Editor's Note: In this episode, Dr Ohman interviews John B. Simpson, MD, PhD, of Sequoia Hospital, Cardiovascular Medicine and Coronary Interventions, Redwood City, California. Dr Simpson invented and commercialized the first over-the-balloon catheter and started several device companies including Perclose and Fox Hollow. This interview was recorded on October 12, 2015.
The First Job: Not a Good Match
E. Magnus Ohman, MD: Hello. I'm Magnus Ohman and we are back with Life and Times of Leading Cardiologists. We are very fortunate today to have Dr John Simpson with us. He is probably most famous for revolutionary changes in interventional cardiology. He changed how we could do things in interventional cardiology, which has had a tremendous impact. I want to welcome you, John.
John B. Simpson, MD, PhD: Magnus, thank you very much. It's a pleasure to be here.
Dr Ohman: Great. So, where did you come from?
Dr Simpson: I grew up in West Texas. I went to Texas Tech University for a while and did not do so well there. And then I went to Ohio State University.
Dr Ohman: Oh, a Buckeye.
Dr Simpson: A Buckeye, which is very good to be right now. After going to Ohio State, I wanted to go to medical school. I applied to a lot of medical schools but got into none, so I got a job as a bank teller.
Dr Ohman: Was this back in West Texas that you went to work as a bank teller?
Dr Simpson: No, I worked as a bank teller in Columbus, Ohio. A very important part of my bank-teller history is that I lost Jack Nicklaus's winnings from the US Open in '67, and it cost me my job.
Dr Ohman: Oh, my goodness! Of course, he's made it up several times over since then, so you shouldn't really worry.
Dr Simpson: I shouldn't worry too much about that now. He knows the story, though, and he wrote me a letter about 3 to 4 years ago and said that he's sorry. He heard that my interaction with his golf career cost me my job. I said, "Yes, it did," but he said he'd heard that it probably worked out okay.
Dr Ohman: That's great. Has anybody in your family been in medicine? What did your parents do?
Dr Simpson: My dad was a builder. My mom was a stay-at-home mom. Some of my relatives are in business, but no one is in medicine.
Dr Ohman: Do you have brothers and sisters?
Dr Simpson: I have one sister. She is a stay-at-home mom, so she's not involved in medicine either.
Dr Ohman: Are all of them local? Did they stay in West Texas?
Dr Simpson: My sister lives in Seattle and I still have family in Texas, but most of my family is currently in California.
On to Graduate School
Dr Ohman: Great. So, you were a bank teller for a short time. Then what?
Dr Simpson: The vice president of the bank suggested that I was not cut out to be a teller. I said he may be right, and he recommended graduate school. I'd already considered graduate school at that time. I had a lot of interest in science, so the bank teller job was not a very good match.
Dr Ohman: What made you think about science?
Dr Simpson: You know, as a kid, I actually wanted to be a veterinarian. That was another thing that I had entertained.
Dr Ohman: That's common in West Texas.
Dr Simpson: I spent a lot of time in the summers on ranches and worked with the animals. This guy with a white coat would show up and make the animals better, and I thought, "Wow, that would be pretty nice to do." But I couldn't get into veterinary school either. I eventually went to graduate school at the University of Texas in Houston and did some research work in immunology that was very popular with one of the scientists at Duke. He saw the work that we were doing and actually helped support my application, which might have been a little bit on the edge, academically.
Dr Ohman: What was it in immunology that turned you on to the science part? That's not something that people usually start with.
Dr Simpson: I think my mentor in graduate school had a fair amount of experience in immunology, and I was influenced by that, but my graduate studies were focused on why a mammalian pregnancy is not an allograft and why the fetus is not rejected as a foreign graft. Because if you graft skin from a fetus to the mom, the skin is always rejected.
Dr Ohman: Fascinating.
Dr Simpson: It's sort of an immunological observation that we make. We just assume that there's something about the fetus being so close to the mom's identity that they would not be recognized, but that's just not true.
Dr Ohman: We'll get to interventional cardiology a little bit later. This is just fascinating. That is a question that most people don't really think about. You started looking at questions that were a little bit unusual. Did you enroll at Duke Medical School in Durham?
Medical School and Further Training
Dr Simpson: I applied to Duke and then, eventually, I got into Duke. I'm going to have to tell you that it was not on my first try but on my second try that I got in. Dr D. Bernard Amos was the scientist in the immunology department who characterized the first histocompatibility antigen in man that has to be matched before any of the other histocompatibility antigens are matched. He had discovered it. He is a great guy, and it was fascinating to see what he was doing and how he got to where he was.
