Charlie has been gathering some of the best scientists in the world to rethink what agency is together and form new connections outside the usual academic constraints.
ABI includes Dennis Noble, Michael Levin, Richard Watson, Josh Bongard, Oded Rechavi, and Stuart Kauffman on its board, among others. Links to talks with them below, and also one with Andrea.
Charlie never got the PhD people kept urging on him. His conviction is a pretty fitting one for this moment, when what school is is in such a shift: Charlies says that “you become qualified to work on problems by working on them.” You don’t wait until you’re ready; you gather good people and begin.
Charlie says this openness was “forged in a crucible of intense suffering.” The hard years made him more patient, more open-minded; fatherhood taught him even more, and still does. The whole ABI project, he insists, only matters if it invites the world in rather than pronouncing answers at it.

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and Charlie have a personal, meandering conversation that moves from family life stories to foundational questions in biology, education, evolution, and meaning. Munford recounts growing up in Mississippi, wilderness canoe trips, Yale literature and polo, organic agriculture studies in Cuba, farming and a New Orleans wild boar sausage business, and a later personal crisis that pushed him into researching chronic disease and biological agency. He argues mainstream gene-centered biology assumes blind variation, but evidence for inherited acquired changes and directional adaptation (horizontal gene transfer, planaria pattern memory, small-RNA inheritance in worms and mammals, maternal grooming effects, genetic assimilation) suggests a missing causal layer and universal cellular learning. They discuss natural selection, Darwin and Lamarck, Barbara McClintock, a Karl Popper “active Darwinism” lecture, ABI’s testable hypotheses, and openness, creativity, and care.

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00:00 Welcome and Brooklyn Invite
04:20 Meet Charlie Munford
04:35 Banana Couch Story
05:49 Kids and Creativity
08:48 Mississippi to Yale Adventures
15:17 Farming Cuba and Sausage Business
18:40 Crisis Sparks Biology Questions
21:38 Agential Biology Explained
30:04 Lamarck Darwin and Natural Selection
36:45 Evidence for Inherited Change
46:21 McClintock and Popper Teaser
47:51 Cells Sense Not Code
48:36 Genes Aren’t Difference Makers
49:45 Popper Versus Selfish Gene
54:06 Agency Without Theology
55:11 Horizontal Gene Transfer
58:34 Three Testable Agency Ideas
01:00:00 Popper And Falsification
01:06:05 Episolution And Cellular Mind
01:12:58 Harmonic Resonance And Sleep
01:17:12 Attention And Surprise Learning
01:20:33 Personal Journey And Meaning
01:26:24 Love Openness And Invitation
01:30:16 Otter Story Farewell

selective focus photography of pathway between tomato plants — Photo by Markus Spiske on Unsplash

A few highlights from this conversation:

Discusisng the hidden causal layer. The Agential Biology Institute (ABI) is built on a provocative premise: there’s a missing causal layer in biology — something that gives cells an intentional direction as they develop — and the dominant gene-centric story can’t account for it. The standard picture treats a fertilized egg as a gene-driven robot that only later, somehow, acquires a mind. Charlie argues that agency is there far earlier and far deeper, and that this is a testable claim that can be explored rigorously.

Charlie walks through a sequence of examples of organisms rewriting their own inheritance in directed, non-random ways. Some examples he gives are: horizontal gene transfer in prokaryotes (by some estimates the source of the large majority of their cumulative genetic change); Michael Levin’s planaria that “remember” how many heads to grow in the electrical dynamics of their bodies rather than in their genes; Oded Rechavi’s C. elegans passing down stress- and diet-responses through small RNAs across generations; diet effects carried into mammalian sperm; and mother mice whose licking and grooming reprograms their pups’ stress biology outside the egg-and-sperm pathway entirely. The recurring punchline: the program is set up to change the program — which a purely blind, Darwinian story shouldn’t allow, and which points to some agential mechanism underneath.

A secret history, and a lost Popper lecture. For listeners who love intellectual history, this is the jewel of the episode. Charlie tells it as a story with “four heroes and two villains” (the villains, he’s quick to say, aren’t really villains — just people whose mistakes got too popular). The heroes: Lamarck and Darwin — yes, Darwin, who genuinely believed use and disuse shaped variation and even proposed “gemmules” to carry that influence into the germline — plus Barbara McClintock, whose “jumping genes” were dismissed for decades before a very late Nobel, and who said the luminous line, the genome is a sensitive organ of the cell. And then Karl Popper, who near the end of his life gave a Medawar Lecture arguing that you cannot explain life without explaining the intentional creativity of organisms. That lecture was written down, placed in a box at the Hoover Institution marked “to be opened in 2029,” and later found and published (as Karl Popper and the Two Secrets of Life) by scholar Hans-Joachim Niemann. It reads as startlingly in tune with what we now know about epigenetics.

Charlie’s reading of Popper is the opposite of the rigid, gotcha version some fans adopt. Yes: scientific ideas can be falsified but never finally proven, because we can never observe the whole universe. But for Charlie the lesson isn’t caution — it’s wildness. New theories don’t come from the data; they come from creativity and imagination, which we then test against the world. That demands real humility and a genuine welcome for strange ideas, since today’s untestable metaphysics can become tomorrow’s experiment.

There are some points where the conversation is narrative and deeply connecting to everyday life and others were it reaches for some surprising speculative beauty.

Threads to follow: the Agential Biology Institute; Karl Popper and the Two Secrets of Life (Hans-Joachim Niemann); Barbara McClintock’s Nobel address; Michael Levin’s work on bioelectricity and planaria; Oded Rechavi on transgenerational RNA inheritance; Dennis Noble’s The Music of Life; Richard Watson on natural induction; David Quammen’s The Tangled Tree.

The ABI main website has a great description of their science, evidence for the problem of agency, and lots about the community we are developing.

Agential Topics YouTube is the conversation ABI has been hosting, including

Resources:

TalkingOctopus.Com is Charlie’s personal website, including a page (/essays) with many essays and the unpublished book, “The Human Body is a Guess,“ also a page (/music) with lots of songs Charlie has written, including “River Song“ which includes the rhyming couplet, “A wise man said you can never step in the same river twice / Because you know it wouldn’ta been the same river and he wouldn’ta been the same Heraclitus.”

