The Science of Peptides

Loren: Let's harness peptides for the benefit of our health. I think that's a shared goal, but what I'm not enthusiastic about is saying we're going to put these peptides through the therapeutic gauntlet to ensure safety and efficacy, and then have a whole other class of peptides where we say it's fine without that. In my view, that's extremely dangerous.

Brent: Welcome to the Life Lab by Death Clock. I'm your host, Brent Franson. The mission of Death Clock is to help 100 million people live ten years longer. Today, we speak with Dr. Loren Walensky about peptides. Dr. Walensky is a professor of pediatrics at Harvard Medical School, principal investigator and attending physician in the Department of Pediatric Oncology at the Dana-Farber Cancer Institute, and director of the Harvard-MIT MD-PhD Program.

Brent: We've been wanting to do an episode on peptides for some time to separate fact from fiction. What are peptides? What does the research tell us about where peptides are useful, where we should be cautious, and how we should think about them? Generally, there's so much discussion around peptides for off-label use—taking something like tirzepatide for someone who doesn't have obesity, or using products from overseas compounding pharmacies like the Wolverine stack and BPC-157.

Brent: So we wanted to go straight to an authority who has spent his career studying peptides to figure out what we need to know.

Brent: Dr. Loren, welcome to the show.

Loren: Thank you so much for having me.

Brent: All right, I've been excited for this episode. This is the peptides episode, so we'll cover all things peptides. But before we do that, can you give us a sense of your background and day job?

Loren: Sure. On the clinical side, I am a pediatric oncologist taking care of children with leukemia and lymphoma. On the research side, I run a chemical biology laboratory focused on pathways relevant to cancer recurrence and relapse, and how to subvert them. One of our main tools to study these pathways and develop prototype therapies is through peptides—adapting natural peptides, making designer versions, and using them both as discovery tools and potential therapeutics.

Brent: Let's start with the basics. What is a peptide? I don't think I had really heard this word until four or five years ago, and now I hear it every day. Can you tell us at a very basic level what a peptide is?

Loren: It goes back to the central dogma of cell biology taught in freshman biology: DNA is the blueprint in our chromosomes that encodes life, which turns into RNA, and RNA turns into protein.

Loren: The fundamental workhorses of our cells and tissues are proteins that act as engines and signaling compounds. Peptides are subcomponents of proteins, made of amino acids. There are 20 natural amino acids.

Loren: Think of each amino acid as a pearl on a necklace. You can combine them into various lengths—some peptides are four amino acids long, some 8, 15, 25, or 50. Once you pass 50 amino acids, you enter the realm of polypeptides or proteins.

Loren: These proteins have distinct shapes. There is a primary structure, which is the sequence of amino acids with different properties, and a secondary structure, which is how the string folds.

Loren: Some fold into coils, others into sheets. Then there is tertiary structure, where these shaped building blocks combine and layer onto each other to create complex shapes.

Loren: The complexity of these shapes allows them to do diverse tasks, from breaking down old proteins to creating enzymes that process fats. Roughly 20,000 proteins run our cells and tissues, all encoded initially by DNA, transcribed into RNA, and translated into proteins.

Loren: Peptides are important because the body uses them as master signals. For example, your brain makes peptides in the hypothalamus, transmits them to the pituitary gland, and secretes them into the blood to regulate various functions.

Loren: Natural peptides in the body can be used to treat diseases. The classic example is insulin.

Brent: Insulin is a peptide.

Loren: That was the original breakthrough peptide drug. It proved a natural biological peptide could become a lifesaving medicine. Before insulin, type 1 diabetes was fatal. In the 1920s, scientists purified insulin from animal pancreases, and later engineered recombinant and designer versions with varying durations of action.

Loren: It established that peptides could safely replace defective human biology, launching the modern biotech era of turning natural peptides into medicines.

Brent: So is it fair to say we all have peptides, which are made of amino acids that keep our cells functioning? When discussing peptides in health and wellness today, we're talking about either synthetic imitations of amino acid chains we need—like insulin for type 1 diabetes—or new synthetic peptides designed to interact with the body, rather than the naturally occurring peptides functioning within us every day.

