FLORA LICHTMAN: Happy New Year. I’m Flora Lichtman, and you’re listening to Science Friday. OK, New Year’s resolutions, I get it. They’re a cliche. I know they rarely stick.
But I like them. I thinking of the new year as a fresh start. I like believing that we, I, have the capacity to change and to evolve.
New year, new me– yes, it sounds like an inspirational greeting card line, but you know what? It’s also true biologically. On a cellular level, we are remaking ourselves every moment of every day.
Just think. By 2027, you will have lost and replaced a mass of cells equal to your entire body weight. And if you really want to talk about starting anew, there are animals that can regrow their own head from a piece of their tail. That is growth mindset.
I find these ideas interesting and helpful this time of year when I’m thinking about how I want to grow, which is why I wanted to talk to Dr. Alejandro Sánchez Alvarado, president of the Stowers Institute for Medical Research, to hear about his pioneering research into regeneration and the science of becoming and rebecoming.
Alejandro, are you on board with my premise? Do you think about your work metaphorically?
ALEJANDRO SÁNCHEZ ALVARADO: It’s inescapable. I think that anybody that works on an area where you can see transformations unfold right before your eyes cannot avoid thinking about metaphors. In fact, most of developmental biology is populated by metaphors.
We describe many of these processes with metaphors. And we’re so aware of that metaphorical thinking that we constantly tell ourselves that the problem with metaphors is that they require constant vigilance because you don’t want the metaphor for to actually become the thing that you’re studying. So yes, we do think a lot about that.
FLORA LICHTMAN: Oh, that’s interesting, the metaphor can actually– you don’t want it to drive the cart to lead the horse or whatever.
ALEJANDRO SÁNCHEZ ALVARADO: Yeah, that is correct. Yes.
FLORA LICHTMAN: Let’s start with this worm that I alluded to in the introduction. We’re talking about a planarian. I think people would recognize them. They’re iconic looking.
They’re flatworms. They have these two little eyespots. They look to me almost cross-eyed. Tell me about their powers.
ALEJANDRO SÁNCHEZ ALVARADO: Yeah. These little organisms that look almost like manga characters, they have been known for almost 300 years. But it became readily apparent for scientists of the time that these animals appear to be impervious under the edge of a knife.
People been cutting them and slicing them in all types of imaginable ways, and they just laugh at it because almost every fragment that is removed from an animal goes on to regenerate a complete organism. Imagine if you were Van Gogh, and you remove your ear. And then out of that ear emerges a second Van Gogh. That’s pretty much what these animals do.
FLORA LICHTMAN: Is there any limit? Can you chop them down to a single cell and they regrow themselves?
ALEJANDRO SÁNCHEZ ALVARADO: Yeah, that is a fantastic question. So there is a limit. You can cut a fragment that contains anywhere between, say, 5,000 to 8,000 cells, and more often than not, a fragment of that size will go on to regenerate a complete animal.
FLORA LICHTMAN: Let’s go back in time. You decide you want to study regeneration. You’ll learn about planarians, and you set out to find one. Tell us about it.
ALEJANDRO SÁNCHEZ ALVARADO: We knew that the planarian that we wanted to work with, particularly the species we wanted to work with, could be found at a park in Barcelona, Spain, called Montjuic and is filled with fountains. Now, this was 1998, but what we wanted to do was to actually set traps in all of the fountains we could find to see if we could actually collect some of these animals.
FLORA LICHTMAN: Worm traps.
ALEJANDRO SÁNCHEZ ALVARADO: Yeah, worm traps. Exactly right. So we do that, and we set all the traps. We think we’re going to succeed.
The next day we went and tried to collect these animals, we didn’t know which fountain. And here’s when we found them. This is the great part.
The least likely fountain had the animals. And this fountain was populated with all kinds of trash. So you could say that the beginning of our work in planarians and therefore in regeneration began by studying pond scum because that’s literally what it looked like. But yeah, we were able to collect the animals and then brought them back to the US and began to generate the lines that we now use in our lab and many other laboratories use in the US and around the world.
FLORA LICHTMAN: Is it correct that most of the planarians used in regeneration labs came from one worm that you fished out of one dirty fountain in Barcelona?
ALEJANDRO SÁNCHEZ ALVARADO: That’s pretty accurate. We set out to establish a line, and what we did was to set individual worms into individual wells of a multi-well Petri dish. And the worm that we selected was in well number four, and that’s the line that we have used to expand into millions of organisms since 1998.
FLORA LICHTMAN: This really gives me major Ship of Theseus vibes.
ALEJANDRO SÁNCHEZ ALVARADO: Yes.
