The future of coronary arteries
Guest Kristy Red-Horse is a biologist who specializes in coronary artery development and disease.
She says the latest advances in treatment of blockages could do away with invasive bypass surgeries in favor of growing new arteries using molecules like CXCL12, known to promote artery regrowth in mice. Red-Horse explains how leaps forward in medical imaging, expanding atlases of gene expressions, and new drug delivery mechanisms could someday lead to trials in humans. But, before that day can arrive, much work remains, as Red-Horse tells host Russ Altman in this episode of Stanford Engineering’s The Future of Everything podcast.
Transcript
[00:00:00] Russ Altman: This is Stanford Engineering's The Future of Everything. And I'm your host, Russ Altman. As we start the new year, I thought it would be good to revisit the original intent of this show. In 2017, when we started, we wanted to create a forum to dive into and discuss the motivations and the research that my colleagues do across the campus in science, technology, engineering, medicine, and other topics. Stanford University and all universities, for the most part, have a long history of doing important work that impacts the world. And it's a joy to share with you, how this work is motivated by humans who are working hard to create a better future for everybody. In that spirit, I hope you will walk away from every episode with a deeper understanding of the work that's in progress here and that you'll share it with your friends, family, neighbors, co-workers as well.
[00:00:50] Kristy Red-Horse: It would be really nice to not have to have a quadruple bypass by opening up your chest, especially if you're an older individual that has some comorbidities, um, so that would be nice. And also, just to bring the opportunity to, if you're going to medically grow new arteries, new bypass arteries, you could do it earlier in the process, before it gets to the point in which you need a coronary artery bypass.
[00:01:25] Russ Altman: This is Stanford's The Future of Everything. And I'm your host, Russ Altman. If you're enjoying The Future of Everything podcast, please spread the word to your friends, family, and colleagues. Personal recommendations are a great way to spread news about the show and make sure that everyone is clued in to The Future of Everything.
[00:01:42] Today, Kristy Red-Horse will tell us how she's figuring out how to grow new coronary arteries with medicines and not with surgery. It's the future of coronary arteries.
[00:01:54] Before we get started, a reminder to spread the news about the show to your friends, family, and colleagues. It'll grow the show, and it'll make sure that everybody is clued in.
[00:02:09] So, coronary artery bypass surgery is something that we can all fear. At some point, many of us develop a blockage in the heart arteries that help feed the heart. That can lead to death of heart tissue and death of the patient. The emergency surgery that often happens is called coronary artery bypass surgery, and what they do is they create little artery shunts that move the blood past the blockage to the downstream parts of the artery so it can supply blood and nutrients to the heart. That's a big surgery, it's open-heart surgery. It requires you to go on bypass very frequently and it is not fun. Leads to a huge scar in your sternum and a long rehabilitation. But now there's a possibility that we may be able to get these arteries to grow bypasses naturally. That by injecting medications, we can stimulate the growth of new arteries that will go around the blockage and connect up with the downstream arteries.
[00:03:10] Well, Kristy Red-Horse is a professor of biology at Stanford University and an expert in coronary arteries, how they grow, and what are the cells and genes that contribute to the growth of arteries, both as an embryo and later on in life. She's going to tell us that she has found some very critical molecules that can stimulate the growth of new arteries that gives a whole new future for coronary artery bypass, such that surgery may be eliminated in some or all cases, and instead we'll be giving medications that get you to grow new arteries.
[00:03:46] Kristy, you're working on ways to grow arteries to avoid surgical bypass approaches. What's the problem with surgery and why are you working to create this whole new way to bypass blockages in these coronary arteries?
[00:04:01] Kristy Red-Horse: Well, the surgery that you're referring to is open heart surgery. So the problem is it's incredibly invasive and it's a huge procedure. So it would be really nice to not have to have a quadruple bypass by opening up your chest, especially if you're an older individual that has some comorbidities, um, so that would be nice. And also just to bring the opportunity to, if you're gonna medically grow new arteries, new bypass arteries, you could do it earlier in the process before it gets to the point in which you need a coronary artery bypass.
[00:04:40] Russ Altman: Okay, so that's very helpful. And yes, I think most of us would like to avoid open heart surgery. So that really makes perfect sense. Um, are there special challenges in figuring out, um, uh, I'm sure there are, um, what are the key challenges for figuring out how to do this in terms of the anatomy of the heart, where you want these vessels to grow, um, and what is the research program that you've put together to try to kind of tackle these in a coordinated logical manner?
