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Denis Noble: “Neo-Darwinism Is Dead” | We Need A Biology Beyond Genes

Essentia Foundation | December 14, 2025



Professor of Biology Denis Noble, best known for creating the first mathematical model of a beating cardiac cell, proposes a profound shift in how we understand life. In this conversation with Hans Busstra, he challenges the long-standing central dogma of Neo-Darwinism: the notion of one-way causation from DNA to cell to organism, with genes positioned as the ultimate governors of biology. Instead, Noble proposes a theory of ‘biological relativity’: no single level—genes, cells, organs, or the whole organism—has privileged causal authority. Causation flows both upward and downward.

Physiological states influence cellular processes, which in turn can reshape the genome. Agency is distributed across levels of biological organisation, and the genome is not a dictatorial blueprint but an interactive participant. Far from rejecting Darwin, Noble sees this as returning to Darwin’s own intuition that evolution requires mechanisms far richer than blind chance. Understanding those mechanisms, he argues, is the next Einsteinian step in biology.

Books by Denis Noble:
The Music of Life: Biology Beyond Genes – https://shorturl.at/fTX4y
Dance to the Tune of Life: Biological Relativity – https://shorturl.at/kfULX
The Logic of Life: The Challenge of Integrative Physiology – https://shorturl.at/ZcReV
The Initiation of the Heartbeat –https://shorturl.at/csWvr
The Language of Symmetry – https://www.routledge.com/The-Language-of-Symmetry/Rattigan-Noble-Hatta/p/book/9781032303949

Topics discussed in the interview:

0:00 Intro
4:43 What causes our very first heartbeat?
6:36 Noble’s 1958 research on the first heart model
8:40 On self-excitation in cells (and what “self” means)
9:24 The central dogma in biology
11:17 Schrödinger’s view of life as a crystal
13:43 To what degree DNA replicates like a crystal
15:16 The amazing error correction in our genome
16:59 How enzymes know when they encounter an error
19:19 “Genes look like a code of life…”
22:05 The merits and limitations of the Human Genome Project
23:39 Can we really say “the cell wants” something?
24:51 Understanding the scales and extraordinary mechanisms in a cell
27:18 What we do and don’t understand
29:16 On Michael Levin’s work
31:23 On cancer
35:41 Neo-Darwinism vs true Darwinism
38:19 Something must have sped evolution up
41:22 The cell controls the genome
44:19 On the metaphysics of chemistry leading to life
46:42 Biological relativity
51:08 The universe as a self-excited circuit
52:18 On Richard Dawkins
54:27 On the difference between causation and association
56:48 The limitations on the predictive power of genomics
58:46 The false hopes around the Human Genome Project
1:00:20 The central dogma in biology has the wrong metaphysics
1:07:03 Noble on Spinoza
1:11:08 How dualistic thinking still limits us
1:13:40 On the nature of the self
1:17:06 How life lives on the boundary between order and chaos
1:18:32 How errors become solutions
1:19:51 A love story between a human and an AI
1:23:58 On quantum biology
1:26:27 On the importance of humility in science
1:28:16 How we crave meaning (and reductionist science has deprived us of it)
1:29:07 Denis Noble singing troubadour poetry
1:30:27 Science must lay down its weapons
1:32:18 What dancing to the tune of life means on a personal level

Archival footage under fair use policy: https://www.youtube.com/watch?v=slRyGLmt3qc&t=28s

The Essentia Foundation thanks the Lorentz Centre in Leiden for their accommodation of this interview: https://www.lorentzcenter.nl/

Copyright © 2025 Essentia Foundation. All rights on interview content reserved.

Written by Essentia Foundation

Comments

This post currently has 49 comments.