Brent: But I need insulin to live, okay. We figured out how to synthetically create it and we give it to you, you know, through, you know, through a shot. Or we are creating some new peptide that we think interacts with the body. Well, and that's contextually how you hear the term peptides. Today, we're not really spending a lot of time talking about the peptides that are just flowing through us and doing their job, as they have been for hundreds of thousands of years.

Loren: When developing peptide drugs, you're taking advantage of normal biological pathways where peptides naturally work. Insulin is a great example: the pancreas produces insulin to regulate blood sugar levels.

Loren: If you lack insulin, it causes severe organ dysfunction, so replacing it is essential. However, manufacturing and dosing must be strictly controlled, because an overdose of insulin can be fatal.

Loren: It's not as simple as synthesizing what the body makes and injecting it. Some natural peptides are vicious toxins, like venoms that can destroy tissue and vasculature.

Loren: Natural peptides carry risks, and manufacturing them raises questions about purity and contaminants.

Loren: Synthesizing peptides in a laboratory requires harsh chemicals, organic solvents, and heavy metals. This process is entirely different from how the body creates peptides.

Loren: Ordering a version from a catalog assuming it's safe because the body makes it is mistaken. This process must be carefully controlled.

Brent: They sound like fire: they can heat the house or burn it down. Peptides can act as venom or as a lifesaver. They interact powerfully with biology for good or bad.

Brent: Popular conversation around peptides began with GLP-1 receptor agonists like semaglutide and tirzepatide for obesity. Since GLP-1 agonists are peptides, how do they interact with our biology to assist in weight loss?

Brent: How are these breakthrough drugs for obesity functioning in the body?

Loren: These drugs are the product of 30 years of research by basic scientists and companies like Novo Nordisk and Eli Lilly. They didn't appear overnight.

Loren: Billions of dollars went into basic science to understand these peptides. There is a vital distinction between peptide drugs that underwent rigorous testing to become approved medicines and untested, unapproved peptides.

Loren: I would feel comfortable taking an approved drug for a relevant condition. However, responding to advertisements for unapproved, untested agents promised to promote longevity or wellness is extremely dangerous. GLP-1 drugs are the modern poster child of approved peptide therapeutics, much like insulin in the 1920s.

Loren: GLP-1 drugs are based on glucagon-like peptide, a natural gut hormone that regulates appetite, insulin secretion, and metabolism. Native GLP-1 stimulates insulin release, suppresses glucagon, and slows stomach emptying to promote fullness.

Loren: Natural peptides break down quickly in the body. Because GLP-1 binds potently to its receptor, scientists engineered longer-lasting synthetic versions that remain active for several days.

Loren: This is transforming diabetes and obesity treatment. It proves peptide medicines can reprogram complex biological processes, altering physical traits and health outcomes.

Loren: It's not just about appearance or losing weight to look trim. Treating obesity reduces cardiovascular, muscular, and neurological risks, dramatically improving overall health.

Loren: GLP-1 drugs are not a passing fad; they result from decades of basic research and rigorous clinical trials. Even with FDA approval, ongoing study is necessary.

Loren: So this is where the revolution has really occurred. But the important thing is, is I wouldn't call GLP one drugs a fad in the sense that these have come from, like I said, decades and decades of basic research, translational research, and then unbelievably rigorous and extensive clinical trials. You know, even though these have succeeded in clinical trials and have been now on the market for for several years, we're still learning about them.

Loren: Consider thalidomide as an example of drug safety challenges. It was approved in Europe for pregnant women experiencing morning sickness, providing immediate relief.

Loren: Later, infants were born with severe limb malformations because thalidomide's impact on embryonic development was unknown during initial testing.

Loren: That experience highlights why long-term health monitoring over 5, 10, or 15 years is essential.

Loren: Post-marketing surveillance is a crucial component of formal FDA drug approval that ensures continuous safety monitoring after drugs reach the market.

Brent: Are peptides hormones? When discussing GLP-1s, hormones are frequently mentioned. Peptides consist of amino acids, so are peptides and hormones the same thing?

Loren: Not all peptides are hormones, but many hormones are peptides. Endocrine organs manufacture and release chemical messengers that travel through the body to regulate target organs.

