Doris Taylor: The Art of the Pig to Human Heart

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0:50I'm Guy Kawasaki, and this is Remarkable People. We're on a mission to make you remarkable. Helping me in this episode is Doris Taylor. Doris is a true pioneer in the field of cardiovascular regenerative medicine. She is credited with numerous scientific and medical breakthroughs. She's also the founder of multiple companies dedicated to cardiovascular repair technologies. I kid you not. She is going to explain the process of creating personalized hearts for humans from pig hearts. P-I-G, like oink oink. Wrap your mind around that. This technology apparently beats the hell out of heart transplants, human to human.

1:37If Apple had invented this process, we'd be calling it desktop hearts. God help us. I'm Guy Kawasaki. This is Remarkable People. And now, here's the remarkable Doris Taylor. First of all, I got to tell you a Steve Jobs story. So Steve Jobs is famous for when he did demos of new Apple products. He would do this blow away demo. And then just when everybody thought it was over, he would come back and they would say, I got one more thing. And then he would blow them away again. And so I have to tell you that my favorite part of the CNN interview was that when it was all over and you're telling Sanjay and the other guy, one more thing, one more thing.

2:25and you talked about lgbtq issues i thought that was just priceless all right oh thank you thank you so much so you're the steve jobs of cellular biology or whatever wow there you go i'll take that comparison to some degree so listen we'll come to the easy stuff about human induced pluripotent stem cell derived cardiomyocytes but let's start with something hard tell us about growing up in mississippi since i know that let's just say there were some issues based on that cnn little section right so tell us about growing up in mississippi the cool thing about growing up in Mississippi. We moved to Mississippi from Europe when my dad died when I was six.

3:22So my mom took us to Mississippi to be near her family because she had three kids, six and under, and found herself as a single parent. But the amazing thing about my mom is when we got there, she said, these people are living in 1865 you don't have to and she pointed out throughout our lifetime ordinary people doing extraordinary things so I think really growing up in Mississippi I saw people, just everyday people, stepping up and making a difference. And that was phenomenal. At the same time, when I went to college in Mississippi, I was naive. I was young. I was naive. I was probably, I think I was 17 when I started college and probably emotionally 12, you know.

4:25And my last semester, my senior year, the dean at the time, for reasons I don't fully understand, accused a number of people of being gay. And I was one of them. so my last semester my senior year of college I was sent home from college we were sent to psychiatrists we were given drugs and they did everything they could to get us to admit we were gay and I remember going home and having a conversation with my mom and she said is it true and I said I don't know because I literally I wasn't even sure what being gay meant OK, because I thought only the girls who played volleyball and met that really stereotypic image of being LGBTQ were.

5:26I knew I was emotionally attached at the hip to my roommate, but I didn't know that made me gay. However, they saw more than I did. And we were basically sent to doctors and all these people to say, admit it. And finally, my mom stood up for us. My mom was phenomenal. She stood up for us. But as soon as I was 21 and could, I left home because it was embarrassing for my family. Because I was, in fact, LGBTQ. I just didn't fully understand the implications of that. X amount of time later, by the time she died, my mom was saying the word lesbian more than I was and talking to parents of kids who were coming out.

6:21And she really continued to make a difference in the world. She was remarkable. So I aspire to make her proud. So I got out of Mississippi. The good news is it got me out of Mississippi. But it also made me realize that being different has costs. But throughout my career then, I've been different. Throughout my life, I've been different.

7:01was it ever an issue to to get your advanced degrees no it was not an issue because when my mom stood up for me what happened is before all this happened I had a really high GPA. So the dean of the academics made an exception, sat down with me and my mom, made an exception, let me go to another university and take the courses I had been failed out of my last semester, my senior year. So if you look at my transcript, it's A's and Bs and occasional not A or B. And then my last semester, it's all Fs. And then she let me go take those courses. I made all As and she let me transfer the hours back and get a degree a year later.