Medium.com page hosts many essays Charlie has written during 2019-2024, including one, “I Found a Loophole in Biology...Optimism“ about my personal life journey to the problem of agency.

Charlie’s Substack now hosts my most current personal essays and thoughts, including the most scientifically significant, “The Double Resonance Conjecture.“

Links & references

Agential Biology Institute (ABI) — Charlie’s nonprofit — https://www.agentialbiology.org/
Charlie Munford, “Episolution: a new principle necessary to a learning-first theory of life” (open-access paper where he lays out the idea discussed in the episode), Communicative & Integrative Biology, 2024 — https://www.tandfonline.com/doi/full/10.1080/19420889.2024.2366249
Agential Topics — the talk/discussion series Charlie hosts, where several of the scientists below have appeared. (No single fixed homepage link; ABI and the Levin lab media page index the recordings.)
Agential talk with Denis Noble
Agential talk with Stuart and Katherine Kaufmann and Daniel Phillips, Frantisek Baluska, and Eric Schaetzle
Agential talk with Alicia Juarrero
Agential talk with Mike Levin
Agential talk about the work of Richard Watson
Agential talk with Philip Ball
Agential talk with Yogi Jäger
Agential talk with Rupert Sheldrake
Agential talk with Terrence Deacon
Agential talk with Matt Segall
Agential talk with Karl Friston
Agential talk with Andrea Hiott

The lost Popper lecture

Hans-Joachim Niemann, Karl Popper and the Two New Secrets of Life: Including Karl Popper’s Medawar Lecture 1986 and Three Related Texts — the book containing the previously lost Medawar Lecture (”A New Interpretation of Darwinism”) — https://www.goodreads.com/book/show/22530221-karl-popper-and-the-two-new-secrets-of-life (published by Mohr Siebeck; also on Amazon). Note: Charlie refers to it in conversation as “the Two Secrets of Life”; the full title uses “Two New Secrets.”

The ABI scientists Charlie names

Michael Levin — famed biologist, bioelectricity, planaria, the two-headed-worm work — https://drmichaellevin.org/
Oded Rechavi — transgenerational small-RNA inheritance in C. elegans (Tel Aviv) — https://www.odedrechavilab.com/
Richard A. Watson — inventor of “natural induction” — https://www.richardawatson.com/ · key paper: Evolution by natural induction, Royal Society Interface Focus, 2025 — https://royalsocietypublishing.org/rsfs/article/15/6/20250036/366154/Evolution-by-natural-induction-II-further
Josh Bongard — https://www.uvm.edu/uvmnews/news/team-builds-first-living-robots and author of one of the books Andrea often references: How the Body Shapes the Way We Think
Denis Noble — legendary scientist, physiologist, critic of the selfish-gene view; his book The Music of Life: Biology Beyond Genes — https://www.goodreads.com/book/show/546661 (also debated Richard Dawkins, referenced in the episode)
Stuart Kauffman — complexity theory; on the ABI board (no single fixed link — search “Stuart Kauffman complexity theory”)

Other people, books & concepts mentioned

Barbara McClintock — “jumping genes”/transposition; 1983 Nobel Prize in Physiology or Medicine; source of the line “the genome is a sensitive organ of the cell.” (Nobel lecture archived at nobelprize.org — search “McClintock 1983 Nobel.”)
Jean-Baptiste Lamarck — use and disuse; “Lamarckism.”
Charles Darwin — “gemmules” (his pangenesis theory of inheritance).
Jacques Monod — the lac operon; Chance and Necessity (the selfish-gene-adjacent view Popper argued against).
Richard Dawkins — The Selfish Gene.
Conrad Waddington — genetic assimilation (the 1950s fruit-fly experiments).
Terrence Deacon — “constraint closure”; his book Incomplete Nature.
David Quammen, The Tangled Tree — popular book on horizontal gene transfer and symbiogenesis (referenced by Andrea).
The Dutch Hunger Winter studies — the post–WWII famine natural experiment on transgenerational effects (search “Dutch Hunger Winter epigenetics”).
Deep Springs College — the wilderness college Charlie credits for the “you can work on any problem” ethos.

Suggested “further reading”

Go deeper: the Agential Biology Institute; Charlie’s own paper, “Episolution”; Niemann’s Karl Popper and the Two New Secrets of Life; Michael Levin on bioelectricity; Oded Rechavi on inherited RNA; Richard Watson on natural induction; Josh Bongard on living robots; and Denis Noble’s The Music of Life.

TRANSCRIPT

Andrea Hiott: Hi, Charlie. It’s wonderful to see you. Thanks for being on Love & Philosophy today.

Charlie Munford: Hi. I appreciate it. I’m excited to be here.

Andrea Hiott: So tell people — who are you? What are you doing? What do we need to know about Charlie Munford?

Charlie Munford: I want to start with a story, because it paints a picture of who I am right now and what my life is like. Last night I was down in the basement watching TV with my two kids. The girl — she’s eight — went upstairs to get a banana, a snack. She brought it down and I was real proud: she shared it with her little brother. She peeled it and gave him half. He’s going to be three on Monday.

Andrea Hiott: Aw.

Charlie Munford: So a while later he comes up to me and goes, “Where’s my banana?” And I said, “I don’t know, buddy.” Then I saw him go over to the sofa, lift up the cushions, and say, “There it is.”

Andrea Hiott: Oh — and it was there.

Charlie Munford: Yep. It was there.

Andrea Hiott: So that’s your life right now. Is there any intentional creativity in that? Because that’s a term you’ve been using in our discussions. What do you see in your kids, and in your own life, relative to that?

Charlie Munford: With kids it’s nonstop. They’re the most creative creatures on earth. Being a dad — every minute is exciting. That’s the most exciting thing in my life, I’d say.

Andrea Hiott: Could you ever have imagined it would be like that before it happened?

