't stand and I still made it to the lab that day, but my wife urged me she said, no. Something's wrong. You have to go to the. And the bottom line is that I had per my bow and I had peri brewing, which as you know, is life threatening. And in the, some students that were in my classes... I said, don't worry about this. This is... I'm just having a kidney new stone. Yeah. It's a lot of pain, but it go away. And that was not it at all.
I went up for emergency surgery, and I had a cl and that taught me that I couldn't waste any time that we had to under understand how the body controlled inflammation. It was a very unpleasant experience to me, but I learned a lot and started to collaborate with Gi pathologist, James Made and his group used an expert on epic Gi epithelial cells, and we started to do the first experiments on how neutrophils talk to epithelial cells and how that acute inflammatory response
can get out of control. When I got back to the lab, I said, oh, we have to study peri. So I switched my research program, and I primarily in an in vitro guy. I like do experiments in test tubes. But it became painfully evident that I needed to bring in animal models. And so it is then that we started to study animal models of peri and self limiting peri gave birth to the resolve. In other words. Yeah. How that inflammation in the peri resolve was dictated by the availability of Epa and Dha
in the system. And to me, this was revelation. Because I didn't think much of the literature at that time around Eb epa and Dha But clearly, there was an an important role for these essential fatty acids in the human development, and it became my mission to figure out how they played a role in enabling the bios of the resolve and the other specialized pro solving mediator for protect and the macro derived mediator of resolution that we named the maurice.
And I'm happy to report that the maurice at least mar 1, the first reason we discovered is very potent in controlling pain and tissue regeneration. And it is in clinical development, and hopefully that company will be in clinical trials for reducing pain later this year and resolve an e 1 is in clinical trials this year from another company and I hope that those companies are successful because they will bring the first precision tools to the clinic for controlling inflammation? Now
why is this so important? Well, because our current pharma while adequate in most cases blocking the initiation of inflammation the thinking was, oh, there's just too many prone inflammatory molecules. We need to reduce them actually leads to a unhealthy state of immune suppression? And why is that important because I 1 would be treating rheumatoid arthritis with an agent that would block a cytokine or, like, tn alpha, would open up the system for rampant infection.
So that's a really unwanted side effect. You wouldn't wanna get Tv as a result of taking care of your Ra. So we think that pro resolution pharmacology will pave the way to developing a whole new set of precision tools for clinicians, And it's also opens up an opportunity to think about precision nutrition and and how can we get the right amount of Epa and Dha in our children in our daily diets. So that we are resilient to the many challenges that come to us each day as humans.
When you had your issues with the peri, were were you taking any anti inflammatory medications, non? Oh, non steroid no. I refrain from that, but the main staple treatment prior to surgery. Was to be on steroids. So steroids also as good as they are in controlling inflammation. They also lead us to a state of immune suppression. It's all about the timing And at certain doses, all of a words his group in Germany showed that steroids like that can actually turn on
Sp production. So it's a matter of timing when and how much to use. And that's a very exciting work. With these non str, they typically will will block, obviously, the production of things like pros land and so they they alleviate pain, but that's basically but then the, you know, that's been the focus within sports medicine community and and a lot of the areas where I'm working, but I... You know, obviously, the comp complications, but those are significant. And I think this is a huge
piece of the problem. Can you explain briefly what the anti inflammatory medications will do to the healing process? Sure. 1 of the big surprises for us. It was to find that if we added a non steroid into an acute inflammatory response, either in the peri or in the lung and an animal model, then non steroid, of course, reduces pros land, in some cases down to 0 production, but this un couples resolution.
And we need a little bit of pros land in e e2 to actually trigger the production of the bio synthetic enzymes that are needed to make the pro resolving mediator. So it's again, it's a situation of temporal analysis and when and where? So when we published those results, they were replicated by many on the groups and working in the areas of rheumatoid arthritis and pulmonary inflammation, doc levi group, but there was 1 very rapid translation to humans by James
Mark worth. And at the time, he working in New Zealand, and he's an exercise ph anesthesiologist And as you said, in the sports arena, and this is unfortunate in the high schools and all of our children have been avid athletes. Somehow, they have the notion that if they load up on non steer before to meet or before to game before a match that this is gonna help them. In fact, that's not the case. At all. It's the most delete
thing that we can do. We actually consider and to push this point of introduce the notion that non steroid and inflammatory drugs as the call today are resolution toxic. And so in James Mark ward study, he studied 60 males before and after strenuous exercise and he was able to replicate our results from the animal models in humans and show that the nsa un uncovered resolution.
