Episode 4 Transcript: The Engineer Who Fixes Hearts

Introduction (00:03): Great science and engineering often begin with a singular hypothesis, but how does a lone spark of innovation become popular science? From Caltech, this is The Lonely Idea.

Rich Wolf, host (00:16): Welcome to The Lonely Idea. I'm your host, Rich Wolf. Today, I'll be speaking with my good friend Mory Gharib. Mory is a prolific inventor and an entrepreneur who has used his expertise in aeronautical, mechanical, and bioengineering to create life-saving medical technologies and devices. Mory, welcome to the program.

Mory Gharib, guest (00:36): Thank you for giving me this opportunity.

Wolf (00:38): Mory, as we sit here at Caltech, I'm reminded of the first time we met. I don't know if you remember this, but it was close to 20 years ago, and I went and visited your lab. I had just graduated, and you were explaining to me basically how a heart works and a heart is developed and evolves from just a few cells. And I was absolutely fascinated by this, and I remember asking someone, "Where did he study biology?" And they said: "Oh, he didn't. He's an aeronautical engineer." So, maybe you could talk a bit about how you got from aeronautical engineering and fluid mechanics and interested in in medical technology. And if you wouldn't mind, go all the way back to the very beginning and your interest in science and engineering.

Gharib (01:20): The first exposure I had, that we need to have a new device for a medical application was when I was in 12th grade. My brother at that time was a pediatric surgeon in Germany and in the summer [was] visiting us, and he told me, "Have you thought [about] how to get the pressure out from a chamber, from a container?" I said, "Oh, you put in a valve and open it up." "So, do you think that we can have such a valve for a human head? Because what many babies suffer from, the pediatric hydrocephalus, is that pressure inside their head goes up." He wanted to have a device that, he explained to me, that goes and drains the liquid, the fluid from the brain into the stomach of the baby. But they couldn't make small valves. At that time, nanotechnology was not heard of, or MEMS [micro-electromechanical system].

Wolf (02:26): And you were just a high school student in Iran at the time.

Gharib (02:32): I was in 12th grade, yeah. And he knew that I was very interested in physics and I used to build things, but, of course, my knowledge of anatomy was so limited. So that idea was forgotten, especially [because] it was summer, and I wanted to have a vacation rather than working. Almost 30 years later, he visited again, at Caltech. He was still a pediatric surgeon, and he brought that up again.

Wolf (03:03): The same problem 30 years later?

Gharib (03:05): Thirty years later. He said they're still using this primitive way of doing it. And it's interesting that we came up with an idea, and I filed it through Caltech, and actually we got the patents. So, my brother and I have a patent on an idea that he actually asked me to work on 30 years before.

Wolf (03:27): A problem he posed to you 30 years before when you were a high school student. Now, you made a departure from that, from medical engineering, and you spent many years studying and training to do aeronautical engineering. How did you get into aeronautical engineering, and then how did that slowly evolve into other things?

Gharib (03:41): I was really interested to study physics. My father was a schoolteacher, a high school teacher. He said: "You know, you're not going to make money out of this. Just think of more practical fields." And engineering was obviously the right choice for me. And now, in retrospect, I really think that he was right, because he knew how I think and he knew that I'm not going to be a theorist. I'm somebody that solves problems, practical problems. So that was the right choice.

Wolf (04:20): So, you had this sort of spark that happened with a conversation with your brother. You depart from there, and you go on and you work on fluid flow, turbulence, jet engines, things like that. And then something happened along the way. You're still a young professor, and suddenly you get an interest in medical engineering. Tell us about that. Where did that come from?

Gharib (04:41): But let me tell you a little bit before that. When I was in high school, one of the biggest problems I felt was that I couldn't get the attention of my professors. I had so many questions. And because [of] large classes—because my father was in public schools, he always wanted me to go to public school—so the large classes [were] the trade-off. So, for me, it was an obsession to go to a school [where] I can have one-to-one interaction with the professor. So, when I was in, I think, 11th grade, I saw in the newspaper in Tehran that there's a school in California [where] the student-to-faculty ratio is three to one. And I said, "Well, that's the place I have to go." So, that's how I actually put all my efforts to make sure I get to Caltech. And it was pretty rewarding, because then I got a chance to get exposed to the creativity and wisdom of people like Hans Liepmann [and] Anatol Roshko. At that time, I took a class from [Richard] Feynman.