Loren: An example is oxytocin, formulated as the drug Pitocin. Made in the brain's hypothalamus and released by the pituitary gland, it travels to target tissues like the uterus to induce labor contractions.

Loren: Oxytocin regulates uterine contractions, milk letdown during lactation, and aspects of stress and pain modulation.

Loren: Though oxytocin is only nine amino acids long, it profoundly affects human physiology. Meanwhile, non-hormonal peptides perform other functions, such as immune regulation and antibacterial defense.

Loren: Hormones represent just one category of biological peptides.

Brent: Regarding obesity, GLP-1 agonists show that viewing weight management strictly as a lack of willpower or poor habit formation is incomplete.

Brent: Human hormonal profiles did not evolve for modern environments with an abundance of processed foods and caloric density.

Brent: In past environments, high-calorie foods were scarce, making immediate consumption advantageous, and physical exertion was mandatory for daily survival.

Brent: Evolution didn't equip us with hormonal regulation for an overabundance of refined carbohydrates and calories.

Brent: Individual variation falls on a spectrum. Some individuals face genetic and physiological factors that make appetite regulation significantly harder.

Brent: These medications assist where evolutionary adaptation hasn't caught up to modern environments, making it easier to resist overeating.

Brent: Would you agree with that assessment?

Loren: That touches on nature versus nurture. We are endowed with genetic baselines that establish predispositions outside our control.

Loren: For instance, some lifelong smokers reach age 90 without developing lung cancer, while others develop severe disease after ten years due to underlying genetics.

Loren: Environmental factors—diet, location, air and water quality—layer on top of genetic baselines. It's an oversimplification to attribute obesity purely to a lack of willpower.

Loren: Richard Simmons showed empathy to people struggling with genetic predispositions to obesity and metabolic disorders, bringing public awareness to obesity as a medical condition requiring care.

Loren: Similarly, mental health conditions like depression and OCD are now recognized as medical conditions deserving objective treatment without stigma.

Loren: High blood pressure is a silent disease that carries severe risks without outward signs.

Loren: GLP-1 medications help shift physiology toward healthier homeostasis, enabling patients to live longer and healthier lives.

Brent: Regarding brand-name semaglutide and tirzepatide treatments like Ozempic, Wegovy, or Mounjaro: you support FDA-approved, as-directed usage for obesity backed by clinical trials and ongoing post-market monitoring.

Brent: However, many people without obesity use low doses off-label to lose weight or curb alcohol consumption.

Brent: Is microdosing tirzepatide for general wellness advisable without an obesity diagnosis?

Loren: This touches on self-regulation and taking unapproved substances versus trusting established professional expertise and study.

Loren: Consider aviation: would you board a flight with a certified pilot with thousands of hours of training, or rely on an uncertified individual operating on intuition?

Loren: Allowing an engineer with limited flight time into a commercial cockpit would be unthinkable.

Loren: Relying on unverified online vendors or Reddit claims for medical advice rather than consulting a licensed physician for an appropriate prescription carries significant risk.

Loren: I prefer safety informed by trained professionals.

Brent: Using that analogy, a patient might view off-label use as an experienced pilot flying a smaller, simpler aircraft than the complex plane they were certified on.

Brent: Patients assume a lower dose for general wellness carries minimal risk under physician guidance.

Brent: Many physicians write off-label prescriptions driven by patient requests.

Brent: If a physician prescribes a low dose of tirzepatide for general wellness, do you still view that with caution?

Brent: Are you less concerned if it's supervised by a doctor?

Loren: The key factor is evidence. Prescribing requires supporting clinical evidence because drugs are evaluated for specific dosages and pharmacology.

Loren: If a pediatric cancer patient reduced their chemotherapy dose in half without data, it could induce drug resistance and cause a fatal relapse.

Loren: Under-dosing an approved medication can cause severe harm. Medications should be dosed based on evidence of clinical benefit.

Loren: Deviating from established data creates unstudied risks.

Brent: Microdosing tirzepatide or semaglutide for general health outside of obesity lacks rigorous supporting data.

Brent: Without established dosing guidelines or side-effect profiles for non-obese populations, unmonitored experimentation carries substantial personal risk.

Brent: As a physician, you advise against off-label use in those cases.