Let me just tell you 1 exciting thing that's happened from that work that I think is relevant to all those listening who loves to play sports. It turns out that the Sp are made to bind muscle tissue, not just le sites.
And that the Sp stimulate the muscle stem cells and a group in Canada discovered recently that 1 of the resolve resolve d 2 stimulated the proliferation of muscle cells from stem cell, and they have reported that thereafter after trying to treat Du muscular dystrophy with resolve and and resolve like agnes would be that's exciting.
Yeah. And you... You... Also, when I was up at the conference that you had up Harvard, they discussed aging in animals and the lack of ability to produce resolution media leading to loss of muscle mass at as we age. Yeah. Well, thank you, David for bringing up that point because it enables me to talk about Hilda ana. Who was a fellow in my lamp from Iceland.
She was the first nutritional I epidemiologist to join the group, and she did that study we looked at the Nih aged mice versus young mice and found that there was a defect in the production of resolution mediator, and I'm happy to make that point because hilda and athlete she was training last year and running, and she had a cardiac event and early morning run and no 1 was around to help her, and, unfortunately, she passed away too soon. So
So that research that she did Yes. It's a big loss for us. On the field, and she just a wonderful investigator and a really nice person to work with. Yeah. And I'm quite a loss. I'm happy that others have taken up the the aging issue and other labs are focused on on that research. But we can thank her for starting that we're indeed, and that's so important as the percentage of the population that's moved into their later
years is grown just immensely. That focus, I think will continue to be very important. Stem talk is an educational service of the Florida Institute for human and machine cognition. A not for profit research organization investigating a broad range of topics, aimed at understanding and extending human cognition lo motion, health span, resilience and performance.
As we discussed earlier, and you know, we just chatted informally about how uncontrolled inflammation is a very prominent component of many, many, unfortunately, common diseases. We talked about arthritis and we'll talk in in the future I think about peri disease, but asthma, cancer diabetes, just the whole slew of them including Alzheimer's, Parkinson's a lot. And so as we think about and the effect inflammation on most of the dreaded chronic diseases.
You know, 1 starts to think that there must be many many therapeutic opportunities for Pms of various kinds. Can you talk about what seems to be an explosion of research in the field in recent years? It seems to have really garnered much more interest than in the past. Could you talk a little bit about that? Sure, well, like all science it was lonely in the beginning, but yesterday on pub med dot gov, just on the resolve of 1784 publications. Yeah. That from groups around the world
sure. That constitutes an an explosion, but there are 2 things going on simultaneously. 1 is increased rec mission that uncontrolled inflammation is important in many, many diseases as you point out, but the other good fortune for us in the resolution field is that several companies have made the resolve and the specialized pro resolving mediator available for research use. We published the first total organic synthesis of each of the molecules to establish their complete stereo chemistry and
confirm how they were. But without having commercial sources so that groups in Taiwan and groups in Japan and groups in Australia could purchase the molecules for example, and all throughout Europe to test in their systems and make new discoveries and teach us how important stimulating resolution is. So 1 of the points I wanna make to you and to your audience is that this is such an exciting system because it's a feed forward system.
We learned that if we give Sp back in a disease model, not only do they control the inflammation, but they also stimulate and endogenous programs to stimulate more production of pro resolving mediator and reduce inflammation to get to a new homeostasis. You've mentioned kind of the super families you have resolve protect and. Can you kinda give us a little bit of an overview of the differences between those and then maybe the timing that they might show up in a healing response?
Sure. The first on the scene, if we're doing a temporal analysis of p the initiation begins the pro inflammatory media is the pros land come into play, the cytokines chemo come into play. And you heard about them in the during Covid because that is the cytokine storm that brings the lung down and sound many individuals during that pandemic. We then shift to production of the toxins and they produced from a ara acid just as the pros land endo the le.
And then the system begins to use Epa and Dha to make resolve, protect, and then late in inflammation when the pro resolving macrophages has come along as they were described by Mitch Mc back in early 19 hundreds, the big eaters they eat the dead neutrophils that have lost their lives in the battle against bacteria or in clearing debris, they need to be cleared. So that temporal sequence is what happens in ideal resolution in a laboratory setting. They're each
structurally different. So the Epa derived resolve come from Eva epa, which is a carbon 20 structure with 5 un saturated double bonds, and we work out the structures of each of the resolve of the E series and 1 that we discovered just in the beginning of the pandemic is resolving e 4 number 4 in the panel.