  3. @carolspencer6915

    December 14, 2025 at 5:58 pm

    Good afternoon Hans and Dennis
    Brilliant shared conversation.
    Super beautiful biology.
    Truly grateful for half a century's worth, of your work.
    We can indeed all 'help it'. For sure!
    Simply thank you Kindly. Story short.
    💜

  5. @C.r.E

    December 14, 2025 at 5:58 pm

    wow @10:05 he actualy said; he had to leave his position in research to actually allow himself to ask the right question(s) and search for the answer. This is the situation of almost all researchers today, they avoid questions during research that contradict status quo and/or the prevalent/expected view.🧐

  11. @1Martinss-o2r

    December 14, 2025 at 5:58 pm

    It is truly admirable when a scientist acknowledges uncertainty by saying, “I do not know.”

    The most disappointing stance a scientist can take is to accept dogma without question.

  12. @MrKrekkie

    December 14, 2025 at 5:58 pm

    Een versnelde evolutionaire sprong kan ontstaan door kruising van gelieerde soorten (tijgers, leeuwen, paarden ezels). In sommige gevallen zijn nakomelingen vruchtbaar en kun je dmv terugkruising ook vruchtbare nakomelingen krijgen die dan in 2 generaties bijvoorbeeld 10-15% groter zijn (leeuwen tijgers voorbeeld). Andere voorbeelden: wolf-coyote-hond introgressie. Cichliden. Helianthus zonnebloemen. Darwinvinken.

  13. @oncaphillis

    December 14, 2025 at 5:58 pm

    This is so painful to watch. He jumps all over the place. Fighting against Watsons central Dogma which is out of the window for at least 50 years
    Assigning hidden agency to Cells and Genes
    and of course the ever looming quantum mechanics

    … And of course the community eats it up in search for their God of the gaps

    Biology has moved on from this. We don't have the full answers, but it's not this mambo jambo

  16. @petersq5532

    December 14, 2025 at 5:58 pm

    when you talk about distance within the cell and you proclaim the cell wall is in Paris, you create a false analogy. when you humanise the distance you also assume the molecular information come with the Southern Rail. in fact they come with a rocketship so while the distance is huge the speed is accelerated as well. with this in mind this is less magical but fantastic nevertheless

  18. @LocalTransportationGuy

    December 14, 2025 at 5:58 pm

    I certainly agree with Denis Nobel and his marvelous explication of cells — two way causation, etc. In terms of Darwinism, I would tend to quibble over what is the "central dogma of Darwinism" and of evolutionism ever since. (I suppose that term has been institutionalized. Will look it up.) As a decades long student of Natural History, I have found that Darwin's colleagues and intellectual descendants made two fundamental errors that have persisted as dogma ever since: (1). They accepted Chuck's speculation regarding a single progenitor of all current life as having arisen from a single common ancestor (or ancestry); and (2.) They consider the notion of morphological and genetic homologies as being confirmational of ancestral relationship. Clearly, zillions and zillions of origins of lives is the more parsimonious assumption. Neither mathematical, chemical, morphological, or genetic homologies are relevant in terms of relationship certainty.

    Thus, finding Darwin's assumptions in terms of origins of species to be problematic, one necessarily must turn to origins of lives (plural). "Agency is fundamental to any living system," as Prof. Nobel has it. In that regards, genetic, epigenetic, other intra cellular and external quantum realities soon become fascinatingly apparent. The cell and its various organelles are fascinating!

  19. @Claudia-bbc9

    December 14, 2025 at 5:58 pm

    No, life did not originate on this planet.
    If we eat, we get a lot of signals and information from the food spreading through our body. If we breathe, we get a lot of signals and information too with all the particles we get in our longs. The energy from light, wind, water is strongly influencing our body and mood. The way we think and move is essential for our well beeing.
    The DNA may be the cookbook instruction, but not the decision which meal has to be cooked.

  21. @privatename123

    December 14, 2025 at 5:58 pm

    Seems like it’s a matter of degree. Everything affects everything else, but inversely proportional to distance, with different strength factors. Life then becomes a management of the distances.

