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Doris Taylor: Building Heart
386 Plays6 months ago
Heart disease claims more lives than any other illness, marking a dire need for viable heart transplants. Yet, the sheer demand for donor hearts outstrips the supply, burdened further by complications such as organ rejection and the continuous need for immunosuppressive drugs post-transplant. Dr. Doris Taylor's pioneering endeavor in engineering bioartificial hearts addresses not just a medical unmet need, but a systemic inequality in transplant accessibility and the encompassing physical, emotional, and financial toll on recipients.
In this inspiring episode of Back of the Napkin, Doris shares her extraordinary journey to becoming a pioneering scientist at the forefront of regenerative medicine.
Doris delves into her personal life, revealing her compelling motivation behind pursuing a career in science. The intersectionality of her life’s experiences has contributed to a more compassionate scientific inquiry, one that resonates deeply with those waiting on the fringes of hope for a life-saving intervention. It is not only the hearts she seeks to build in the lab that embody this sentiment, but also the metaphorical 'building heart' — the cultivation of courage, empathy, and resilience — that she instills in everyone she encounters.
A key part of the conversation focuses on Doris's groundbreaking work in creating the first beating bioartificial heart, which holds the promise of revolutionizing transplant medicine.
Key Takeaways:
- Dr. Doris Taylor’s work in regenerative medicine has led to the development of the first beating bioartificial heart, a potential game-changer for transplant medicine.
- Cardiovascular disease is a leading cause of death worldwide, and Doris's efforts aim to address the significant unmet need for donor hearts.
- The process of creating a bioartificial heart involves decellularizing a donor heart to create a "ghost heart" scaffold, which is then repopulated with cells tailored to the recipient. Doris's personal challenges, including being an LGBTQ individual in academia and dealing with professional hardships, provide an impactful narrative of perseverance and resilience.
- Organamet Bio, founded by Doris, is aiming to commercialize the technology to manufacture patient-specific bioartificial hearts, which currently estimates a cost of $300 to $500 million to reach the first human trials.
Resources:
- Dr. Doris Taylor's LinkedIn: https://www.linkedin.com/in/doristaylor/
- Organamet Bio website: https://organametbio.com/
Recommended
Transcript
Diverse Origins of Discoveries
00:00:03
Speaker
A discovery is said to be an accident meeting a prepared mind. But every story behind a discovery is different. Perhaps the idea is conceived in a light bulb moment or a brainstorming session or captured in scribblings on the back of a napkin.
Untold Stories of Scientific Pioneers
00:00:21
Speaker
Here we introduce you to scientific pioneers taking you beyond their publications and into innovation corner to hear the untold stories behind their discoveries.
00:00:33
Speaker
This podcast is brought to you by Biotechny and I'm your host, Alex Maloney.
Bioengineering Hearts with Dr. Doris Taylor
00:00:41
Speaker
32% of all deaths are due to heart disease. That's five times more than cancer or any other disease. And the only definitive cure for the heart failure resulting from heart disease is a heart transplant. But that means for someone to live someone has to die.
00:01:03
Speaker
So what if there was a solution? What if we could bioengineer a heart from the patient that needed its very own stem cells, avoiding the need for a deceased human donor?
00:01:16
Speaker
Well let me introduce to our guest today who has made this her mission. Dr Doris Taylor is CEO of Organimet Bio and has pioneered autologous organ bioengineering. For those outside of the cell and gene therapy regenerative medicine fields, autologous means the cells being used originate from the host.
00:01:40
Speaker
The opposite of this being allogeneic, which means the cells that go back into the recipient are from another source. Based off Doris' pioneering discoveries in making functioning organs from someone's very own stem cells, we're able to obtain hearts that are matched to a patient by sex and by size. As you'll hear, these are incredibly important considerations for heart transplants.
00:02:08
Speaker
But even for the lucky recipients who receive a heart now, there are still a huge number of challenges that they face. They have to take immunosuppressant drugs for the rest of their life. And these are incredibly expensive and pretty unpleasant to take. So having a bespoke heart for a patient adds an additional benefit to just demand and availability.
00:02:35
Speaker
Doris is one of Time magazine's top 100 most influential people in the world and from this interview you're going to see why. She's resilient, she's determined and no one is going to stop her reaching her goal of helping patients, giving them hope and building heart. Welcome to Back of the Napkin.
00:03:02
Speaker
Hi Doris, welcome to Back of the Napkin, it's great to have you here. Thank you Alex, it's a pleasure. Thanks Doris, it's a super cold early morning in Boston here, snow on the ground, so great to be able to do this actually in person.
Personal Influences on Dr. Taylor's Career
00:03:18
Speaker
I want to start by telling you a story. So I was telling my three-year-old daughter last night about who you are. And I said, hey, honey, do you remember when it was your birthday? This was a couple of months ago. And we went to the Build a Bear factory. I don't know if you have these in the US. She picked this bear, which to all intents and purposes is like a bear cadaver. And she takes it up to the lady who's going to fill it with stuffing.
00:03:45
Speaker
The lady then fills the bear with stuffing and she gave my daughter this little heart to put in and she says, give it a kiss and put it into your bear and make it special. And I said, well, Doris does that, but for humans. And my daughter kind of pulls this amazed face and she says,
00:04:04
Speaker
And does she kiss the hearts too? I didn't have the heart to tell her about kind of organ, uh, organ rejections. That's a story for another time. Oh, that's a fantastic story. And it reminds me of when we first started doing this and one of our hearts didn't work. One of the guys in the lab at the time said, did you love it enough?