Loren: Medical practice should be guided by supporting data rather than intuition, which is unreliable when determining safety and efficacy.

Loren: While titrating doses under medical care can be appropriate for managing side effects, prescribing unproven dosages leaves patients on uncertain ground.

Loren: Off-label use of approved drugs is one issue, but the rising use of completely unstudied compounds in humans poses an even greater risk.

Brent: Where does responsibility lie for widespread off-label prescribing?

Brent: GLP-1 sales generate massive revenue for manufacturers like Novo Nordisk and Eli Lilly beyond obesity treatments alone. Should primary care physicians avoid this practice?

Brent: How do you view physicians who prescribe GLP-1s for general wellness?

Loren: Off-label prescribing has a long history in medicine. In pediatric oncology, early chemotherapy drugs were initially approved based on adult trials, meaning pediatric use was technically off-label.

Loren: Pediatric drug development often lags because of safety concerns in children, which delays access to treatments. Ironically, recent breakthroughs like CAR-T cell therapy were first proved in pediatric cases.

Loren: Gene therapies for metabolic disorders and sickle cell disease were similarly pioneered in pediatric populations.

Loren: Medical practice allows flexibility to adjust doses or apply known safe medications to new indications where appropriate.

Loren: There is a vast difference between off-label use of FDA-approved drugs with safety records and using unapproved compounds that have never been tested in humans, where individuals effectively become subjects in unmonitored trials.

Loren: And mass like, for all these other agents that we're talking about that are FDA approved.

Brent: Semaglutide and tirzepatide have cleared FDA testing and post-market safety tracking. Using them off-label under doctor supervision carries lower risk than taking unapproved experimental peptides like the Wolverine stack.

Brent: The Wolverine stack lacks FDA review entirely. Is it fair to say approved GLP-1 off-label use requires caution, whereas unapproved peptide stacks should be avoided completely?

Brent: And what I would hear you saying is don't go anywhere near that. It's never been through any kind of FDA approval process. And that's a very different category. So one is I wouldn't do it. I'd be cautious about it. But okay, I understand that it's happening. Turns out some gluten. And then the second category that we're about to talk about, which I assume you're going to say, don't go anywhere near it.

Brent: Is that an accurate summary?

Loren: GLP-1 dosages were established for weight management and blood sugar control. Doctors may explore lower doses for patients who experience side effects like nausea.

Loren: In a doctor-patient relationship, clinical decisions adjust dosages based on the established safety profiles of approved drugs used across millions of patients.

Loren: Off-label use of approved drugs relies on established safety data and manufacturing standards, unlike unstudied compounds. Many vital oncology and psychiatry applications originated through off-label care backed by robust safety profiles.

Loren: A fundamental distinction exists between off-label uses of regulated drugs and unapproved peptides marketed for general wellness to bypass regulatory oversight.

Brent: Off-label uses can lead to main applications, as seen with erectile dysfunction drugs originally developed for cardiovascular conditions.

Brent: Consider the Wolverine stack, a combination of BPC-157 and TB-500. These lack FDA approval and human testing.

Brent: While animal models and self-experimentation show some promising anecdotes, how do you evaluate these compounds?

Brent: Are you optimistic about where research into these peptides might lead over the next 25 to 50 years, even if you advise against using them today?

Brent: Many individuals report rapid recovery from injuries using the Wolverine stack. Is there genuine scientific promise behind these experimental peptides?

Brent: How should people view unapproved experimental peptides?

Loren: It's important to understand the two distinct regulatory tracks. Standard FDA drug approval requires preclinical testing, Phase 1 safety trials in humans, Phase 2 efficacy trials, and large Phase 3 trials comparing the candidate to existing treatments.

Loren: Once safety and efficacy are established, the drug receives FDA approval and enters post-marketing surveillance.

Loren: Compounding pharmacies operate under a separate framework. The FDA maintains lists governing compoundable substances: Category 1 includes acceptable substances, while Category 2 lists prohibited substances due to safety concerns.

Loren: Being listed in Category 1 does not guarantee that a compounded product is safe or effective. It simply permits pharmacies to compound agents to support general wellness.

Loren: That level of regulation offers no guarantee of efficacy, human safety, or consistent product quality. Comparing off-label use of rigorously evaluated FDA-approved drugs to unstudied compounded peptides mixes two completely different categories.