And this molecule is important in instructing the macrophages in the spleen to clear old red blood cells, So this is a ph physiological mechanism that's not necessarily evo by an acute inflammatory stimulus. U. So there are ph physiological rules, not just path rules of the resolve. The next structures to come along with the protect and the protect are trying, and they are also produced from Omega 3 central fatty acids, but here this... The precursor is Dha.
And then the D series resolve kicking, and they're the base structure old Dha in each molecule of the D series we carried out the structural motivation of, and they each activate different receptors. Holy cow. We have receptors for each of the major families, and those receptors stimulate resolution. 1 of the really exciting things that's come off. Well, I'm excited about it is that a a company in France has followed all our were on resolution, Os, they made an agonist
antibody. An antibody that will activate the resolve an e 1 receptor, and they demonstrated that that antibody can help in cancer models in reducing pain and reducing inflammation? Now why is that so exciting, Trolley?
Well. The big pushback for me in trying to make my medics with companies has been the enormous cost of making the scale up of these what seem like simple molecules, but they actually quite difficult to s In some cases, the steps are 22 steps So that makes manufacturing of the molecule by total organic synthesis, very, very challenging and very costly Now I never thought that cost is gonna
matter when it's gonna improve life. But as you know, that's a little naive, and that's what companies live by is being able to make a profit. So that's why I'm so happy to see agonist antibodies emerge as a wait to stimulate resolution. I think it'll change health care completely honestly. Yes. I agree as well. In fact, far our listeners, I think I I'd like to mention an article that you did back in 20 17 that I particularly liked. It was in the journal of my molecular aspects of
medicine. It was sort of like a an overall review sort of thing. It was really excellent, and it talked about Sp marking the dawn of resolution because theology and pharmacology, and it was it was a really good overview article. We'll provide a link in the show notes, to the article for the listeners so they can read it as well. Oh, good. So happy that you liked that. You know, that was really can a a tribute to my colleagues and students and fellows. That have worked with me over the years.
That was a special issue of the journal molecular aspects with medicine Is that 1 of my former of fellows, who's a professor in the Uk talked to Jasmine Dolly, edited the the series. And there are articles in there by all our colleagues and form students. But in the review that... It's basically a preface to those chapters in the special issue. And III tried to hit the high points. And as I recall, I discussed in the introduction, Claude Bernard because Claude Bernard was...
Very influential and my learning about biomedical sciences, and he wrote The study of experimental medicine. Introduction to the study of experimental medicine in 18 65. Wow. And in that book, he describes that each of the disciplines, the dawn of physiology and pathology and chemistry, each develop as separate disciplines. Any urged us to have inter discussions.
And that's, I'd have to say is the hallmark of my research is it's a multi disciplinary approach, chemistry, cell biology, pathology, interacting with different disciplines, internal medicine, surgery and learning their perspective in oral medicine, peri disease you mentioned, and I learned from them all and we work together on this common mission, which is our mantra. We repeat in my lab meeting every week, our mission is to help us many people
as we can. Mh So I also in that short article focused in on the importance of Luca site traffic and this repertoire of edema ne infiltration and the non recruitment of mono site in macrophages, which is the acute inflammatory response now people get that confused with acute inflammation, and I think medical school is so jammed with so much to learn.
That people don't have an opportunity to recall this chapter 3 in Robinson and Cor on inflammation, and I urge all the medical students saying graduate students and clinicians out there, dust off fear Robinson and Kat and take a look at that chapter. And I was very fortunate to work with professor C, this the chair of pathology here, and he was very, very instrumental in my career development.
And I have to say that I've been fortunate with mentors, but every academic mission needs just not 1 mental mentor, but half a dozen mentors as we take this journey. I think we too often hear that epidemic tale of 1 giant mentor, but we all stand on the shoulders of multiple giants if we're going to be successful. Absolutely. I I use the things that you've been teaching every day in my practice and working with teams and athletes and veterans, I mean, this has made such an impact
on on their lives. I wonder if if we can take just a simplistic sort of for for some of our audience that aren't as scientifically minded or their background maybe makes it a little bit confusing. 1 of the ways that I described this in terms of how I discuss this with an athlete, the difference between inflammation and resolution. If I am I, I'm 5 1180 pounds. So... And and I'm in my fifties.
