Are soundwaves the future of cancer treatment?
At a recent public lecture, Dr. Clifford Cho gave attendees a look at an emerging technology called histotripsy, which uses highly focused soundwaves to mechanically destroy tumors.
Cho uses histotripsy to treat liver cancer in his clinical practice at University of Michigan Health-West, where he is chief medical officer. He also leads a research lab at Van Andel Institute, where he and his team study the biological aspects of histotripsy to better understand its full potential.
Watch the lecture below:
Video transcript
Note: The following transcript has been edited for readability. Click a timestamp to jump to that part of the video.
Maranda [0:02]
Hello! We are so glad you have joined us here today at Van Andel Institute’s Public Lecture Series. I’m Maranda from WOOD TV8, and I am excited to tell you that today is going to be an incredibly enlightening lecture and I am so glad you have taken time out of your day to join us. Today we’re going to hear about the promising new way to treat liver cancer called histotripsy. This innovative, non-invasive treatment uses ultrasounds to disrupt tumors for an immune response, which helps the body better fight cancer cells. Now, I know all this sounds very futuristic, and you’re like, “How does all of it work?”
Well, I am so excited that we have an absolutely terrific expert on hand to explain it all. Dr. Clifford Cho is a surgeon-scientist whose pioneered-pioneering discoveries led to FDA approval of histro, histotripsy as a treatment for liver cancer. He is a professor here at VAI’s Department of Cell Biology, Chief Medical Officer at the University of Michigan Health-West, and a professor at the University of Michigan. He’s brilliant. You know, we’re always talking about exciting research that happens in our state, and I am so proud that this treatment was invented and developed right here in Michigan. The groundbreaking research took place in Ann Arbor at the University of Michigan, and it was first offered as a liver cancer treatment there in 2024, so this is brand new.
University of Michigan Health-West is the second place in the state to offer the treatment and the first in our home of West Michigan. As of December, this treatment is available in 18 states. In addition to treating people at the University of Michigan Health-West, Dr. Cho explores this treatment and how it can enhance the immune system’s ability to fight cancer. Today he’s going to share the latest in this leading-edge therapy and showcase how this treatment could play a role in improving cancer care.
At the end of our session, we’ll have time for some questions and answers after the presentation. Please hold your questions until then. If you’re joining us virtually, feel free to use that chat function and we’ll get to as many of those questions as we can as well. I’ve had the privilege to chat quite a bit with our professor-doctor, and you are going to truly enjoy today. So please join me in welcoming Dr. Clifford Cho.
Dr. Clifford Cho [2:40]
Alright, good morning everybody. I’m gonna pull a Marco Rubio here. You know Maranda was, we were just talking about, “You’re not thirsty, are you?”, “You’re not thirsty, are you?” I was like, “No.” Now I am. <Laugh>
Well, thanks for coming everybody. So as Maranda mentioned, my name is Clifford Cho. I’m one of the newer faculty members here at the Van Andel Institute. And I really appreciate you coming. I, I wanted to, by way of introduction tell you something about myself, which is that I, I’m actually current <laugh>. It’s my wife currently holding down two part-time jobs. Which for me is, is, is great. As Maranda mentioned, I’m one of the newer faculty members here at the Van Andel, but I’m also a cancer surgeon through the University of Michigan.
And for me, having these two part-times, part-time jobs is great ’cause you know, when I’m in the lab, I get to try stuff that I would never be allowed to do, you know, in the operating room, for instance. And then when I’m in the hospital — thank you — when I’m in the hospital you know, I see a side of cancer that I think I would never get the opportunity to see if I was in the laboratory. And so, I decided that maybe what I would do today is talk to you about three things that strike me as being super impressive that I’ve come to appreciate just from kind of running between these two worlds, the kind of laboratory/research side of cancer and the clinical/hospital side of cancer. And, these are the three things listed here. I’m gonna talk to you about the immune system a little bit because honestly there is like a small universe of miracles going on in your body right now and I just wanted to share some of that with you.
The other thing that I find super impressive, in a very evil way is, is cancer. You know, it’s one of these things where the more you learn about cancer, I think you’ll start to agree with my sort of feeling, which sometimes feels like, it almost feels like someone has shared like our body’s blueprints with cancer, ’cause it seems to know exactly what buttons to push sometimes. But the other thing that I find super impressive is, is West Michigan. And I do want to talk a little bit about how or why we made the decision to move our histotripsy research program. Histotripsy, as Maranda mentioned, is, is just a new technology; a way of using sound waves to treat cancer. But we made the very intentional decision to move it here to West Michigan for a number of reasons that I did want to, sort of, compare notes with you about.
So the first immune system, so just as an illustration of how amazing the immune system is — do you guys know how many stars there are in our galaxy? Right? Of course you don’t. Why would you? I mean, there’s no reason to know stuff like that. You could just look it up on the internet. And so when you do you’ll find out that there are a hundred billion stars in our galaxy. So that’s 10^11. So 10 with 11 zeros, which is far too big for any of us to conceptualize.
So, to put it into context you know, the average person who has a full head of hair has about a hundred thousand hairs on their head, which seems like a lot. So you multiply that by a million, and that’s roughly how many stars there are in our galaxy. And then take that number again and multiply it by another million, and that’s a fairly large number that you can see here. And that’s how many different things that your immune system can recognize.
Not only that, but your immune system can recognize whether any of those things belongs to you or doesn’t. Whether it’s a self thing or whether it’s a foreign thing. And just in case you’re interested, I mean, these are some other things that have exceptionally large numbers, one of which to me doesn’t make any sense. As big as that number is, it turns out, mathematically, it’s actually not as big as the number of possible NCAA championship brackets <laugh>, like, to me that seems wrong. Like I, I think someone messed up the calculation there, but nevertheless.
So, to illustrate just how, like, amazing this immune system is, so let’s take a like a, like a case study. So let’s, let’s, you know, a case study of a person. Let’s, let’s call this person me, for instance, and let’s set it, you know, circa 1975. So picture me roughly 1975, I’m thriving. You know, I’m living in New York, I’m living with my parents. ‘Cause I was like five at the time. And my mom was doing this thing at that time where every time she found out that there was a kid in the neighborhood who had chickenpox, she would basically take me over there and make me play with that person for hours, even if I didn’t know the kid very well. <Laugh>. And I, I, some of you are old enough to know that this is actually a thing that you know, that, that you did to your, to your children and stuff. And, and the rationale was, was because that way I would get it and then I would be immune to it, right?