Charlie Munford: No. I had a buddy — a pretty rugged guy, we ride horses and shoot guns together — and when I was about to have my daughter, my first kid, I asked him, “What is it like?” He’d had a daughter a couple of years before. He said, “You can prepare — you know your life is going to change, you’ve made plans, you’ve seen it happen to other people. What you can’t prepare for is how you’re going to change.” I said, “What do you mean?” He said, “Two years ago I could never have predicted that on a nice Saturday morning, when the fish are biting, the one thing I’d want to be doing is sitting on the living room floor playing dolls with my little girl.”

Andrea Hiott: That’s very sweet. What’s your life like other than kids right now? What’s happening?

Charlie Munford: I feel like I’m in the middle of the most incredible adventure of my career. And I’ve had a pretty adventure-filled life — I’ve done a lot of unusual things, had a lot of experiences most people haven’t.

Andrea Hiott: Okay, you have to name one or two.

Charlie Munford: I’ll tell you three stories. The first — I grew up in Jackson, Mississippi, spending a lot of time outdoors hunting, fishing, and trapping with my granddad, my dad, and my friends. My parents were both lawyers, well-to-do, but they really believed in public education, so they sent us to public school in Jackson. Some of the schools were pretty rough around the edges.

There was a boy in my middle school — and this is relevant to parenting, to wondering how much to protect your kids. I used to wonder how bad you had to be to get sent to juvenile detention, because all this bad stuff would happen. There was a boy named Two Pants Kelly. Do you remember sagging — wearing your pants really low? Back then it was a big deal. He sagged so much they made him wear two pairs of pants to school, so they called him Two Pants Kelly. He punched a teacher in the face. He’d pull the weave out of a girl’s hair and run around the gym with it. He threw another boy off the bleachers — and he was still there, never got sent to juvie. Then one day he brought a loaded gun to school, mad at some boy, and went from classroom to classroom looking for him. They did a lockdown — this was before all the school shootings. Our history teacher, Mr. Martin, chased him out of the school barehanded, across the street, caught him, and took the gun away.

Andrea Hiott: Oh gosh.

Charlie Munford: And then they sent him to juvie.

Andrea Hiott: So that’s what it takes. Don’t do that, anyone.

Charlie Munford: I had a great family. My parents took care of me and gave me a lot of opportunities. In high school I went to a camp called Keewaydin and paddled canoes — I paddled all the way to Hudson Bay with a group. For six weeks we didn’t see a single other person. That’s how far up in the wilderness we were. Afterward I went to a college that was also in the wilderness, and then I went to Yale. At Yale I was invited to join the Elizabethan Club — a place where people serve tea on really nice china, wait on you, and you sit around looking at the original Shakespeare folios. That’s the club. And I joined the Yale polo team and played horse polo.

Andrea Hiott: Why did you go to Yale? What was your subject?

Charlie Munford: I was interested in literature. I was reading poetry.

Andrea Hiott: So that’s why you were reading Shakespeare folios.

Charlie Munford: Yeah. It was all very incongruous, because I’d just come from working on a ranch in Nevada, working as a driller at the bottom of a gold mine, packing mules in the Sierra Nevada — all this gritty stuff. And then there I was at the Elizabethan Club and on the Yale polo team, traveling to Oxford and Cambridge to play polo.

Andrea Hiott: Was it hard to suddenly be in such a different world?

Charlie Munford: It was very hard. Cognitive dissonance. But it was fun too. I paid my dues to the polo team by mucking out the barn, so I felt a little different. But that’s how you take on new things — as adventures — and you see where they go.

Andrea Hiott: I like that you were in a lot of different worlds that didn’t really fit each other. I moved a lot as a kid, so I compare it to that — completely different regularities around you, and you figure out how to deal with a lot of them.

Charlie Munford: Exactly.

Andrea Hiott: You said this time of your life is so exciting and powerful. What’s that about?

Charlie Munford: Many years later I had a business — a wild boar smoked sausage company down in New Orleans.

Andrea Hiott: Wow. How did you end up in New Orleans? You were at Yale and then you’re doing sausage?

Charlie Munford: I moved back to Mississippi and started farming. As an undergrad I’d gone down to Cuba to study organic agriculture — behind the communist curtain. Cuba had this amazing system. It probably doesn’t exist anymore, but when the Soviet Union collapsed they lost their food subsidies, so they allowed private enterprise, but only in local farming. They had this incredibly vibrant, entrepreneurial local food system.

Andrea Hiott: Amazing that you got to see that.

Charlie Munford: It was very cool, and I got obsessed with it. So I moved back to Mississippi to start a farm and raise food. One thing led to another and it became a local meat company. New Orleans has some of the best restaurants in the world — hundreds of world-class restaurants — and my business sold meat to them. That’s how we started the wild boar sausage company. It was all connected.

Andrea Hiott: Did you ever publish any books or poetry? You’re a very good writer — your Yale training paid off.

Charlie Munford: Thank you. No, I haven’t. I’ve written a lot but never collected it into anything. Part of it is that my interests are so specific. I’ve become so enmeshed in this particular problem at the foundation of biology that I’ve been impatient to work on it with other people, rather than writing about it in a context where no one sees what sort of problem it is. Now that I’m president of the Agential Biology Institute, we’re actually raising money to do the empirical experiments that will demonstrate what we’re talking about. That’s becoming the main focus of my life. I feel like I’ve been looking for 25 years for some way to make this real — and now it’s here.

Andrea Hiott: How does the agency and the biology fit into everything you’ve said so far? Were you already thinking about these ideas? Did you study biology?

Charlie Munford: When the wild boar sausage company failed — tragically —

Andrea Hiott: I have to laugh because you’re laughing. “The wild boar sausage company failed tragically” is a funny statement.