Wolf (05:48): Famous physicists and engineering professors here at Caltech.

Gharib (05:51): And also Feynman. Where else you could get such exposure? And one thing that I learned from Anatol [Roshko] was that you shouldn't be technicians of the field. That means we shouldn't get trained to just look at one thing. He said that's for other schools. That's how he basically expected us to think about every aspect of even the simplest problem—not just one angle.

Wolf (06:21): What a great idea. We shouldn't be technicians of the field. Well, there is something that I've noticed from all of our conversations over the years. Let's come back to the heart and cardiology, because that was really your first foray where you took fluid mechanics and you started to apply it to solving some interesting problems for medical devices and therapies. Could you give us an example, maybe talk about one of your original heart valves or heart pumps and how you thought of that and what enabled you to come from way out of left field into trying to solve this?

Gharib (06:47): The first time that I was exposed to a cardiovascular problem was when David Sahn, who was the head of pediatric cardiology at UCSD, showed up in my lab, and he had a mechanical heart valve in his hand and he said, "Do you know what is this?" I did not; I had no idea. I said: "No. What's that?" He said: "It's a heart valve designed by a surgeon in Norway. That's the only thing we have. We put in humans, and it works. The problem is that it has so many problems. Sometimes, as a surgeon, I would like not to put in people. I wouldn't pick it out for myself." So that was a good challenge. And I said, "This is no different than flaps on airplanes. If we can solve problems like that, why can't we solve the problem of a human heart valve?" That's where I was wrong, because nature was so amazingly smart in making things that we are not even close. So, I realized something: Instead of trying to mimic it, try to get inspired by it.

Wolf (07:56): What do you mean by inspired by it?

Gharib (07:57): We can basically make a heart, 3D printing of the heart—but would it pump like a heart? Would it beat like a heart? The life in the heart is not something that you can mimic. You need to come up with a different way of doing that. And that's where bio-inspiration comes in. We, as humans and with all the technology, advanced technology, we have developed, still we cannot create materials that nature creates. But we are smart. We can create other things that nature cannot. So, that's how I looked at the problem. Let's see what we can do to improve the existing designs. In the meantime, go back, see how nature actually makes it. Don't look at the final product. That's how we started to look at the origin of how nature manufactures things. And that was like an open book of design. Let's see where does it start and how did it evolve? Now what you're saying is that, yes, we look at those problems by looking at the origin of things. And this is actually what is—not in my group but many groups in Caltech—a key to our success. That's where you do the fundamental research, because fundamental research means to look at the basic fundamental parameters that make things happen. Okay. So, for me, it started like that.

Gharib (09:19): What we started to do is that we looked at the heart of the zebrafish. [The] zebrafish is a tiny fish—zebra because of a stripe—but in the first four days of its life [it] is invisible. Transparent. That means you can see through it and see the heart. But the problem is [that it is] so small, you need to have devices to look at it. Fortunately, I was in a place [where] people like Scott Fraser, pioneers of new biological optics, worked. So, he and I got together, and we used his three-dimensional confocal system. And we mapped the whole field, the whole heart of this zebrafish, as it started at 300 cells to millions of cells. In four days [it] went through being just cells that didn't know what to do, to cells that in a coherent way pumped the fluids and sustained life. And that's where we got the idea that life is aquatic. If you can make the circulation, you can sustain life. And you could see it in front of you in four days how nature built up a system to sustain life.

Wolf (10:31): Starting from a single chamber up to more complicated ...

Gharib (10:34): More complicated as the fish grow around it.

Wolf (10:37): Let's use that as a buildup to the thing that I think is one of the most fascinating inventions that you and your team have developed, which is the ability now to take something as simple as a cell phone—I can hold an iPhone up to my carotid artery, and you can tell me about the structure of my heart. You can tell me about how well my valves are working. You can even tell me the efficiency with which my heart pumps. This was obviously many years of taking your background as a fluid mechanics expert, an aeronautical engineer, and applying it to the heart and understanding the heart. And you've spent a long time doing that. Yet it culminated in this incredible invention that you and others developed that potentially could revolutionize the way people are treated and the way we diagnose problems with our heart.