I shouldn't be playing any professional sport. But if I for some reason, get stuck on a pitching mound for a professional baseball team as a joke. It wouldn't take a more than 1 or 2 pitches to figure out that I'm a mistake. So getting me off the field is sort of what I described to the athlete as the inflammatory phase, an excessive inflammation would be pulling more than me off the field, either way you look at we're gonna lose until
you get a replacement. Is that inaccurate or or somewhat maybe useful way of describing this in terms of the difference between inflammation resolution and how it affects people? Yeah. I think that's a great analogy because it's important to provide mental images to people that they can relate to if you're speaking to an athlete a baseball player, that's very, very appropriate. If you're speaking to a surgeon and, I don't think so. Absolutely.
They're won't very far. Yeah. No but search gets it why we need to control inflammation and certainly, the critical care docs get why we need to understand what's going on in sepsis. 1 of the other things we introduce is this concept of an I immune resolve and rather than a blocking agent that we would have an agent as a therapeutic that would stimulate the body's own
ability to resolve. And we came up with that by doing in the laboratory, the first quantitative assessments and introduce some very simple calculations in a systems approach to studying how plus resolves. And there was 1 review that doctor of M Per already did for children, which I thought was really cute in the frontiers of immunology. He published resolution for kids. And, yeah, it's worth looking at It sounds really interesting.
Charles, let's talk about some of your more recent research at d laboratory Can you give us an overview of the research currently underway in the lab? Well, we have ongoing studies detailing the bios of resolve. Working out the complete stereo chemistry of transient intermediates, which is really challenging. And then other studies that are going on in the lab that are addressing how to activate resolution during infection and how to clear infectious
inflammation. And then we have ongoing collaborations with Doctor Levi laboratory looking at the impacts of environmental triggers environmental agents on the resolution and how they cause inflammation. And 1 of the very exciting projects we just got funded from Nih is with a cancer researcher or deepak Pan at the hospital cancer expert looking at how to stimulate resolution of inflammation around solid tumors to reduce the tumor burden, and those are so exciting.
Keeps me happy coming into work every day. So that's roughly what we have going on at this time. And I I should say that I'm very, very fortunate to be a Grant of the National Institute of General Medicine, helped us enormously because the base were of resolution and working out the bios of each of the members of the super family of pre resolving media was supported by a program project grant that I led for 10 years that was supported by N gm, and I've been supported by Gm
from my entire Career. The other institute that's really been incredibly important is C in developing this work. And there I served as a principal investigator, program director for a p 50 cent grant where we used peri disease as a demonstration of controlling inflammation. That's about it. Yeah. So last year, you had another article on the proceedings of National Academy of sciences that was titled resolve and d 1 prevents in j
swarming and transplant lungs. And this this provided some insights for therapeutic enhancing per resolution pathways to minimize early le sight mediated tissue injury and promote healing following transplantation. Can you talk about the progression in that field? And how this impacts us? Sure. I really love this study because in the Or, and particularly in transplant, there's a phenomenon called ref low injury. Where a surgeon when the clamp a vessel to work in an in an area to repair
it. When they open the clamp the sites that come rushing out in the blood. They have become preemptively activated and they hit that lung and start to cause collateral tissue damage. And the reason why I like this study with Daniel in his group so much is that they have a tool photon microscope and it's possible to visualize what's going on during this ref flow injury.
So first, in in humans, we were able to get from Daniel and his colleagues, human graphs and analyze them using Lc cns sms, and we could follow the temporal production of the pros land, luca and the resolve. In this primary graph dysfunction. And then going to the animal model where it can do real time movies, doctor Lee and his group has made these extraordinary movies using dual photon microscopy, of the lung where you could see the neutrophils swarming.
I urge everyone to to just common take a look at those movies, they're available on the P website. And what's so convincing and so dramatic as when giving resolve in d 1, it stops the swarm you can see that it stops the swarming over the le sites and prevents collateral tissue damage and you can visualize all this in that study. And the the reason why I like it so much is because this is the primary action of the resolve when they are produced to control excessive site traffic.
