Speaker 1: Pushkin. Not long before he died, Steve Jobs made this big, sweeping,
Speaker 1: very Steve Jobs claim. He said, the biggest innovations of
Speaker 1: the twenty first century will be at the intersection of
Speaker 1: biology and technology. A new era is beginning. If Steve
Speaker 1: Jobs was right, if biotech over the next fifty years
Speaker 1: develops like computers did over the past fifty years, then
Speaker 1: we are about to see wave after wave of just
Speaker 1: extraordinary innovations in medicine. Very high on that list of
Speaker 1: innovations human body parts made in the lab. I'm Jacob
Speaker 1: Goldstein and this is What's Your Problem, the show where
Speaker 1: I talk to people who are trying to make technological progress.
Speaker 1: My guest today is Nina Tandon, co founder and CEO
Speaker 1: of EpiBone. Nina's problem is this, how do you grow
Speaker 1: human bone in a lab and do it at a
Speaker 1: price that makes economic sense. In our conversation we talked
Speaker 1: about how EpiBone is growing human bone that's being used
Speaker 1: even now to treat patients, but also we talked more
Speaker 1: broadly about the field that EpiBone is part of. It's
Speaker 1: a field called tissue engineering. Maybe just to start, like,
Speaker 1: what is tissue engineering? Well, tissue engineering is a branch
Speaker 1: of engineering that's devoted to the creation of surrogate body parts. Okay,
Speaker 1: the future, Yeah, one stop body shop for human prepare
Speaker 1: to what extent is tissue engineering the present? What tissue
Speaker 1: engineering is actually happening in mass production, normal medicine. Now,
Speaker 1: that is a good question, and I think you know
Speaker 1: an easy way to think about it is, you know,
Speaker 1: if you and I were to do a thought experiment
Speaker 1: of what would be an easy tissue to grow, what
Speaker 1: might you say? None? I would say it sounds crazy
Speaker 1: hard to grow tissue, all right, right, Well, maybe something flat, okay,
Speaker 1: maybe something with a single cell type. Maybe a tissue
Speaker 1: then regenerates on its own. Skin okay, boom rites a
Speaker 1: skin is a flat tissue, single cell type, and regenerates
Speaker 1: on its own. Okay, has a lot of stem cells
Speaker 1: in it, and so regenerates on its own. Like you
Speaker 1: get a cut, you get a scrape, and magically a
Speaker 1: week later or whatever, you have new skin there. Yeah.
Speaker 1: And so in the early two thousands, we saw two
Speaker 1: products in the late nineties early two thousands be released
Speaker 1: to the market, I believe, for burns and diabetic foot
Speaker 1: ulcers something like that. And so that's the first that's easy.
Speaker 1: So you have this moment twenty years ago, people are
Speaker 1: making skin graphs in the lab and there's sort of
Speaker 1: big dreams. So if we can do skin, maybe we
Speaker 1: can regrow everything in the lab. And so when do
Speaker 1: you get into the field, When do you walk into
Speaker 1: the story. I was an electrical engineer coming out of
Speaker 1: undergrad and I had worked as a software programmer for
Speaker 1: a telecom company. So this was not what I thought
Speaker 1: I was going to be doing with my life. But
Speaker 1: nine to eleven happened. I was living in the suburbs
Speaker 1: for the first time in my life, and I got
Speaker 1: a little bored and started taking classes at the local
Speaker 1: community college in anatomy and physiology. And I think because
Speaker 1: I was so lonely, because I was so kind of
Speaker 1: starved for that type of engagement, I really got into
Speaker 1: this class and I decided I was gonna, you know,
Speaker 1: I had to follow this. So I applied to the
Speaker 1: bioelectrical engineering track at MIT and got in for a
Speaker 1: PhD for a PhD program, And so it's at MT
Speaker 1: that you sort of discover this emerging field of tissue engineering. Yeah. Yeah,
Speaker 1: And when you discover it, like, what do you think, oh,
Speaker 1: my gosh, it's so cool this woman, Gordona, who was
Speaker 1: one of the professors, and I just connected with her
Speaker 1: as a person. To discover that one of the nicest
Speaker 1: people that I knew at MIT also happened to be
Speaker 1: experimenting with using electrical signals to grow hearts, and that
Speaker 1: I was like, wow, I need to know if maybe
Speaker 1: she might want to work with someone who's an electrical
Speaker 1: engineer on that, and she did, And that was really
Speaker 1: felt like destiny to me because I thought to myself,
Speaker 1: I mean, I'd already fallen in love with the heart
Speaker 1: at that point through my studies, so it really spoke
Speaker 1: to me. And the idea that we could copy those
Speaker 1: electrical signals to try and coax embryonic stem cells into
Speaker 1: becoming heart cells or you know, to essentially coax the
Speaker 1: tissue to form that to me was intoxicating. So how
Speaker 1: do you get from there? I mean, you fell in
Speaker 1: love with the heart, but you didn't end up starting
Speaker 1: EPI Heart, You started EPI bone, Right, how do you
Speaker 1: get from from there to starting your company? Cardiac tissue
Speaker 1: is on the end of the spectrum in terms of difficulty.