00:04:32
Speaker
So it really, they really are, each one of these hearts is very special. You get attached to them. Yeah. So you might not kiss it, but you show it love in other ways. That's right. So let's get to know you then, Doris. Tell me a little bit about yourself. Where did you grow up?
00:04:54
Speaker
I actually was born in California, lived in Germany until I was six. My dad got sick when I was six and we moved to the US. So I lived in New Jersey for a short period of time with relatives while my dad was in the hospital, then Texas, and then my dad passed away.
00:05:21
Speaker
So I was six and we moved to Mississippi where my mom had sisters, had family, and I grew up there. So I grew up in the Deep South at a time when people were changing the world and that's part of what made me who I am. What got you into science? I think
00:05:48
Speaker
Well, I've always been curious, but I think what got me into science was my dad dying, one, and my not wanting anyone else to ever have to go through that. And then number two, I had a twin brother who was born with cerebral palsy, and I saw him
00:06:16
Speaker
go through life differently than a lot of other kids. And what he had to struggle with, and when my mom would take him for treatments or different things, I would see other kids who had cerebral palsy who were thrilled. I'll never forget seeing a boy
00:06:41
Speaker
who had the biggest grin on his face and he was probably 12 years old or I think he was older than I was. I think he was 12 years old to me that he was grown up, you know. And I asked why he was smiling and he just learned how to sit up. Wow.
00:07:04
Speaker
And those moments changed me because I saw everything my mom did for my brother. I saw people asking questions. I just I don't know. I science wasn't what I thought I was going to do. I thought I was going to be a clinician. And then I realized pretty early and I actually had a
00:07:35
Speaker
teacher in college say, why don't you consider science? And I said, that sounds like the most boring job in the whole world. No way. No. Here I am. What subjects did you like at school? Language. Yeah.
00:07:54
Speaker
English, language, I loved. To me, language, grammar, all of those things made perfect sense. Science to me was facts. It wasn't
00:08:13
Speaker
At the time, when I was young, I didn't understand that it was questions and answers. I thought it was just facts, details. And so it wasn't until I got older and saw experiments that science intrigued me.
00:08:39
Speaker
So talk to me then about your going to college and things. What did you want to do at college? I wanted to become a clinician. I wanted to go to medical school. I wanted to become a clinician. I took all the science courses.
00:09:00
Speaker
The two things I did in college, one was science, the other was, well, three things. One was science, one was, I did technical work in theater, and then I did politics, campus politics. And those are the three things that have kept me sane my whole life, politics, science, and kind of,
00:09:28
Speaker
Art. OK. So you are. So I got it. I got a degree in science. Thought I wanted to go to medical school. Got offered a job right out of college. That with ironically with Ross Perot and his data processing company.
00:09:56
Speaker
And I didn't know anything about data processing, but I said, I think I'm going to take it. One, it'll get me out of Mississippi. Two, it'll give me a chance to see if I love science or not, because if I'm doing something else for a couple of years, I'll either want to go back and do science or I won't. So it worked. So it worked. You loved it. OK, so you go and do a PhD at UT Southwestern. Southwestern, yes.
00:10:27
Speaker
post-doc at Albert Einstein College of Medicine. We have Leslie Leinwand, who is one of my mentors and role models, and I can't let you go past that without mentioning the impact she had in my life. Yeah, tell me more about that.
00:10:46
Speaker
Leslie, Dr. Line 1, Leslie is an amazing scientist, first of all. She's a molecular biologist. She taught me
00:10:59
Speaker
about an area in an area about which I knew nothing. But more than that, she was a role model as a woman running her own lab, being respected, having the.
00:11:20
Speaker
respect and admiration of other members at the institution. She just really was someone I could emulate and she helped me realize I could do science. So after this, this is something that's inspired you then going to start your own group then.
Advancements in Cardiovascular Gene Therapy
00:11:42
Speaker
Yes. Then I got recruited to Duke by Bill Krause, who's a cardiologist. Dr. Krause, Bill, is also an amazing human being, as good a human being as he is a clinician and scientist, which is awesome.
00:12:10
Speaker
When I got recruited to Duke, it was because we had been doing some gene therapy work in Leslie's lab and some cardiovascular gene therapy. I went to Duke. Part of the goal was to bring that technology there. And it was also for me to learn and be in Bill's lab. And initially, I was not
00:12:38
Speaker
faculty. I was kind of that instructor level thing. And Bill, to his credit,
00:12:48
Speaker
negotiated, when he got offered a big promotion at Duke, negotiated a faculty position for me as part of his promotion. Without him, I wouldn't have the career I have now. He does sound like a good person. He was. He is a fantastic human being. I've seen him change not only individuals' lives, but do work that has enabled
00:13:18
Speaker
him and his colleagues to have an impact in the community by working with the community, not against the community. It's really been very educational for me.
00:13:32
Speaker
Sounds like you've had some really instrumental people then in your career who have had a huge impact in the direction you have taken. That's accurate, I have. And what's also interesting at the same time is that I've watched them and learned from them
00:13:57
Speaker
But I would say that in terms of understanding how to navigate the system, I probably did not take advantage of them to the degree that I could have. I didn't really ever say mentor me, teach me how to navigate. And that's one of the things that if I
00:14:19
Speaker
If I were doing my career again, I'd do a little differently because I've never had a strong advocate mentor who was helping me understand the systems, academic systems, clinical systems, because I've always been in clinical departments.