Dr Ohman: You were doing this at Duke?
Dr Simpson: That was at Duke, yes.
Dr Ohman: You talk a little bit about him as a mentor at Duke. You went to medical school at Duke. How was that training? How did it match up with the teller job in Ohio and graduate school in Texas? How did you feel about your training there?
Dr Simpson: Duke training, of course, is extraordinary. I don't care where you come from. Everybody recognizes that Duke training is really good. I had a special advantage, though, because I studied in graduate school and got a PhD. Duke was a perfect fit for me because, with my PhD, I could get credit for the third-year research year at Duke, and I could finish medical school in 3 years.
Dr Ohman: You were accelerated.
Dr Simpson: For the longest time, I was not. And then I was. Accelerated might not be the right term, but I was able to get credit for some of the work that I had done in the research field.
Dr Ohman: You finished medical school and then you had to decide on surgery, immunology, or medicine. What went through your mind?
Dr Simpson: That's a very good question that might be kind of hard to answer. I did have the immunology experience and felt that I didn't use very much of it at Duke beyond just working with Bernard Amos. And then I thought I should go to a hospital for my internship and residency and that it should be at a place where I can take advantage of my immunology experience. At that time, Stanford was a good pick because they were doing a lot of heart transplants. It was very early in cardiac transplantation. Norman Shumway, who was the famous cardiac surgeon at Stanford, knew that I was applying. He said that was very interesting and kind of supported my application for a fellowship after I'd finished by internship and residency at Duke. He said, "It's great. I'd be happy to have you in the program," but didn't think that I would be all that useful. In terms of my immunology background, they had a lot of immunologists, but he said he thought it would still be nice to have me in the program.
The Free Lunch That Changed His Life
Dr Ohman: You went to Stanford?
Dr Simpson: I went to Stanford, and it was while I was at Stanford that I met Andreas Gruentzig. He came to Stanford to give a talk on balloon angioplasty. I saw the flier and it said, "free lunch."
Dr Ohman: That always goes down well. Although the new rules have done away with those.
Dr Simpson: They have, but this was a long time ago. I said, "Well, I get a free lunch. But this is crazy. This guy is going to put a balloon into somebody's coronary arteries and blow it up and they're going to get better? I just cannot imagine it, but it would be worth listening to." And so I did. I went to the lunch. When I left the lunch, I told my wife, "He's either going to revolutionize the treatment of vascular disease or he's going to go to jail. I think jail is more likely for Andreas." Several months went by and I thought nothing more of it. Then one day, I had a complication in the cath lab where I dissected a lady's circumflex coronary artery and created a huge flap just with an angiographic catheter. I thought, if I just had Gruentzig's balloon to push the flap back up, maybe she could have had flow. She ended up with a large infarct. I went to the chief and said, "I'd like to go learn about angioplasty from this guy, Gruentzig. He gave a talk here 4 or 5 months ago. And the chief said, "Hmm, no."
Dr Ohman: Who was your chief at the time?
Dr Simpson: Don Harrison was the chief at the time, and Don was kind of suspicious of interventional cardiology.
Dr Ohman: Like many people at the time.
Dr Simpson: Every person. I mean, Andreas Gruentzig was the only one who was not.
I also wanted to learn about it, but I still was not all that sure. Harrison told me that I'd have to pay my own way, and he said, "I think you're going for a ski vacation." I said I'm not going for a ski vacation. So I paid my own way to Zurich and came back. I saw some cases that were fascinating, but they didn't work all that well in retrospect. The narrowing would go from about 90% down to 60%, and I thought, "Wow."
Dr Ohman: "Great success."
Dr Simpson: That's a success. We came back and ordered all the equipment from Gruentzig. I got everything except the balloon.
Dr Ohman: When you say you didn't get the balloon, do you mean that he wouldn't share it?
Dr Simpson: Correct.
Dr Ohman: Interesting. So you were a man with some tools but not all of them.
Dr Simpson: And the only tool that I really needed was the balloon.
Dr Ohman: Of course, I remember the first patient that Andreas did. A number of years ago here at the Transcatheter Cardiovascular Therapeutics (TCT) meeting, the patient actually came. He did well for 20+ years. It's remarkable. So, you were back at Stanford and you had some of the equipment. How did you set out to overcome this issue?