Speaker 1: There's a lot of intermediate hard end of growing tissues
Speaker 1: mechanically at most metabolically active tissue in the body, multiple
Speaker 1: cell types arranged in a very specific manner. So really
Speaker 1: the most difficult you could possibly imagine, and bone is
Speaker 1: in the middle. It's a complex shape, but we could
Speaker 1: solve that using digital fabrication, and we could use a
Speaker 1: single cell type to engineer a pretty high quality bone.
Speaker 1: So it was clear to me that if I wanted
Speaker 1: to be involved in translating that's the word we use
Speaker 1: in the field, translating science towards the clinic in my lifetime,
Speaker 1: I should probably you work on a tissue that's closer
Speaker 1: to the skin side of the spectrum than cardiac. Right,
Speaker 1: so you start epic bone, you decide to work on bone.
Speaker 1: That's like almost ten years ago now, and today you
Speaker 1: do have this engineered bone. You're doing a clinical trial
Speaker 1: and as I understand it, right, this is bone that
Speaker 1: is going into people's jaws, where typically a surgeon would
Speaker 1: cut a piece of a patient's own bone out of
Speaker 1: some other part of their body. But you're growing the
Speaker 1: bone in a lab basically from scratch. So tell me
Speaker 1: about the clinical trial that's going on right now. Okay,
Speaker 1: so patient I think I'm allowed to say this. Patient
Speaker 1: one suffered a traumatic injury due to a car accident,
Speaker 1: and so we provided bone to help reconstruct the jaw.
Speaker 1: Patient two had suffered from a degenerating jaw resulting in
Speaker 1: airway obstruction, so we provided bone to help elongate the
Speaker 1: jaw and relieve that airway obstruction. Patient three, he was
Speaker 1: born with facial asymmetry that would only be correctable by
Speaker 1: taking bones out of some other part of his body
Speaker 1: to reposition his jaw, and we were just able to
Speaker 1: grow bones for him using a small sample of his
Speaker 1: fat tissue. So you know, whether it's for cancer, trauma,
Speaker 1: or congenital defects, people need bone. It's bone is the
Speaker 1: most transplanted team in material after blood. And so he
Speaker 1: is three. The number of patients in the trial, that's
Speaker 1: the we've done six. Oh, he's done six, Okay, yeah,
Speaker 1: And what is the total number of patients you plan
Speaker 1: to enroll? That's the fully enrolled. So that was our
Speaker 1: phase one too. That was our phase one two, first
Speaker 1: in human, first in class. Basically safety and a little
Speaker 1: bit of efficacy. That's what phase one two, that's right, Yeah, yeah,
Speaker 1: in a little bit of efficacy, and hopefully we'll move
Speaker 1: forward with a phase three in the not too distant
Speaker 1: future where we'll be able to help a few more patients.
