Epistolution Musing №8: Epistolution is Not Just Epigenetics
Dear Friends,
This letter is part of a weekly series of brief thoughts I would like to share with you, either because I’ve come across your related work in biology or because you’re a person I like. I discovered an interesting problem in 2019, a problem I can’t forget. Epistolution is the unknown biological mechanism necessary to explain purposive activity that activates genetic influences.
This week I’m taking another detour in response to two excellent questions from readers. One reader urged me to learn more about epigenetic inheritance. He said the problem I am writing about isn’t a new concept, rather it already has a large and growing literature attached to it. He claims that mechanisms such as methylation have already been worked out for it. The other reader wanted to know how, if epistolution is indeed an important process, is it inherited? Both of these questions are very helpful.
The first question is excellent because it allows us to discuss levels of explanation in biology. Epigenetic inheritance is, as this reader pointed out, “organisms adapting without genetic change.” In this sense, he is correct and this is an example of epistolution at work. But this is not at all what I mean by the term, “epistolution.” I was forced to make up the word after three years of reading because the current literature contains no concept that matches what really needs to be explained. What needs to be explained isn’t how the modifications are made by organisms to their DNA, it’s this: what type of process is the organism, fundamentally, that it could make such adaptive modifications while living?
He has identified the right phenomenon at the wrong level of explanation. He has confused an effect of epistolution for the concept itself. Epigenetic inheritance is not all there is to epistolution, not by a long shot. It is just one effect of epistolution that proves that epistolution is taking place. A few other clear examples are embryonic development, wound healing, regeneration, cancer, learning, memory, creativity, and swarm intelligence. Each of these quite distinct processes is a clear effect of epistolution. None of them alone can substitute for it.
Biologists invented the concept of epigenetic inheritance to solve the problem of how organisms could, through methylation, chromatin modifications, RNAs, extracellular vesicles and other subcellular machinery, alter the patterns of gene expression in their germline cells. I am glad that this work is blossoming and I celebrate these results, but this is not the problem-space epistolution works in. It’s only a lower-level example that proves we need the more general concept. We need to know the general mechanism of life as well as the specific mechanism of epigenetics. All the molecular biology in the world cannot tell us what an organism is if we cannot generalize. I’m naming the empty void that needs to be filled.
I take issue with the paradigm in which the organism is seen as a mechanical consequence of knowledge saved in the heritable material. I dispute that whole conception. I don’t think the organism relates to its genome in that way. The genome is, as Barbara McClintock said, “a sensitive organ of the cell.” I invented “epistolution” to describe the more fundamental general mechanism that allows the genomic “organ” to be used to help find problems in the world.
In his letter, the reader seemed uncomfortable with the fact that I haven’t identified exactly what the mechanism is that I’m writing about. But this is the entire point of all my work. I’m trying to raise funds and build a team to write programs that can discover the epistolution mechanism that finds problems. This sounds like a vague abstraction but it is not. When it is found it will be a specific algorithm and also a class of algorithms. They will be codeable in software and compilable in hardware. Epistolution will be a concrete engineering principle.
If you accept that twins learn divergently but adaptively, logically you must accept also that genetic influences require a more fundamental universal mechanism to activate them appropriately. Otherwise there is just no way to explain this adaptive behavior. I’m not writing about a known but about a known unknown. Before I wrote about it, it was largely an unknown unknown. I can’t write about the actual mechanism because it hasn’t been discovered. This is just a result of our position at this point in the history of biology. We have not discovered this general mechanism because we haven’t yet thought clearly about the consequences of our fundamental concept of life. You can’t find anything unless you look for it.
As I thought about the reader’s misunderstanding, I realized I could do a much better job defining epistolution more clearly. Perhaps the following clarification is in order:
I wrote: Epistolution is the unknown biological mechanism necessary to explain purposive activity that can’t be accounted for by genetic influences.
It should read: Epistolution is the unknown biological mechanism necessary to explain purposive activity that ACTIVATES genetic influences.