Does this translate over into areas such as, an ischemic stroke or ischemic my cardi after cardiovascular or disease event? Absolutely. These cellular molecular events, huge translate to cardiovascular
disease. Organ transplant is a major major issue where we see all these things happening, but in atherosclerosis atherosclerosis in cardiovascular disease, these are happening over a long period of time, decades in some cases, the vascular endo epithelium and surrounding tissues become inflamed And there's a very nice war in the area of atherosclerosis some cardiovascular disease being done by a number of groups 1 is talked Gabby Fred crew at albany Medical. He's a former of member of my
crew. And Magnus Beck, a cardiologist a Carolyn institute, and he's working in this area, and they have published some really elegant studies demonstrating how resolve can reduce the sequel of inflammation and as sclerosis in cardiovascular disease. I was very fortunate some years ago back in 2006 in 2007 to work with Larry Chan is an endo knowledge at Baylor and Larry was able to make in a rabbit, a trans rabbit that over produced the enzyme that's responsible for Lip fox and resolve
production. And 1 of the things we were saw is that those rabbits didn't get atherosclerosis and they had a very diminished acute inflammatory response in skin on challenge They were, like super rabbits. Lucky rabbits, I guess. Yeah. And the reason why I mentioned the rabbit is because much of what's known about the path biology. Of atherosclerosis comes from the Watt knob rabbit model. Mh. Where taking a high lipid cholesterol intake leads to an
plaque and those rabbits. And the cool thing is that my colleagues and I was not involved in this study when they treated the rabbits para that had inflammation, they did not get any atherosclerosis atherosclerosis. The vessels will clean. It just amazing. That's Tom Van dyke group working with another imaging specialists in the area of lipids at d you. Jim Hamilton. Nice study.
So we will put a link in the show notes to Gabriel Fred article that you mentioned, looking at the evidence that supports Sp as therapeutic tools for the treatment of Arthur Squad a cardiovascular disease sometime in the future. That leads to a sort of a follow up question here. You mentioned rabbits, and that research is is very interesting. That, you know, the natural diet for a rabbit isn't very much like a
natural diet for humans I would assert. But in any case, What I'd really be interested in, are there any clinical trials in the works that you know of that will test whether increasing Sp in vivo in humans. Can indeed affect art progression. I think that would be really fascinating. Yeah. You're absolutely right, Ken that is a tall order. That's a very expensive long type of study to do, but nonetheless,
it is extremely important. And Magnus beck the cardiologist that I mentioned at Car institute, he was able to secure. A ground from the Eu across multiple countries where they are going to be testing exactly that and I'm fortunate to be a member of their scientific advisory and watching how the data comes in and I I do believe that they will be successful Because these mechanisms are highly, conserve the cross species all the way from fish to human.
It's really interesting and very hopeful for the outcome of that study. Charles, you have 2 children who are currently in the military. And your third is potentially on the way into the military. What are your thought on a need for the use of Sp in the military population. That's a very deep question, David. And because I'm... It's emotionally tied to trying to do research that will be helpful in the battlefield and say, well. Where did you get that?
Idea from. So well, I was invited to the San Antonio Battlefield research sent a few years back to give the Bass pruitt lecture and doctor Pruitt was a trauma surgeon
the military. And on that occasion, I got a chance to see some of the very important work that they're doing at that site, and started a collaboration with the Doctor rios on using some of the Sp, I mean they're a synthetic form to protect ear damage from acoustic injury, and he has developed a model for blast injury, And what happens in the battlefield is instead of a soldier steps on a explosive device the day after perhaps losing a limb, those soldiers
lose sight due to a retinal detachment from the blast shock and 1 of the Sp neuro protect and dew 1 protects from that and animal models. Retinal detachment. And I I didn't have an opportunity to tell you, but the neuro are produced and the retinal pigment epithelial cells. That's 1 of the places that make that specific Spf. So I'm hoping that we can get some of those molecules
into the battlefield kit. And then the other approach, which I think is so vital is would many have called nutritional armor to help increase the resilience in the battlefield by specific support of the Sp system? I say, well, how are you gonna do actual? Well, since it's taken more than a lifetime to make mime and to launch the idea of precision therapeutics in resolution, resolution pharmacology.
1 of the really fortunate things we stumbled into is that marine organisms not only make And Dha they also fake resolve, and they make them in high amounts. So it turns out that when you purchase at the local store, your omega 3. Fatty acids most of them come from the Peruvian ant anchovy So Anchovies very rich in Epa and Dha so you wanna get anchovies on your pizza. But the cool thing is that they're very rich. Anchovies and the intermediates in the bios
of resolve. So why is that important? Because if you give the intermediate resolve, they're used at about a hundred times more efficacious than Epa and Dha. And then, we thought that they were only bios synthetic intermediates. It turns out that they also carry potent biological actions, 17, 1 of the molecules we described is very potent in regulating pain, and 18 e, which is an intermediate e series bios of res is very potent in regulating cardiovascular function.