Loren: So it's just that that level of FDA regulation just means that the substance can be compounded. There's absolutely no requirement that it has to be safe. It has to be effective in humans in terms of what they're ultimately making with it. And there's no guarantee of consistent quality and what's being administered to a patient. So I think, you know, that is the so when you talk about off label, it's really just two completely separate things, you know, because you could have on label an off label use of an FDA approved process, which is extremely rigorous in some cases, goes into, if not hundreds of thousands of patients before it gets approved for regular human use.

Loren: Unstudied peptides bypass clinical trial standards under the guise of supporting wellness or speeding recovery. Relying on online anecdotes is far removed from clinical evidence.

Loren: These peptides occupy a grey market area as unapproved therapeutics labeled for research use only to avoid oversight while being sold to consumers.

Loren: Consumers buy these peptides out-of-pocket through wellness clinics, anti-aging practices, or telehealth sites. Because insurance doesn't cover unapproved substances, adverse events and outcomes go unmonitored.

Loren: As a peptide researcher for 25 years, I favor subjecting promising peptides to established research processes to evaluate safety and efficacy in humans before broad use.

Loren: Deregulating compounds to bypass oversight delays true understanding, as rigorous science is required to validate therapeutic claims.

Loren: Safety standards like FDA oversight exist to protect public health based on past medical errors.

Loren: Bloodletting was once widely practiced despite causing harm. Similarly, early excitement around Human Growth Hormone (HGH) overlooked its tendency to stimulate tumor growth alongside muscle tissue.

Brent: Certain experimental peptides stimulate growth hormone release, which carries risks of promoting malignant tissue growth.

Brent: Regarding BPC-157 and TB-500 in the Wolverine stack: rather than assuming efficacy or dismissing potential, these peptides should be rigorously studied through basic research supported by federal funding and private philanthropy.

Loren: Subjecting candidates to scientific scrutiny is what delivered cures in pediatric oncology. Bypassing research and injecting unverified compounds carries unnecessary danger.

Loren: Even thoroughly vetted drugs can reveal unforeseen long-term risks during post-market tracking. Vioxx was approved as an effective anti-inflammatory for arthritis, but long-term data later revealed an increased risk of heart attack and stroke, leading to its withdrawal.

Brent: Bypassing regulatory guardrails entirely has led to severe public health disasters. In 2012, contaminated injectable steroids from the New England Compounding Center caused a fungal meningitis outbreak that killed dozens and sickened hundreds, resulting in new federal legislation.

Brent: In another incident at an anti-aging conference, attendees suffered critical illness and required mechanical ventilation following unverified peptide injections at a booth.

Brent: Independent testing of unapproved direct-to-consumer peptides revealed inaccurate dosing, heavy metal contamination, endotoxins, and bacterial or fungal contamination.

Loren: Injecting unverified substances into the bloodstream without safety controls poses extreme risks. Rather than being driven by marketing hype, we should invest in formal research through institutions like the NIH, NSF, and Department of Defense to evaluate peptide potential safely.

Loren: Bypassing scientific methodology ultimately slows down therapeutic discovery.

Loren: What is the status of current FDA discussions regarding compounding restrictions for certain peptides?

Loren: In 2023, the FDA removed roughly 20 peptides from the list of allowable compounding substances due to safety concerns, such as cancer risks, severe allergic reactions, and lack of human clinical data.

Loren: Compounding pharmacies legally challenged the decision on procedural grounds. Upon conducting a formal re-review, the FDA maintained that restrictions should remain based on safety risks.

Loren: Subsequent policy debates consider revisiting those restrictions under arguments for expanded patient access. However, scientific and regulatory experts express concern that loosening restrictions without clinical trials prioritizes political and commercial interests over evidence-based patient safety.

Loren: Is there a reasonable middle ground to streamline the FDA review process to evaluate promising peptides faster without sacrificing safety rigor?

Loren: We share the goal of harnessing peptides to advance human health. However, establishing an unregulated secondary tier of peptides based solely on public interest or market demand is dangerous.

Loren: The appropriate path forward is funding scientific research to evaluate these compounds in animal models and controlled human trials.