FLORA LICHTMAN: You know what I’m talking about?
ALEJANDRO SÁNCHEZ ALVARADO: Yes. Yes. Is it the same animal?
FLORA LICHTMAN: Yeah.
ALEJANDRO SÁNCHEZ ALVARADO: This is the same animal.
FLORA LICHTMAN: This is the ancient philosopher paradox where, if you replace every board of the ship, is it the same ship? But it really makes me wonder, what makes an individual an individual?
ALEJANDRO SÁNCHEZ ALVARADO: That’s a great question. Again, this is the kinds of things that, when we deal with regeneration and we deal with the restoration of tissues, we have to grapple with. So it’s not just biology.
It’s also the ability that these organisms have to question what you think you understand. This is the beautiful thing about working with these organisms. So is it the same individual?
You could say that, biologically speaking, cannot be the same individual because, since 1998, I would presume that every single cell has eventually turned over, meaning that new cells were made from pre-existing cells to replace the pre-existing cells. So just like the Ship of Theseus, the ship looks the same, but the individual components are actually new.
And so then you ask the following question. So is there a difference between astronomical time and biological time? Because, astronomically speaking, these animals, when we collected them, had been in captivity for almost 27 years, since 1998 or so.
But it’s not really the same animal. It’s been ingesting food that did not exist at the time, so these are new molecules going into the system. But somehow what persists is the form and function of the animal.
And so how do you codify that in a system that is constantly turning over? You mentioned it at the beginning of the program that we’re turning over enough cells equivalent to our body weight. So how old am I?
I had a cell that just was born as you and I are having this conversation. That cell is probably 30 seconds old. I’m 6′ years of age. So what is 61 years of age? The collective of cells. But individual cells are not.
So while we like to keep track of time astronomically because it’s convenient, I don’t think biology is keeping track of time that way. I think they’re doing something completely independent from the passage of time as we measure it.
FLORA LICHTMAN: That biological time is different from astrological time?
ALEJANDRO SÁNCHEZ ALVARADO: Exactly. And I think that, for some systems where turnover is a part of their lifestyle, there’s definitely an opportunity to dissociate one from the other.
And so this relates to a number of things. What determines how long a cell gets to live? What determines how long can you keep them around? And then the collection of all of those cells and their interactions with each other will also change through time. In the end, what you end up with is with a collective of individual and independent events that somehow come together be the thing that we call an individual.
So I guess what I’m trying to say is that beneath this stable outward appearance that we give to the world belies constant change. So how do you keep constancy under the effects of constant change? It’s a miracle, I think, that we’re not falling dead like flies every second.
We’re turning over so many cells, and our body just does it. The lining of our gut is the equivalent of the surface area of a tennis court that gets resurfaced every week. Just think about owning a tennis court that you have to resurface every week. It’s a huge amount of work. And if we’re lucky, we do it for 80 years and longer.
FLORA LICHTMAN: I’m going to be honest, I have chills.
ALEJANDRO SÁNCHEZ ALVARADO: Well, I get them too, whenever I think about these biological conundrums. And the reality also is that we don’t understand any of this. We know so much about, how an embryo arises from a single cell after an egg and spermatozoa come together. We’ve studied that to great, great levels of granularity.
But come birth and then go past the teenage years and go into midlife, I don’t think we really understand how all of these biological interactions, how all of these properties align with each other to allow us to live for as long as we do. And given that the life expectancy of our species has increased so much since the discovery of antibiotics, we’re now in territory that I don’t think our systems had not had prior experience with because most of us in our species, if we were 100 years ago, 200 years ago, we would not make it to 60.
I would be a wise old man, 200, 300 years ago, a miracle of not getting sick. People would just die like crazy. But now we have a population in the world that is aging, and we don’t understand why and how many of the ailments that afflict us today arise. And that’s because we haven’t really studied the adult condition.
And it is in adulthood that most of these organisms display their regenerative prowess, whether we’re talking about planarians or we’re talking about salamanders or we’re talking about fish is the adults are incredibly good at regenerating. And I think that’s a consequence of the properties that allow those systems to stay put together so they can carry out their functions beyond embryogenesis. And I just don’t think we have a clear understanding of how those processes operate.
FLORA LICHTMAN: Well, what do they have that we don’t?
ALEJANDRO SÁNCHEZ ALVARADO: Yeah, that’s the $1 billion question because, when we look at the composition of their genetic information, when we look at their genome, what we find is that– and this is true for almost every other multicellular organism on the planet– we share more with the rest of nature than we think.
