Introduction to Agential Biology
PART 1: Introduction
Our project is called Agential Biology Institute or ABI for short. The ABI is founded because we think there is a missing causal layer in biology that gives cells an intentional direction as they develop, and we are building the infrastructure to study that causal layer. We think there is a paradox or a contradiction at the very heart of biological theory and we have a new set of experiments we think can make enormous progress on this problem.
If we can work out the mechanism of cellular agency, it would be the most high-impact discovery ever made in biology, because it would give us a scientific theory of cellular coordination. This would revolutionize our approach to cancer, autoimmunity, diabetes, even aging. It would also transform the way we think about the next level “up,” too — organisms coordinating with one another and with the world. These are problems like addiction, crime, war and peace, social media, and AI. It would give us a new picture of what is possible for organic life as a whole.
The general consensus in biology today right now locates agency at the end of development. In this story humans begin as single cells which are gene-driven robots (it follows instructions coded for in its DNA). The zygote divides and the human grows larger, and at some unspecified point, the causation flips and there is a “mind.” The human starts obeying the mind’s instructions (as well as the genes’) - instructions shaped by the outside world. That is agency.
We have new evidence that this is not the right story, because now we know organisms, even single cells, can change themselves and their genes in a heritable way. They can cut, splice, edit their DNA, and they can inherit in many ways outside of DNA pathways.
These results compel us to think of DNA as an information resource that cells use rather than a set of instructions. So how does this actually work? If this mechanism is present in every cell, we are asking: what are the common features of all cells and all organisms that could be the mechanism of this universal cellular learning — this agency?
We have an incredible team of advisors, research partners, and staff at ABI that are truly world-class. All our research partners have labs, they have post-docs, and they have institutional support. So why aren’t these tests already being done? The kind of research questions we have, questions of teleology, can only be asked and answered outside of normal institutional funding because they are intrinsically outside the paradigm of genes-first biology. We are developing tests of philosophical concepts, tests of teleology and function, tests of cognitive theories that depend on very different premises. They require interdisciplinary partnerships and conversations that cannot possibly happen within normal strictures because the answers have to be integrated from different domains, different labs that look at the problem in different ways.
So for example, Denis Noble is on our board, he’s a fellow of the Royal Society who invented systems biology. We also have Stu Kauffman on our board, an inventor of complexity theory. Michael Levin is a research partner, he’s published in Science and Nature and been in the New York Times several times for his groundbreaking work making two-headed planaria and frog skin cell robots. Other research partners include Oded Rechavi, a Schmidt Science Polymath who studies epigenetic inheritance, Josh Bongard, who pioneered work in swarm robotics, Eloi Camprubí, who studies chemical origins of life, and Richard Watson, who invented natural induction, a computational framework.
We are talking about a set of specific testable hypotheses that have never been tested before. Whichever way each test goes, the results will be decisive and will tell us which way to turn in our search for this mechanism of agency. Agential biology is poised to be the deepest transformation in our thinking since the concept of the gene was invented.
PART 2: Teleology
Let’s return to the problem of agency for a minute. Biology has an agency problem. The problem is that purposive trying is excluded from the theory of cells but we can’t understand life without it. I want to address two issues that are really important that people tend to misunderstand:
The first is the controversy about epigenetics, or the inheritance of acquired characteristics, the fact that most of what is learned is not heritable.
The second is the false distinction between bodies and minds.
As I mentioned, lots of new evidence shows that organisms can change their DNA (and the way it's interpreted) in ways that appear purposive — in ways that are nonrandom. However, it is true that most of the change that happens during an organism’s lifetime is erased when the sex cells are made, especially in humans. Humans are an unusual species in that our genomes are especially well-protected from change. For example, if your grandmother learned to play the piano, you weren’t born with that skill already developed. This prompts some people to claim that “epigenetics is fake.” It’s true that most epigenetic changes are not heritable and the effects of the ones that are can be quite mild. But that isn’t the right standard. The existence of ANY epigenetic inheritance is a problem for theoretical biology.