Loren: This issue is personal to my work. My laboratory studied enfuvirtide, an early injectable peptide drug approved for HIV in 2003.

Loren: Although oral treatments eventually replaced twice-daily enfuvirtide injections for mainstream HIV care, its viral-entry inhibition mechanism applies to other viruses, including RSV, influenza, SARS, and Ebola.

Loren: My laboratory demonstrated that engineered peptides could inhibit SARS coronaviruses. However, securing long-term research funding remains difficult because interest wanes between viral outbreaks.

Loren: We have developed candidate peptide therapeutics for Ebola that lack research funding despite ongoing outbreaks. We must invest in formal peptide research to unlock their true therapeutic potential.

Brent: If you could travel 50 years into the future and search one topic regarding medical advancements, oncology, or peptides, what area of research would you look up?

Loren: I would look at the progress made in targeting historically "undruggable" intracellular proteins. Small molecules fit into small protein binding pockets, and antibodies target large extracellular surface proteins.

Brent: Peptides occupy the middle space between small molecules and large biologics.

Loren: Peptides can bind flat protein surfaces and complex interfaces that small molecules cannot target.

Loren: To fully realize this potential, we must overcome delivery challenges into cells and stabilize peptide structures to prevent rapid degradation in blood and tissues. Techniques like peptide stapling help retain active biological shapes.

Loren: In 50 years, I anticipate whole new classes of peptide-based therapeutics successfully treating targets that are currently unaddressable.

Loren: Dr. Loren Walensky, thank you for your time and research.Thank you very much.

Loren: The Life Lab by Death Clock is recorded in Boulder, Colorado, and San Francisco, California. Produced by Patrick Godinho, music by Patrick Lee, and hosted by Brent Franson, founder and CEO of Death Clock.

Brent: But is there if we were to give RFK the benefit of the doubt or the people, if we were to steal, man, basically some some reasonable interpretation of this, and I think you would alluded to this earlier, maybe the answer isn't what they're proposing, which is, hey, just I don't drop all these regulations and let's bring these things back or let's allow, you know, let's make it easier to get some of these peptides that haven't had any human testing.

Brent: Maybe maybe that's not the answer, but there does seem to be some truth to, hey, the FDA process very expensive. It's very slow. It could be accelerated. Would you directionally support some version of, hey, let's figure out a path that's a that's as rigorous as we've been, but where we can get the answer a little bit more quickly because that does seem reasonable.

Brent: Hey, let's we want to know more quickly than 30 years.

Loren: Well, I don't think it's 30 years, but I think that the approach, the goal is what we've discussed. Let's let's harness peptides for benefit of our health. I mean, I think that's a shared goal. Certainly as a peptide researcher, you know, I'm also extremely enthusiastic. But what I'm not enthusiastic about is saying, you know, we're going to put these peptides through the therapeutic gantlet and make sure that they're going through all the clinical testing that's required to ensure safety and efficacy.

Loren: And then we're going to have a whole nother class of peptides where we're just going to say, hey, you know, people want them. People think they work. So that's good enough, right? That's in my view, extremely dangerous. So the better approach would be to say, you know what we're excited about these 19 or 20 peptides. Let's actually study them.

Loren: Let's actually get the data to see what they do, how they do it. How do they perform in animals. And then, of course, how do they perform in humans? And let's do a real study. And I think that's where the notion of just saying, oh, we're going to move them into a different pathway and deregulate them and let it be the Wild West and let everybody just take what they want.

Loren: You're really delaying the process because you're not collecting any data. You don't know what harm is being done. There's always a bias toward people going on the internet saying how great things are, you know, and advertising them in that way. And there's certainly a hype to promote them, to make money for the folks that are profiting from it.

Loren: So my view is, yes, peptides have the potential to be amazing. And if anyone's excited about these, let's actually study them in a real way. Let's invest in peptide research in America. Let's double down on it. And you know, this is a somewhat personal to me because I have examples of this in my own laboratory in future tide.

Loren: It's a peptide drug that was one of the earliest approved peptide drugs for HIV. Now yes, it was an injectable twice a day. It had the liabilities of peptide therapeutics that got, you know, broken down in the body. And then it was replaced by all the oral therapies that worked very well for HIV. So this peptide injectable kind of didn't, you know, stand really this test of time.