Charlie Munford: It did fail tragically. That year was really bad for me. I’ve always been interested in nature and our place in it — that’s how I got into local food. But that year was terrible. The business failed, I was going through a divorce, I’d just had my first kid, I got a presumptive diagnosis of cancer, and my dog died. All these things happened at once. I got falsely accused of things and sued. It was the worst constellation of things that’s ever happened to me. But I was really pushed out of my worldview — pushed into asking, “What are we? What are we doing here?” I’d been thinking about chronic disease, because I’d struggled with high blood pressure, high cholesterol, weight. And I was very dissatisfied with the explanations you could find. So I got drawn into the question of biological agency, and it got deeper and deeper and more interesting. There’s a whole hidden story — a secret history of biology — that I’d love to share.

Andrea Hiott: Where did you start? Reading books about Darwin?

Charlie Munford: I started with chronic disease research — what’s at the root of these conditions? The questions were already all around me, because the whole premise of the local food movement is that the needs of modern society are out of sync with the environment, and we’re even out of sync with our own physiology. There are received ideas about that which I didn’t find satisfying, so I was primed to look for deeper explanations.

The premise of the Agential Biology Institute is that there’s a hidden causal layer in biology — a missing causal layer that gives an intentional direction to cells as they develop. The project I’m in now is about building the infrastructure to study that missing layer. It’s necessary because the fundamental theory we have — the gene-based theory — makes predictions, and those predictions have been refuted. The prediction is that variation is blind. Instead we’re finding all these examples of organisms changing themselves and their DNA in heritable, directional ways. That’s not allowed by the theory, so we need a deeper theory that incorporates it. And that implies there’s a universal mechanism for learning in all cells. If we uncover that mechanism, it reframes everything that has to do with cellular coordination.

Andrea Hiott: And what problems come from cellular coordination?

Charlie Munford: The hardest problems we have: cancer, autoimmunity, neurodegeneration, aging itself. And beyond that — we’re groups of cells, so the same principles apply when we coordinate with one another and with the world. Now you’re into addiction, mental illness, crime, war and peace. A much deeper and more expansive set of consequences. But they all emanate from the story biology tells: that life begins with no agency. A human begins as a single cell — a zygote — and a single cell is supposedly just following genetic instructions.

Andrea Hiott: You’re saying that’s the normal story we all accept?

Charlie Munford: That’s the dominant view across the life sciences: at the beginning of development it’s just a gene-driven robot. Then the human gets larger, and at some unspecified moment there’s a mind. From then on the human follows instructions from their mind, independent of just DNA and environment — an intentional directionality they follow through learning. That leads biology to ask questions like: what gene leads to what protein, what protein to what mechanism, what neurotransmitter to what behavior, what enzyme to inflammation? Piece by piece. But because of this evidence of Lamarckism, we need a more synthetic set of questions — what are the common features of all cells and organisms that could produce a universal learning mechanism?

Andrea Hiott: You mentioned Lamarckism — you’re partly talking about epigenetics. For those who don’t know: that’s the typical story you just laid out, but you’re questioning it. How would you describe the shift that’s been happening in how we think about genes?

Charlie Munford: There’s a short part and a long part. The short part: people have been finding results showing inheritance of acquired characteristics — that’s called Lamarckism — and setting them aside. There are two criticisms of the idea that we need to study biological agency.

The first: “If those changes are in the direction of reproductive fitness, they must have gotten there from prior natural selection.” That’s not logically necessary — there are other ways they could get there — but it requires imagining some outside-the-box theory involving time reversal or multiple universes. I’m actually somewhat sympathetic to that criticism, because I don’t think this directional change is necessarily in the direction of reproductive fitness. I think that’s a correlation, not a cause.

Andrea Hiott: You don’t think life is all about that.

Charlie Munford: No — although it is a hypothesis, and a testable one. The second criticism: “Suppose this variation is either in the direction of reproductive fitness — in which case natural selection put it there ahead of time — or it’s blind to reproductive fitness, in which case it has no evolutionary salience.” But that’s wrong, because organisms could be trying to do something else, and from that set of variations natural selection chooses the ones that have reproductive fitness. So the whole purpose of life could be something other than reproductive fitness, and it would still require reproductive fitness to get into the future as a lineage. Those are two separate questions. What we’re trying to do as individuals — that’s the question of our creativity, our intentional directionality — is separate from whether we get into the future. Natural selection is a perfectly good mechanism; there’s nothing wrong with it.

Andrea Hiott: What is natural selection, for people who think they know but might be thinking of something else?

Charlie Munford: They almost always are, because they’ve been misled. This whole history has four heroes and two villains.

Andrea Hiott: And the villains aren’t really villains — this is the novel you’ll write of it.

Charlie Munford: Right, they’re not really villains — just people who made mistakes that turned out to be way too popular. So: Jean-Baptiste Lamarck, a biologist around 1800–1810. His work was really good for its time, because science didn’t even have a theory of organic change yet. People thought every species had been there for as long as life had — they were operating from the assumption that God created them all in seven days. Lamarck’s theory said it’s not like that; life changed through geological time. That was radical, and that’s what he was known for in his time.

What he’s known for now is something he’d be shocked to find attached to his name, because everyone believed it and he didn’t invent it: the idea that use and disuse shape variation. That’s a common-sense idea — good solutions to a problem in nature look like the organism got there by trying to solve that problem. His example was the long legs of wading birds: it seems like, in the course of trying not to get their feathers wet while hunting in shallow water, the birds achieved longer and longer legs through their intentional creativity. Virtually all biologists believed use and disuse influenced variation until maybe the 1890s. Darwin believed it too — it wasn’t a fringe view for him, it was core to his theory. In The Origin of Species he mentions use and disuse as a source of variation eight times, according to [Denis] Noble.

Andrea Hiott: This is definitely not the story most people tell.

Charlie Munford: Not at all what you learn in school. Darwin then invented a theory of how those bodily influences could wind up in the eggs and sperm — he called them gemmules: small particles circulating through the bloodstream carrying the influence of the use and disuse you choose to do.

Andrea Hiott: Gemmules — G-E-M-M-U-L-E-S? And Darwin came up with this?

Charlie Munford: Darwin. Lamarck and Darwin shared the view that use and disuse had some influence over variation. Neither believed that everything you acquire in your lifetime is inherited.