00:14:43
Speaker
And so I think I've done well in my career, but I think I've done well in my career because I've been surrounded by a great team and we've been able to do some really cool things. And I have some, I've been lucky and privileged enough to have some, I love synthesizing ideas. That being said, the mechanics of academics, whole different conversation.
00:15:15
Speaker
So I want to come on to the next chapter then, Doris, which is when you moved to the University of Minnesota. You're the director of the Center for Cardiovascular Repair.
00:15:26
Speaker
Tell me about this move and what were you doing specifically? So before that move, I had been doing cell therapy in the heart. My group at Duke was the first group to show you could transplant cells into the heart and get functional repair pre-clinically. So we were doing cell therapy. I got recruited to the University of Minnesota and I took that position because
00:15:54
Speaker
One, they had a stem cell institute, which was run by Catherine Murphy at the time and was phenomenal. And two, they had one of the only stem cell institutes in the country at a time when we were fighting to be able to do stem cell research. Okay, so that was number one. And number two, I wanted to convince myself that
00:16:19
Speaker
The cell therapy work we had done and the papers we had published weren't just because I was at Duke, that I could do it beyond Duke. So I moved to Duke and then started realizing that cell therapy was not the panacea I thought it was. And that I had this, I remember this moment where I went
00:16:49
Speaker
Oh, cells respond to their environment.
00:16:54
Speaker
Stem cells, what do they do? They respond to their environment and they become like cells in their environment. But we're putting stem cells in a scarred heart, a damaged region of heart with no food, no clothing, no shelter, and asking them to grow up and become healthy heart cells. There's probably something wrong with this. And so I started calling it the real estate approach to cell therapy. Location, location, location.
00:17:23
Speaker
And that made me start thinking about and to give credit where credit's due. Ray Chu had published a paper, and Ray was from Canada, had published a paper showing that some of the stem cells that he had put into heart at the same time are fairly contemporaneously.
00:17:45
Speaker
had differentiated into osteoblasts and more like chondrocytes and osteoblasts, so bone and cartilage cells. And we were like, okay, that's not what you want in heart, right?
00:18:02
Speaker
So it made me and my team and I start thinking about the fact that maybe it wasn't just the cells that we needed to be thinking about. And wouldn't it be cool if we could get rid of the unhealthy environment and recreate a healthy environment? And that led to
00:18:27
Speaker
We were doing experiments where we were trying to get cardiocytes. And the way you get cardiocytes, and I had learned this at Duke from Gus Grant, is you would take a heart and you would hang it in this chamber, we called the Langendorf Chamber, and you would put enzyme through it. And when you put the enzyme through it, through the aorta, because you could
00:18:52
Speaker
You could send a solution through the aorta. You would break down all the collagen, what we called it collagen, in the heart, and you would loosen all the cells, okay? That was a typical way to get heart cells. And we said, what if we did the opposite? And instead of trying to break down all the collagen, we tried to break down all the cells.
00:19:22
Speaker
And that was being done already in a dish to create heart valves. You would take a heart valve and you'd put it in a soap solution and you'd kill all the cells and wash out all the cells and you'd end up with this thin valve that was a cellular. We decided to try it with the heart and it worked. And once it worked, it changed everything. It was like, oh,
00:19:54
Speaker
So then we started working on trying to build a heart, trying to retake everything out, get a scaffold, because what was missing was that environment, that healthy environment, and
00:20:12
Speaker
And then it was also what else was missing in terms of being able to build anything. You could grow heart cells in a dish. That wasn't a heart. You needed an environment in which you could put those heart cells to function like a heart, and you had to be able to feed them. And what's still missing today, 20 years later almost, is the ability to grow blood vessels well for an organ, right?
00:20:43
Speaker
We had the blood vessels there. So all of a sudden, it was like eureka. We have this perfect tool to let us now try to rebuild the heart.
00:20:56
Speaker
So the first thing we did was take other hearts and isolate those cells and then put, but we would take neonatal hearts because adult hearts, different issue, but the physiology doesn't work. So you'd take neonatal hearts, put those neonatal hearts back in that scaffold, and a year later we had proved we could repopulate that scaffold at least to some degree and get something
00:21:26
Speaker
that was beating and I was like, wow. So I've got to ask you about this moment then.
Creating a Beating Bioartificial Heart
00:21:33
Speaker
So we're now talking about this landmark paper, which you published in Nature Medicine in 2008. Right. Using Nature's platform to engineer bioartificial hearts. Tell me about the first time the heart beat. So that's one of those moments. I wasn't...
00:21:57
Speaker
standing in the lab when that happened, right? Because you're a PI, you're not always standing in the lab. You're doing all the administrative things that go along with running a lab. So I was not standing in the lab and I got...
00:22:13
Speaker
And back then, it was an email, not a text, right? I got an email from someone in a lab with an attachment. And I was like, OK, I need to look at this. So I opened the attachment and. And I looked at the it was a video and I looked at the video when I was like. Is this what I think it is, you know, and.