Many of the genes that planarians and other organisms use to drive regeneration you and I have. Many of the processes that allow a unformed tissue to turn into a neuron or a muscle or even an eye during regeneration, you and I have.
So why is it that regeneration is so broadly but unevenly distributed across the animal kingdom? We really don’t know, Flora. We really don’t know.
FLORA LICHTMAN: Because it seems like it would be useful.
ALEJANDRO SÁNCHEZ ALVARADO: [LAUGHS] Yeah, that’s the understatement of the century, of the new year, I think. Yeah, that is the understatement of the new year. It would be extremely useful for us to understand where the differences lie because imagine if we had the understanding of how to generate neurons from pre-existing tissue. That would help us prevent things like Alzheimer’s, strokes in the brain.
Or imagine we could do the same thing for hearts, for cardiac tissue. Once those tissues are damaged, there is no way to repair them. And the reason why we think we can conceivably, in the future, be able to activate those processes is because we’re already doing a lot of regeneration with other tissues.
Our liver regenerates. Our skin regenerates. Our olfactory neurons regenerate. So it’s not like our bodies are foreign to the properties and capacities to regenerate.
It’s just that it seems that some cells have lost the ability to read the score that allows them to play the symphony of regeneration, and others somehow kept it. And so if we can figure that out, I think we could make a significant impact in alleviating a great deal of maladies afflicting us and our loved ones.
FLORA LICHTMAN: Where are we with harnessing this fundamental biology for medical use, years away, decades away, still further yet?
ALEJANDRO SÁNCHEZ ALVARADO: Yeah, I think I’ve given up on predicting things.
FLORA LICHTMAN: Wise, yeah.
ALEJANDRO SÁNCHEZ ALVARADO: Yeah, because the reality is that we’re moving at a remarkably fast rate. The science that I did at the beginning of the year 2000, barely 26 years ago, is unrecognizable to the type of science that I’m doing today.
FLORA LICHTMAN: Really?
ALEJANDRO SÁNCHEZ ALVARADO: All the technologies have changed so immensely. I think that we are at a very, very interesting and important inflection point in the history of biology. I think that the 21st century is the century that is going to see biology occupy the adult table of the sciences. It’s going to sit probably at the head of the table where mathematics, physics, chemistry normally sit.
Biology is usually in the kids table because we don’t have laws. We don’t have this. We’re always sitting I think– we always feel like, oh my gosh, we want to go to the grown-up table.
But I think this is going to be the century. And I think the reason for that is because we have access to technology that allows us to collect data with almost no discipline. And so what is going to come out of all that wealth of information is a massive synthesis that will allow us to produce, very likely, entirely new principles in biology that will help us answer some of these really, really long-standing questions that have refused to succumb to scientific query.
So I think that it might be possible, Flora, that in the next 5 to 10 years, we might be able to replace a specific cell types. I’ll give you one example we already have, the restoration of corneas. You can actually go to the space that sits in between your pupil and the white of your eye, remove some cells from that tissue, put it on a Petri dish, grow it, and begin to differentiate it into a cornea, inject those cells back into an eye where the damaged tissue has been removed, and the cornea is restored.
So the fact that we can actually restore our own cornea with our own cells suggests that there is something really fundamental we’re not understanding here. So who knows? Our children and their grandchildren are going to be exposed, with a little luck, to a medical practice that is almost unimaginable today. I’m very optimistic that that is going to be the case.
FLORA LICHTMAN: This is a perfect new year segment because you do have a very optimistic outlook, which is a good way to start the new year. It’s not like an existential crisis problem for you, thinking that you’re a whole new you every year.
ALEJANDRO SÁNCHEZ ALVARADO: It is not. It’s actually an exciting– it’s an exciting possibility because it’s the promise of being better. You have an opportunity to do better.
And so I think that’s actually a very motivating force that, OK, well, today it’s down the drain. But tomorrow there’s going to be a new me. At least part of me is going to be new, so let’s try it again one more time.
FLORA LICHTMAN: I think that’s the perfect place to leave it. Doctor Alejandro Sánchez Alvarado studies regeneration, and he is the president and chief scientific officer at the Stowers Institute for Medical Research in Kansas City, Missouri. Alejandro, thank you so much for joining me, and Happy New Year.
ALEJANDRO SÁNCHEZ ALVARADO: Happy New Year to you, too, Flora, and thank you very, very much for having me.
FLORA LICHTMAN: This episode was produced by Rasha Aridi. Thank you for ringing in the new year with Science Friday. And here’s to a happy, healthy, and, of course, nerdy 2026. We’ll see you tomorrow. I’m Flora Lichtman.
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