Dr Simpson: Of course, this was in an era where the regulatory processes with the US Food and Drug Administration (FDA) existed, but they were less stringent than current processes. I wanted to make balloons, but I had no interest at all in using them in humans at that point, and I only knew how to do things over a movable guidewire. I had only used catheters over movable guidewires, but Gruentzig's system was not a movable guidewire system. I didn't know how to use it, so I thought, well, I need to experiment with it. I needed to build one where I can move the balloon over a guidewire. It was the only thing that made any sense to me.
Dr Ohman: That's very important. I think that many people who do angioplasty now will not remember those fixed-wire balloons that Gruentzig used. You were moving the field with just intuition. What made you think about that?
Dr Simpson: I had a genuine interest in how it works. I don't know how to describe that, to be honest with you. I wanted to know. And I thought that if you could do this, it could really change things in a very favorable way. Somehow, I felt like it was good. Also, there was another issue about being at Stanford at the time. You're surrounded by a lot of infrastructure — all kinds of plastics, extruders, and people who know how to crosslink polymers in plastics and make balloons. It's a fertile environment for exploration, so I think that really worked to my advantage.
Dr Ohman: We jump forward greatly here in your career. Family came along here at some point?
Dr Simpson: The family was coming along the whole time. We had three girls while I was at Duke as a medical student. I think I kind of set a record for a medical student.
Dr Ohman: I think nobody has actually beaten that.
Dr Simpson: That's going to stand for a while, huh? The girls were growing up and our son was born at Stanford in California.
Dr Ohman: He played basketball, I believe.
Dr Simpson: He played basketball for Duke for 4 years, and I think it was one of the most amazing experiences in his life.
Dr Ohman: Yeah, winning a national championship.
Dr Simpson: Being on that national championship team was extraordinarily special. He learned a lot from Coach K [Mike Krzyzewski]. Everybody learns a lot from Coach K. I appreciate all the stuff that he learned, but now he's on time everywhere he goes. He would not have learned that from me. As you know, today, I was 5 minutes late. Coach K would have canceled the practice and the interview and I'd be running sprints out there. It's really remarkable what he learned from the coach. He's also a curious individual who is not easily discouraged, and I think that's one of the traits he learned from working with Coach K. You learn that you're going to have to play hard and it's not going to be easy.
Dr Ohman: So you have four children — three girls and one boy. Is anybody going into medicine from your family?
Dr Simpson: No, nobody went into medicine. Some talked about it off and on. Our youngest daughter probably looked at it the most seriously. I would say that my son, JD, looked at it a little bit, too. I hope it wasn't that I was a bad influence on them and kept them from selecting medicine as a career. I think they have different talents and they made the right decisions.
Building the Balloon
Dr Ohman: Well, your talent has been so important for interventional cardiology. So, you were getting the plastics and all those things together. How does one build a balloon from nothing?
Dr Simpson: You go and talk to the plastics company and say that you need a balloon that's about this big. The goal was to have a 4-mm balloon. It has to blow up to 4 mm. That's what Gruentzig said he was using.
Dr Ohman: So that's only for large vessels, basically.
Dr Simpson: Of course. And that was still too big for almost any of the vessels that we were going to treat. Thank goodness we didn't know at the time. The plastics company said that they had some material in stock that they could give me, so I didn't have to pay for it. I didn't have any money, anyway. They gave me the plastic that was the right size. It was the electrical insulation on the F-4 Phantom. It was military-grade material. It had a lot of flame retardant in it in case the plane crashed. That is all carcinogenic, so they had to take out the flame retardants and extrude it without the flame retardants. And we started building and playing with the balloons. We were just playing with it to see what we could do. We really just wanted to test it in animals.
Dr Ohman: How did you feel when you first tried it in the animal?
Dr Simpson: Well, that animal died, so I didn't feel so good.
Dr Ohman: Oh, dear.
Dr Simpson: Nor did NASA, because this was a NASA ape that they had been teaching to smoke.
Dr Ohman: Wow.
Dr Simpson: It fibrillated and we did not have a defibrillator that would work for this very, very large animal.
Dr Ohman: Wow, but you weren't discouraged. There is a theme here. You weren't discouraged by this.
Dr Simpson: I have to say that that was pretty discouraging. But not enough to stop.
Dr Ohman: Okay.