Andrea Hiott: What were the gemmules doing?

Charlie Munford: Carrying some influence from your physiology, through the blood, down to your germline cells — your eggs and sperm — where it could be transmitted to your children.

Andrea Hiott: And Darwin wrote this? In The Origin of Species?

Charlie Munford: In a later book. This was his theory to explain variation. Darwin and Wallace co-invented natural selection: there’s variation in populations, and nature decides which ones perish without reproducing and which reproduce most. Through heritability, that affects the future makeup of the population — it explains evolution. Lamarck already had a theory of evolution; Darwin and Wallace added rigor by pointing out that nature selects between variants. But Darwin believed those variants were not blind with respect to use and disuse. What’s now called Lamarckism didn’t come from Lamarck, and it was believed by Darwin.

Andrea Hiott: That’s confusing, because you learn that Darwin was just about selecting for traits that lead to more reproduction, and that Lamarck was the one saying your engagement with the environment can change your body in a way that’s passed on. But we now have evidence for that, right? At least short-term, in animals — the way we live and certain conditions actually influence what passes down.

Charlie Munford: The current theory says changes to the inherited program must be caused by blind chance and filtered by natural selection — otherwise the change is caused by the program itself, which is circular and can’t be valid. A program can’t say “scramble me,” or you could only run it once or twice before it self-destructs. So we need to add an agential mechanism to explain the program adding information during the organism’s lifetime. I have six examples that prove this happens.

One: the most typical organisms on Earth are prokaryotes — the majority of the cells in our body, and the majority of organisms in every natural environment. Single cells can’t help but inherit acquired changes, because the whole organism becomes the offspring when it divides. When they’re challenged by an antibiotic, they acquire resistance — how? They trade genes with one another. That’s horizontal gene transfer. The best recent estimates are that about 81% of the cumulative genetic change in prokaryotic genomes is due to horizontal gene transfer. Does that sound accidental? If life were Darwinian rather than agential, every aspect of the organism’s lifestyle would be organized to prevent that kind of change. Instead it’s the main cause of genetic evolution. The program is set up to change the program in response to stress — and that requires an agential mechanism.

Two: body-plan information is supposed to be written into the genes, where it can’t be altered. One of our strategic partners at ABI, Mike Levin, studies planaria, which reproduce by being cut in two — both pieces regenerate. He’s shown that if you block the transmission of electricity between cells at a critical time, you can make them regenerate into two-headed worms — and then indefinitely, every time they’re cut, they regenerate into the two-headed form, without any genetic change. The pattern memory for how many heads to have is written not into the genome but into the attractor states in the electrical dynamics of the worm’s body.

Three: another ABI partner, Oded Rechavi in Tel Aviv, showed that C. elegans worms produce small RNAs in response to viruses and to starvation, and in both cases they’re inherited for several generations. The longer the heritable response persists, the more likely it is to continue into the next generation — a kind of epigenetic momentum. He also showed the cytoplasm alone is sufficient to carry the inherited signal. The worms are set up to change their own program to adapt to diet and stress.

Four — now mammals: the Rando lab at UMass showed that male mice on a low-protein diet delivered small RNAs to their sperm, giving the offspring different cholesterol synthesis in their livers. Other labs have shown human sperm contains abundant small RNAs produced in the epididymis — produced by the body — that correlate with the father’s diet, his metabolic state, and even IVF embryo quality. So the program is set up to change the program in response to diet and stress — in humans.

And one more, even more amazing: studies in mice show that the licking and grooming behavior of mother mice stably programs adult stress reactivity in their offspring, by methylating a particular location on the genome in hippocampal neurons. That reprograms the young to grow into mothers who lick and groom to the same extent. The behavior is transmitted from mother to daughter entirely outside the normal sperm-and-egg pathway — the licking reprograms the genome in the hippocampal neurons directly. That’s the program rewriting the program without even touching the genes in the zygote.

Andrea Hiott: How long did that last — into the next generation?

Charlie Munford: Often it doesn’t last very long, but in principle that doesn’t matter, for two reasons. First, if the stimulus doesn’t persist across generations, then removing the change when the condition is gone is also adaptive. If an organism is changing in response to its environment, it’s not just keeping changes forever — it removes them when they’re no longer useful. Second, there’s genetic assimilation: if an organism adopts a new trait or habit or lifestyle epigenetically and stays in it for a while, the selective pressures on its genes are to recapitulate that same behavior. Conrad Waddington discovered this in the 1950s with fruit flies — he could induce a change, then by selecting for it, cause it to happen without inducing it. It became genetically encoded through selection alone. So a trait can move from “something I discovered through my creativity, intentionally” to “something genetically encoded that I have a propensity to do.” That shows how learning can give directionality to evolution, even with a genetic underpinning.

Andrea Hiott: “Learning can give directionality” — that’s a good way to say it. Why is this so controversial? Epigenetics is a terrible word to some people. Isn’t there a Dutch study from after World War II, where wartime starvation caused changes in the next generation?

Charlie Munford: Yes — a natural experiment where the experience of starvation changed the phenotype of the children and grandchildren of the people who lived through it.

Andrea Hiott: So we’ve seen this in animals and in humans. Why do people freak out about the idea?

Charlie Munford: Because it removes the whole grounding teleology of life. People are incredibly attached to the idea that life is about survival and reproduction — competition, red in tooth and claw. This challenges that whole framework of what we’re doing here. What ABI has done is figure out ways to make that empirically testable — with all the repercussions we think will follow.

Andrea Hiott: This reminds me of Popper, and “active Darwinism.” How does that relate?

Charlie Munford: In the 1980s, two people really tried to alert the world to this way of thinking. The first was Barbara McClintock, a Nobel laureate who did her work in the 1950s on maize — corn plants. She found that when they were stressed, they could reorganize their chromosomes.

Andrea Hiott: The jumping genes.

Charlie Munford: Jumping genes — transpositions.

Andrea Hiott: Of course, everyone thought she was crazy, because she’s a woman talking about jumping genes. But she eventually got the Nobel Prize and it was all confirmed.