00:22:43
Speaker
Let's just say probably the words I said were probably not suitable for prime time, but it was like, oh my gosh. It was like, wait. And I sort of got on the phone, I called the lab and I said, is this what I think it is? And I got a yes. And I was like, oh my God. Oh my God. Here we are. And it was one of those wow moments in life where
00:23:09
Speaker
I've only had a couple of those wow moments in science, and that was one of them. And I still have that videos. You know, it it it changed everything. And. So then I was like, I have to see this when in a lab and and, you know, really trying to trying to wrap your mind around what you're seeing.
00:23:39
Speaker
sitting there. Even for me, who knew what we were doing, had said yes, had worked through the process, it still was this moment of incredulity of—I can't believe that's actually happening.
00:24:01
Speaker
Incredible. Like, what is going through your head? Are you kind of... I don't know, are you sort of processing it? Like, what do we do next? Like, this is actually work. Well, it was like...
00:24:12
Speaker
Oh, my God, this is possible. You know, this is possible. And then then you start wrapping, you know, of course, if you're a scientist, you start wrapping your mind around all the OK, well, what does that mean? How many cells do we need? How do we get them there? What did we do? Can we do it again? Yeah. And and what was so
00:24:36
Speaker
cool and remarkable about this whole process of being able to create these scaffolds and then create these organs is that it became very apparent very quickly that it would work for any organ, anything that got a blood supply, any organ, any tissue, and that
00:25:01
Speaker
The heart was the pinnacle, was the hardest, and that some of the others were a lot more straightforward. That being said, we went for the heart in part because it was probably because it was harder, but also because
00:25:22
Speaker
There's a huge unmet need. And if I'm being completely honest, because it beats and you can see it and you can go. Well, number one, you can go, yes, no. And number two, you can go, oh, my God, that's it's humbling every time you see it.
00:25:45
Speaker
Let's get on to this unmet need then. Tell me about cardiovascular disease because we don't talk about this. Heart disease is the number one killer of men, women, and children on the planet. 32% of all people, all deaths are due to heart disease. Five times more than cancer, more than any other disease on the planet.
00:26:14
Speaker
That means, and in the U.S., you're not from the U.S., I am. In the U.S., it's estimated that of people over the age of 18, 48 percent have heart disease. 48 percent. That means if both of us were from the U.S., one of us would have heart disease.
00:26:36
Speaker
And it also is not something that we talk about. Sure, people have heart attacks. Sure, people have heart failure. But we think that's somebody old. We think, oh yeah, my grandfather, my dad, when he was 60, had a heart attack, whatever. Men, women, children. And so the ultimate cure
00:27:03
Speaker
The only definitive cure for heart failure is a heart transplant. On average, in the US, there are about 2,700 to 3,000 people waiting for a heart every day. We transplant about 10 hearts a day.
00:27:25
Speaker
That's a huge number, and that's in the US. Worldwide, the number is obviously much larger and much fewer in terms of transplant. I've heard you say if you want to increase your chances of getting a heart, there's something you should do. You should move to a state without a motorcycle helmet law.
00:27:50
Speaker
That's crazy. It's crazy. It's true. I mean, there aren't enough donors. For hearts, you have to transplant the heart within four hours, approximately four hours of death. There's some work being done to extend that period, but it's not an unlimited period.
00:28:13
Speaker
So you have to be within a certain range. If you have heart failure and you need a heart, you have to be near a hospital when the heart becomes available. You have to be available. A lot of times you end up wearing a pager and living near the hospital so that when that goes off and your heart's available, you have to be ready to go. It's not
00:28:38
Speaker
And if you're lucky enough to get a heart today, every day for the rest of your life, you take toxic drugs to keep from rejecting that heart, because the heart doesn't match your body. So if I got someone else's heart, every day I would take multiple pills that can cause high blood pressure, diabetes,
00:29:06
Speaker
Kidney disease, they leave you immunosuppressed, and we all understand immunosuppressed at a new level since the pandemic. They can put you at risk for cancer, and many people get cancer from those drugs, and they're expensive. So you're trading one disease for another by getting this heart transplant and any organ transplant.
00:29:36
Speaker
It's also true that organs are not, unfortunately, transplants do not occur equitably, I would say, in the U.S. If you look at the National Research Council publication from last year, I believe it was,
00:29:58
Speaker
Even though African Americans have a higher incidence of heart failure, they receive fewer transplants than non-African Americans. If you're Caucasian, the average weight for a heart is about 315 days. If you're a person of color, it's at least six months longer, maybe more.
00:30:22
Speaker
And you don't get referred for a heart transplant if your socioeconomic status is such that you can't pay for the drugs or you don't have the insurance that will pay for the drugs. So that rules out a lot of people. So it's not equitable. It's got to I mean, and yet it's killing everybody. So what if we could build a heart that matched your body?
00:30:50
Speaker
We could make them available, we could make them accessible, and you wouldn't have to have the toxicity that goes along with that, and they could truly be a cure rather than a stopgap measure to keep you alive. They could keep you living rather than alive.
00:31:14
Speaker
So I think you've carved out this unmet need so well here, Doris, and this is now your mission that you're going to help with this problem.
00:31:27
Speaker
You touched on it there a bit, but I want to ask you more about the differences between men and women hearts. So you are looking to build these hearts, but I want to ask you about some of these considerations. How do you make, well, is there a difference between a male and a female heart?