7:53Wait, why were they all Fs? They flunked us out of our courses when they kicked us out. Oh, for being gay. Yeah. Yeah. Wow. So I actually think this is all speculation on my part looking back, but knowing more now, I think the dean, not the academic dean, but the dean who did all this, I think she was probably a closet case. And I think she was probably doing some purging because she was uncomfortable with how outspoken some of us were about rights. And so one of the coolest things in my life is a few years ago, I got to go back to that university and deliver the commencement address. What? Yeah.

8:41Oh, my God. A lesbian gave the commencement address? Yes, and they nominated me for the National Most Distinguished Alumni, and I won. So, full circle. Okay, that is a great story. That is a great story. Okay, so now we got the special Steve Jobs moment covered. let's start off with something my simple mind can maybe comprehend and help listeners comprehend what is a stem cell oh that's simple that's very simple stem cells are simply cells that can do two things they can make more of themselves or self-renew and they can quote differentiate or become a number of different things. So they can become a lot of different tissues.

9:41We all have stem cells in almost every tissue of our body and then our bone marrow and our blood. So stem cells are not the scary cells that everyone thinks about. They're simply cells that actually repair our body for most of our lives. But as you get older, they don't repair as well. So this is not an infinite supply. As we age, our stem cells decrease in number and the ones we have decrease in potency. And the example I use to show that the best is if you think about it, when you're two years old and you fall down and scrape your knee, it turns red. That redness is inflammation. And that's the key right there.

10:32Inflammation is nature's cue to say, help, I've got an injury. Send me cells to repair it. So when you're two, those cells come and they repair it. And an important piece is they repair it from the outside in. Think about that. When you scrape your knee, never starts healing on the inside moving out. It's always on the outside moving in, right? Well, the same thing happens inside our body. When we get an injury, our body says, help, I've got an injury. That's inflammation. Send me cells. And stem cells get mobilized to the spot. And if the right cells get there and repair the injury, they turn off the inflammation.

11:21if they but when you're 52 or 62 when you fall down and you scrape your knee you still get the inflammation you still ultimately if for the most part you heal but you no longer regenerate you repair and you repair with a scar and so that's because our cells have lost number and potency Wait, now this is going to be a really stupid question, but in a sense, you're saying that inflammation is a good thing because it calls for the cavalry. That's exactly right. Acute inflammation is a good thing. But then what happens if you put ice on an injury and you try to reduce inflammation? Are you telling the cavalry, okay, don't come?

12:07You know, you ask a very interesting question. No, at the same time, because you don't fully turn off the inflammation, you reduce it. One of the things that people learned early on in heart disease, for a short period of time, after someone had a heart attack, they would give steroids to try to turn off the inflammatory response. And what they found is that giving steroids could actually cause more injury because you did exactly what you said. Those stem cells never got there to form a scar and the heart could actually rupture. So steroids are now contraindicated. You never give steroids after a heart attack for exactly the reason you just talked about.

13:03but let me also say acute inflammation is nature's cue you want to turn that off when you get the repair if you don't get the right cells there then your body ramps up the inflammation and it says hey i said send me cells and then you start recruiting the wrong cells there that are pro-inflammatory and that's when a chronic inflammation cascade happens and that's not good that's when you start getting all the secondary injury sounds like our political system but i digress that's a whole five-hour conversation so listen i heard this rumor that you have scientific proof that women are superior to men at the cellular level.

13:58Pray tell, please give us the details. First of all, there's so much data, where do I start? But I'll start with the fact that if you look at the numbers of stem cells and potencies of stem cells that exist in a number of organs and tissues, they're different in men and women. And women seem to have more of the reparative cells, whereas men have more pro-inflammatory cells in their bone marrow and sometimes in their blood. And I make the joke, but that doesn't surprise me. But really, it could actually begin to explain in part why men develop things like heart disease earlier than women and that women catch up later as they age and those cells go down.