Charlie Munford: Exactly. Because it wasn’t supposed to happen — but it did. In her Nobel acceptance speech, 30 years after the work was published — around 1983 — she said, “The genome is a sensitive organ of the cell.”

Andrea Hiott: Beautiful. Let’s pause on that. We think of DNA as a computer program that just gets read off. She’s saying it’s a sensitive organ — the cell is interacting with everything around it in a living way. Sorry — and then Popper?

Charlie Munford: Right — the cell is feeling and sensing the world, and part of that is how it uses its genome. Genes are supposed to be difference-makers, but now that we can read genomes, we see they’re not difference-makers in the way we thought. In principle they can’t be, because every cell in your body — hair, blood, muscle, teeth — has the same DNA. So something else is making the difference.

Andrea Hiott: DNA is obviously very important and there’s an amazing continuity through it. But the living, the action, the rest of the cell — I heard you say once that if you squished the DNA up into a football, the rest of the cell would be all of Central Park. We’ve been thinking everything is this little bit of DNA.

Charlie Munford: Right. So Popper spoke out against the selfish-gene view, articulated in the 1970s by Jacques Monod and by Richard Dawkins with The Selfish Gene. That idea took hold and still holds sway — the idea that sure, there’s flexibility as DNA is interpreted, but the DNA causes itself to be interpreted a certain way. Monod discovered the lac operon: a place in the DNA of E. coli that gets encoded one way in the presence of one sugar and a different way in the presence of another. It’s an on-off switch built into the genome. He extrapolated from that to say the whole organism is basically an operon — everything we do is just genes switching themselves on and off to reproduce the genes. We’re just a program the genes are orchestrating to get themselves into the future. It’s backwards, and counterintuitive, but it was persuasive enough because it let scientists avoid the whole question of teleology — of where our purpose comes from.

Popper was wise enough to be aware of this trick. In his Medawar Lecture he argued against the idea that blind mutation plus the action of the environment is all we need to explain. He said it’s impossible to explain life without explaining the intentional creativity of organisms — they get themselves into situations that affect the conditions of their own natural selection. He didn’t say where that energy and intention came from, but he had a deep epistemology of how knowledge arises.

Andrea Hiott: Did he actually call it “active Darwinism”? And this was the late ‘80s, near the end of his life?

Charlie Munford: It was two years before he died. He gave this Medawar Lecture; it was written down, but the transcript was put in a box at the Hoover Institution marked “to be opened in 2029.” I don’t know why. A scholar named Hans-Joachim Niemann found it and published it — the book is called Karl Popper and the Two [New] Secrets of Life. It’s Popper’s thoughts about Darwinism, and they’re totally in tune with what we know now about epigenetics and Lamarckism, and the way organisms are clearly upstream of their DNA sequences in some way. We don’t yet have a scientific theory of how that can be.

Andrea Hiott: Can we read that lecture now?

Charlie Munford: Yes, you can buy the book. It’s great — Karl Popper and the Two Secrets of Life, or something like that.

Andrea Hiott: So who are the heroes and who are the villains again — although I try not to put things in dichotomous terms?

Charlie Munford: Lamarck and Darwin, and McClintock and Popper, were all trying to tell us there’s a way to have natural selection and agency. It’s not one or the other. It’s not natural selection versus God — you don’t have to leap to “God directs everyone what to do.” You could have a biological mechanism for agency, and that’s a testable possibility.

Andrea Hiott: Is this related to gene transfer — that book The Tangled Tree?

Charlie Munford: Yes. You have to think about it from the selfish-gene perspective first. There’s supposed to be an inherited program, and its instructions are supposed to be faithful to themselves. You can’t have a program that says “scramble me.” So they built intellectual scaffoldings to protect that idea. One: there’s no Lamarckism, only blind variation — which never made much sense. Another: the Weismann barrier, the idea that the germline is locked away and unaffected by variation. Both scaffoldings have been destroyed. Horizontal gene transfer means most genetic change in prokaryotes comes from borrowing from other lineages — the program shouldn’t say “break me and borrow from another program,” but that’s exactly what’s happening.

Andrea Hiott: Horizontal — meaning it’s not coming from your parents. You’re getting it from someone not even related to you.

Charlie Munford: Exactly. And then there’s transposition — McClintock — and symbiogenesis, and symbiosis, all of which call into question where the beginning and end of an organism really is.

Andrea Hiott: The point is, the “gene as programmer” idea is running into a lot of trouble now, from all kinds of directions.

Charlie Munford: Right. Denis Noble debated Richard Dawkins on stage recently and totally demolished him.

Andrea Hiott: Denis Noble also brought Lynn Margulis and others to debate those guys way back — he was onto this a long time ago. And The Music of Life is a beautiful book, which connects to some of what Richard Watson is doing too. But most people still think “gene as programmer.”

Charlie Munford: So far there are three testable hypotheses within agency — and there could be more. One I’d call “evolution-first agency”: agency isn’t universal to the whole tree of life, it evolved, but it’s still very important. I think that one’s refuted, but it’s worth testing. At ABI we want to make as many of these ideas testable as possible — to parse them into actual physical experiments that can decide one way or the other.

Andrea Hiott: Are you really trying to decide one way or the other, or also to open up the space beyond a rigid way of thinking?

Charlie Munford: A deep part of rationality, which is overlooked, is that ideas can be proven wrong but not proven right.

Andrea Hiott: So we’re back at Popper.

Charlie Munford: Back at Popper. This is core to how we try to approach things at ABI — open-minded but rigorous and logical. We’re not saying, “There are many possibilities, so we’ll just write papers and not decide.” Popper was writing about the difference between math and science. In math, all of it is one big tautology; if you prove something, it’s proven. But a theory that attaches to the world always has predictions you can’t verify, because you can’t look at the whole world — the whole past and future of the universe. So there’s no proof like that. What instances can do is prove your theory wrong: if you’re rigorous about what your theory says, you can look for a case where nature disagrees, and then throw the theory away. And crucially, looking at the world doesn’t hand you the new theory. The new theory comes from creativity — from your wild imagination — trying to integrate the facts you know into something testable.