Speaker 1: And so how does the process work. So we take
Speaker 1: two things from the patient. One, we take an image
Speaker 1: a CT scan, which is like a three dimensional X ray,
Speaker 1: so we can extract three dimensional data out of that
Speaker 1: and design a perfect puzzle piece shaped biomaterial that will
Speaker 1: be the eventual shape of the bone. We also take
Speaker 1: a small sample of fat tissue from the patient so
Speaker 1: we can extract the stem cells out of it, so
Speaker 1: those cells can attach to the scaffold, proliferate, lay down
Speaker 1: new matrix, and essentially turn that biomaterial into living bone.
Speaker 1: It takes about three weeks for bone. So you take
Speaker 1: a CT scan to get the image of the shape
Speaker 1: of the bone you need, and then from that you
Speaker 1: make when you say a puzzle piece, you make basically
Speaker 1: something that is the shape of the bone you need
Speaker 1: made of stick or something. What is it made of?
Speaker 1: So we take a cowbone, strip all the cellular material
Speaker 1: out of it, so we're left with essentially protein and
Speaker 1: mineral and it's a very porous material. It looks like
Speaker 1: pumice stone and you can infuse cells onto that and
Speaker 1: the cells kind of recognize that matrix as being a
Speaker 1: place that gives them a cue towards differentiating them towards bone.
Speaker 1: It feels bony enough to these cells that they say, okay,
Speaker 1: let's let's make the rest of this bone. So right,
Speaker 1: so you have this puzzle piece made of cowbone essentially, right,
Speaker 1: that's in the right shape. So that's kind of one
Speaker 1: one track. And then on the other track, you're taking
Speaker 1: fat from the patient. You're getting the stem cells out
Speaker 1: of that fat, and stem cells are cells that can
Speaker 1: become any kind of cell. Right, So, yeah, we've got
Speaker 1: the cowbone puzzle piece, we've got the stem cells from
Speaker 1: the patient. What exactly how happens next? Well, this is
Speaker 1: our secret sauce. The bioreactor. So a bioreactor is just
Speaker 1: a fancy word for a cell culture system, like a
Speaker 1: place where you can culture cells in and so we
Speaker 1: get those cells to turn to grow up and turn
Speaker 1: into bone. So so just to be able to see it, like,
Speaker 1: is the bioreactor a metal box? What actually does it
Speaker 1: look like? You know, you imagine a little bone and
Speaker 1: then you imagine the reverse image of that bone. So
Speaker 1: a little gasket that like covers that bone perfectly, and
Speaker 1: that gasket has holes in it so I can perfuse
Speaker 1: liquid food through it as it grows. And that gaskets
Speaker 1: contained in kind of like another canister where we can
Speaker 1: have fluid that comes in and fluid that comes out.
Speaker 1: It's about the size of a coke can, and the
Speaker 1: fluid input and output are attached to a pump, so
Speaker 1: it's constantly pumping. And that whole contraption, which we've made
Speaker 1: quite efficient in terms of sizes about a shoe box
Speaker 1: in terms of size, and we can stack them up
Speaker 1: so that we can grow many at a time. Great,
Speaker 1: So you take the cowbone puzzle piece, how do you
Speaker 1: get the stem cells to like go on to the
Speaker 1: puzzle piece and grow. Yeah, we perfuse them very slowly
Speaker 1: and the cells attach. And that's part of why the
Speaker 1: biomaterial is so important, because you know, a piece of
Speaker 1: decellularized bone has a lot of these nanostructure attachment sites
Speaker 1: that cells recognize and glom onto, and so there's a
Speaker 1: period of time where the cells attach. Most cells in
Speaker 1: our body are attached to some sort of three dimensional
Speaker 1: matrix and then they start to proliferate. And lay down
Speaker 1: even more matrix. So they proliferate around sevenfold and they
Speaker 1: fill up that porous structure. So even though it was
Speaker 1: porous at the beginning, it looks like bone at the
Speaker 1: end of huh. So you take the puzzle piece, you
Speaker 1: put the puzzle piece into the reactor, and then you
Speaker 1: send the patient stem cells into the reactor and they
Speaker 1: attached to and grow over the puzzle piece in within
Speaker 1: as well, they're filling up the three dimensional YEA, yeah,
Speaker 1: it's not a pancake. It's not a pancake. It's it
Speaker 1: it's like a honeycomb or something. It's really important to
Speaker 1: get the cells in three D. You know, a lot
Speaker 1: of people can grow cells on a Petrie dish, but
Speaker 1: grow cells in three D is a that's a big challenge.