You know, it was 1975. I was, you know, it was my mom. I mean, it all sounds very innocuous and, and, and harmless and quaint, but if you actually know like how viruses work, it really wasn’t quaint or harmless at all. So essentially, if you think about it, what my mom was trying to have happen was she was trying to have me inhale enough of a load of viruses so that some of those viruses would glom onto the surfaces of some of my healthy cells that were lining the inside of my throat. And if enough of them leached onto the surface of my cells, then what they would do is they would actually like extrude their alien DNA into my cells. And the DNA would warm its way into the nucleus of my cell. That’s where my cells make my proteins.
But they would basically hijack all that machinery. They would instead use that viral DNA to make viral proteins. And so my cell, which normally made my proteins, would now be making virus proteins. And those virus proteins would assemble on the inside of the cell and these new viruses would come together. And suddenly there’d be tons of viruses inside those cells. So much so that it would kill the cell, that the cell would literally explode this violent death. And as it exploded in this way, all those viruses would be released. They would then go out and look for other cells and the whole cycle would start over and over again. You know, I think it’s fair to reason that my mom didn’t know this, but the reason why she was doing it was very well-intentioned and it was because of the fact that I would get immune.
And the reason why that happens, if you actually think about it, it actually highlights a moment of what I sort of think of as unseen heroism that takes place during this cycle that I was telling you about. I mentioned that these cells die, this explosive violent death where they basically spill all of their contents and things. But it turns out that just at that moment of death, these cells actually do something that feels very selfless. It’s like the equivalent of someone who’s about to succumb to a house fire and pulls a fire alarm. Not because it’s gonna save herself, but because it might save other people. It would also alert, you know, the fire department that there’s something bad that’s going on here and you ought to come check it out. It’s the same concept. In the moment of dying, these cells also release these things called pathogen-associated molecular patterns or danger signals.
They release these danger signals that are the equivalent of pulling a fire alarm. And what these things do is they call the attention of the immune system. It basically tells the immune system, you really should come check this out, ’cause this is not normal. This is not right. So the first responder, you know, for our immune system are these cells called antigen-presenting cells, or APCs. And what they do is they come check it out. They are drawn to the presence of these danger signals and they check things out. And essentially what they do is they clean up the mess. They, they pick up all the debris of all these dead and dying cells, and they look at all the stuff that’s in this debris, and they kind of check it out and they take little bits of this debris and they show it to these other immune cells called T cells.
And now, some of the debris that they pick up belong to my own cells. And the T cells recognize that those are fine, you don’t have to worry about that. But every now and again, it picks up a little piece of a virus, which the T cells recognize don’t belong to me. And that’s where that number that I was kind of telling you about, I can’t remember, it was like 10^16 or 10^18. Those are the numbers of possible things that our immune system can recognize. Included in that number was the chickenpox virus. So even though my body had never seen the chickenpox virus before, it actually came equipped with a bunch of T cells that recognized nothing but chickenpox virus just in case something like that should ever come along. And so, when those T cells actually recognized the thing that they knew to be foreign, this magical thing happens.
The antigen-presenting cell basically turns that T cell on, that T cell becomes activated, it starts to proliferate. And at that point it’s like, it’s like a bloodhound that’s picked up a scent like it. It now goes out on the hunt and it looks for anything that looks like that virus. It hunts it down and it kills it. And so that’s why, you know, what ends up — oh, and by the way, in case you think I just made all of that stuff up — these are actual photographs of like all of the partners. So like, that’s what a virus looks like. That’s what a cell looks like. That’s actually what a cell looks like as it’s, as it’s exploding and releasing all of these viruses and things. This is an antigen that, that APC, that’s picked up this thing and it’s showing to a T cell and the T cell that gets all activated and stuff.
And so, you know, eventually what ends up happening is if I got the chickenpox virus, I would be sick for a little while, but then would go away and then I would never get chickenpox virus again, right? And you know, in truth, I actually got chickenpox virus a bunch of times. It’s just that from the second time onward, my immune system was so good at recognizing it that it basically fought it off before I even recognized that I was sick, right? So a lot of people have asked for a long time, “Well, if the immune system is so good at recognizing and eliminating viruses, why does it seem like it’s so bad at recognizing cancers? Why does a cancer start off somewhat innocuously like this and yet inevitably turn to something like that?” So I’ll tell you, there are sort of, generally speaking, three reasons why this is the case.
The first reason is that cancer does a great job of hiding from the immune system, which actually is pretty remarkable. So let’s say as an example, let’s say you looked just like me. Let’s say you were, I don’t know, middle aged Asian, this, you know, this tall or, or this short whatever. And you had my blood type whatever. Let’s say I took a couple of my cells and I injected ’em into your body. You know, what would happen is that like within hours, your body would recognize that those cells were foreign. It would basically hunt those cells down and kill ’em. That’s why, you know, like when we do kidney transplants, for instance, we have to take immune suppressing medications for the rest of our lives. And so viewed in that context, it’s really actually somewhat remarkable that cancer cells do such a good job of hiding their unique aspects on the inside that to the immune system, by and large, they oftentimes look indistinguishable from your own cells, which is a pretty sneaky thing to do, but it’s actually worse than that.
Sometimes cancer cells do get recognized, and when they do, they have an insidious ability to turn the immune system off. So I mentioned before that in the context of a viral infection, you know, this APC picks up a little bit of virus and it turns on a T cell once in a while. Something like that can happen with a cancer cell where you have a little bit of a cancer cell, the APC picks it up, shows it to a T cell. But the weird thing is, is that what cancer’s able to do is it totally changes this conversation. So instead of that T cell becoming activated, that T cell actually shuts itself off the cancer, sort of convinces the T cell that in this particular context, you don’t have to worry about this. If you see this thing, it’s fine, just ignore it.
And so it essentially turns the immune system off. But the third reason, and this relates to something that we’re quite interested in the laboratory, has to do with this phenomenon of how cells die. It turns out that cancer cells die very quietly. And so, as an analogy you know, if you live in Michigan, you see lots of deer. Let’s put a finer point on it: If you live in Michigan, you see a lot of dead deer. And unless you’re a hunter, you see those dead deer largely on the side of the highway like M-6 and stuff like that. And it’s always very noisy. It’s very dangerous, it’s very violent. There’s a lot of whatever, like fur and blood and hooves and stuff like that. And it’s a, it’s a big mess. And eventually somebody gets called and somebody has to clean it up.
It’s a very noisy death. I am actually going somewhere with this. So, someone told me once that when an elderly or sick deer knows that it’s about to die, and maybe some of you can validate this, when it knows that it’s about to die, it does this thing where it walks away from its friends and family — someone’s nodding, so I guess this is true — and it walks deep into the woods, where it’s all by itself and it just lays down and dies. Which, until seven seconds ago, I didn’t actually know if that story was true until you … <laugh>. But even if it’s not true, it’s somewhat moving, I think. But, but it, I think it totally explains why you never like, walk around the park and just run into a deer that’s died of natural causes. Like, I, that’s never, I don’t know, I don’t think, that never seems to happen anyway.