[00:05:09] Kristy Red-Horse: Right. Well, there's multiple challenges. Uh, the first challenge is discovering what makes arteries grow. And it turns out that what makes capillaries, so very small vessels grow, is not exactly what makes big arteries grow. And so when the idea of medical revascularization, where you add a molecule to the heart to get the blood vessels to grow, when that came about, people discovered molecules like VEGF and FGF, uh, certain molecules that make blood vessels grow specifically. And they injected them into the heart, but it turns out those molecules make the small capillaries that, uh, are where oxygen exchange occurs, they make those grow.
[00:05:55] And so what we need to do now is understand how specifically arteries grow so we can get the bigger blood vessels to get the more blood flow coming in and perfusing those smaller vessels. And so that's the first challenge that we need to, uh, understand the proteins that will make the arteries grow. Another challenge is the fact that those proteins that make them grow are pleiotropic. And so they have functions all over the body. And so you really need to target any therapy or any stimulation of these particular pathways to the heart, to very specific places.
[00:06:34] Russ Altman: Ah, so, because you don't want arteries growing all over the body, so you have to make sure it's in a controlled, just where you want it.
[00:06:41] Kristy Red-Horse: Right. And it turns out that these pathways, uh, will stimulate your immune system, they'll stimulate, uh, all kinds of growth of different cell types in the body, not just arteries. But you're right, you don't want arteries growing everywhere as well. Um, and so those are some big challenges. And the way that my lab has taken on this challenge is we, like many other people, had this idea that if you understand how the embryo generates arteries de novo during embryonic development. Then perhaps you could reuse those same pathways to regenerate them in a injured heart or in a diseased heart. And so we spent about ten years studying embryogenesis and coronary artery development in the heart.
[00:07:32] Russ Altman: Wow. Okay. So that's really exciting. So the, yes, it does make sense that understanding how they got there in the first place would then help you understand how can we get them to grow. So, um, before we get into the details of the science and where you are in this process, um, there's like really basic questions, I guess, about, um, is your goal, you use the phrase in your writing, collateral arteries. So maybe it would be useful to define what you mean by a collateral, uh, artery. Um, so let's start with that.
[00:08:01] Kristy Red-Horse: Right. A collateral artery is a very special artery. So normally in your heart or in the whole body, arteries are bringing blood to an organ or tissue, including the heart, and they branch off like, uh, tree branches. They get smaller and smaller so that they can bring a lot of blood to these tiny blood vessels called capillaries, and that's where oxygen exchange occurs. And so that's normally how it's set up. It looks like a tree. However, there is a special case in which instead of branching like the tree branches, they'll make rungs of a ladder. So if you have rungs of a ladder, you have the opportunity that if one is blocked, then blood flow can go across to another artery and be able to still have a direction to send blood flow to a tissue. And that,
[00:08:54] Russ Altman: Okay, so it sounds like a lot like a bypass when you do it surgically, you're creating this kind of extra bypass. But you're telling me, and that's very exciting, that, uh, there are actually naturally occurring bypasses sometimes.
[00:09:08] Kristy Red-Horse: Yeah, these are natural bypasses. And the amazing thing is that our bodies have the ability to grow these natural bypasses at baseline. The problem is, is that only it's been estimated about twenty percent of people have the ability to grow collaterals in their heart.
[00:09:28] Russ Altman: Wow.
[00:09:29] Kristy Red-Horse: Um, and even those collaterals that they grow might not be as big as we would want them to function perfectly.
[00:09:37] Russ Altman: Under what circumstances would one of these lucky, it sounds lucky to me, lucky twenty percent, um, under what circumstances do they do that? Is it kind of random or do they do it in response to like a lot of exercise where they need extra blood? Uh, why does this happen naturally?
[00:09:53] Kristy Red-Horse: So we don't exactly know the answer, but we have some hints by looking at patients and then looking at our mouse experiments. And the idea is that if you have a slow growing blockage of your coronary artery, you have this slow hypoxic response, or where there's low oxygen because there's lower blood flow. And that slow response will trigger the processes that create these collaterals over time. So if you're an individual that has the certain variants in your DNA that allow these proteins that are directing this process to be expressed really well, then you'll, over time, grow a collateral artery. One thing is that we don't know if some people are just born with them, and then keep them for a long time. So that's another possibility, but these are very hard to study. These questions are very hard to ask about humans.