Gharib (11:19): When I started to look at the circulation in human or vertebrates, I realized that what's been missing is that we are compartmentalizing it so much that we don't see how things work together. [I'll] give you a simple example: If you go to a doctor, even today, the best cardiologist, they look at the heart as a pump and the rest of the aorta and all the vessels as plumbing. We didn't look at it like that, because we realized how much your heart depends on the vessel that it works on, and how much those vessels depend on the pumping. [I'll] give you an example: Without the pumping of the heart, no valves would form in the human body.

Wolf (12:04): Incredible. So, basically, the pumping itself is what causes the valves to form during the genesis of a heart.

Gharib (12:08): So, if I, for example—that's what we did with the zebrafish. We stopped the heart and just fed the body by different means. Okay? No valves form.

Wolf (12:17): So, the pumping, the mere fact that you're pumping blood and that you're moving fluid around, is what causes biology to create valves?

Gharib (12:28): That's right. And the valves, once they've generated, the pump, the heart, is going to depend on it. So, you can see, eventually you create ...

Wolf (12:36): A virtuous cycle.

Gharib (12:37): A virtuous cycle. It's very important. That's something that other people didn't see. But we saw that, without the valve, still this heart was pumping. And the way it was pumping was not the shape that you see later on. It was a different thing. You'd never suspect, just a tube.

Wolf (12:56): And by shape, you mean the mathematical and mechanical shape?

Gharib (13:00): Of course. So we took that concept, and we developed a mathematical model for it, and we showed that, yeah, it's very simple. It's exactly the same equations that you use to predict how a shockwave spawns from the walls. And the same elastic waves that the pump creates [are] a cause for tuning of the vessels and formation of the valve. But before formation of the valve, that tube was a pump itself, and we got inspired by it. So, we actually built a pump without any valves that we call an impedance pump. And you know better than I do what kind of application ...

Wolf (13:39): Well, as I recall, you basically built a pump that doesn't open and close. You essentially send a wave down the outside of the tube, and the mere fact that you're sending a wave down the outside of the tube causes pumping.

Gharib (13:51): That's right.

Wolf (13:51): Which is essentially what's happening in the earliest stages of a heart.

Gharib (13:54): Yeah. So, this background—think about it—has taken about 15 years. Correct? So, we see that these waves are so important. There are waves that actually create life and the human circulation as we develop. So, we said, "Okay, what else do these waves do?" They carry information. They're like radar, you know, just send a wave, and ....

Wolf (14:17): And so the heart is a radio.

Gharib (14:20): That's right. So, the heart is a source, and this pumping that it does while carrying nutrients and carrying the waste out. In the meantime, you have information. That information has not been looked at before we started to look at it, the way we looked at it. It's like if I send a wave, and radar hits an airplane and comes back, correct? Every time your heart pumps, beats, it sends a pressure wave that goes through all your body. And then you flex back waves. The waves are bringing back information. If I knew how to decode that information, I could say a lot about the vessels. I could say lots about the source, which is the heart. And that's how we started to think of a model that is a heart and the vessels and the waves connecting them.

Wolf (15:08): So, for our listeners, you make it sound so simple and elegant and it's one of the beautiful things I've heard you lecture about before, and the ways that you lecture as well. But I have to tell you, I'm sitting at my desk a couple of years ago and I get a phone call from someone that you know, a cardiologist in Virginia, who calls me and says, "I've just seen a presentation by Niema Pahlevan," who was your postdoc, now professor at USC. And he said: "For the first time in 30 years, someone has shown me that there really is more than just the basic things we learned from heart sounds. There really is an incredible vast ocean of information from heart sounds." You've now taken that to the next step, which is you've democratized it in a way that regular everyday people potentially will be able to just upload an app on their phone and learn about their heart. Or someone who potentially has chronic pathology with a valve will be able to monitor that periodically.

Gharib (16:00): This device that you're talking about is one of the components of our thinking. What's important here is to make this viable. Of course, we can always measure our heart rate, correct? Well, what can I say about it? What can I use that for? So, we have to bring that kind of power to the people that use it.

Wolf (16:20): You have to be able to take this incredible invention and turn it into a therapeutic benefit.

Gharib (16:24): That's right. And we are lucky because we are right at the juncture with AI and machine learning and the ability that we have to collect information, store the information, and actually use it as training models. It opens up a huge door for all kinds of devices to come out and be useful.