Andrea Hiott: I like this. Popper was resisting Hume and induction — falsification, theory-ladenness. But your turn on it is interesting: it means we need to be more creative and wild.

Charlie Munford: So many people — even fans of Popper — take it the wrong way and become rigid and hard to talk to. The attitude I’d criticize is “what I see is all there is, and it will last forever.” When Monod looks at E. coli and sees an operon, that’s the attitude. Dawkins too: “This is the only possible explanation for life; everything else is theology — it’s either this or God.” That’s not rational. Rationality is imagining all the consequences of your idea and then checking whether the world agrees — and it always eventually disagrees. That’s why there’s no end to science. To me, that gives us tremendous humility, and makes me want to welcome crazy ideas — because, as Popper said, metaphysical ideas often become testable much later. It’s not worth dismissing ideas that sound crazy; they might be worked into something, and turn out closer to the truth.

Andrea Hiott: So it’s not that you’re saying everything is wrong. You’re opening up the way that everything we do changes everything that can be done. The experiments and falsification matter, but you’ve put the wildness back in — and the idea that we might never fully solve this, even as we make progress. That’s a kind of holding of paradox.

Charlie Munford: If we wait for the evidence, we’ll never solve it — we have to have a guess before we know where to look.

Andrea Hiott: At some point you even say the body is a guess, or life is a guess.

Charlie Munford: Right. I see the whole problem in those terms — but that’s one hypothesis about agency.

Andrea Hiott: Is that where your term “episolution” comes from?

Charlie Munford: Episolution is a family of possible solutions to agency — not the only one. Within it there are at least two testable ideas. Episolution is the idea that there’s a universal mechanism for learning in all cells, and that it’s prior to evolution — a foundational core principle of life.

Andrea Hiott: So you’re saying mind is there from the beginning?

Charlie Munford: That’s accurate — though not necessarily conscious mind. It’s not the same as the problem of consciousness, but it is intentional directionality, and I think it implies a certain curiosity — a willingness to be epistemically active, to get better knowledge from the world.

Andrea Hiott: Is that why you say it requires a self?

Charlie Munford: Natural selection presupposes a self, plus reproduction, inheritance, and variation. But you don’t just find a self — a self is something that has to be maintained. If it’s not maintained by a genetic program, it has to be maintained by some other physical process, or we don’t have a scientific explanation. There are families of solutions for agency that involve multiple mechanisms. Terrence Deacon has a theory of constraint closure, for example, in which life has directionality but it’s essentially put there by natural selection. Episolution is the other option — a universal learning mechanism in all cells, where the directionality is put there by the organism, present from the beginning. The purpose of life is learning about the world, not necessarily surviving and reproducing. Of course you don’t become a lineage unless you survive and reproduce — but that’s not necessarily what you’re trying to do.

Andrea Hiott: So what’s holding it all together? A self doesn’t just come by itself from evolution — can you walk me through that?

Charlie Munford: There has to be something that accumulates knowledge. Within episolution there are two possibilities. One is a Bayesian, inductivist picture: an organism is a network, deformed by contact with the environment; the deformations follow an algorithm that lets the system generalize — that’s learning. Richard Watson calls that natural induction. It could be a very deep network that learns something deep about the world in a multidimensional way, and that explains life’s directionality.

The other possibility is more Popperian — my personal preference, though these are all testable. And you’re working with a lot of biologists to test them.

Andrea Hiott: You’re working with quite a team.

Charlie Munford: Let me name some. Denis Noble, a Fellow of the Royal Society, who debated Dawkins on stage. Michael Levin, one of the most famous biologists in the world, published in Science and Nature. Richard Watson, the inventor of natural induction. Josh Bongard, who built the first living robots. Oded Rechavi. Eloy Campuzano, Joanna Javier. Stu Kauffman — one of the inventors of complexity theory — is on our board. Serious people. We’re trying to make these questions testable, with that Popperian open-mindedness that there may be an even better way to formulate things.

So: deep natural induction is one hypothesis. Constraint closure is another. The third is my favorite, because it’s closely based on Popper: the idea that harmonic resonance maintains the self. Harmonic resonance passes through things, so there’s a boundary to it, but it integrates information in an analog way, unlike any other physical process. The reason I think it can explain the origin of the self is sleep. That’s actually how I came to this problem in the first place — thinking about sleep. Why do we spend eight hours asleep? From a reproductive point of view that’s totally unfit — why can’t we just pursue mates and food until we starve? We can’t. And all cognitively complex beings sleep — even cephalopods, squid and octopus, and they do REM sleep, and our common ancestor with them was back in the Cambrian.

The hypothesis is that harmonic resonance has two modes. One is a sleep mode, where you’re cut off from sensory perception so that the internal harmonic resonance within your body can become phase-locked — constructive and destructive interference in the oscillations until they become a congruent whole. Once they’re congruent, you wake up and enter the world as a congruent being. But your interaction with the world through perception changes your harmonics again and degrades them — introduces disharmonies. That’s why you can’t stay awake forever: the disharmonies would overwhelm your congruent system and you’d disintegrate.

Andrea Hiott: That relates to certain ways the brain works. And there’s the theme of oscillation all through the body — Denis Noble talks about music, Richard does too. In a general way, are we oscillating with the environment and with ourselves at all these different scales? Or is that going too far?

Charlie Munford: That’s not going too far. It’s a testable hypothesis, and there are at least two other ways it could be — but it’s my favorite, because it would explain the largest number of mysteries.

Andrea Hiott: You said something about sleep being conjecture and waking being refutation. What does that mean?

Charlie Munford: A conjecture is a guess — it has consequences. We form a guess about the world, about what’s possible and impossible, while we’re sleeping. Then we wake up —

Andrea Hiott: With our bodies, literally — our bodies are the oscillating possibility, and when we wake we falsify the day?