Speaker 1: But we've seen that the bones perform their mechanical duties
Speaker 1: on day one. You know, patients are able to eat, speak, drink,
Speaker 1: all the things that you'd want to do after the break.
Speaker 1: The problems Nina and her teams still have to solve
Speaker 1: to get lab grown bone approved and into widespread use. Also,
Speaker 1: how should we think about the pace of progress in
Speaker 1: tissue engineering and in biotech More broadly. Now back to
Speaker 1: the show. So I want to talk about sort of
Speaker 1: the future and what you're working on next in a minute.
Speaker 1: But before we do that, I mean, you've been in
Speaker 1: the field now for twenty years. Your company has been
Speaker 1: around for nine years, and so tell me about the
Speaker 1: progress of the field in the time you've been in it.
Speaker 1: Tell me about the progress of the field in the
Speaker 1: twenty years. What has what has happened faster than you
Speaker 1: might have expected, what has happened slower? And like where
Speaker 1: are we now? What is happening in tissue engineering right now?
Speaker 1: There was a technology developed for cartilage, cartilage in a
Speaker 1: couple of generations of cartilage, so that's been established as
Speaker 1: like another tissue that can be engineered. There's another company
Speaker 1: called hum Site which makes tissue engineered vasculator. They are
Speaker 1: very close to getting in approved for commercial use. They
Speaker 1: are hope within about a year or so. They're a
Speaker 1: publicly traded company. So so vasculature, Just to be clear,
Speaker 1: like blood vessels, they're making blood vessels. Blood vessels. That
Speaker 1: seems hard. It's hard. Yeah, it's hard. It seems hard.
Speaker 1: You gotta get the tube. It's a tube. I don't
Speaker 1: know why that seems harder to Me's a that. Yeah,
Speaker 1: hollow organs are a step above flat tissue for sure.
Speaker 1: And UM and there's their founder, Laura Nicholson. What she
Speaker 1: learned in growing vasculature was that cells needed flow, not
Speaker 1: just flow of liquid, but pulsatile flow. Be interesting, you're
Speaker 1: moving like pulsatile, like like the way the heart beats.
Speaker 1: And it's not like a river. It's like, yeah, exactly,
Speaker 1: it's not a river. And so that's that was her
Speaker 1: genius discovery. And they are you know, they've treated UM
Speaker 1: soldiers and civilians in the Ukraine who need who need
Speaker 1: blood vessels. UM. They are close to commercials. Has the
Speaker 1: progress of tissue engineering been slower than you would have
Speaker 1: thought twenty years ago? Yeah, I think my notion of
Speaker 1: time was very different following years ago. You know. Now
Speaker 1: I'm like, oh, twenty years okay, that's nothing. A human lifetime,
Speaker 1: that's nothing. You know, what can be done in a
Speaker 1: human lifetime? Not much? You know, that's like more my
Speaker 1: kind of gallows humor. Now, things move slowly, slash wisdom,
Speaker 1: slash wisdom. Yeah, sure, but like yeah, things it's a
Speaker 1: glacial I like to tell people this is like a
Speaker 1: slow motion marathon in a way like this past twenty
Speaker 1: years have you know, blinked and been gone in a heartbeat.
Speaker 1: But yeah, it takes a long time to do things.