The point being that there’s two ways of dying. And for cells, that’s also true, too. There’s a noisy way, which is this, what we call immunogenic cell death. It’s a very noisy inflammatory way of dying that calls the attention of the immune system. But there’s also another way of dying. It’s a very quiet involutional way of dying where cells just sort of shrink and disappear and never call the attention of the immune system. And that’s called non-immunogenic cell death. You know, a good example of that immunogenic cell death is what happens when a cell gets infected with virus. And we kind of talked about that, but here’s the frustrating thing. Like, we kill cancer cells all the time, right? We kill ’em with ablation, we kill ’em with chemotherapy, we kill ’em with radiation treatment. But the frustrating thing is, is that almost every single one of those induces this sort of non-immunogenic cell death.
So it kills cells in a way that never really calls the attention of the immune system. So that’s another reason why cancer does such a good job. And again, in case you think I made that up, these are photographs of actual cells that are undergoing these two types of cell death. So, you know, I think about this a lot. I mean, on the one hand you have the immune system, which is so incredibly potent and flexible, and it’s got such a good memory. It’s so good at eradicating viruses and stuff like that. And on the other side, you have cancer, which is so sneaky and evil and hides from the immune system and turns it off. And many times it feels very much like a wrestling match, right? Like, and sometimes you don’t know who’s gonna win. This is a painting I found someone imagining the all night wrestling match that took place between Jacob and God.
And it’s kind of like that. And I don’t, I’m probably interpreting this the wrong way, but I, when I look at this, I picture the blue guy to be Jacob just like straining, like demanding to be blessed. And I picture God as the one whose face you can’t see kind of reaching up towards Jacob’s hip. I actually looked at it again this morning and I actually think I have that wrong. I think the other… but I like the way that I’m interpreting it better anyway. But I, I do think that the the relationship between cancer and immune system is very much like this. And so, you know, my thesis, I guess, is that I think that sound waves are just one example of a thing that we can use to kind of tip that balance, sort of, tip the balance of that wrestling match a little bit toward our favor.
And, and as Maranda said, the particular sound wave technology that we’re interested in is this thing called histotripsy. What what histotripsy is actually is, it’s a way, it’s a, it’s this disruptive new technology that we now have that allows us to take tumors inside your body and essentially just mechanically kill them and reduce them into this liquid debris. And that dead liquid debris gradually just gets reabsorbed by your body. But the neat thing about it, I think, is that we can do it totally non-invasively. So we don’t need to use needles, we don’t need to use scalpels or radiation. We don’t need to actually stick anything into you, ’cause it uses sound waves, which sort of sounds weird. So, if you think about it, sound waves, like what, if you think about it like, I’m talking to you right now, which is another way of saying I’m like taking ideas in my head and I’m sort of transporting them if you’re listening, like, into, into your head, right?
But I’m doing it without physically touching you, which is convenient and, you know, socially appropriate and stuff <laughter>. But the way that it works is, is that my lungs are pushing air through my vocal folds. They’re vibrating the air, creating these sound waves that get to you. They hit your eardrums that gets converted by nerves into a signal that your brain sort of recognizes as sound and words, right? So you know, I can modulate my sound. I can change the frequency. The frequency is like the pitch. It’s the number of cycles there are within a second, and it’s measuring hertz. So if I were to increase my frequency — and I’m not gonna do that — then my voice would sound like it’s getting higher. So middle C is like 260 hertz, high C is a thousand hertz. If I start talking to you above 20,000 hertz, you won’t be able to hear me anymore, right?
It’s like, like your dogs would be able to to hear me, which would be funny. Like, they’d be like, what? Histotripsy, I mean <laughter>, that’s interesting. Anyway, sorry. But anyway, but histotripsy, the way it works is it actually uses a tremendously high frequency of 1.5 million hertz. Just to put it into context. The other way that I can modulate the sound waves is with the amplitude. That’s like the pressure. If I increase the amplitude, it just sounds like I’m talking louder. So normal conversation 0.02 pascals, that’s the unit of measurement rock concert 20 pascals, there’s 20,000, 200,000, excuse me, pascals of pressure inside your car tire. If you go past 680,000 pascals, it’s enough pressure to, to break your skin. Histotripsy plays at a level of 70 million pascals. So the way it works is this, this is a technology that was invented at the University of Michigan like 20 years ago.
What the invention really came from is the discovery that if you took a bunch of these high-amplitude, high-frequency sound waves and pointed them all to one point in space, that one point in space where they converge undergoes these like pinpoint tiny but massive pressure fluctuations. If you, if that point in space is inside your body, then it creates this phenomenon called cavitation microbubbles, which are shown on the right. And if you think about it, if you move the focal point of these sound waves through the tissue, then you’ll move these microbubbles along. And as you do so, what you’ll do is you’ll reduce any tissues that are in its path into this liquid debris. That’s how it reduces tissues without you physically having to, to touch you and stuff. For example, if you pointed this thing toward heart muscle and then looked at the heart muscle under the microscope later, this is what it would look like.
And it’s really kind of striking. I mean, there is like, you can see there’s a straight line. And by the way, like you can’t, like with a scalpel or like, there’s nothing else that will allow you to create a straight line that you can see on a microscope like that. But a straight line between the treated zone and the untreated zone, you see heart muscle cells that are literally torn in half where half of them has been reduced to liquid debris. You know, obviously there’s not a lot of utility to pointing this thing at the heart, ’cause, you know, but there is a lot of utility in potentially applying this therapy toward tumors. If you could reduce tumors into liquid debris, the problem is it took like 15 years for the engineers to kind of control and harness this energy to the point where it could be like a clinical device.
But they eventually did get there. So about five years ago, we conducted an international multicenter clinical trial, which is really the only way that you can test if a new therapy is helpful. We did a trial where we used histotripsy to treat people with liver tumors just to see if it was effective and to see if it was safe. We actually called that trial Hope for Liver. And without going into all the details, when we collected all the data, what we found out was that when we tried histotripsy to treat someone’s liver tumor, it was technically effective. It was technically successful over 96% of the time. And the other nice thing was that over 93% of people didn’t experience any side effects as a result of that treatment. So after we published those data, the U.S. Food and Drug Administration shortly thereafter approved it for use against liver tumors.
That’s how these new technologies roll out. So that was like at the very end of 2023. So beginning in early calendar year ’24, it became available for use for patients. The University of Michigan was one of the first centers to use this therapy. But it’s, the clinical adoption has actually been pretty rapid. I mean, right now I think there are close to 40 centers around the world that have the technology. In the first year of approved use, over a thousand patients with liver tumors have received histotripsy treatment. The University of Michigan actually was the first hospital health system to have two devices. And we intentionally parked the second device here in West Michigan at the U of M hospital that’s down the street. And we’ve been treating patients with liver tumors for, like, five or six months now.