14:54Also, the repair process has to be different in men and women because women have to be able to maintain a pregnancy. And if women had the same pro-inflammatory, get rid of everything foreign cells that men do, I think we wouldn't be able to maintain a pregnancy. Now, I've never, I haven't proven that, but that's my underlying hypothesis. I don't want to beat a dead horse, but you just said at the cellular level, men are trying to get rid of everything foreign. That is another metaphor for our political system, but I digress. Now, this is kind of off the wall, but as I learned this in doing research for you, what happens if we go like full Margaret Atwood and men start harvesting female stem cells to prolong their lives?

15:57Is that possible? I'll tell you an experiment we did, and we can draw a conclusion from that. What got me involved in this is in a science lab when we wanted to see if atherosclerosis, the buildup of plaque, actually could be reversed by using stem cells as a therapy. So we did an experiment and we wanted to be able to track the cells. And at that time, the way you tracked cells was you gave male cells to females and you gave female cells to males. And you looked at where the Y chromosome was. Okay. So we did that experiment where we had these animals that had really high cholesterol and really high inflammation.

16:45And we gave male cells to females and female cells to males. The female cells repaired the injury. The male cells had no effect.

16:58We're back to that metaphor, aren't we? And so could female cells have an effect in males? Absolutely. However, I also think that there are ways to actually have those endogenous effects. Talk about endogenous repair. And I've done experiments over the years looking at a lot of different alternative therapies that actually can have an impact on the number and potency of your stem cells in blood. Exercise matters. We did a small experiment on acupuncture and showed that it increased the number of circulating stem cells. One of the coolest things I ever got to do in my life is draw blood from one of his holiness, the Dalai Lama's monks before and after he meditated and show that his circulating progenitor stem cells went up 40 percent in 15 minutes.

18:08What? Yes. So there are all those things we've been told all our lives, exercise, meditation, acupuncture, stress reduction, all of those have an effect on our actual physiology. Before you ask me another question, let me just say one more thing. Stress is another word for inflammation. And if you don't believe that, look at a president before and after four years. I saw your slide, yes. Their stem cells fail pretty fast. And I also saw a thread in your coverage that there are people who think we should not do this kind of cellular research. What would be the rationale to not do research in this?

19:01I think there are a lot of people who mistakenly believe that stem cells only come from a fertilized egg or an aborted fetus. And that is not the reality. As very few to zero studies are actually being conducted with any kind of embryonic or fetal stem cell these days. These days, the research is being done from either stem cells from your own body or stem cells that have been created from your blood in the laboratory, the so-called induced pluripotent stem cells, or from stem cells from someone else that are donated for your use. So I think it's based on misinformation and fear. We can't study black history.

20:00We can't study stem cells. We're narrowing the fields down, but I digress again. I support your digression. And I want to say that I view regenerative medicine as a healthcare inequity issue. And when we get to organ transplant, we can talk about that. If you're a Caucasian individual, the wait time for a heart is about a year. If you're an African-American or a black individual, it's one and a half to two years, if you even make the list. And we don't even have good data on Latin people or on Asian people or on people from other ethnicities. All the data are about the Caucasian population. And the Caucasian male population, right?

20:57Right. If you look at cardiovascular stem cell studies, the average percentage of women included, much less people of color, is 17%. So we do not include women at the same numbers as men, even though heart disease is the number one killer of men, women, and children on the planet. okay so now to move on to your exciting work first if i may let me see if i got this straight okay so basically you bank a person's heart cells you create a universal scaffold from a pig's heart and then you use a baby shampoo like product to wash out the pig's heart cells and then you grow 350 billion heart cells from the person's bank and immerse the pig's heart in it and the cells know what part of the heart to grow and all of this takes 90 days and bada bing bada bang you have your personalized new heart did i get that right you got that close you got that close yes Yes.

22:17What did I miss? So we don't bank heart cells. We bank a person's stem cells. Okay. So first we take blood. We create these induced pluripotent stem cells from a person and then we bank those. that takes about 12 weeks and then we have to grow the cells to grow the 350 billion and then we turn them into heart cells because heart cells don't divide and make replicate and make more of themselves if they did we could probably repair the damage in our own hearts we wouldn't need all these therapies. But you're right, we take the equivalent of baby shampoo, wash out the pig cells. It's kind of cool, isn't it?