The scientific paradigm we are in in biology is called Neodarwinism. Neodarwinist theory actually has a very strict standard for the sources of variation. The variation must be blind for the theory to work logically. If a theory is formulated rigorously, then just a small bit of specific evidence can falsify it. We already have way more evidence than we need to falsify Neodarwinism. The existence of ANY degree of non-random epigenetic inheritance renders Neodarwinism a critically flawed theory. Which leads us to search for a better one. So some of our assumptions will have to change.
An organism can be considered to be running a program of some sort. The question is how has all that information gotten into that program in the first place? The existing assumptions of biology say that the instructions of life are generated by blind chance, and random changes to the program are responsible for accidentally arriving at good instructions, instructions that result in a living, surviving, reproducing being. The reason this explanation focuses on the DNA is because that is the only place where information is inherited faithfully, where everything is encoded digitally and corrected for errors.
But there is something important to understand: The DNA is largely identical in all our cells, but cells change the way DNA is turned on and off. That’s called epigenetics. That is why starting from one zygotic cell, our bodies differentiate and become bones, muscles, hair, blood, organs, etc. When the sex cells are made, most of those epigenetic changes are stripped away, but not entirely all of them.
The changes that make it through to the next generation are often tiny, minuscule differences but they are very, very important. Those variations are the source of all the directionality in evolution. So for example a lineage runs from chordate worms to jawed fish to dinosaurs to bald eagles, to trace just one lineage over hundreds of millions of years. All the changes that made that eagle from its ancestor the oceanic chordate worm are coming from that tiny bit of variation that persisted after most of the changes were wiped away. Natural selection wipes away all the variations that don’t work, but that doesn’t define which variations occur. Selection is a non sequitur when we are trying to explain what variations occur in the first place.
The key question is this: are the changes that pass through to the next generation completely random, or do they have something to do with the function of the parent organism, given the conditions it was living in? For example, one of our research partners, Oded Rechavi, has shown that starvation in C. elegans worms causes them to modify the pool of heritable small RNAs that regulate nutrition, making their offspring a little more resistant to starvation. Well, of course, you might say, of course those changes are a little bit in the direction of function, because the parent worm was trying to survive, and changed itself in order to survive. It’s actually hard to imagine an organism not passing along a little bit of all the adaptation it has done during its lifetime due to all the stresses it has encountered. Especially if the organism is a single cell, its entire body becomes the two daughter cells, so where else can the adaptation go? It has to go to one or the other daughter cells. Of course it passes along some beneficial changes, because it was trying to survive.
But that is the intellectual trap right there. The word “try.” The word “try” in that sentence is introducing what we call teleology. It is introducing the intention to do something. It’s introducing purpose. That is an illegal move in textbook biological theory. There isn’t supposed to be any trying involved, only blind chance. That is the paradox we are working on.
The problem is we cannot understand the behavior of animals and plants at all unless we interpret them as trying to do something. Teleology is always smuggled in, you see. It’s always assigned to minds, to psychology, and supposed to only be in metazoans with neurons. If all the trying comes from minds, and all function comes from bodies, then we are in this philosophical trap called Cartesian dualism that can’t connect these things. The mind and body. The mind is nonphysical and the body is physical. But we can see, on some basic scientific level, that they are one thing. Bodies and minds always travel together, and they can’t do without one another, and they both have causal influence. We can see that trying happens everywhere in living beings. We call it different things: homeostasis or adaptive plasticity or basal cognition or nature vs. nurture, but it all amounts to the same thing. So what is the connection between these two ways of understanding organisms? How do we scientifically connect body and mind?
There is a key unlock here. In order to make sense of this situation, we have to make a big frame shift. This is the deep part of this agential biology idea, and it has big repercussions. If you think about what it means to be a learning system, it means that you take information that you gather and integrate it for some purpose. Purpose is intrinsic to the idea of learning. Purpose is what makes information meaningful. But if you are an individual learning about the world, the domain you are learning in does not include any natural selection. Natural selection is not an event you can learn from in your lifetime — since the act of selection is linked to your death and your total lifetime fecundity — this is a score that is only counted up after you as an individual are gone. You learn from things that happen to you, from trial and error. You learn from trying. So what are you trying to do?