But my research laboratory, which is upstairs, studies this largely because of an experiment that we did a few years ago. And the experiment looks something like this. This is what it looks like inside a mouse’s melanoma cancer. If you look for immune cells, which are shown in brown, you do see some from time to time, but not many. And the reason is ’cause mouse cancers, just like human cancers, again, do a really good job of hiding from the immune system. But if you take that same type of tumor and you treat just a part of it with histotripsy, what we found was that there were tons, now, of immune cells that were infiltrating into the tumor, and specifically, they were infiltrating just into the areas of the tumor where there were still cancer cells left behind. And, just to put it into context, like, we’re unable to generate this sort of thing with other therapies like radiation or surgery or whatever.
But the striking thing to us was that if you did it in a mouse with multiple cancers, so let’s say multiple cancers, but you only treat one cancer, and then you looked inside one of the untreated cancers. We still saw evidence of immune cell infiltration into those distant tumors as well, suggesting that it was triggering not just a local phenomenon, but, like, this system-wide effect. This is actually something called the abscopal effect, which I tried to draw here. But the idea is that, you know, you treat one tumor, but then you could see an effect in a distant tumor. The thing on the right is just growth curves, like the exponential growth curve is what happens normally to tumors. That really slow-growing tumor is one that we partially treated with histotripsy, but that one in the middle was just an innocent bystander tumor that happened to also be in the body of a mouse that had histotripsy treatment, but that one wasn’t actually treated.
And you could play around with this model. You can, for instance, have a mouse that has a skin cancer with lung metastases, but just treat the skin cancer. And if you look inside the lung, we see that there’s a substantial reduction in the number of lung metastases, even though we didn’t, you know, point the thing at the lung. So, you know, we’re interested in right now is figuring out, like, why is this happening? How is this happening? And I’ll just summarize a couple of the reasons that we’ve discovered. When I showed this to you previously, I mentioned about how there’s, broadly speaking, two ways of cells dying. One is this immunogenic pathway, and the other that cancer cells largely are susceptible to is this non-immunogenic cell death. So we were curious to know like, is histotripsy able to induce this immunogenic cell death?
And what we actually found was there’s actually two kinds of death that histotripsy causes. So, picture that’s a cancer and picture that’s like the place where you wave that histotripsy energy toward, the part of the tumor that gets exposed to histotripsy. It just undergoes a mechanical death. The cells just get torn apart, they just disappear. So it’s nothing particularly interesting about that. But the interesting thing though, is that if you actually look at the surviving cancer cells that are next to the treatment zone, they begin to die, but they’re not directly killed by histotripsy. They’re actually killing themselves through a suicide pathway that’s called necroptosis. Necroptosis is this bizarre thing that cells for some reason sometimes do to themselves. They, they stop what they’re doing, they put all of their energies into creating these massive pores, these massive holes in the cell surface.
And these pores are so big that all of their guts basically spill through the pores and the cell dies. But if you look for this necroptosis under normal conditions, you never see it. This is a tumor, and looking for necroptosis, you don’t see it. But after histotripsy, what we found was that in the part of the tumor that was next to the treatment zone, there’s a lot of green and a lot of red. The green and the red are basically the two proteins — they make up that pore that I was telling you about. So a lot of this necroptosis going on, the idea behind necroptosis is it also releases all those dangerous signals that call those immune first responders, those APCs, into the scene. We look for APCs. Normally you don’t see them inside a tumor. But after histotripsy, the area of the tumor that you treated with histotripsy is full of these APCs shown in green. And what these APCs are designed to do, as I mentioned, is they’re designed to activate T cells and the T cells are supposed to come and kill cancer cells.
Under normal circumstances — the T cells are shown in green — under normal circumstances, you see a few of ’em, not many. After histotripsy treatment, you see a lot of those green T cells. But the interesting thing is, is that the cancer cells that they’re surrounding are turning red, which is in this case signifying that they’re, that they’re dying. And that’s both in the treated tumor, but also in those distant abscopal tumors as well. So the other reason, though, that histotripsy seems to be doing this effect actually has to do with the fact that all of us, like cancer cells — or, cancer cells are like us. I guess that’s what I meant to say. And, they’re also like cats in that we’re all like a product of our environment, right?
So, there’s also another phenomenon where if you take a cat and you make it live inside your house and you feed it and you keep it warm and give it a comfortable place to sleep, after a while it becomes this. It’s this domesticated, high-maintenance house cat, right? <Laughter>. If you take the same cat and you force it to live outside, you don’t let it ever come inside, you force it to find a place to sleep in the rain, it has to kill birds or whatever to survive. That same cat will get all muscular and mean. It’ll become a feral cat. It’s the same cat, it’s just a different, you know, set of different environmental stressors and stuff.
So, it turns out one of the differences between normal cells and cancer cells is sort of analogous to that. I found some things on the internet. Apparently some people have tried to take in a feral cat and domesticate it. As far as I can tell, I don’t know that that’s possible. But it is sort of an interesting thought experiment to wonder, what if you could change the environment of a tumor to make it more comfortable? Could you actually tame cancer cells to make them easier to kill? And I’ll, and I’ll show you what I mean.
So, the thing that determines in the body if something is comfortable or not is oxygen, actually. You know, our whole body has oxygen, we’re breathing in oxygen. All of our tissues come with these nice blood vessels that bring oxygen from our lungs into the tissues, ’cause all of our cells like oxygen, and that’s, and that’s happy. And one cell type, by the way, that needs a lot of oxygen are immune cells. They, they use up a lot of oxygen and stuff. And so, the thing about cancers is that they grow so quickly that the blood vessels can’t keep up. And so your average oxygen level in a tumor is really low.
The other thing that happens is, is that there are a lot of signals in the tumor that keep the blood vessel growth very misshapen. See how the blood vessels were all twisted and stuff like that. So, it maintains very low oxygen levels, and you would think that that would be bad for the cancer cell. And it is, sort of, but the cancer cell adapts to it and, kind of like a feral cat, it becomes even stronger as a result of having to live under those circumstances.
And as a result, they become harder to kill with chemotherapy. They become harder to kill with radiation therapy. They become better at metastasizing into different sites. And the other thing that happens is that immune cells that try to come into a tumor, they basically are starving to death. They don’t get enough oxygen and they can’t work. And I’m not gonna go into this in much detail, but this is a mouse liver cancer where everything shown in green and red are areas of hypoxia, low oxygen, and any cancer looks like that. However, if you take the same type of tumor cell in a mouse and just treat a portion of it with histotripsy, this doesn’t last forever, but for about a week or so that hypoxia goes away. So there’s like this window of opportunity that opens up after histotripsy where the oxygen levels actually increase in the tumor.