  22. @clavo3352

    December 14, 2025 at 5:58 pm

    Forgive my poor contribution but maybe it will create an impetus rain that results in a flood.
    I think it is important to know about the ideas Matt Richtel wrote about in "AN ELEGANT DEFENCE" and Sid Mukherjee's "THE EMPORER OF ALL MALADIES". This video interview deserves a fee based Zoom participation discussion.

  24. @vittorio4866

    December 14, 2025 at 5:58 pm

    It's time for scholars like Noble to leave their chairs and start looking around. There are many theories in circulation that have moved past these discussions.

  29. @Ro1Gg2Bv3

    December 14, 2025 at 5:58 pm

    The first heart beat is after 28 eight days of the existens of the embryo, that is after one moon circle. It starts to beat because of the male and female electromagnetic opposite in the embryo cells. In their created electromagnetic field.

  32. @HarmonicScaleFramework

    December 14, 2025 at 5:58 pm

    *Testable predictions inspired by Noble’s “biological relativity” (save for future verification)*

    1. *Bioelectric reprogramming beats gene edits (speed & reversibility).*
    Prediction: Modulating tissue-scale voltage patterns will switch cell fates faster and more reversibly than CRISPR in matched models.
    Test: Side-by-side time-to-phenotype and off-target burden; reversal by removing the voltage cue.

    2. *Context-dependent protein function is the rule, not the exception.*
    Prediction: A sizable fraction of “single-function” enzymes will show alternate functions when moved from cytosol to membrane or scaffolded microdomains.
    Test: Proteome-wide relocalization assays with functional readouts.

    3. *Rhythms without a gene clock.*
    Prediction: Stable cardiac-like oscillations persist in engineered cells with key “pacemaker genes” knocked down, if electromechanical coupling networks remain intact.
    Test: Knockdown + gap-junction-preserving cultures; quantify oscillation stability.

    4. *Stress guides variation (non-random mutational spectra).*
    Prediction: Under defined environmental stresses, mutation spectra and domain shuffling enrich along pathways relevant to the stressor, beyond neutral expectations.
    Test: Longitudinal whole-genome tracking with pathway-level enrichment statistics.

    5. *Genome as an organ: epigenome leads, sequence follows.*
    Prediction: Durable expression state changes can be induced epigenetically and later “fixed” by targeted sequence edits that mirror the prior state.
    Test: Induce state by chromatin/voltage cues, then observe convergent edits over passages.

    6. *Cancer = loss of global constraint, not a single driver.*
    Prediction: Restoring tissue-level electrical/mechanical constraints suppresses malignant behaviors even with driver mutations present.
    Test: 3D tumor models; apply bioelectric/mechanical fields; measure invasion and metabolic normalization.

    7. *Polygenic scores stay weak without context.*
    Prediction: Adding real-world context signals (inflammation, stress, social factors) will outperform pure polygenic risk in prospective disease prediction.
    Test: Head-to-head AUROC/ calibration in longitudinal cohorts.

    8. *Placebo is a physiological control signal, not noise.*
    Prediction: Placebo responders show coordinated autonomic–immune state transitions (HRV↑, IL-6↓, cortisol normalization) that predict clinical benefit.
    Test: Pre-registered biomarker panels in blinded RCTs.

    9. *Agency is distributed and measurable.*
    Prediction: Interventions that increase cross-scale coherence (cell→tissue→organ) improve goal-directed adaptation metrics (e.g., wound closure efficiency) independent of sequence changes.
    Test: Multiscale coherence indices vs outcome across perturbations.

    —
    If these hold up, they support Noble’s point: **causation in biology runs both ways**—genes matter, but context organizes.

  38. @ts88589

    December 14, 2025 at 5:58 pm

    Excellent discussion. I am thinking along those lines for years now and im not a genius, just someone who thinks clearly and logically about life and consciousness. There is still so much resistance to new ideas.

  42. @Alex-ff7oq

    December 14, 2025 at 5:58 pm

    I found this channel a few months ago while searching for more information about Bernardo Kastrup's work. Now I'm absolutely in love with these interviews. Thank you so much for sharing this high-level knowledge with all of us!! ❤

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