23:11It's a little scary, but it's cool. And then we put a person's cells into that scaffold. We actually inject them in with the robot now. And then we have to teach that how to mature, how to grow up and become a mature heart. And that takes another 12 to 14 weeks. So yeah, it's a six to eight month process all told. But we just talked about the wait list for a heart and how it's over a year now. It fits within that time frame. Plus, most people who are gonna who have a heart attack know that at some point in their life they're gonna need a heart what if we did this before they had to get so sick and we could actually give them a heart in advance and the cool thing is because it's made from their own cells then you don't have to take the toxic drugs that go along with an organ transplant today one of the eye-opening things for me was I thought, thank you, God, I got a heart transplant.

24:20Life goes on. But then I learned you have like$30 ,000 worth of drugs and these drugs cause other things to happen. So it's not like you walk out of that hospital and life goes on. It's not the Hollywood ending that we think. I agree with you. That was a hard realization for me that essentially when you get an organ transplant today, you're alive. It's true. But you're trading one disease for another. You're trading your heart disease or your kidney disease or your liver disease for high blood pressure, diabetes, potentially cancer because you're immunosuppressed, and then ultimately more renal failure down the road, kidney failure down the road.

25:08So as a young woman said to me recently, she said she received a heart transplant at 18 and she sent me an email and I asked her permission to use this. So I have her permission, but she said, it's been eight years of medical visits, biopsies, and drugs. And she said, I have gone from, it's true, I don't have heart failure anymore, but instead I have OCD, and anxiety because I'm terrified that I'm going to die because I forgot so busy, I forgot to take my drugs one day. Going back to that process. Yes. It sounds like every step is hard in creating a personalized heart, but what's the hardest step?

25:58I think for, well, to date, the hardest step for us has been growing the cells to the numbers we need because all the tools and reagents we needed to do that didn't exist. And it took me years of my life to figure out the reagents and tools we needed, 12 to 14 years of my life. However, let me also say, for the most part, overcome that hurdle, although it's still outrageously expensive and now we're trying to get the cost down and so the hurdle we face most now is convincing ourselves that stem cells from every person are gonna make a mature heart so now we have to train every one of these hearts to grow up and be mature and we just have to do it over and over and over to we're convinced our process is robust enough because nobody wants a heart that beats most minutes everybody wants a heart that beats every minute up next on remarkable people that being said if we are successful we will decrease the overall cost of organ transplant by up to half because you won't then need all the drugs, you won't have all the hospitalizations afterwards, you won't have all the consequences downstream.

27:42Become a little more remarkable with each episode of Remarkable People. It's found on Apple Podcasts or wherever you listen to your favorite shows. You're listening to Remarkable People with Guy Kawasaki. When you came up with this idea, being the lesbian woman that you are, did people fall over saying, yeah, this is possible, let's do this, here's a grant? Or did you constantly face naysaying and it can't be done, it shouldn't be done, not possible? What was that like? So let me first say that this idea came out of my lab at the University of Minnesota. OK, and the University of Minnesota was phenomenal in supporting the endeavor and getting the word out and helping us show the world that that this concept was feasible.

28:37However, after that, when I left the University of Minnesota and I went to Texas Heart Institute, we still, we had great support from the state of Texas, but grants were harder to get in this space. And I think in part, so when we first came up with the idea and we tried to get it published, the experiments took a year. Getting it published took over two years because the reviewers said, some reviewers said, if she has a heart that's still beating, she didn't wash all the heart cells out. Other people said, this is not novel. Someone else said, it's impossible. And I was like, how do you reconcile all this?