And without going into it in much detail, one of the things that we’ve learned is that weeklong window of opportunity is what enables all of these other things to happen. It doesn’t last forever. We are sort of working on ways to try to get that window of opportunity to stay open a little bit longer. But the end result is something like this. These are MRI scans, believe it or not, of a rat with a liver tumor. I have tried to circle the liver tumor in yellow. So this is one type of liver tumor in a rat that’s very aggressive. It just keeps growing and growing and growing until it overtakes the rat. You can kind of see from one week to the next, it just gets bigger and bigger. If we took that same type of tumor and just treated the middle of it with histotripsy, at first, nothing happens.
The tumor continues to grow, but then, after a while, in a delayed fashion, it actually starts to regress. And if you actually look inside the tumor, it’s ’cause there’s a lot of immune cells that are infiltrating into there. This is a rat with a slightly different type of aggressive liver cancer. These cancers don’t grow that big, but they metastasize. So you go from having one tumor to six tumors to like 25 tumors or so over the course of a couple of weeks. If we take this tumor type and just treat at an early stage part of it with histotripsy, in a delayed fashion, the rest of the tumor begins to shrink and eventually goes away. But more importantly, it never has the opportunity to metastasize. So here’s the thing. Now we’re that we’re doing it in people, we are actually seeing examples of this in people, too.
So this is a human with metastatic colon cancer. This is published. So, but, this person has numerous tumors inside his liver, only one of which was treated with histotripsy. And this person had such advanced disease that there was no other therapy available. So it, you know, had histotripsy treatment and then sort of went on his way. But what the interesting thing was, is that despite the fact that this person was getting no additional therapy, although he didn’t notice it right away, beginning after about a week, and then after a month, then after two months started to see that the other tumors were gradually starting to regress and go away. Now the truth of the matter is, this doesn’t happen all the time. It doesn’t happen as often as we would like it to happen, but it does seem to happen.
So, the thing that we’re very interested in now is trying to understand why this happens, when it happens and how we can make it happen more frequently. And so that’s what our program is designed to do. I mentioned to you that we have a clinical histotripsy program at the University of Michigan hospital down the street, down 131. University of Michigan in West Michigan does all of its cancer care in conjunction with the Trinity Health System, this thing called the Cancer Network of West Michigan. And so, we have a histotripsy unit there. I have a clinic, I gotta go there this afternoon. And we meet patients with liver tumors and if it’s appropriate, we offer them histotripsy. But the thing that we do differently is, is that we ask all of those patients if they would be willing to give permission to participate in this research project.
It involves them getting a biopsy of their liver tumor before we do the histotripsy, and then another biopsy of the liver tumor after the histotripsy so that we can compare in one person, like, are we seeing a difference? Are we seeing an effect? We then take those samples and bring ’em up 131 up to our laboratory at the Van Andel Institute here. And that’s sort of outlined here. And, and the VAI here, as you may know, is just blessed with this incredibly strong biorepository and core facilities that allow us to do all of the testing that you can even imagine to think of, to try to understand, you know, to do these. Does this necroptosis, does this immune response to these hypoxia changes, do these take place in in people as well? And our plan, of course is to not have this just go unidirectionally, but we wanna learn from the things that, the studies that we do here and try to come up with ideas for are there things that we can do to do histotripsy differently to get these results to happen more often?
And what the way that that’ll go back toward the hospital with clinical trials; we’ll develop clinical trials to do histotripsy differently to see if we come up with ways to make this effect a little bit stronger and a little bit more frequent. Those data will, excuse me, will then be generated and analyzed at the Van Andel Institute again. So there’s like this closed loop of sort of, continuous scientific and, and clinical feedback. Importantly, I do want to mention that similar sort of translational partnerships between the University of Michigan and Van Andel Institute are already underway in other diseases that may be near and dear to your hearts as well. Osteoarthritis, Parkinson’s disease, inflammatory bowel disease, pancreatic cancer, some rare genetic disorders. So, this is really just a template for a bunch of other things that we’re doing. I’ll close with this. You know, I think you know this already, but Grand Rapids has, like, an unusually dense concentration of clinical and scientific expertise.
Like, I know you know this, but you probably take it for granted ’cause you’ve been here the whole time. So take it from someone who just kind of moved into the neighborhood, like it’s really pretty remarkable and rare for a city the size of Grand Rapids to own things like the Van Andel Institute and have a presence from the University of Michigan and the Cancer Network of West Michigan. And those are only the, those are just the groups that I work for. I mean, you also have BAMF with all of their incredible diagnostic technologies. You have START Midwest, which has an unbelievably powerful clinical trial infrastructure. You have Corewell Health, Trinity Health, Mary Free Bed Hospital Hope Network. I mean, I hate to say this, but Michigan State University is pretty awesome here. My favorite, Calvin University — and, and I’m, and I’m clearly leaving places out, but you know, a lot of people, some of you in this room have expended a lot of effort and resources to create these institutions.
In some cases it’s been lifetimes of effort and resources. So all those institutions exist. I feel like now we’re sort of at the time where now we mature into the next phase, which is where we connect with one another because I really think this place has already become an epicenter of sort of health science treatment and discovery. And with that, I’ll stop. I’ll thank you all for taking time out of your day to come. That was an awfully generous thing for you to do, especially, you know, with the cloudy weather. And it’s not like we fed you or anything like that. So thank you for coming. I do wanna also thank the patients, too, because you know, it goes without saying that all of this type of work is, is not just motivated by, but actually enabled by patients who are willing to participate. I mentioned to you that like, you know, we ask people if they’d be willing to participate and, I’ll be honest with you, like, they all say yes. Listed a bunch of names of people in our laboratory and also our partners here in Grand Rapids, some of our funding sources, et cetera. And with that I’ll stop and, and love to, if you guys have any advice or questions and stuff, I’d be happy to talk about those things. Thanks very much. <applause>
Maranda [39:31]
Did you love it?
Audience
Yeah.
Maranda [39:34]
So, I’m sitting here, first of all, I think you need to turn all this into a video game so kids can learn about viruses. I mean, you broke it down in a way that just got me excited to learn. And I think that’s what these Public Lecture Series do. And Van Andel has done a great job of giving us the opportunity to peek inside the labs to see the kind of work you’re doing and to truly bring hope. And when I look at the work you’re doing, I sat there just thinking the whole time. I’m so thankful people like you are willing to do this kind of work and to just keep pushing the envelope. So, I think I speak for several of us. Thank you for giving me a lot to look forward to. <Applause>
At this time, we’ll open it up to questions. If you have a question, feel free to raise your hand. We’ve got some friends who will be bringing microphones around. Wait ’til the microphone is passed to you and then you can go. And we’re gonna start with you because you were the first one up. Go ahead right here in the, yes, we’ll send the microphone right down for you. Raise your hand for it. There you go. Thank you.