Speaker 1: I think I've gotten better at being more honest or
Speaker 1: realistic in terms of estimating how long something's going to take,
Speaker 1: because you can't rush the science. And it's really, you know, interesting,
Speaker 1: you say, oh, it sounds so futuristic. I think a
Speaker 1: lot of people believe that this should happen, and there's
Speaker 1: very few people that have the skill set to make
Speaker 1: it happen. You know, because if you watch science fiction,
Speaker 1: and or if you watch I don't know, even Star
Speaker 1: Wars or the Marvel movies, there's always examples of people
Speaker 1: getting healed with technologies like tissue engineering, so people assume
Speaker 1: that that's going to happen. Like Luke Skywalker got a
Speaker 1: new hand, So why can't I get a new hand totally? Totally?
Speaker 1: Or in Waconda, you know, they just regenerated, or you know,
Speaker 1: there's all these technologies in pop culture. Even in Grey's
Speaker 1: Anatomy they had episodes of tissue engineering. And yet it's
Speaker 1: very hard and it takes a long time. And so
Speaker 1: I'm glad that I've been working on this particular tissue
Speaker 1: because you know, it's been ten years as a company
Speaker 1: and we've brought it to where it's never been before.
Speaker 1: And now the challenges a lot more with a lot
Speaker 1: of that technical de risking behind us. The challenges are
Speaker 1: more or less of will this work in a living
Speaker 1: system and more towards will this work in a clinical setting?
Speaker 1: Will this work in the economy? And I find that
Speaker 1: to be extremely exciting when you say will this work
Speaker 1: in the economy, that's a big interesting question that we
Speaker 1: really haven't talked about yet. So so how do you
Speaker 1: think about that? How how are you approaching that? You know,
Speaker 1: unit cost economics need to work. That's where the biomanufacturing
Speaker 1: comes in. Automation of cell culture is a big driver.
Speaker 1: It's a very artisanal process, you know, using our hand
Speaker 1: pipets and expensive, right, artisanal and hand this that that
Speaker 1: that is expensive, right. I don't want an artisical bone.
Speaker 1: I want to mass producing bone, right yeah, right. Creating
Speaker 1: the infrastructure that allows for automated biomanufacturing is a big
Speaker 1: piece of it. We're not the only ones that need
Speaker 1: to be working on that um But then also I
Speaker 1: think scientifically and clinically being very clever in terms of
Speaker 1: the end points you're measuring in your clinical trials so
Speaker 1: that you can make the economic case. For Look, if
Speaker 1: we're going to give you this piece of tissue, it's
Speaker 1: going to save you surgeries down the line. That is
Speaker 1: very interesting, And like, tell me specifically what that means
Speaker 1: in the case of the of the jawbone easy economic
Speaker 1: cost of avoided. What is the economic cost avoided for evybone? Well,
Speaker 1: if you had evybone, you don't have to do an
Speaker 1: extra hour or half hour of surgical time, you don't
Speaker 1: have to put the patient in the ICU for as
Speaker 1: much time for recovery. What those all are very easily
Speaker 1: calculatable costs. So so that economic case is as important
Speaker 1: to me as as the clinical case. So if things
Speaker 1: go well, when do you think you might actually be
Speaker 1: approved and out in the world twenty six, twenty seven? Okay, yeah,
Speaker 1: not crazy if you had at maut a future but
Speaker 1: a while yet. So for some people that's forever. For
Speaker 1: some people they're like, oh, that's pretty soon. I wonder
Speaker 1: if the sort of absurd rate of development of basically
Speaker 1: semiconductors right, basically if Moore's law, and the development of
Speaker 1: computer technology has messed up our sense of the rate
Speaker 1: of technological development. Like if we have come to expect
Speaker 1: so funny that you brought up law, Well, you were
Speaker 1: an electrical engineer, so you know than I do. Yes.
Speaker 1: So in biotech there's a joke called e Room's law,
Speaker 1: which is if you spell more backwards, what do you get?