Loren: It was, let's just say replaced. It's still out there, but it's been replaced in the mainstream. The mechanism of how infuse tide blocked HIV is shared by many viruses that people will recognize RSV, the flu, SA's Ebola. That's in the news right now. The mechanism of developing a peptide to block the ability of the virus to get into the cell, and fever tied was the proof of concept for that all the way back, approved in 2003 when these other viruses came online like SARS and Ebola.

Loren: You know, my laboratory got involved and saying, well, can we learn from and to make inhibitors of these other viruses? And the answer was yes. And when you looked at SARS, the first SARS in 2002, 2003, the SARS that emerged in 2019, in this area, that the peptide could work to inhibit it 100%, the same as it was back in 2002 2003.

Loren: But you couldn't get funding for it. Why? Because these outbreaks come and go, and by the time your grandkids reviewed, right, the crisis is over and then no one wants to invest to make sure that the next crisis can be averted. And so we're seeing that play out right now for Ebola. I've had something on the shelf, just like in future, tied for Ebola for years.

Loren: We published it back in 2024. I can't get funding for it. Right. It's a peptide therapeutic. There's biases against peptides, and yet there is nothing out there right now for this outbreak in DRC and and in Uganda for Ebola. You know, so my answer to you about the these other peptides that we've been discussing and this peptide that's sitting on my shelf in the lab is we should be investing in peptides because there's remarkable, you know, potential there that has not been invested in yet.

Brent: Wonderful. So last question. And this can be related to the peptide topic. It can be related to your own work really really to anything. If we could go forward in a time machine 50 years and we could pull up the ChatGPT equivalent and just ask a question around something that happened, we could see where some line of research went.

Brent: We could see what happened with some cancer that you're keeping an eye on, or what happened with these peptides. What are you looking at? What's the if you could do, you know, a search on one topic 50 years in the future to see what happened with that, with the advancement of that science or the advancement of our understanding of something, what would it be?

Loren: I for me, you know, there's this area in medicine called the quote unquote targets, right? The folklore based upon the true reality of the history of medicine making that there are targets that have been very difficult to drug. And so one of the classic examples of that are proteins that are inside of ourselves. So we're very good at making antibodies to target very complicated proteins on the outside of ourselves.

Loren: Right. And we're very good now at engineering cells that may recognize those proteins on the outside of the cells. We're also really good at making small molecules that easily get inside cells and can crawl into little tiny holes within proteins to stop a particular activity or induce a particular activity. The area that's been the most challenging, in my view, are perfect for peptides, which is the middle ground between very tiny things and very, very large things.

Loren: And here you have the biology that is living in all of us right now that has taken advantage of little, little proteins, little peptides, things that are much smaller than proteins, but things that are much bigger than small molecules. And I think that the benefit of those of that size of a drug is that it can bind to flat surfaces that can't be drug by small molecules.

Loren: It could bind to complicated interfaces that are too complex for a small molecule. And that's going to be, in my view, the sweet spot of peptides. In order to get there, we have to overcome a couple of challenges. One being how do you get these things into cells? Some go in by themselves, some can be engineered to go in.

Loren: And then how do you overcome the classic liabilities of peptides, which is one of the things that I've been working on for 25 years, which is this use of the stapling technique to try to fold them in the right shape, in just the right shape, the shape that they need to make that key fit into the lock, and until it gets into the lock and gets into the cell to reach the lock to keep it stable enough so it doesn't get degraded in tissues and in blood.

Loren: And we are not there yet. Uniformly, there's some really exciting things happening right now, but I would bet that in 50 years, looking back, you know, we're going to have new classes of drugs, many of them based upon natural peptides that will be able to fill the hole that that that is exists right now in this quote unquote, target space.

Brent: Wonderful. Doctor Lauren Walensky, thank you so much for your work. And thank you for your time.

Loren: Thank you so much.

Brent: The Life Lab by Dethklok is recorded in Boulder, Colorado, sometime San Francisco, California, produced by Patrick Godinho, music by Patrick Lee, and hosted by yours truly. Brent Franson, founder and CEO of Dethklok.