Audience Member [40:33]
Is there something special or unique about a liver tumor that made you proceed with liver tumors first?
Dr. Clifford Cho [40:41]
Yeah, that’s a great question. Not really. The reason it was, because unfortunately lots of people have liver tumors, it’s like a favorite place for cancers that start elsewhere to end up metastasizing to. The livers are very friendly place for lots of different cancers to grow. And so it sort of allowed us to target a wider population of patients and things. There’s also a lot of experience with what we refer to as liver-directed therapies. Lots of other options that we have for treating liver tumors, but they’re all pretty invasive. They’re either pretty invasive or they’re not very good. And so we felt like it was an opportunity for improvement as well. And also some of us were sort of kind of like myself interested in the liver to begin with, so there’s probably a little bit of bias that crept into there, too.
Maranda [41:35]
I have a question for you. As you look at the liver, you have said you’re looking at other, other treatments as well, you’re researching and exploring. What are you seeing as some of those other areas where you’re like, this is gonna work?
Dr. Clifford Cho [41:46]
Yeah, right. Well, I would say the nice thing about histotripsy is, is that it really doesn’t care where the tumor is. Like it’s just a matter if you can point the sound waves at it, then it, you know, it also doesn’t really care what, whether it’s a breast cancer or pancreatic cancer or lung cancer. I mean, so, that’s kind of nice, right? Like a lot of other therapies would work great for melanoma, but don’t work at all for kidney cancer and et cetera, et cetera. But this is somewhat agnostic as far as that goes and stuff. And so, it definitely, in the laboratory, our laboratory and others, we use it for lots of things outside of liver cancers. There is, but the way it works with clinical therapy is you have to prove that it’s safe and effective, like with a clinical trial before you can just start doing it, which totally makes sense.
And so there is a clinical trial that’s almost done actually with kidney tumors. There’s lots of kidney tumors and things. And so it’s actually way easier to treat a kidney tumor than a liver tumor. So that, that I’ve done. There’s also a trial that’s underway. It’s actually underway in Europe, but for pancreas tumors, as well. And I understand that’s going well. I, there’s a lot of experimental laboratory experience with using it for brain tumors. You wouldn’t think so, but actually the brain is a very attractive target for histotripsy, ’cause it sits still, it doesn’t move around and stuff like that. And so, so yeah, so, I suspect that it can be used for at some point along the way, if it works for liver and pancreas and kidney brain, then it, I don’t think you have to test it out for every application eventually, I think they’ll let you use it for whatever, you know.
Maranda [43:26]
Mm-hmm. Yes.
Audience Member [43:29]
How accessible is histotripsy for hospitals to adopt based on, I guess, cost of technology, development of technology and with that, where, what might we see this technology go in the next 5, 10, 20, 25 years?
Dr. Clifford Cho [43:48]
Yeah, that’s a great question. Thank you. So, how hard is it to, I mean, like, like everything else in medicine, I mean, it’s not cheap. I don’t know if I’m allowed to say how much it costs, but it’s actually compared to lots, it’s not as expensive as like getting a CAT scan or some CAT scan or something like that. But so there is, you know, the investment that’s necessary for the hospital to build it. The, I didn’t really go into this, but the whole thing is robotically guided. And so it, it like, I mean, I’m not exaggerating. A knucklehead like me can do it. Like, literally what you do is you tell the machine go, you know, like this is where the tumor is at. And literally you push a button and then you find things to talk about for like 15, 20 minutes and stuff. It does it all by itself.
And so, I’m not saying run out and do it. I mean, you have to be medically qualified. I think … but, but in any event, so there’s not a, there’s not a big ramp-up that’s necessary in terms of the technical expertise. There is like, a day of training and stuff that takes place. But, the reason why it, I think is relatively easy for hospitals to use is because, like I said, liver-directed therapies, like every major hospital does ’em. This is like an easier version of liver-directed therapies compared to all the things that providers are typically used to doing. And so I think the adoption is relatively quick in that regard. As far as I think you had asked about like hurdles and stuff like that.
I mean, with any new technology there’s like a, like a trust-building phase of the technology. I think physicians very appropriately are cautious, right? Because, you know physicians, they’re sort of cognitively inclined to want to see evidence and proof before they jump on a bandwagon, which I think is a good sort of cognitive ethic to have and stuff. And so I think we’re still in the sort of trust-building phase. Like, we recently, I mentioned that we published the initial results, which, honestly, it was like, here’s what happens within one month of treatment. Like, that’s great and all, but we recently published what happens now after a year of, you know, a year after treatment. And even still people are like, yeah, can you tell me what happens? Like after five years? And we’re like, no, <laugh> because you know we can in four years and stuff like that.
So but, I think the momentum seems to be building we see that in insurance companies. Like, at first there weren’t that many insurance companies that would cover it, which again, totally makes sense. It’s an untested thing. But, gradually more and more insurance companies as, as they see it, sort of, being asked for more often more and more insurance companies are covering it. So, sorry though, so, to answer your your question, I think in five years, I mean, I feel like there’s been enough momentum that I don’t see this, like, going away. You know, like, definitely when it first came out, there was a question like, is this gonna be, ’cause that’s happened before, right? Like, I mean, I’ve seen it, like, I’ve seen the latest and greatest like liver surgical technique and stuff, and then three years later you’re like, “Hey, whatever happened to that thing?” And so, but I, I feel like we’re past that point. And so,it’s definitely like, like a virus, like it’s infiltrated like our practices, like a lot of things that we used to do, we used to treat with other methodologies, we now just treat with histotripsy. ‘Cause It’s actually just, in many ways it’s, it’s more convenient. And it’s just easier on, on people. Thanks for the question.
Maranda [47:26]
Next question.
Dr. Clifford Cho [47:28]
This is Mike Liang, Mike’s a Calvin Freshman, who is joining our lab in two weeks. He’s awesome.
Mike Liang [47:42]
Thank you. So, oh, this is loud. Okay, so, what are some side effects that patient can experience when undergoing this therapy?
Dr. Clifford Cho [47:50]
Yeah. Right, right. So thank, so that’s, that’s a great question, Mike. And so, that’s why we did the clinical trial, was to basically count up all the potential side effects. And so, just so you know, the way this works in a clinical trial is, is that like if you get therapy X, like you get watched like a hawk for like three months, and then if you develop, like, a cough, like someone’s like, oh, cough. You know, like, they check it down and stuff like that. And so but then you put all those things together and then you said, do your best to make a determination. Like was this actually related to the treatment or was it because you ran into, you know, like your sick kid’s teacher or something like that?