29:24and finally I said to an editor thankfully who was then phenomenal I said look today a heart can live four hours once you remove it from the body after four hours you cannot transplant a heart so if we took a heart and exposed it to soap and kept it alive for seven days that's worth publishing anyway. And that's when the editor got on board and said, yeah, you're right. You've jumped through enough hoops here. And we got it published. But even then, it felt a little bit like we were flying in the face of conventional wisdom. And it's been a little bit of an uphill struggle to get the funding because this is not inexpensive.

30:16This is not a$250 ,000 a year research grant. This is, I've got to prove it's going to work. Every heart costs$60 ,000 to$80 ,000 just for the cells, just for the cells because the reagents are not made at this scale. And so the reagents are made for research, which is a million cells. So we have to pay a million times 450 times three worth of reagents for one heart. Okay. So now we're in obviously the intensive investment stage, but let's say everything goes well. What's this heart going to cost? today a heart transplant for an individual yeah over the lifetime of their transplant costs about 2.8 million dollars wow yeah the reimbursement cost for organ procurement today and everything that goes into that is on the order of 350 000 okay everything we've budgeted is that 350 $50 ,000 cost for these hearts.

31:35That being said, if we are successful, we will decrease the overall cost of organ transplant by up to half because you won't then need all the drugs. You won't have all the hospitalizations afterwards. You won't have all the consequences downstream. And my My commitment is to doing everything I can to make this accessible, including spending some percentage of our profits going forward once we're a profitable company to make these hearts available to people who otherwise couldn't get them. It's about we're working every day to build a heart. But the reality is we're all building heart on the planet if we choose to.

32:25My mom taught me we're all in this together or we're all going to go down separately. And I truly believe that we need to be in this together. Just for clarification, are you saying the goal is to go from$3 million to$1.5 million or from$350 ,000 to$175 ,000? So our goal is to go for right now, the whole cost is 3 million, but that includes all your hospitalization and everything. Wait, the 3 million is for a traditional heart transplant or your transplant? No, a traditional heart transplant. Our goal is to reduce that by 50%. Okay. So a million and a half and you get your personalized heart without all the after effects.

33:13Right. and the drugs and the yes okay now how does dean cayman fit into this because what you're using segway scooters to get from that's right we've got our hearts on little boxes on a segway no dean cayman has built what is called the advanced regenerative manufacturing initiative in Manchester, New Hampshire. So Dean has essentially converted the old mill yards in Manchester to biomanufacturing. He's built clean rooms. He's built educational and workforce development endeavor. A number of years ago, he received a$80 million Department of Defense funding to make this possible. And Dean has been one of the biggest proponents of our work.

34:11He's not only supported our efforts there at Army, but has helped us get access to speaking opportunities and exposure that I think will enable us ultimately to get this funded. okay now i just cannot resist asking you this next question i think i have maybe five republican listeners and i'm about to lose them right now uh oh so let's just say that maybe donald trump or ron desantis needs a heart transplant and they could benefit from your personalized heart made with their own cells and now they won't have a whole thing of cancer and all these after effects but ron and don i have to tell you that this technology was invented by a lgbtq doctor so your heart is kind of a woke heart and it uses stem cells and it came from a pig Do you still want this?

35:24I cannot wait for that day when they have to figure out, oh my God, I'm going to get a woke heart. There's no question in there. I just want to see your reaction. You're putting me in an awkward situation. I know. It reminds me of when we did the first research and we showed that we could build a rat heart, which was the first heart we built. David Letterman said something to the effect of scientists at the University of Minnesota have created a rat heart in a laboratory. Maybe there's hope for Dick Cheney. So

36:06I'm just saying maybe we've come full circle. Yeah and of course the irony is that his daughter is one of the sane ones. And I actually wondered early on if people would be afraid of the pig heart. But today, people get pig heart valves. They get pig heart vessels. And I sat down with a couple of religious folks and leaders, and I asked them what their reaction to the use of pig organs was. And they said to me, the sanctity of human life comes first. That's good. Huh. And no one from PETA has reached out to you and say you can't kill pigs to save humans? We don't kill pigs. We don't kill pigs.