00:31:53
Speaker
Well, so first of all, one of the things that we've discovered was when we wash all the cells out, what's left is being called the ghost heart kind of colloquially. That ghost heart is a protein structure called the extracellular matrix. OK. And it really is like the two by fours for a house. It's a framework on which the cells sit.
00:32:21
Speaker
and organized and it allows them to contract together. What we found is that extracellular matrix in male and female animals, at least, is mechanically different. In young females, it's much stiffer.
00:32:45
Speaker
than in males. Males catch up with females later in life, but the stiffness is very different in heart, in kidney, in a lot of organs. And I believe that that is due to the fact that women who get pregnant, their blood volume increases.
00:33:12
Speaker
in women who get pregnant, their blood volume increases and they have to be able to pump more blood, okay? And when they give birth and that blood volume decreases, their heart has to be able to revert and revert quickly. And I actually believe that in the women
00:33:33
Speaker
who don't revert quickly, those may be the women who get peripartum cardiomyopathy because they don't have that capacity. At any rate, the underlying framework is different. It's also true that your heart size has to match your body.
00:33:55
Speaker
So if you're smaller, you need a smaller heart. If you're larger, you need a larger heart. And oftentimes with the donor, you don't get that choice. The donor is a given size, which decreases your chance of getting a heart. We can pick a scaffold off the shelf, choose the size, choose the
00:34:22
Speaker
sex of the donor. So we use pig hearts as our scaffold. By working with specific vendors, we can get pig hearts of a given sex and a given size and a given age and use those to build small hearts
00:34:47
Speaker
potentially pediatric hearts that'll grow. Hearts for smaller people, whether they're women or small men or teenagers or whatever. So there are differences between men and women. There are differences in the makeup as well as the size. And we've had to think about all of that in creating these hearts.
00:35:15
Speaker
So tell me about the process then. So you get the heart, you de-cellularize it, you get this ghost heart. Right. And I've heard you describe it as using baby shampoo. Right. And the only thing I could think when you said about baby shampoo was that would be great when they do eyes because it won't sting the eyes. That's hilarious. I love it. You understand my world.
00:35:40
Speaker
Tell me about the crisis. Basically, our process is to use the blood vessels of the heart to deliver agents that will first burst the cells and then wash all the cell debris out of the heart.
00:36:00
Speaker
We now use a process that is a high salt solution and then a low salt solution followed by a very low amount of detergent like baby shampoo to wash the debris out. So the high salt and low salt burst the cells and then wash them out to some degree and the detergent finishes that process.
00:36:26
Speaker
You get rid of all the the protein, the fats, the lipids. You get rid of everything that is cellular and you leave that extracellular matrix protein scaffold. So you have blood. You have all these holes where the cells used to be and all the blood vessel branching and trees without cells. So all the canals, all the conduits, if you will, without cells.
00:36:56
Speaker
Then you have that scaffold. That scaffold can go on the shelf and be stored for a period of time as long as it is stored appropriately in the cold with some degree of moisture, it can be maintained.
00:37:17
Speaker
So our goal, if you want to manufacture a heart, if you want to build a heart in a lab, it's one thing. If you want to manufacture a heart, it's a whole different thing. And what you have to think about is you get that heart in.
00:37:34
Speaker
You need to make that heart prepare that heart that you're going to use as a scaffold and put it in a sterile environment into which it in which it remains until you have a finished heart. Because you don't want to transfer and increase the risk of infection. OK, you can't kiss it.
00:38:02
Speaker
Right. So we we take this heart, we put it in a cradle, what we call a cradle. We remove all the cells, decellularize it. It goes on the shelf. Meanwhile, we're growing the cells for that heart and we have to grow two different kinds of cells. We have to grow blood vessel cells and then we have to grow everything else.
00:38:27
Speaker
And what we've learned is that in our hands, creating the blood vessels first means that
00:38:39
Speaker
When we put the heart cells in, they have the right cues from the blood vessels. There's an interaction there that I don't fully understand that enables the heart cells to get fed and mature appropriately. So first we realign all the blood vessels in that ghost heart.
00:39:03
Speaker
and let those cells mature. So we're feeding that heart constantly under those conditions. We have markers that tell us when those are mature. And once that happens, we've kind of had to reverse engineer timing of growing the heart cells to know that those heart cells need to be ready.
00:39:30
Speaker
to go into that heart at that point. We inject them in, and we're working with a company called Advanced Solutions to do that robotically. They've partnered with us, and so we inject the cells robotically into that heart. We've done it by hand for years, but doing it by hand means, again, you run the risk of contamination.
00:39:56
Speaker
So figuring out a way to do it robotically, you get the cells in, and then because we're using human IPS cells, they're very immature. Very, very immature. So we've had to then begin to electrically and mechanically
00:40:16
Speaker
create the conditions that let those heart cells mature. And every heart is a little bit different. So we hook them up to the equivalent of a pacemaker, but we're pacing at multiple different sites in the heart because initially the cells aren't connected.
00:40:37
Speaker
We've put in all these different islands of cells and they're quivering, they're contracting, but it's each cell contracting individually. And then over time as they spread out, mature, divide a couple times because they're IPS cells and they can, they're IPS-derived cardiomyocytes and other cardiac mesoderm, okay?