So do you see in Au situations, let's say, pilots or, you know, other extreme environments do you see a preventative aspect that may be used from, let's say, taking Sp over the counter? Yes. They would absolutely I do hope that this is the direction that I'm having a greater visibility to larger your audience what should give me an opportunity to do today will dawn all people that this is really preventative medicine. And that if we use precision nutrition, we could raise our resilience.
And, yes. And then to use the therapeutic approaches more and more extreme cases. You mentioned a phrase nutritional armor earlier. And Joel Hi is 1 of the people that coined that, and I remember he visited here and gave a lecture back in 24 team about nutritional armor and he was stressing the importance of fish oils and related substances. So I I hope he's been tracking your work since then, because I'm sure he would find it really interesting.
I know Joe Well, he was an Nih and I was on the board of scientific advisors at the Institute he worked in which was n anti triple And he was a student of Norman salem and Norman has done some of the most impactful work in thinking about Epa and Dha in nutrition. And he's demonstrated how important and his team how important Dha is in neural development. Yes. So we don't, Joe. Sure. Joe is a psychiatrist by training and he been aware of, the importance of omega 3 in the diet and preventing
suicide. Yes. Partly, due to my interactions with him. At the time was on the defense science board, and, of course, the issues having to do with injury brain injury, but also suicidal dial were issues for the board. And in 1 of the reports, it talks about, there should be more focused on nutritional armor and on thinking
about Dha and other kinds of approaches. And so it it was very hard to get it in the report because defense science board reports are normally dominated by things based in physics or things or computer science or, you know, not something biological. And so it was interesting process. What I can tell you is that there been some very nice studies in Tb, the traumatic brain injury that was done by initially by the research center in Kentucky for
Tb. And they showed that in repetitive Tb, a per progressive model in animals that resolve, E1D1D2 all protect from Tb. And that's an issue that also crosses over not just from the battlefield but also into sports today. Absolutely. That work stimulated others in the area of Alzheimer's, and neuroscientist to look at, how the Sp, regulate and protect in neuro
inflammation inflammation. And there, we had shown very early on that micro cells a brain micro cells make resolve, and those cells are like the macrophages of peripheral blood, and they're the ones that are thought to be in an excessive pro inflammatory state in disease like. And just yesterday, I read a paper from the Car group group, the neuroscience group working on Alzheimer's and how they used Mar 1, 1 of the Sp to protect from advancement of Alzheimer's deceased.
That's Mary Sc group. And they also did a very cool study that came out just about a year and a half ago where they gave Sp intra in the mouse and it was in an alzheimer's mouse, and they found that those mice got their memory back in my base studies. Really impressive and reduced the neural inflammation. And 1 other line of research, which I think is very important. That's come up from Japan about, Sp is that they may actually be the molecules themselves and endogenous antidepressants.
Mh. That is interesting. In the sports world, there's a big focus on recovery and healing because the high number of injuries and nagging chronic mu problems. Does it make sense to focus more on resolution in this context rather than thinking sort of anti inflammatory in the traditional or old sense of understanding. Yes, David. This is something we need to pound the table about because traditional anti inflammatory therapies delay wound healing. That's 1 of the unwanted side effects.
But the natural progression of resolution back to homeostasis is tissue regeneration. And we have found that there are additional molecules that are produced during the resolution phase by the Sv sp pathways that stimulate tissue regeneration. And we found that in a very cool system in p area. If we cut p area in half, this little worm will grow back both halves
in, like, 5 to 7 days. But if we added 1 of these molecules that we isolated from resolution phase and then determined its structure, we could shorten that regeneration period. So tissue regeneration is part of the resolution cascade, the resolution code. And a follow up to that, at your conference, I noticed there were several papers discussing sleep and how resolution and sleep kind of interact or what the what the play is. Do you mind touching on that as well?
Sure. The sleep group is over at the Bi, and Monica hack is the senior there and I just serve as a mentor to the fellow that presented. She showed disrupted sleep study And in disruptive sleep, the pro inflammatory media just go up in peripheral blood. And there's a deficit of Sp. So I was quite surprised to see that and those analyses were done by the group in Michigan, and it really suggests that that to get full sleep cycle 1 has to over
inflammation. So there, I think the Sp could have a a real therapeutic impact in enabling people to skip over, if you will, disrupt sleep pattern. And I think that could have enormous impact in the general public in military and in sports world as well.