The genes of an organism, if we can say that genes learn, they learn as a lineage — across generations, not within them. The domain of learning is the persistence of alleles within a gene pool — the population of alleles (which is different versions of a gene) shifts over time based on natural selection. But for an individual to learn, to add something to the program that can be inherited, that’s functional, it has to be for a different reason. This is the important part: There has to be a different primary purpose if individuals learn. They cannot possibly be trying to survive and reproduce. They must be trying to do something else.
This key unlock is where our first ABI tests become relevant. Because teleology is actually readily testable, all we have to do is control rigorously for natural selection. Some theorists impute a lineage-level purpose to life, survival and reproduction, inheritance. But there is another possibility.
So my guess as to what they are trying to do is this: We, all living cells, are all trying to understand causation. We are looking to see what wiggles what. Even bacteria in this view of life are like natural philosophers. They are like human children. To some tiny degree they are trying to increase their own causal knowledge, their understanding of what causes what around them. This is the possibility that being is for knowing. Survival and reproduction may be accidental. It doesn’t mean they don’t happen, just that they are an accidental side-effect of knowledge. That would explain why new mutations in bacteria have sometimes been shown to be random with respect to reproduction.
I suspect that organisms are trying to know something about the worlds they live in based on the bodies they have. This is the concept of epistolution. It’s a word I invented that combines epistemology and evolution, and means something like “universal cellular learning aimed at causality.” This would mean that the directionality of variation, the organizational force that makes a trait a trait, that makes DNA functional, is the drive toward knowledge, understanding.
You see truly random variation in an organism looks like fatigue, or aging, or disease. A novel trait is already a coordinated thing. It’s already organized. It’s an aesthetic, creative change. That is what is being presupposed in Neodarwinism, that a change equals a new trait rather than just disintegration into a pile of mush. If these changes are created to understand the world, then they are indeed random with respect to survival and reproduction, but they are morally and aesthetically creative and valuable.
The possibility of epistolution changes everything. It explains what we see in nature in a much deeper way than the theory we have. And the amazing thing about it is that it is testable. We can test that basic assumption. The big unlock is to accept that teleology is an intrinsic part of biological explanation and then empirically test between the two teleologies of inheritance and epistolution. Epistolution is a new possible teleology that is agential. It integrates body and mind into one system.
Beyond that there are tests that can be carried out that would really open up this field, and there are several plausible theories of cognition to test between that are compatible with the teleology of epistolution, as well as others to test if the correct teleology turns out to be inheritance.
For example, we can look at heritable stress responses in lineages without natural selection. We can study memory and learning in the other parts of the cell, such as the membranes, the structured water, and the microtubules, and understand what is holding information in an analog way. We can study assemblies of cells that have no evolutionary history, like Michael Levin’s anthrobots and xenobots, and see what they can discover without natural selection. We can build models of Bayesian network Hebbian learning or harmonic resonance that correspond with cell-level dynamics and see if these models do in fact have an epistemic curiosity — to see if they scale intelligence. This project can constrain the models we have of cell behavior with a totally new way of interpreting biology that makes more sense. This could lead not only to much better therapies, but to engineering true understanding: intelligence outside of biological material.
You will notice that none of this addresses the question of consciousness, because consciousness is just one aspect of mental phenomena. The rest of the tree of life, presumably, is conscious in very different ways from our own, and we are conscious very differently when we are asleep, knocked out, meditating, or on drugs, yet we are alive in all these states. We cannot possibly know much about the problem of consciousness until we study teleology in a rigorous scientific way. But in order to do that, we have to look at nature in a new way.
This way of looking at nature gives us a new picture of our own motivations and links them to the living systems around us. It portrays all beings as moral beings, as sentient, as aware, as active and purposive. Morality is a natural phenomenon, and so is technology. Because we come from biology! This agential point of view does away with the intellectual separations that hold us out of the theory of life and put us on a pedestal. We are not on the throne above nature, we are just parts of the living system.