00:41:04
Speaker
That means they can give rise to all the cells we need. We put them in, we put them in the atrium, we put them in the ventricle. We start that electrical pacing and we start giving the heart a blood pressure to work against so that we can feed the heart appropriately through the coronary arteries. We start giving it a intraventricular and intraatrial pressures, mechanical load,
00:41:34
Speaker
so that those cells know their muscle. They're basically having to work harder every day as a muscle, and they start maturing over time as we do that. And about a month out, instead of having all these little islands of cells that are breathing differently, you get enough there that they synchronize.
00:41:59
Speaker
And then you start seeing the actual contraction and a wave of electricity through that heart. And that's when you're like, we're going the right, we're going there this time. It sounds pretty challenging, these things you're doing, Doris.
00:42:20
Speaker
But talk to me about how, so matching this heart to a person, so you talked about the IPSCs, but how are the patients? So the idea is if you need a heart, and when someone has a heart attack, for the most part, some percentage of people don't survive their heart attacks, but of the people who survive their heart attack,
00:42:49
Speaker
90% go on to develop heart failure over time. And after you develop heart failure, the mortality is still around 50% at five years. The only solution there is either a mechanical device, an LVAD, a total artificial heart, or a new heart.
00:43:19
Speaker
Our goal is to provide those new hearts, but you have a heart attack, you know you're gonna develop heart failure, or let's say your father had a heart attack and your brother had a heart attack and your mother had a heart attack, or let's say you're a child born with congenital heart disease. You know at some point in your life you're gonna need a heart.
00:43:42
Speaker
So you get a tube of blood drawn or a few tubes of blood drawn and you get IPS cells created from your blood and those cells are banked. The idea is to have those cells made and banked as soon as you know you're going to need a heart because that process takes time. Making those takes months.
00:44:10
Speaker
And then growing, we need for every gram of your heart, your heart's about the size of your fist.
00:44:18
Speaker
So in an average person, and it's anywhere from 125 gram adult, 125 to 400 grams, okay? For every gram of heart, you need 1.1 billion cells to build a heart. That means I need 100 billion, 125 billion at the least.
00:44:43
Speaker
and 500 billion at the most. And that means, and I can't use every one of your cells to build your heart, right? I need some over here. So we have to create those cells for you.
00:44:58
Speaker
First, getting the iPS cells made takes time. Expanding those cells, the only thing we can't change is time, right? Biology cells only divide so fast. You don't want them to divide any faster or you've just created a cancer cell probably, right? So we need the time to grow those cells and that can take
00:45:26
Speaker
a few months, okay? Then we need to grow your heart. And that probably takes another four months, three to four months, going through that whole process. So really, this can be a six month, eight month, 10, 12 month process. However,
00:45:50
Speaker
We can start that way before you need a heart, which, you know, today you only get put on the transplant list when you're really sick and you have no other alternative. We can say, OK, you had a heart attack or, hmm, you know, you've got.
00:46:13
Speaker
You've got heart disease. Your dad died of it. Your brother died of it. Your mom's got it. I hate to tell you, but let's talk about the clock here. You should probably start thinking about this. Or you've had a heart attack. Let's say you had a heart attack. We could start talking about building your heart then, which means we're not waiting three years, four years for you to develop heart failure and then start talking about it.
00:46:42
Speaker
at that year to date. So we haven't mentioned OrganiMet
Establishing Organimet Bio
00:46:48
Speaker
yet. This is the company that you... OrganiMet Bio is the company I've started to manufacture these hearts. During the pandemic, I left academia and
00:47:08
Speaker
decided if not now when. And we started this company to manufacture these hearts. We're doing the work that we're doing in Manchester, New Hampshire right now at an organization called Army BioFab that was put together by Dean Kamen in Manchester. And we
00:47:34
Speaker
As you can imagine, this is an incredibly expensive endeavor. How much does it cost? Right now, because when you try to grow those billions of cells, the biggest cost right now is growing those billions of cells. Why? Because we have to grow hundreds of billions
00:48:00
Speaker
and all the reagents we need were made to grow hundreds of millions, not hundreds of billions. So we're having to pay for reagents at a cost that hasn't been at scale yet, right? So we anticipate ultimately that the cost of building these hearts, the first
00:48:27
Speaker
100 hearts, it's going to take us $300 to $500 million to get to clinic, right? We know that. So the first 100 hearts are going to be really expensive.
00:48:44
Speaker
After that, the costs are going to go down because people are going to see that it's worth growing those reagents at scale. It's worth doing all of this, the first life we save.
00:49:00
Speaker
will change everything. Unfortunately, what we need are people who are willing to partner with us and take that risk now. And that's a hard sell in today's biotech environment. That being said, it will change the world of transplant medicine forever.
00:49:19
Speaker
I have no doubt, Doris. So how long do you think it could be? In your mind, how long would you like to be before you're in the clinic? If I had all the resources in the world, if I had all the money I needed, six years, five to six years. The longer it takes to raise the right amount of money, the longer it will take until we get there. So it's going to take
00:49:46
Speaker
$300 to $500 million to get this to first in humans. And people say, can't you do it cheaper? And I've said, yeah, yeah, I can do it cheaper. Do you really want a cheaper car? Put your mom. You tell me if you do, let's talk. But I don't want one of my mom.