So, and so, what was the, oh, and so, yeah, so the <laugh>, so the side effect profile, thankfully, looks to be quite low, which in a way it’s not that surprising because you don’t have to, like, you literally don’t have to stick anything through the skin and stuff. Like, a common experience among patients is, you know, they’re like, “Did you actually do it?” sort of thing. But I don’t wanna, I don’t wanna sugarcoat, I mean, like we, you have to be very careful, like I mentioned, like, where those ultrasound pulses point, like, it’s very destructive. And so if you don’t do it right, if your robot robotic guidance doesn’t work right, and if you accidentally aim it at the heart, you know, or something like that, like, you will, it won’t, it doesn’t care. It will create a hole in the heart and stuff like that.
So, we, you know, we put a lot of — it’s interesting, like, initially we were super conservative with how we, like, if it was anywhere close to a blood vessel, like, we wouldn’t treat it, then you gradually, as it’s like riding a bike, you take more chances and after a while you learn that it’s actually okay to do this thing and such. And so the side effects tend to be like I said, the risk of a side effect that someone could reasonably attribute to the therapy. I think that side effect rate was about 6.5%. But a lot of those things were things like itching, you know, like a rash or a fever, you know, things like that, so.
Maranda [49:56]
Here in the purple, or we, let’s go there. And then here.
Audience Member [49:59]
I’m interested in the technology side. So, kinda a chicken and the egg. Was this someone culling an IP portfolio when came across this sound concentrate or it said, “Hmm, that’s kind of cool, what could we use that for?” Or was it more of someone said, I want to create cavitation in a cell, and they went off and invented this sound concentrator?
Dr. Clifford Cho [50:21]
Yeah, right. I’ll answer the best I can. I mean, I, I know the scientist who was, like, the co-inventor of the technology and I’ve heard her story, it’s a neat story. So, so she was a graduate student working in the Department of Biomedical Engineering. And this is the way it works, you know, like upstairs with the Graduate School, like if you’re a graduate student, your boss says, “Hey, work on this thing,” and so you do it.
And so, his thing was, you know, figure out a way to use these, you know, high-energy ultrasound pulses, but come up with a way to do, I think he called it like knifeless surgery or something like that. And so that’s how it, all, that was the initial motivation was to see if there was a way that you could use harness sound waves in a way that could, you know, like, make little holes or incisions in tissue without actually physically having to do it. So that was the initial genesis of it. I know there’s, I don’t know all the details, but I think like at some point along the way, someone at the University of Michigan was smart enough to create a company and that eventually went independent. And that’s the company that manufactures and sells the device and that sort of thing. But I don’t know all the details of that. Yeah.
Maranda [51:36]
Interesting. And the woman in the purple, right? The middle. Yeah.
Dr. Clifford Cho [51:42]
She’s the one who knew that deer actually do …
Maranda [51:45]
Yes. You wanna share more about the deer? That’s great.
Audience Member [51:47]
I’m a hunter.
Dr. Clifford Cho [51:49]
Oh, okay. So you’ve seen lots of … Yes. Sorry,
Audience Member [51:52]
You have to know your prey, you know, to be able to hunt.
My daughter had part of her lung removed her second bout with cancer. Could this reduce the number of surgeries to remove cancer, as, you know, opposed to traditional?
Dr. Clifford Cho [52:14]
Great question. I think it, it’s a, I think it absolutely could, it, you know, I don’t want to evade your question, but it, you know, it obviously depends on the circumstance. Like there are some circumstances where it totally makes sense to do histotripsy. There are other circumstances where it makes no sense to do histotripsy and stuff. But, but in an effort to, to address your question directly, yeah. Like, we are seeing patients all the time now where theoretically you could operate or you could do histotripsy. I mean, without going into it, like, I have clinic this afternoon and I’m looking forward to having that conversation with somebody this afternoon.
And it, and this is what happens with the new technology. Like when we were first having that conversation, we’ve always aired toward let’s do the tried and true. You know what I mean? Like, like, you know, we only have one chance to, to get this right. And so we were very conservative, and we would typically do what we had always done and stuff.
But I have to say that like, as our experience grows and, and as we see like how much different the recovery is from this compared to like when I cut out some part of someone’s liver, it is definitely become increasingly difficult to not offer it. You know what I mean? But we do our best, you know, as I’m sure your doctors did with your daughter. Like do our best to sort of, you know, explain the whole panorama of options and try to make a decision to together. But, but I do think so, like, I do think that there’s a future for, you know, less invasive stuff like what I do, and more non-invasive stuff like this.
Audience Member [53:54]
Hello doctor. This wouldn’t be considered quite an outpatient service — there’s some recovery time?
Dr. Clifford Cho [54:03]
Yeah, yeah. Thank you for the — it is outpatient, it is. So, we actually, so, for the liver, we actually do it under general anesthesia, but only because like every time you breathe, your liver does this. And so if you take a really big breath, your liver will move even more and stuff. And so we actually have been doing general anesthesia, not, not because of pain or something like that, but because it allows us to control the respirations more evenly. Like, if I told you right now, don’t vary your respirations for the next 20 minutes, like, it would be like torture, right? Like all you’d be thinking about is your breathing and stuff like that. So, but, when we first started doing it, we a hundred percent kept everyone in the hospital overnight just because we didn’t know. But then like nothing happened. And so I would say, I can’t remember exactly, but I would say like after about 10 months, I feel like everyone who was doing this was like, this is a waste of hospital resources. And so now we just tell people that the expectation is that, that you know, it’s like a colonoscopy. You wake up, you have some crackers, and if everything looks good, you go home.
Audience Member [55:16]
How often can you have treatment? Once in three months, or?
Dr. Clifford Cho [55:22]
Say that — I’m sorry.
Audience Member [55:24]
I’m sorry. How often can you do this?
Dr. Clifford Cho [55:25]
Oh, yeah, yeah.
Audience Member
Three months, six months.
Dr. Clifford Cho [55:27]
Right, right. Yeah. That seems like a — thank you for the question. How often do you, I mean, it seems like a answer that we should know the answer to, but we actually don’t. So like, I mean, well, we do, I mean, you could do it, it’s so well-tolerated that you, I mean, if you, if there was a compelling reason to do it, I suppose you could do it every Tuesday, you know, or something like that, but with some crackers. Yeah, <laugh>. But for, it’s, it’s complicated because lots of times, you know, nowadays almost, almost never is somebody just getting one type of therapy, right? Like they’re getting chemotherapy, but they’re also getting immunotherapy. And also I add radiation treatment to this thing and someone operated on this, and so you’re sort of mixing this into other sort of complicated regimens and things like that. So, at least from a physiological standpoint, there’s no reason why you couldn’t do it in a, in a repetitive way, but it totally depends on the circumstance. But yeah, it’s a great question.