The reader’s misunderstanding is very understandable. He gathered from scanning my musings that I was writing about adaptation that happens outside of genetics, but I’m not. I‘m writing about what happens fundamentally between the self and the non-self that allows genetics to take effect, that allows an organism to develop and exist in the first place. It’s an entirely different way of looking at the process of life. It’s not the details of inheritance but the fundamental thing that is unexplained. The question isn’t what does an organism do to its genome to make the genome behave correctly; it’s what is an organism, after all?
A preoccupation with the details of inheritance also underpins the second reader’s question.
The reader asked how epistolution is inherited. The answer is that the process of epistolution does not ever stop, but continues indefinitely through the material overlap between parents and offspring. Each of us is a cellular bud that sprouted from the epistolution process that was already taking place in LUCA (the last universal common ancestor of every life form on earth), and it was taking place before that in the very first organism that ever was. The learning-first proposal is that an epistevolving system makes knowledge and it uses the phenotype and also the genome as a memory bank. As long as the system continues working, it has no need to be recreated from scratch, its inheritance is inherent in its continual functioning process.
In epistolution studies one could think of every cell as a brain and every entire multicellular organism as a larger brain. As in a brain, the present state of the entire structure isn’t really functionally distinct from the memory-holding part. Each cell both has a memory bank and it is a memory bank; the entire body is the same. This is because all parts of the body, as the body adjusts adaptively, are subject to mutation and subsequent error-correction. Organisms are continually reformulating the way each part of the body relates to the umwelt adaptively, including learned changes in their memory. DNA is a bank of memories, but it is adjusted by a different process. It changes on the timescale of generations, rather than in seconds, and it is adjusted by natural selection (Darwinian genetics.) The epigenome is epistevolved, while the genome is evolved. The genome within cells is the only part of the organism whose configuration is adjusted directly by Darwinian means. The rest is adjusted by epistolution alone.
Both reader’s questions turn on the role of heritable material. The assumptions about this are so deep-seated in our current biology that it is very hard to uproot them, even for me. Let me take a different approach. Let’s think about the difference between a particle and a process.
No matter what your theory of life, it must involve both an heritable particle and an heritable process, that much seems obvious. The genes-first theory placed particles in the primary role. But DNA alone in a petri dish, as Denis Noble likes to remind us, does not come alive. On the other hand, without a heritable complex particle, information about how to make intricately detailed proteins and RNAs would be lost, and with them the ability to formulate elaborate adaptations.
There are two possible directions the arrow of causation can run. The particle can ultimately control the process, or the process can ultimately control the particle. It can’t be both because there must be a repository of knowledge somewhere that can’t be corrupted by the stochastic cut-and-thrust of the process of life. That is why the Weissmann barrier was so important to the genes-first theory. The theory went that nothing that happened to the phenotype could corrupt the instructions contained in the genotype. But if the Weissmann barrier were true, twins would diverge randomly from one another, not functionally. If twins executed programmes contained only in the genes, then their encounters with their surroundings would not inform their behavior except through the survival and reproduction of their genes. Every instruction for how to live life would have to have been the same for each twin. But if the process controls the particle, life can only strive to learn the conditions of the surroundings to greater and greater fidelity. The uncorruptible repository of order is the Universe itself. That is probably why multicellular life has evolved from unicellular life, but not the reverse. Life wants to know more.
If you think about it, natural selection actually provides a barrier against the genetic particle taking control of the process of life. If genes were all-powerful instructions, it would create enormous incentives for plasticity to evolve because any lineage that encountered conditions that varied significantly would be driven to extinction; an invariable set of instructions couldn’t cope with them. So the more ways a system could break symmetry adaptively in response to changes in the surroundings, the more fitness it would gain. This would lead back to a circumstance where the surroundings executed more and more control over the symmetry-breaking (decisions) of the system, and gradually the genetic control would be lost. The price for this would be that life that depended on precise genetic instructions would be required to remain very, very simple, perhaps no more complex than a snowflake or a crystal of quartz. Any more complexity than that would be selected against by varying conditions. And in fact, this is probably exactly why we don’t see any variable adaptive crystals in nature.
Be Kind, and Be Brave.
Love, Charlie