00:50:13
Speaker
Yeah, do you want the heart from wish or do you want the one that has been prepared as good as a heart can possibly be? Right. What motivates you, Doris? What motivates me? You know, some days I'm not as motivated as I could be because it's discouraging trying to raise money to do this when people
00:50:39
Speaker
Everyone's very risk averse right now until someone in their family needs it. And then it's a little too late to be risk averse, to not be risk averse about this because we can't just turn it around. So there are days when I get demotivated. But what keeps me going is probably there's several things. One is
00:51:07
Speaker
I think about the people who've called me and said, can you help me get a heart for my daughter? You've probably heard me tell the story about the woman who came to see me in my lab and said, my daughter was born with congenital heart disease and what got me through, got me through every night in the neonatal intensive care unit was you.
00:51:36
Speaker
or the father who had a hereditary heart failure and knew he had passed it along to his kids and came to me and said, you're not building organs, you're building hope.
00:51:50
Speaker
And that's what keeps me going. The people whose lives are going to be impacted by this, that and the fact that I have the support of my family, I have the support of friends, I have the support of the team who has stuck with me and stuck with this over the years. And and then people like you who want to hear about it and are as
00:52:20
Speaker
who are as awestruck by it as I am and get it that this is this is really cool, number one, but it's also really important. And I just hope. That there are people out there who. Get it that they can help change the world forever by helping us do this.
00:52:48
Speaker
And that's what motivates me, wanting to change the world, wanting to make a difference in the world. And building heart has become, you know, I get pushed back all the time. It costs so much, why don't you just quit?
00:53:09
Speaker
You know, people are it's hard to raise the money. Isn't it time to quit? Isn't it time to give up? And, you know, I've had to sit in my room in a room by myself and ask myself those questions. Is it time to quit? And every time I think maybe because we're not getting all the support we need, I think.
00:53:35
Speaker
a commitment to people whose lives are at risk. I can't quit. And I'm having to learn to build my own heart in this process as a result. You know, as a woman in science,
00:54:01
Speaker
I've been called every bad name a woman can be called, right? Because I'm focused and I'm driven and I'm, by Jove, get out of the way if you're not going to help, right? We're building a heart. We're not. We're not.
00:54:20
Speaker
Growing cells in a dish, we're building a heart, and that takes 24-7, 365 sometimes. Those hearts have to eat every day. And I've gotten a lot of pushback in my career for being too aggressive about that or too pushy about that. And what makes me smile is as I learn more about
00:54:49
Speaker
people and about myself. You know, I have a slide now that says, how do you know you're doing it right? And the next slide is they call you the B word. And then the next slide is a road sign of a juncture of two streets, one of which is better and the other one is best. And I say my new B word is best.
00:55:19
Speaker
And it's, unfortunately, it's true. And it's actually also really challenging. And I would, you know, let's do this podcast again sometime, turn the microphone around, and let me ask you some questions about, you know,
00:55:46
Speaker
People want work-life balance, and I totally support work-life balance. I'm about building heart. And I'm trying to figure out how you balance that with building a heart.
00:56:02
Speaker
when that heart has to eat every Saturday and every Sunday, and it has to eat 24-7. And if it gets hungry at 6 p.m., you have to feed it. And we can't always predict that. So how do you balance that with people who now want to work eight to five or nine to five?
00:56:29
Speaker
And don't want to work on the weekends. I've tried to hire people Wednesday through Sunday or Tuesday through Saturday. That used to be a lot easier than it is now. So I'd love the take of someone from your generation telling me, how do you do that? How do you balance that? Because people's lives are at risk and I don't know the answer.
00:56:56
Speaker
I would love to do that, Doris. I think, you know, it's a really important point and there's something I could certainly speak to, you know, having a young daughter now and trying to balance everything. You have to send me that slide as well, by the way. I will. I think we all need that slide in our lives. What do you do or what else are you doing? What else do I do in life? Doris, yeah.
00:57:21
Speaker
Well, I told you I like language. I love to read. I love to write. I've I've decided I'm going to write a book. OK. I'm writing two books. One is the story of building this heart, of course, and and. And the team that's been through this process over the years
00:57:49
Speaker
And in addition, it's going to be my perspective on building this heart. No one else's but mine. But it's also going to be stories about people building heart because I you heard me say I grew up in Mississippi. And one of the things I remember my mom saying to me is that
00:58:16
Speaker
You just got to do the right thing. And and she pointed out over and over when ordinary people were changing the world and doing extraordinary things. So I want to
00:58:31
Speaker
include stories about people who were either role models for me. I live in Montgomery, Alabama now. Rosa Parks, obviously. Dr. King, obviously. But there's so many everyday people who are building more heart on this planet just by virtue of small things they do or large things they do. So interspersing those stories, that's one book.
00:59:01
Speaker
The other book I don't talk about, and it's going to be a lot more personal, and it's hard for me to talk about, but I want to talk about it because I'm going to be extraordinarily vulnerable here. I haven't had this conversation elsewhere publicly.
00:59:29
Speaker
When I was working on building the heart at the University of Minnesota, and all of this PR hit, and we were trying to figure out how to deal with all the PR, the University of Minnesota helped me hire an executive coach.
00:59:46
Speaker
And the executive coach came in and we did work together and we talked about, you know, how do you say certain things? And I needed guidance. And at one point she said to me, have you ever considered that you might have Asperger's?
01:00:05
Speaker
And I said, no, I didn't really know what that was. And I was like, no. And and yet I knew my twin brother had some autism. And I had to start thinking about that.
01:00:24
Speaker
Well, it made me angry, it made me sad, it made me depressed, because I didn't want to have a label attached to my name, okay? So I started learning more, but I avoided that label for a long time.