Speaker 1: Because we're sort of the opposite of that, it gets
Speaker 1: twice as expensive and twice as slow every year. Yeah,
Speaker 1: and the FDA is backlogged and there's just been so
Speaker 1: few approvals over time, it's really gone down. So I
Speaker 1: think everyone understands that no one wants to hurt people
Speaker 1: from a regulatory standpoint, no one. They don't want to
Speaker 1: hurt people. Entrepreneurs and companies, we don't want to hurt people.
Speaker 1: But there's a risk benefit to you know, if you
Speaker 1: if you hold back innovation, sure fewer people will get hurt,
Speaker 1: but also a fewer people will will get these breakthrough treatments.
Speaker 1: There's regulation, and that's clearly important, but I feel like
Speaker 1: also the body is just super complicated. Like I feel like,
Speaker 1: even independent of regulatory bottlenecks, it's just very hard problems
Speaker 1: it's hard, but it does feel like, well, I'm climbing
Speaker 1: a mountain that's worth climbing, and you know we'll get there.
Speaker 1: We'll be back in a minute with the lightning round,
Speaker 1: including a very compelling argument that ourselves are intelligent. Okay,
Speaker 1: that's the end of the ads. Now it's done for
Speaker 1: the Lightning round. What's one tip for finding a mentor?
Speaker 1: M who's your professional crush finding? I'm run, sure, yeah,
Speaker 1: you're professional crush. That's that's how that's Identifying a mentor
Speaker 1: is like, who do you have a crush? How do
Speaker 1: you find a mentor? How do you find a mentor?
Speaker 1: Here's my answer. Good people lead you to good people.
Speaker 1: I like all of those answers. As a former McKinsey consultant,
Speaker 1: do you think McKinsey is overrated or underrated? I think
Speaker 1: I think neither appropriately rated. They're appropriately powerful. I mean,
Speaker 1: they do good work and they're full of very earnest people,
Speaker 1: and my goodness, do they know how to make a
Speaker 1: two by two matrix out of any problem? Um? Good?
Speaker 1: I like broken down to do a two by matrix? Um.
Speaker 1: What's been the most surprising thing about running a company?
Speaker 1: I think, how much your psychology gets amplified. You know,
Speaker 1: just think how much of the company is a mirror,
Speaker 1: and if I'm having a bad day, it amplifies to
Speaker 1: the team. It just makes me have to just really
Speaker 1: take my own mental health and really seriously. Downward dog
Speaker 1: or Warrior one, Oh, down dog? I think I love them? Well, yeah,
Speaker 1: Warrior one, I'd say Warrior two. Okay, good, I love yoga.
Speaker 1: I could talk about that for a long time. What
Speaker 1: do you understand about human body that most people don't
Speaker 1: That sells are intelligent all of our selves. Intelligence isn't
Speaker 1: only in the brain. Intelligence is everywhere in the body,
Speaker 1: at the cellular level. What do you mean by that, Well,
Speaker 1: we tend to think of intelligence as being in our brain,
Speaker 1: and that places like our heart are dumb. It's a
Speaker 1: dumb pump that listens to the brain. But the heart
Speaker 1: is thinking on its own. It's making a lot of
Speaker 1: decisions about how much blood to pump and send signals
Speaker 1: up to the brain, but also does plenty of thinking
Speaker 1: on its own. The eye isn't just a camera. The
Speaker 1: eye contains a lot of decision making processes about what
Speaker 1: we're seeing before even sending the image up to the brain.
Speaker 1: The optic nerve is the largest amount of data compression
Speaker 1: known in biology. So intelligence is distributed throughout the body.
Speaker 1: And I don't think a lot of people think that,
Speaker 1: but I know that, and I love that about the body.
Speaker 1: It makes me, It makes living in a body fun
Speaker 1: for me. Nina Tandon is the co founder and CEO
Speaker 1: of EPIBOE. Today's show was produced by Edith Russolo, edited
Speaker 1: by Sarah Knicks, and engineered by Amanda kay Wong. I'm
Speaker 1: Jacob Boldstein and just one last quick note. We're going
Speaker 1: to be off for the next couple of weeks and
Speaker 1: we'll be back with a new episode on Thursday, April twentieth,