Dr Simpson: And NASA canceled. They were going to send some more animals, but they said no more animals for you. There are a lot of things that happened on the way that were very discouraging, but I don't know exactly what the threshold is that would actually make me stop. I must have a pretty high threshold.
Dr Ohman: What was your breakthrough, once you got over this?
Dr Simpson: The breakthrough for us was being able to build a device that would go in and out over a guidewire. It was something that was not otherwise available. Also, I call myself a pretty average interventionalist, and I could make it work. I think most interventionalists are more average than Gruentzig. Gruentzig could make the fixed-wire device go anywhere. It could not be imagined that you could do what he did. The movable guidewire system gave me so much flexibility in terms of being able to position the wire. It could be controlled so that we could aim, guide, and direct the wire. You can't do that with a plastic tube. I think that was the breakthrough, for me, finding something that the more average interventionalist could make work.
Dr Ohman: That's pretty good. This was the famous balloon, the Simpson-Roberts balloon. How did you get to your next device? What was the piece that said, "Okay, I'm done with the balloon now"?
Dr Simpson: Well, the balloons worked frequently, but not always. It seemed that maybe instead of trying to squish all this material in, it might be better to clean it out. That was my initial goal. We had a fatal complication during a balloon angioplasty, and at the autopsy, I took a Cope biopsy needle and put it in the left main coronary artery to see if I could biopsy the lesion that caused the patient's death. And it worked. I just cycled the needle a couple of times and took out a fair amount of plaque. I thought, "Well, if that could work there, then maybe we should be building a catheter that would do that."
Dr Ohman: Next was directional atherectomy.
Dr Simpson: Next was directional atherectomy. That was the [Devices for Vascular Intervention] DVI device, but it was hard to use. Ultimately, stents were easier to use and became a much more widely adopted technology.
Dr Ohman: Since that time, you've branched out in a whole host of different aspects of different devices. What has been the incentive for you in these different areas? You've done devices that close arterial access ports. You've done a variety of devices. Do you see a problem and say, "Okay, I need to fix this"?
Dr Simpson: I would say that that is almost always the case. Sometimes it's a personal problem. For example, the Perclose device came about because I was responsible for holding the groin of all the patients who had Coumadin on board when they were stented at Stanford. I would hold it for hours and I would say—
Dr Ohman: There's got to be a better way.
Dr Simpson: I remember one day, Tom Fogarty took one of the patients to surgery and I went with him. After just one stitch, the bleeding stopped. So I told Tom, "If all you need is a stitch or two, I can do that." I don't want to make it sound like I was lazy, but it wasn't good holding groins all the time, and if there's a way to do it otherwise, then it seemed like we should do it. I gravitate toward that. If there is a problem that is clinically relevant and we can solve it, we should.
A Message to Young Innovators
Dr Ohman: That has been your strategy. What would you tell young doctors who have this innovative and inventive mind? What can they learn from your story? What do you think is the biggest thing you learned while working on all of these different inventions over the years?
Dr Simpson: I don't know exactly how to answer the question. I would say that it's a lot about perseverance. It's perseverance in spite of some difficulties and some hardships. It comes at all levels. Sometimes, funding for the companies is a huge hardship. Sometimes it's the outcome. Sometimes it's criticism from your peers. Not every interventionist in the country is necessarily interested in innovation. Many would like to just keep doing it the way we've always done it. It's easier and simpler.
Dr Ohman: Familiar.
Dr Simpson: Familiar, comfortable.
Dr Ohman: I worry a little bit, now with healthcare reform, that some of these innovation pieces that take time may not happen and that people who do innovative things may find it hard to have the ability to tackle all the things you did. You were clearly overcoming a lot of hurdles in the beginning.
Dr Simpson: It was never easy, but I'm not sure that it's any harder now. Everybody is always saying it's so hard, talking about Obamacare, and I don't believe that. I think that you really need to be willing to commit, work hard, and persevere to drive a program forward that is going to be clinically relevant.
Dr Ohman: Maybe it takes some West Texas stamina.
Dr Ohman: Maybe it takes a little craziness. I don't know. Maybe you should want to be a vet first.
Dr Ohman: I want to thank you, John, for spending some time with us here. It's a great story, and we have a lot to learn from it. I want to thank all of you who have participated with us today. Thank you.
Disclosure: John B. Simpson, MD, PhD, has disclosed no relevant financial relationships.
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Cite this: E. Magnus Ohman. Life and Times of Leading Cardiologists: John Simpson - Medscape - Feb 10, 2016.