Yeah. I I see in the professional sports world, but also with friends of mine that are you know, either either vet veterans or, active duty population, in fact of a friend that is involved in human performance based, active duty and He does some... He's in the reserves as well, but 1 1 of the things that he told me recently is since he started taking these Sp, he sleeps better. In his forties now, he is getting better times on a lot of his physical testing that he was getting when
he was in his twenties. So it's having huge. And that's the only change that he's made. And I see that across the board when I'm dealing with athletes that those kind of improvements. It's really outstanding. On a personal note, I've been taking Sp for a long time. Don't even remember how long, but quite a while, in particular, the pro resolving. I think it's called That pro resolve. Yeah. Pro resolve. And the other 1 is Meta active. Sp active yeah 2 that that I personally take?
Well, you'll be happy to know that they are the same pill sold by very happy. The actually, I'll say a little anecdote there. You know, to sort of jump start that getting it to humans I gave the Spanish company Biotech that had this, and and this is actually an important point for your audience. Okay. So supplements, do we really need supplements? Well, if you're eating a well balanced diet, maybe not? So some supplements are synthetic molecules like vitamin C, b 12, etcetera, and that's
definitely needed. In the case of of the Sp active, those are the natural Sp isolated from Peruvian and Anchovies. And the silo corporation had at that time, around 20 12, the world's patent in dominating what's called C 2 based
purification. So there was no organics that would ever touch, no solvent, the molecules And so as I mentioned briefly earlier, we found that the peruvian trophy ads Sp and the intermediates Sp and I obtained the patent on that, which I gave to the Biotech group for 1 dollar why. Because I wanted to see this get to people as fast as possible.
And if they did that, I'm so happy they did and their first customers were meta and meta that has done and is doing a wonderful job in making educational material available about Sp and doing nice clinical studies showing that taking the Sp act reduces pain and having those tools available for people like Doctor Le, this opens up even more potential uses because it's only until you get a tool in a physician's hand until you really know where things are good for. Yeah. Does that
make sense? Absolutely Sure certainly does from my perspective. Yeah. I totally agree with you? Yeah. So very soon you'll be teaching us what we really need to do with the Sp active. The... And I'll tell you a story that that makes me... That there are 2 things. You know, I you must heard in what I'm saying that my basis is really in molecular pharmacology, you know, that I love that stuff. So the first is the discovery of the viagra molecules. Okay. This...
You know, no 1 went out to specifically discover something for Ed. This was a side effect of a a cardiovascular program that pfizer had to block pho, and it turned out that their molecule block that's it. That regulates a cyclic Gmt and and and relieve... I'm, I'm trying to figure out a delicate way to say this. But yeah Yeah. Dysfunction Ed. Okay? Then this is a a really important problem. The other 1, which is really cool is Lu, which is used. It's a it's an eye drop to lower
intra pressure. It's actually across the land and my medicare analog that was developed by Astra. And when that compound went into use. The side effect noted by the op was sent, people got extra long eyelashes It was a side effect, and the other side effect was it turn brown eyes blue. Oh, wow. So you can imagine there's a need for both of those, and so businesses has grown up where companies make the compound and put it in cosmetics for
people who like to have low eyelashes. So I I'm anticipating that just like we learned, and I didn't anticipate it. I didn't even expect it that muscle was gonna make Sp. When we found that adipose tissue, fat made pro inflammatory mediator and the Sp were pretty shocked at that. So I think there are some unexpected things to come up both in the clinical observations and our continuation of these investigations is gonna teach us how to use this information in the best way pops sold
to help as many people as possible. Yeah. Be great. Looping back to the early days of your career. I just wanna tie back to that little bit because Stem talk has many, many listeners in graduate and medical school. So we get a lot of correspondence from med students in graduate students and physicians as well. But we're really very interested in these young budding scientists and and physicians. And you know, they they have a lot of passion.
I understand there were 2 books that you read earlier in your career that really had a big impact on you, and maybe we... Maybe we should share this with with these folks. 1 was the art of scientific investigation? And I understand the other was men like gods. What stood out about these books and would you still recommend them to young investigators and graduate students and medical students today. Yes. Wow. That's a great question. Thank you. So the auto scientific investigation by beverage.
I still ask people to take a look at it. Beverages is a professor of Pathology, at University at Cambridge, and this is the only book I know that tries to operationalize preparing to do research. And in the first page, it says Scientific research is not itself a science. It is still an art or a craft. And I believe that is very true, and he gives some inspiring pearls throughout the book and tells people how to go about preparing yourself to make discoveries.