[00:10:49] Russ Altman: Right. Okay. So one more kind of background question is coronary arteries, I think, are pretty special because they have to endure pretty high pressures. They're working, like the arteries that are supplying blood to the heart are also experiencing very high pressures as the heart is squeezing to push the blood out. Um, part of that blood that it pushes out, of course, is going into the coronary arteries, which are keeping the heart muscle healthy. And then the rest of it is going to the whole rest of the body. So these seem to be pretty special arteries. And I want to ask from your perspective, as a biologist who studies these, are these arteries special? And do you have to consider the special operating conditions of these arteries when you're kind of figuring out how to grow collateral ones and add to the vasculature of the heart?
[00:11:36] Kristy Red-Horse: Yeah, that's a good point. And the specialness that, uh, we think about these arteries is that whenever you are shunting blood away from the periphery, if you are in a fight or flight response or something, uh, they respond differently. So they open up when a lot of your periphery arteries will close down, because your heart is the number one priority and your brain is the number one priorities. Um, so they're different in their response to vasodilators or things that make the arteries widen or squeeze. So that's kind of the specialness.
[00:12:11] I think what you're referring to is when the heart beats, they kind of get, uh, pressed and squeezed. Um, yeah, we don't know a lot about how that affects their biology, but they seem to be fine with that. But they do fill whenever the heart is in a relaxed state. Um, but in our studies in mice, we haven't really, uh, detected whether that's going to really, uh, affect our ability to grow the arteries. I think that's kind of a separate issue. And the reason I say that is because these developmental pathways that we can put in the heart and regrow the arteries, uh, they seem to be very similar to the ones in other organs. So, uh, I think, in terms of developing an artery and making it persist, maybe that's not going to be our number one.
[00:13:04] Russ Altman: So thank you very much. That establishes a lot of basics about why we need to have these collateral arteries to help feed the heart. The sources of optimism that some people are showing these capabilities even without engineering or medications. And so now let's go into some of the things that you have discovered that are pathways to this hoped for reality. So where are we at our understanding of the cellular, cells and molecules that you would need to manipulate to get collateral arteries to grow in the heart?
[00:13:34] Kristy Red-Horse: Right. Well, that's a very exciting moment right now because what we did was to study development of these collaterals and then re-establish those pathways in the adult in a model of heart attacks. In a mouse model of a myocardial infarction. And we were able to discover a particular molecule called CXCL 12 that when we inject it, we can make collateral arteries grow.
[00:14:03] Russ Altman: Wow.
[00:14:03] Kristy Red-Horse: Yeah, that was really exciting. Um, however, whenever you're doing mouse studies, you always have to have this big question mark of is that going to really affect humans in the same way? And you may know about this big wide gap of curing mice of cancer, heart disease, whatever. And then it goes into making human medicines and it just fails. And so this is a big problem. And this is a question mark we always have. So we need some sort of information or clue as to whether this pathway would work in humans. And we were lucky enough to make a collaboration with Tim Assimes and his group at Stanford. Uh, and he did this human genetics analysis, this GWAS analysis, to look for variants in DNA that are associated with a developmental phenotype in human coronary arteries. Uh, and this was a very special study because he's part of this group that has all of this data where they had phenotyped the structure of the coronary arteries and also genotyped, um, the individuals. So he could make this for them.
[00:15:18] Russ Altman: They had the DNA and they also knew what had happened in their, um, artery growing journey.
[00:15:26] Kristy Red-Horse: Right. Yes. There's a trait, um, that we can look at on a picture of the heart basically, uh, angiogram. Uh, and so when they did that, the very highest peak that was significantly associated with coronary development in humans was right beside this gene, CXCL 12, that is the protein that we injected and made the collaterals. And so at this point, we feel really confident that human collateral arteries will form and be patterned by this protein CXCL 12. And now we feel really confident that we could potentially translate this and redevelop them, re pattern them into these collaterals, into these rows of the ladder.
[00:16:12] Russ Altman: Yes.
[00:16:12] Kristy Red-Horse: As part of a bypass, a medical bypass.
[00:16:16] Russ Altman: So tell me a little bit more about exactly what you did to these lucky mice. So did, was it so simple, and I'm just saying this as a question, that you could, wherever you injected the drug is where they sprouted, or is it more complicated than that? Because it seems like, do you have the ability to control the location of these collateral arteries that grow?