01:00:47
Speaker
And I don't I still don't fully embrace labels, right? That being said, I said to my family, OK. This executive coach said this, what do you think? Dead silence in the room. I'm like, oh, yeah.
01:01:09
Speaker
You know, I guess everyone else in the world thinks that I don't, right? Well, as I look back at my career, it explains a lot. It explains a lot of why I used to always say to everyone, I want to be upfront with you. I don't do subtle. If you're going to try to if we're talking about something,
01:01:36
Speaker
I'm not going to necessarily read your subtle cues about it. You need to be really upfront with me. And I never knew that those were related. For example, fast forward the book. The book is about
01:01:57
Speaker
how to be in the world with someone like me who sees the world a little bit differently than you might, but it's written with humor.
01:02:09
Speaker
And it could be a book written by an introvert, because I am an introvert, but for example, one chapter that's written about having people over for dinner is, who are these people and why are they in my space? And it's really about
01:02:33
Speaker
What's going through my head when I hear, OK, let's have a bunch of people over for dinner versus which is, oh, my God, they're going to be a whole bunch of people and I'm going to have to figure out what to talk to them about. And it's not going to be about work. And what do I do? And oh, oh, my God. And how you can avoid that being stressful.
01:02:57
Speaker
how I can, how if you were the person having a dinner party with me, you could, and how together we could. So it's stories like that about life and about, hopefully it'll let people laugh at some things that otherwise are very stressful. Because I've had some very stressful moments in my career that when I look back, I go, oh,
Future Plans and Reflections
01:03:24
Speaker
I didn't understand, and I didn't know I didn't understand, and I didn't know how to help someone understand me, consequently, and maybe that's why things went a little wonky.
01:03:43
Speaker
You've made me very excited to read these books, Doris. You will have to send me a signed copy of these as you have really sold it to me. And, you know, sharing these kind of vulnerabilities and, you know, addressing them is so important. And I think for people to have access to read things like this, like I can't think of anything I'd want to read more than.
01:04:08
Speaker
Well, thank you. And I thank you. And, you know, it's taken a lot of support from a lot of people to be able to do that. And, you know, I think it is it is vulnerable and it is, you know, I think my
01:04:33
Speaker
I think the people who've had to live closest to me in my life, my family, really deserve a huge amount of credit for putting up with me most of my life and helping me see some of these things.
01:04:54
Speaker
You know, the things I look back on in my life that make me cringe are really things I can now understand a little bit differently. And we all have those things. And we find our best way forward if we're lucky. And I feel very lucky.
01:05:18
Speaker
We do. So Doris, I want to draw attention to the CNN health talk that I see you. That is an absolutely fantastic talk, by the way. Thank you. And I would direct any of the listeners to this talk. Type in Doris Taylor CNN and you'll find it. Stop the page.
01:05:37
Speaker
So after giving this fantastic talk and, you know, you already have kind of like the audience, you can hear kind of them crying because of how much hope you've given people. It's so fantastic. And it's just kind of closing out. And you say, I'm going to read the exact quote you said, if that's okay.
01:05:55
Speaker
You say, can I say one other thing? As an LGBT girl who grew up in Mississippi and got kicked out of college for being gay, kicked out of college for being gay, I never thought I'd be standing on a stage doing something like this. I can feel it in my throat now when I watch that.
01:06:17
Speaker
That was one of the most amazing things I've heard, and I feel so privileged today for you to have come and been on this podcast and shared your stories. Oh, thank you. And we are coming to the end of the episode, Doris, but I'd like to give you the opportunity to end this episode by saying one other thing that people need to hear. So one other thing. Just show up and be who you are in life and
01:06:47
Speaker
and be kind. You know, as an LGBTQ woman who grew up in Mississippi, I didn't always see a way forward. And I feel the same way as, you know, when this executive coach put a different label on me, it was like, I don't know what that looks like going forward.
01:07:19
Speaker
And on the other hand, if we don't stand up and say who we are and and let people see that we as who we are are doing things to move to just live our our best lives, then then nobody has hope. And, you know, I remember my boss.
01:07:47
Speaker
And when I lived in Texas, Texas was trying to pass a couple of laws that basically made it legal to fire you if you were homosexual. And I worked for an institution and got a lot of money from the state. And I remember my boss asking me about my life and saying,
01:08:17
Speaker
I'm doing my best to protect you. That was five years ago. So. The world isn't always nice. We don't always see the best in each other. We don't always show the best in ourselves. But. Can't we all build a little more heart?
01:08:47
Speaker
I think that's a great way to end, Doris. Thank you. Thank you. How can people get in touch with you if they want to reach out or follow you? I do have an Instagram account, Dr. Doris Taylor. I'm on LinkedIn and go to the Organimat bio website, my contact information email,
01:09:14
Speaker
and more is there. And I'm stay tuned for the books and a new website that will be coming out the next couple of months. Stay tuned. We'll leave links to all of those in the description. And let me say, you know, back of the napkin, if I were going to write one thing on the back of the napkin, it would be. Rules with a circle and a slash through it.
01:09:43
Speaker
Don't let anyone tell you that you have to follow the rules. Well, I'm about to hand you that napkin, darling. So thanks so much, darling. Thank you. See you.
01:09:56
Speaker
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01:10:19
Speaker
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01:10:28
Speaker
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01:10:51
Speaker
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