Wolf (16:48): One of my other favorite experiences with you was [when] I visited your lab one time and you said, "What do you think of this image?" And I thought you were kidding me or that maybe I needed a new prescription for my glasses, because it was a blurry image. It was a beautiful colorful image, I'm sure, but it was just blurred for me. And you said, "Now, watch this." And you clicked a button on the mouse, and suddenly it was a three-dimensional image. You'd been working on some stuff, I think for the Department of Defense at the time, and you'd come up with this incredible way to create 3-D pictures with a single image. That, today, is part of a regularly used technology in dentistry. But yet it's another example that's not fluid mechanics, but it was another example of an interesting problem that you wanted to solve or maybe used mathematics or some other aspect of engineering. Tell us a bit more about that. How did you come about it, and how did you end up thinking that it would be useful for dentistry?

Gharib (17:39): So, somebody at JPL said, "Okay, we have a problem with the spray of the fuel, and we don't know how to take pictures of this." And I liked photography, so I volunteered to work over there.

Wolf (17:55): That was very fortunate for the Jet Propulsion Laboratory.

Gharib (17:57): Well, eventually I worked there for a couple of years. I got this idea [about] how to track particles in space, but the problem was that these particles are moving in all directions. The idea was that you [could] use a hundred cameras from different directions, and so naturally I said, "We need to buy 10 cameras." And the supervisor at that time said: "No, you have only one camera. Can you do it?" I said, "I don't think so." He said: "Well, you're a Caltech graduate student. You should be able to." It was really insulting to me, somebody saying that, because I said, "Okay, I'll show you." So, then I remembered an idea that people who don't have glasses, sometimes they can see focused images by just putting their hand in front of one eye and moving it back and forth. So the image becomes focused and comes back and forth.

Wolf (19:00): Much like when someone's trying to determine which is their dominant eye.

Gharib (19:03): That's right. So, I said, "Look, how do I translate this to a single camera so that at all times you have that moving kind of plate, we call it the aperture." Just one thing to note is that it resulted in an aperture with three pinholes. Then I found that, actually, if you take any lens and put an aperture with three pinholes, it made the image focused. But the images are separated. So, all I needed to do was write software that brings those images together and then extract the depth. It was as simple as that.

Wolf (19:43): And why dentistry? How did you think of dentistry?

Gharib (19:47): Dentistry was different, because then I wrote a proposal to [the] Navy and, [the] Navy saw the concept and we built a large camera for detecting underwater mines.

Wolf (19:59): So, this was on submarines to be able to take pictures?

Gharib (20:01): Submarines, and also bubbles [inaudible] in a noisy bubbly flow. But one day I was at the dentist, and they put this impression, and the guy said, "I wish we could get rid of this." And then they told me there are some other people who have these big cameras to do the same thing. It reminded me of the same situation I had at JPL. I said, "Can't you use this?" So, I had a friend at that time who started a company based on that. We built the first handheld high-resolution scanning camera a now the big company actually got it from Caltech, licensed from Caltech and is making it. But the same concept.

Wolf (20:44): But, again, a much a much cheaper, more elegant solution than what had existed before. Much like what you've done in cardiology.

Gharib (20:51): Getting back to coming from different fields. I have not taken a single course in optics. I have not taken a single course in biology.

Wolf (21:01): I want to stop there because I think that's such an important concept, which is—and it's something that's absolutely part of the core of what we do at Caltech, and, in fact, it is even the core for our undergraduate students—which is [that] understanding first principles of mathematics, physics, chemistry in particular enables you to do so much. So, Mory, I want to move to another topic, and I know it's a very, very personal topic for you. And it came about for a very personal topic for a friend of yours. I recall that many years ago a friend called you and said that his son was suffering from a form of glaucoma that affects young people and that he was really distraught that there was not a better way to treat the glaucoma. The drugs weren't working for him that are typically prescribed, and the laser procedure that is often done was not going to work for him. You were inspired by this, but there's more to this story than just glaucoma. I wonder if you could talk a bit about the Glaukos shunt and what you did to create that and what that's done for glaucoma patients.