[00:16:35] Kristy Red-Horse: Right. So it's, it sounds, uh, really unbelievable, but it was so simple. The very first experiment, we did many, many experiments leading up to this, but the very first, uh, experimental heart attack that we did, we injected right at the site where we know we want the collateral arteries to form. So it's at the junction between the flowing arteries and the ones that we had experimentally blocked.
[00:17:00] Russ Altman: Yeah.
[00:17:00] Kristy Red-Horse: We injected it right there, and we formed a lot of collaterals. There was just one injection, and we formed a lot in two weeks.
[00:17:09] Russ Altman: Wow. Okay. So, and so it sounds like this was an even better result than you might have been anticipating when you designed the experiment.
[00:17:17] Kristy Red-Horse: Right. This was one of the moments of you know, working for three or five years on something, and then culminating and laying the groundwork, and then actually the very first experiment working. So that was a special moment.
[00:17:32] Russ Altman: So what can you tell me about this molecule and what it does? What's its normal function? Why do we have it? Um, why isn't it being used all the time by the heart to grow new collaterals? Um, it sounds like a very important molecule. So what do we know about it and its function?
[00:17:48] Kristy Red-Horse: Well, we know that it has a really important role in the immune system and immune cell trafficking around the body and including how you traffic and keep your blood stem cells in your bone marrow and when you release them. So it has a lot of effects on, and that's how it was discovered. But then it was discovered for that, and they may knock out mice to study the organismal level of this, and they surprisingly found that the arteries were messed up. And they were not developing properly. And so it turns out, the receptor for this secreted protein, it's a secreted protein that, uh, talks to neighbors, neighboring cells.
[00:18:28] Russ Altman: So that, when you say secreted, that means it just gets released into the bloodstream by whatever organ produces it.
[00:18:34] Kristy Red-Horse: It gets released into the bloodstream, it gets released into the intercellular space. So like, if two cells are beside each other, it'll get released by one and the neighboring cell will respond. Because it has a receptor, uh, on the surface, the cell surface, and this receptor is highly expressed on artery cells. And so what it does is guide the artery cells to migrate out. So it's calling artery cells into the space in which it is present. So it's called, something called a chemokine, a chemokine.
[00:19:13] Russ Altman: And that's why you did get this very nice effect of having it happen right where you injected it because it, it signaled to the local cells and they started building arteries as they are programmed to do.
[00:19:24] Kristy Red-Horse: Right, right. They migrated into the area where we injected and then they did what they were going to do. They already know how to build these arteries remarkably.
[00:19:34] Russ Altman: This is The Future of Everything with Russ Altman. More with Kristy Red-Horse, next.
[00:19:50] Welcome back to The Future of Everything. I'm Russ Altman and I'm speaking with Professor Kristy Red-Horse from Stanford University. In the last segment we learned the basics of coronary arteries, coronary artery bypass grafts as a surgery, and some of the new discoveries that are making us think about medical ways to grow new coronary arteries.
[00:20:09] In this segment, I'm going to ask her about guinea pigs, which have a really interesting set of coronary arteries. And also, I'm going to talk about some of the new advances in scientific instrumentation that allow her group to do this work now, which wouldn't have been possible ten or twenty years ago.
[00:20:27] So, Kristy, I know that in addition to the mice work that you talked about in the first segment, you also do work with guinea pigs. What's the deal with guinea pigs?
[00:20:36] Kristy Red-Horse: So, guinea pigs are unique among mammals in that they are completely refractory or resistant to a heart attack induced by a coronary blockage. So, during development, we found that they form these perfect collateral arteries as part of their developmental process. And not only do they form them, but they are large enough and organized in the perfect way, so that they completely reroute blood flow. And we want to know why they do that. And so we're busy studying how they develop the arteries, so we can not only rebuild arteries, but build the perfect collateral, just like they have.
[00:21:22] Russ Altman: Okay, so, so many questions. But first of all, do they get cholesterol buildup? Like, is that an issue? Because I would imagine that if they are, have all this like backup system for blood flow, that means that maybe they do get blockages. But is that known? Do they have blockages in their other arteries?