Yep. I would definitely tell people to go out and get it It's out of print. I think the last print thing of it was in 19 57, but you can get almost anything today out there on Amazon. So dude take a look for it if you're interested in the career in science, the art of scientific investigation. And what about the other book? Men like gods. What's that about? Well, okay.
That That's an h g wells book that he wrote towards the end of his life that really into weaves many of the concepts that he had in his other books, like time machine and war the worlds. And you can hear, III like Sci. I don't have as much time to read it these days, but men like gods was particularly, Interesting to me at the time because it's a it's about an English newspaper man who's driving on a road, mean, this is in the late 19 twenties.
And he and several other, I would say, representative of society at that time were transported to a parallel universe in time and Earth 3000 years ahead so. And and then, you know, this is a Utopian society and the main character demons is really enamored by the whole society, but they become jeopardize buy the the viruses that the people from an out time brought to them, and so they had to be isolated
on a on an island. So it brings up a lot of concepts that like in war of the worlds H she wells, you know, in the end, we don't defeat the invaders. They get defeated by the microbes of Earth.
I I just I just like those frames shift ideas, and I I encourage people to read not only science outside of your area of interest, but to get stimulation from other sources from reading books that you like and from listening to music and and going out and running and getting your undo up and smiling every day, the other book that I thought was... And I think is very important There were 2 other books. For the medical students, the book that was transformative
for me was Arrow Smith. Oh. Yeah. And and that's not the rock group. It is Sing sinclair Lewis Arrow smith. Yeah. Famous book. Yeah. It's in and it picks up a medical student in his early years and carries him through the clinical trial and the forces that come to bear during this epidemic that they face. Yeah. I was Saint sinclair Lewis book and he was the first literature Nobel Lau from the in United States. So it's definitely worth reading.
And the other book is an obscure book that I found that I just love and I still copy a page from it and hand it out to members of my crew during a lab mid and that's Maxwell Malt, MALTZ. He was a plastic surgeon and he wrote a book of his experiences, towards the end of his career that he called Psycho cyber. So what is that, troy? Well, this is where you could program. He believes the brain was like a computer. You're putting good stuff. You get out good
stuff. And you can program yourself to be positive and have a positive impact on those around you. And he learned this apparently by performing plastic surgery on people. He noticed that if someone came to him and said oh, you know, my ear are too toothpick, you know, can you can you take off the lopez so. And after he did that in 21 days after the surgery, he noticed that there was a personality change, And so he documented that it wrote this book for us.
Interesting. Yeah. Very. Well Charles, this has been great fun. And we've enjoyed talking with you very much, and I'm sure our listeners will as well. Absolutely. Thank you for joining us today. Keep up the good work. Yeah. That's for sure. Well, thank you so much, David and can for giving me this opportunity to expose our passions and to tell people about our mission, and I hope
that others will take it up. And if you're interested, do right to me may take me a little time to get back to you, but I certainly will. Thank you so much, guys. Well, you're quite welcome, Moe fascinating interview and thank you for your important work. Yeah. Thank you very much. Stem talk done stem dot com. Stem? Talk stem talk. I'm 1 of those people we talked about today who finds Sp to be a revolutionary
new field of research. I'm grateful for the work that Charles has done in pioneering the potential of Sp to promote the natural termination of inflammation. In addition to my performance medicine practice where I see a wide variety of high performing patients and athletes and retired in active military members. These patients have inflammation as as a result to persist and injuries and trauma, I'm a big fan of Sp because of the positive impact that they have had on so many of my patients to me.
This discovery is nobel worthy information as I believe it will transform health care in the near future. I suspect, David, that 1 reason you are particularly fond of Sp among others is because they allow a person to avoid anti inflammatory drugs and their numerous side effects. Here at I c, we've worked a lot with military populations who suffer inflammation as a result of persistent injuries. So the potential of Sp to promote the natural resolution of inflammation is something I am keenly
interested in. As Charles has pointed out in the past, anti inflammation is not equivalent to pro resolution. Anti inflammation suggests a blockade of signals and cells. Whereas pro resolution suggest an activation of signals and cells quite different. This is David Lame, signing off for now. And this is Ken ford saying goodbye until we meet again on Stem talk. Thank you for listening to Stem talk.
We want this podcast to be discovered by others So please take a minute to go to itunes to rate the podcast and perhaps even write a review. More information about this, and other episodes can be found our website, stem talk dot Us. There, you can also find more information about the guests we interview.