Charlie Munford: It sounds like a category error, but it’s not. We literally are a physical guess about the world. The problem I think this solves is that attention is scarce. We’re not like the cameras on a Google Street View truck — we don’t take in very much. My favorite example: when I drive into town, a 20-minute drive, I pass maybe five to ten million trees — I live in a forested region. On a normal day I don’t notice any of them. But if I saw a tree made of glass, or turned upside down with its roots in the air, or painted purple, I’d remember it for the rest of my life — because it was something I thought was impossible. Those refutations become part of our body. We have a general sense of what’s possible out there. It’s not a specific prediction — if I turned a corner and a school bus came instead of a fire truck, it wouldn’t be a big deal. It’s a sense of what’s possible and impossible, built from certain moments — the ones that stick with you and become foundational, because they changed your whole sense of causation.

Sometimes they’re surprising, painful moments. I didn’t realize that the moment I stepped on someone’s knee when I was 17 and really hurt them would stay with me forever — I still feel a cringe of guilt. Why was that the moment I learned that people are sensitive, that people are vulnerable even when they don’t seem it? It wasn’t that I predicted one thing and was wrong. A whole new possibility opened up.

Andrea Hiott: That reminds me of the stories you told at the beginning, and of how you’ve described philosophy as being about avoiding mistakes — very Popperian. You’re not really noticing, in the way you said, and something comes along and shocks you, and you never forget it, and it changes your trajectory.

You said you started this whole exploration into agency and biology because you were having a really hard time. You seem healthy now — I hope everything’s okay. How do you see that very difficult moment leading to where you are now, testing big ideas with some of the most important scientists in the world?

Charlie Munford: I feel incredibly lucky. Blessed. These questions are so important, and I feel lucky to have found something to work on that really matters. I don’t have the problem some people have in midlife, feeling that what they did has no meaning — everything in my life has an extreme amount of meaning, and I’m very lucky for that. Part of it is also the sense that problems usually can’t wait until you’re ready to solve them. When I discovered all this, people kept telling me, “Charlie, you should go get a PhD, become a professor.” And I thought, “There’s a problem to be worked on here. You become qualified to work on problems by working on them.” So I started gathering people together with Agential Topics, inviting luminaries — like yourself — to speak.

Andrea Hiott: I was lucky to be included.

Charlie Munford: It’s just a willingness. I was blessed with a sense — partly from Deep Springs College — that if you try, there’s no problem you can’t work on. You just have to start.

Andrea Hiott: I love that, and it reminds me of intentional creativity. We’re at a strange moment where everything is changing about what school even is, what degrees mean, how we educate ourselves — you can go on YouTube and basically go to Harvard now. So it’s beautiful that you just decided to do it — and not by yourself. You went looking for people with knowledge in all these different ways: philosophers, biologists, everyone. What would you like to leave people with about that idea?

Charlie Munford: The main thing: a lot of people who want to be taken seriously adopt an attitude I really dislike — “what I see is all there is, and all there ever will be.” They try hard to convince you there’s nothing more out there. That’s dogmatic and judgmental, but it’s also irrational. We can’t look at the whole universe, so we have to be humble about what we can look at, try our best to look at the things that really matter, and then take them seriously. In biology, people have been believing and disbelieving the same theory at the same time — instead of taking the theory seriously, saying “here’s what it says,” looking at nature, and being honest when that’s not what’s happening. Let’s take our own results seriously and invent new possibilities, because it’s wide open now.

Andrea Hiott: I like the wildness coming back in. And one thing I really appreciate about you is that you clearly care about all this — you can feel it — with a kind of humbleness, even as you do so much. Since it’s Love & Philosophy, I want to ask: is this coming from a place of care, even love? How do you see those words in relation to what you’re doing and what you’ve been through?

Charlie Munford: So much, yes. It was forged in a crucible of intense suffering. I had an intense period of suffering, and it made me really open-minded, and a lot more patient with other people. I was very impatient when I was younger — I’m still a little impatient — but being a dad is part of that. You just realize.

Andrea Hiott: It’s interesting you started with your kids. That love and care is how you wanted to open this conversation — which is about rethinking even reproduction as the driving force. You’re trying to expand that, even as you get more particular and more falsifiable.

Charlie Munford: That’s exactly right. Richard is a co-founder, and Joanna, and there are other really good people — Josh Wolk, Dina Rudick, Lizzy Devane. We all share a sense that this is a bigger thing: that if we just do experiments and don’t interpret them for the world — if we don’t invite the world in — we’ve missed it. It really has to be inviting, bringing everyone in to look at this, experience it, and help us learn what it means. That’s everything. We’re all in a situation now that we don’t understand — societally, politically, everything. We’re in new waters; things change quickly. We can’t afford to be too rigid. We have to open up to other people and listen.

Andrea Hiott: I appreciate that you opened instead of closed. A lot of us go through hard times and it’s hard to stay open, to open our hearts. It’s interesting that your heart opened through the suffering. None of us is perfect and life is still hard, but you can see what the opening brings in — things you never could have imagined back then. And thinking about your kids, and all the generations to come, reproduction can mean something else too: your ideas, all of this, set paths forward for what’s possible. Is there anything else on your heart you want to share before we go?

Charlie Munford: I’ll share something special that happened to my daughter recently, because of love. My daughter loves otters. She’s really into otters — she’s always had an otter stuffy, it’s her favorite. She has an otter and a possum, and they’re friends, and she’s very proud of them. Her mom recently took her to a zoo in Belgium that has an amazing otter exhibit — and a hotel room built into the otter exhibit, where you can spend the night, and the window of your room is the otter tank.

Andrea Hiott: Whoa. She must have been thrilled.

Charlie Munford: She put her otter stuffy up in the window, and the real otter came over and said hello to it.

Andrea Hiott: That’s so sweet. I love that — and it brings the other creatures of the world back in, along with your beautiful daughter. That’s a very happy way to end. Thank you, Charlie. I really appreciate all you’re doing, and thanks for inviting me into your world a little bit. It means a lot.

Charlie Munford: Thanks so much. I appreciate it, Andrea.

Andrea Hiott: All right. Bye.

Charlie Munford: Bye-bye.

Love & Philosophy

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