[00:21:40] Kristy Red-Horse: No, and actually it's pretty unique to humans to have this problem with atherosclerosis and building up plaques and blockages. So our rodent models, we have to change genes in them so that they will actually get these fatty plaques in their arteries. So who knows why evolutionarily they have grown these? We have one idea, and that's because they evolved at very high elevations in the Andes Mountains in Peru.
[00:22:15] Russ Altman: Yeah.
[00:22:15] Kristy Red-Horse: And so we know that that, remember I talked about that slow hypoxia could be what's driving some humans to make collaterals, perhaps since they evolved at hypoxia, they evolved to have these collaterals. We don't know if that's true, that's a hypothesis. But, um, they certainly make them.
[00:22:33] Russ Altman: Yes. And it's very attractive because, you know, anybody who's been at high altitude knows you lose your breath, it can put stress. So if they evolved a way to manage that stress, it seems like it would offer an advantage. Okay. So are they using these same molecules, the magical molecules that you injected into mice, or is it a whole different story there?
[00:22:55] Kristy Red-Horse: Right, so we don't know yet. What we did find, we did a gene expression analysis between them and mice, which don't have any collateral arteries during development. And we found some of our favorite pathways being, uh, up regulated in the guinea pigs. Um, and we're currently in the process of doing functional experiments to test whether this is actually the case.
[00:23:19] Russ Altman: It also, I know that you know, you mentioned before that you've studied embryology, and it raises the issue. And now you're telling us about the guinea pigs, which basically, they do this not in response necessarily to stress, but they just do it as part of their normal development, kind of anticipating potential problems down the line. And I wanted to ask, is your vision, if these molecules really work out, do you imagine using them like late in the game when there are problems? Or do you imagine we might start trying to use them before problems develop? I don't know, in the mid adulthood or even early adulthood for people who are at high risk, to try to avoid all the problems that might happen and not have to do it at the last minute. I know this is early and I know that you're not there yet, but do you have models for how you might, um, deliver such a capability?
[00:24:09] Kristy Red-Horse: Right. I really believe and I hope that we can get to the point where it's pre-emptive.
[00:24:16] Russ Altman: Right. That's the word. Thank you.
[00:24:17] Kristy Red-Horse: About this new way of looking at coronary arteries, which is quite popular right now. So instead of going into this invasive procedure where you fill the heart and the coronary arteries with a dye that you can see the structure, now you can just go get a CT scan. And many people are doing that now and seeing very, very early plaque buildup and characterizing this very early plaque buildup. And so I have envisioned in long term, since so many people are getting that procedure, maybe it would be a pre, uh, preventative strategy perhaps one day.
[00:24:53] Russ Altman: Yes. I do remember from my medical training, they told us that during the Korean war, when young soldiers died and they did autopsies, they were noticing early signs of cholesterol development, even in eighteen, nineteen year olds, which was, now this was with the diets of the 1940s and fifties. But I don't think we should give ourselves too much credit for improving since then. And so this is a problem that starts very early. So for these exciting molecules, like the, um, I think you said CX, it's CXCL?
[00:25:23] Kristy Red-Horse: CXCL 12.
[00:25:25] Russ Altman: 12, CXCL 12. Why haven't we been studying them forever? So it sounds like a series of really careful observations led to this, and then you had this experiment, this very exciting experiment with the mice growing collaterals. Um, and you said it was known to be important for a lot of things beforehand. Um, something must have changed to make it clear that this was an important molecule and that it was involved in these systems. So, what's going on with your capabilities for measurement and observation that enables you to identify this now?
[00:25:56] Kristy Red-Horse: Right, right. So what happened was we gained the capability and the techniques to image the entire heart. And so I told you that there's lots of arteries there, but they're normally like tree branches. And so we can see the tree branches. But if you do what we used to do forever, which is study the heart or other tissues by making thin tissue sections, and then immunolabeling arteries or other cell types and looking at them. Um, but what happened was this revolution in microscopy and tissue clearing and now machine learning ways of quantifying the entire vascular tree, um, that we can identify collaterals and quantify them. And the reason it's so hard and why you need the 3D imaging is because they're just like the other arteries in their expression of proteins that we use to label them. The specialness is that the rungs of the ladder. So we have to be able to see the 3D rungs of the ladder to be able to study whether we grew them, whether we didn't, etcetera.