Gharib (22:06): For me, it was really heartbreaking to see a father saying, "My son's eye actually collapsed because the surgeons were trying to do laser [surgery] and poked in the wrong hole." He asked me to meet another doctor, and I didn't know anything about the eye and physiology of the eye. I knew about the diseases like glaucoma, macular degeneration. This doctor, Dr. Hill, Rick Hill, explained to me the physiology of the eye, and I just realized how much fluid mechanics is there that I do know. So I asked them ... so they challenged me: "Can we have a system that is not complex, that we can implant, and it can monitor the pressure in the eye? Not only monitor, actually regulate it?"

Wolf (23:03): Regulate and relieve the pressure in the eye by removing the fluid.

Gharib (23:07): Yeah. And they said that we cannot put an electric pump, we cannot put moving things [in the eye], because any moving component eventually is going to break. And based on some of the discussions I had with Rick Hill, I realized and appreciated that it's really like a one-way valve. But I could not have a valve; I had to design something that acts like a valve. So, I came up with this idea, again, from basic research, that in a certain range of Reynolds numbers—it's a parameter using fluid mechanics—flow in some geometries can go faster in one direction and slower in the other direction without having a valve. So, that weekend I went to this jewelry [shop] on Lake Avenue, the guy that actually fixes my watches, and I drew something and said, "Can you make that small from gold?"

Wolf (24:13): Fascinating, from a jeweler?

Gharib (24:16): A jeweler. I don't want to mention the name of jeweler. And it's as small as one millimeter. It was bigger than what I wanted, but that's all he had. I took that thing to Rick Hill, and he implanted it in a rabbit in two weeks, and it worked.

Wolf (24:33): Incredible.

Gharib (24:35): And then the question was how to manufacture it. That's another challenge. It took more time for me to think of how to make it out of titanium, but it really solved the problem of glaucoma without any medication.

Wolf (24:50): That's now a shunt that's available on the market called the iStent.

Gharib (24:51): That's right. A million people have it now.

Wolf (24:54): But there was another aspect of this, because it was also potentially a discovery to help you treat that same hydrocephalus problem that your brother brought you when you were a high school student in Tehran.

Gharib (25:05): Yeah, the same concept actually came up: how to design valves without being a valve—just the question of scaling it up and down. But I think we started with the difficult problems, making it as small as a human hair for your eye, to something which is about one centimeter for a shunt.

Wolf (25:29): And how did the conversation with your brother go 30 years later?

Gharib (25:31): He still wants to see whether we get a royalty out of it.

Wolf (25:39): The last thing I want to ask you about, Mory, is—and I've noticed this among so many great inventors and discovers—is you're so free to talk about all the people that were a big part of everything that you did. How are those relationships important in guiding the way this is done?

Gharib (25:55): The other day I was thinking about this. I realized, when I'm by myself, I don't come up with any good ideas. But I realized that it's only through interaction that I become a problem solver. That for me is like a trigger, a mechanism.

Wolf (26:12): Mory, in some ways, Caltech is the perfect place for you, because with only roughly 280 faculty, if you walk outside your door at a large institution, there are several other faculty members who all study fluid mechanics, and you can only orbit around them. But when you walk outside your door, there's maybe no one who studies it, and you're going to run into biologists and chemists, and, as you described, that echo chamber that you're in, where you're bouncing off and interacting with other people, and that helps inspire—not only shows you the problems, but helps inspire you how to solve the problems. In some ways, this must be the perfect place for you.

Gharib (26:48): There's no doubt that we are what we are because of the environments that we live in. We are all a reflection of Caltech, and the opportunity that it provides, interacting with the best minds. I always tell any colleagues or junior colleagues that you're amazingly smart, you're fantastic, but look at yourself in five years or 10 years, and tell me which one you like: the one that entered or the one you are now. And I think that's the best measure. I think that's amazing, how we have created such a culture, such an environment, so conducive. It's so fertile, it's amazing—like some areas [where] you drop a seed, a tree grows. It's like that.

Wolf (27:37): Well, with that, I think that's the perfect place to punctuate our conversation and end. I am truly grateful to spend the time with you, anytime, and this was a wonderful opportunity to explore some of the many great things that you've done for science, for engineering, and, as we learned today, for society. So, on behalf of all of the listeners of The Lonely Idea, thank you, Mory.

Gharib (27:56): Thank you.

Conclusion (27:57): The Lonely Idea is produced at Caltech. Learn more about Caltech innovators and their research at www.Caltech.edu or connect with Caltech on Facebook, Twitter, Instagram, and YouTube.