Maranda [56:27]
So, I’m listening to you and I’m thinking, this sounds like the magic bullet. What are the downsides?
Dr. Clifford Cho [56:33]
Yeah. Well, I, I wouldn’t call, yeah. So right. The downsides, well, yeah, so there are some downsides. So, like I mentioned, like you have to be very careful with where you point this thing, right? So, for instance, just a quick anatomy thing, so, your liver sits underneath your right diaphragm and and it’s like this, it’s like your liver’s here, your diaphragm’s like this. And you could do a lot to the liver. Like, you can cut out, you know, two thirds of somebody’s liver, and they will do okay, but if you make a hole in someone’s diaphragm, it’s like a big problem, right? And so, I always tell people, we’re always very careful to tell patients, but also providers that there’s a little bit of a blind spot, which is at the very top of the liver that’s right next to the diaphragm, where it’s probably not a good idea to treat.
And you know, like, it’s frustrating, ’cause like as soon as you recognize that, like, it seems like everybody has a tumor right at the top of the, the liver and stuff like that. So, so there are some downsides because like, I think you have to be cautious because of the potential risk of just collateral anatomic injury and stuff like that. I think the other downside is, is that as optimistic as I am, I think we have to be cautious. We need more evidence and stuff like that. So there’s still a lot of learning curve and stuff to do.
Maranda [57:56]
Well, one more question in the back and we will wrap up. Thank you.
Audience Member [58:06]
This is wonderful and this is kind of for the future and you kind of covered it, but in the whole cancer treatment regimen, how would you see this? Would this be exclusive? What specialist? Would there be another specialist added to your team? And would you be doing this? Where would it fall in line with like chemo and radiation and other therapies?
Dr. Clifford Cho [58:29]
Yeah, right. So as far as, if I’m interpreting your question, the first thing was like, who does it? Like, what, yeah, so it’s, it’s actually interesting. So I, my clinical background is I’m, I’m a surgeon. I work a lot with another flavor of physician called an interventional radiologist. And we work together a lot. Right to this point, the adoption has been almost 50/50 between interventional radiologists and surgeons, actually. Which I thought it was gonna be more like maybe 80/20 radiologists and surgeons, but it’s actually closer to 50/50 with one exception. Apparently there’s some radiation oncologist someplace in the United States who’s doing this, too. But I think the point being that as long as you have an appreciation of, like, the anatomy and stuff, I don’t know that it has to necessarily live within one specialty. And then your other, oh, but then, I’ll also tell you, too, and I’m not an engineer, but apparently the next iteration that they’re working on is to downsize.
I don’t know if you saw, the machine has a certain girth to it and stuff, but there is a thought that they might be able to sort of downsize it so that it’s, like, on a little, like, a little thing like this, and you could just sort of put it on someone’s skin and stuff like that to treat like a breast cancer or something like that. Theoretically, if it’s that easy, you know maybe that would open it up to other specialties and stuff like that. But your other question has to do with like, how do you integrate it with other therapies? And I think that’s, like, the question that I wonder a lot about. I mean, I will tell you one thing, we were talking about this earlier, but like for instance, if I’m operating on you, like, I have to wait a month and a half, like we have to stop.
If I’m operating on somebody, we have to stop their chemotherapy, let it sort of wash out of their system for, like, a month and a half in order for them to be well enough for me to operate. And then after the operation, we have to wait typically another month and a half to give them time to recover so that they can go back onto chemotherapy. ‘Cause you just can’t be fighting two battles, like two wars on two fronts or whatever. But the nice thing about this technology is, is that it’s so low touch that you know, we routinely, like, you get chemotherapy on a Tuesday and you get histotripsy on a Wednesday, and you know what I mean? Like, so we don’t have to juggle those things around, even, like, blood thinners, like I never operated on somebody who’s on blood thinning medications, but we’ve actually stopped stop holding that, like, people on blood thinners and we treat them with histotripsy.
So, that definitely gives us a little bit more freedom to be creative with how we integrate this into other technologies. The thing that I’m really interested in is a lot of people are getting immunotherapies, right? Like that’s, that’s the big thing. Like therapies that are designed to rev up their immune response against cancers. We have some reason to think that maybe histotripsy does that too. So one thing that we’re always interested in is, you know, do we do histotripsy in conjunction with immunotherapy to see if there might be some way of synergizing the effects of those two. But all those things, I mean, this is why we do this clinical research is try to get like objective answers to, to some of these questions.
Maranda [1:01:41]
So I always like to end these presentations with the question, “What gives you hope?”
Dr. Clifford Cho [1:01:47]
What gives, you mean like, yeah, in the work, belief?
Maranda [1:01:52]
Yeah. Or, well, I guess I’ll take it all, you know, in the work you do every day, are you seeing progress and things happening so quickly that you can’t wait to get to work to see what’s next? Or is it the, the progress you’re seeing patient patients you’re treating? What’s giving you hope?
Dr. Clifford Cho [1:02:07]
Well I mean, ’cause I say, like, from a global standpoint, what gives me hope is, you know, our God is good and is and is strong, but I think that what gives me hope here, I think you should, well, you can’t, I don’t think you can do this, but you should run around upstairs —
Maranda [1:02:23]
Wanna around upstairs? <Laughter>
Dr. Clifford Cho [1:02:26]
There are so many smart people here. Like, I don’t know if I can name that I had dinner with, I’m just gonna say Travis Walton, he’s like a structural biologist here, and we were just having dinner and just, you know, talking about whatever. And like, talking about, like, every night he reads 10 pages of this mathematical treatise that someone wrote like 20 years ago when they were trying to figure out, I didn’t even understand it, but I was like trying to understand how to do like electron microscopy and stuff. And like, he doesn’t even really need to know it, but, like, he gets, but like listening to, he gets, like, so much, like, joy out of, like, this process of working hard to learn something new. And I’ll be, I’m just gonna tell you, I’m not wired that way, but there are like a lot of people like that here. That gives me tremendous hope.
The other thing that gives me tremendous hope is patients, like, and I don’t, I only know cancer and stuff, but cancer patients, like, they’re way, they’re way more courageous than you, than any of us think we would be in that circumstance. I know there are people here who can attest to that and stuff, but they are active participants in all of these discoveries. I would say those are the two things that gimme hope.
Maranda [1:03:44]
You give me hope. Let’s give him a big round of applause. <Applause>
To find out more about the exciting work he’s doing and all the other brilliant people upstairs, you can go to vai.org. Also, while you’re there, if you’ve enjoyed today — I have certainly enjoyed today — we have three more of these Public Lecture Series. We would invite you back to join. You can find those on our website. The next one will be in September. And we’d love to have you tune in. You learn something every time you come, and it truly does just give me hope. So, thank you so much. Thanks for joining us today, and have a great afternoon. Thank you.