[00:27:05] Russ Altman: Okay. And so this microscopy plus a little bit of computation is allowing you to look at the heart, um, in ways that we, where you can identify where these phenomenon are happening and then, and presumably then make measurements on the molecules that are present. And, uh, you know, if they're up, more or less present than usual and kind of dissect it. One thing I didn't ask you before is, you mentioned that the way capillaries, the very small vessels grow, is quite different from how arteries grow. When you see these collaterals, are they entirely new buds? Like, you use this very nice tree analogy.
[00:27:40] Are these new branches that are connecting to other branches? Or are they already existing connections that are being like grown to be bigger and stronger and bigger pipes? So is it a new budding or is it the, um, differential development of things that were already there?
[00:27:57] Kristy Red-Horse: It can happen both ways. So there could be these small little connections that get signals to grow from the smaller vessels. Or, and what we've studied most, is when they're growing out from the preexisting arteries, growing out from both sides to meet. And so both of those things are opportunities.
[00:28:19] Russ Altman: Wow. So that is an amazing thing. So the idea that two sets of cells could be growing towards one another in kind of a concerted way. That sounds interesting. So are they sending signals of some kind to say, I'll meet you in the middle, type stuff?
[00:28:36] Kristy Red-Horse: Well, we found their, the signal is CXCL 12 for them to grow out.
[00:28:41] Russ Altman: Ah. So they're basically chasing the CXCL 12.
[00:28:46] Kristy Red-Horse: Right. That's right.
[00:28:48] Russ Altman: Oh, very interesting. So how, um, what is the future? So in the last minute, tell me, uh, you're in the middle of this very exciting time for your lab. You know, you did this mouse experiment, it's like remarkably successful. Um, I'm guessing you're not allowed to just grab some humans off the street and inject CXCL 12 into their hearts, even though I'm suspecting a small piece of you wishes you could. So what is the future of this research program to try to get to the kind of vision that you have?
[00:29:18] Kristy Red-Horse: Right. So the future that we need to do now and what we're currently doing, is design a way to just inject something into the blood and have it hone right to the heart, right where we want to make the collaterals. And so there are many details I'm not telling you today about the fanciness of the molecules that we have to design to do that. Um, but the exciting part is because people have been making so many atlases of gene cell, gene expression and cell types, and publishing those and making them publicly available. Then we're able to look for different markers that we can use to just put something in the blood and have it stick to the area in the heart that we want it to. And so that's what we're doing now.
[00:30:05] Russ Altman: So focused delivery. Focused delivery. That's, it's a great idea. And so what, but, and what you're just, if I'm understanding, you're saying that these atlases can tell you what are the kinds of molecules in the area of the heart, or even more specifically certain areas of the heart, that are only in the heart. And therefore, if you can figure out a way to target them, you can deliver a payload, I'm going to call it a payload, of CXCL 12 just to the area that needs it.
[00:30:31] Kristy Red-Horse: That's right. And that's, uh, and luckily there are those specific proteins that we found in these atlases. So that's another reason why we're incredibly excited right now.
[00:30:43] Russ Altman: And in terms of, and these might be too early unfair questions, but I'm greedy. So forgive me. I think you said that in the mouse when you did the injections, you saw results in a couple of weeks. Um, do we have any data about how quickly a human might respond to this CXCL 12 injection or targeted delivery? Um, what kind of timescales are you imagining for like functionally significant new artery growth in humans? Or is that a black box still?
[00:31:12] Kristy Red-Horse: That, that's a black box, honestly. Um, I'm hopeful. I'm very hopeful, but I have a feeling it's going to be different with people of different ages and different states. Your metabolic state in your body really affects the plasticity of cells and how they can differentiate and migrate and grow and form new structures. And so I think understanding that's going to be, uh, something that we're going to want to do as well.
[00:31:44] Russ Altman: Thanks to Kristy Red-Horse. That was the future of coronary arteries.
[00:31:47] Thank you for tuning into this episode. You know, we have more than 250 back episodes in our catalog. You can listen to them on a wide variety of topics and learn about The Future of Everything. If you're enjoying the show or if it's helped you in any way, please consider rating and reviewing it. Especially we like to get fives, but only if we deserve them. That'll help spread the word about the show, and it'll also help us improve based on your comments. You can connect with me on many social media platforms, including LinkedIn, Threads, Bluesky, and Mastodon, @RBAltman, or @RussBAltman, where I share about every episode. You can also follow Stanford Engineering on social media @StanfordSchoolofEngineering, or @StanfordENG.
