Orch OR

Consciousness and Orch OR

I became interested in consciousness as an undergraduate, and in medical school in the early 1970s worked in a cancer lab and studied mitotic cell division. The precise separation of chromosomes and formation of dividing daughter cells were performed by mitotic spindles and centrioles, composed of self-organizing protein polymers called microtubules. Fascinated by their apparent intelligence and purposeful behavior, I wondered whether the microtubule polymer lattice processed information as a molecular computer, to organize cellular activities. If so, could this be somehow relevant to consciousness?

Following medical school I trained in anesthesiology at the University of Arizona, mentored by the department founding chairman Burnell Brown. He convinced me the best way to understand consciousness was to understand how anesthetic gases selectively block it, sparing non-conscious brain activities. In my academic career I’ve researched anesthetic action, microtubules and consciousness, as well as high frequency jet ventilation, chronic pain therapies, neuromuscular blockade, brain monitoring during anesthesia and transcranial ultrasound brain therapy. With engineer and physicist colleagues I developed models of microtubule information processing at deeper, higher capacity levels within neurons, and in the 1980s challenged mainstream ideas in neuroscience and artificial intelligence (‘AI’).

Following an interest which began in medical school in the computational capacity of microtubules inside neurons, Dr. Hameroff proposed in the early 1980’s that microtubules functioned as molecular computers. Hameroff’s 1987 book Ultimate Computing suggested downloading consciousness into microtubule arrays.

In the mid-1990s Hameroff teamed with British physicist Sir Roger Penrose to develop the controversial theory of consciousness called “orchestrated objective reduction” – Orch OR theory – in which consciousness derives from quantum computations in microtubules inside brain neurons, quantum computations connected to the fine-scale structure of spacetime geometry. Dr. Hameroff has published five books and well over 100 research articles, and appeared in the film ‘What the Bleep do We Know?’ and numerous TV documentaries on the problem of consciousness including BBC, Discovery Channel, History Channel, PBS, OWN, Huff Post Live and the film “What the Bleep?”

But one day someone said: “OK, there’s all this information processing in microtubules going on inside neurons. How would that explain consciousness?” I had to admit I didn’t know, but fortunately he suggested I read ‘The emperor’s new mind’ by Roger Penrose (1989), which I did.

In it, Roger proposed ‘objective reduction’, ‘OR’, self-collapse of quantum superposition due to spacetime geometry, as a solution for both the quantum measurement problem and the ‘hard problem’ of conscious experience. It was audacious and brilliant. He was suggesting a ‘quantum’ mechanism for consciousness connected to the fine scale structure of the universe, but needed a quantum computer in the brain able to modulate neuronal functions. To me, microtubules fit the bill perfectly, and Roger agreed when we met. In the mid 1990s we published the Penrose-Hameroff theory of ‘orchestrated objective reduction’ (‘Orch OR’) which suggests consciousness arises from quantum vibrations ‘orchestrated’ in microtubules inside brain neurons, orchestrated vibrations which are proposed to interfere, ‘collapse’ and resonate across scale, control neuronal firings, and generate consciousness.

Orch OR was viewed skeptically, as quantum technology requires extreme cold to avoid thermal decoherence. But evidence has now shown 1) functional quantum behavior in photosynthesis proteins in sunlight, 2) coherent vibrations in microtubules at ambient temperatures in a multiscale hierarchy spanning terahertz, gigahertz, megahertz, kilohertz and hertz frequencies, 3) anesthetic action on microtubules rather than membrane proteins.

Testing Orch OR

For Orch OR to be feasible, microtubules would need to sustain functional quantum states spatially and temporally. Microtubules are polymers of the protein tubulin, each of which has 86 ‘aromatic’ amino acid rings (tryptophan, phenylalanine and tyrosine) of delocalized ‘pi electron’ resonance clouds. These electron clouds form non-polar (water-aversive) regions inside tubulin which are friendly to quantum-optical effects like fluorescence, phosphorescence, van der Waals coupled dipole oscillations, delayed luminescence, and superradiance. These non-polar regions are also precisely where anesthetic gases bind and act by weak, quantum interactions to selectively block consciousness.

To test Orch OR we set out to 1) demonstrate quantum optical states in microtubules at physiological conditions. If demonstrated, we would then 2) test effects of general anesthetics upon the microtubule quantum optical states. Failure to find quantum effects in microtubules, or, if found, determination that they were not dampened by anesthetics, would effectively ‘falsify’ Orch OR (Hameroff, 2021).

With funding from the Templeton World Charity Foundation (‘TWCF’; $230,000 over 2 years) program in ‘Accelerating Research in Consciousness’, Stuart Hameroff and Sir Roger Penrose convened an experimental group including Jack Tuszynski (U Alberta), Greg Scholes and Aarat Kalra (Princeton), Aristide Dogariu (Central Florida), Travis Craddock (Nova SE), and M. Bruce MacIver (Stanford). Two sets of experiments were planned and have been performed over the past two years.

At Princeton, Greg Scholes and Aarat Kalra studied tryptophan fluorescence lifetimes (‘TFLs’) in tubulin, and microtubules. Laser-induced optical excitations propagate far further, and persist far longer through microtubules than expected. Two different anesthetics (etomidate, and isoflurane) both significantly alter TFL excitation time and distance in microtubules (Lewton, 2022).

In Aristide Dogariu’s lab at the University of Central Florida, brief pulses of blue light shown on microtubules and tubulin proteins resulted in apparent ‘light-trapping’, and then re-emission in a process called delayed luminescence (‘DL’), apparently mediated by quantum ‘superradiance’ (Celardo et al., 2019). Tubulin units re-emitted half the light after hundreds of milliseconds, and microtubules re-emitted after more than a second. The experiments were repeated with anesthetics etomidate and isoflurane, and also a structurally related anti-convulsant (but non-anesthetic) drug. Both anesthetics, but not the anti-convulsant shortened the DL/superradiance time.

Superradiance and other quantum optical effects in microtubules support Orch OR, and could be essential for consciousness. We are writing up both studies, and planning further experiments with anesthetics in the gas phase to look for reversibility in superradiance inhibition, and compare different anesthetic potencies with their known potencies in rendering humans and animals unconscious and unresponsive. If those sets of potencies match, superradiance in microtubules would be, at least, a presumptive correlate of consciousness.

A new paradigm in neuroscience

Increasing evidence suggests functional aspects of consciousness and cognition operate and extend in a scale-invariant hierarchy, both 1) upward from the level of neurons to larger and larger neuronal networks and networks of networks in the brain, but also 2) downward, inward, smaller, to deeper, faster quantum processes in cytoskeletal microtubules inside neurons.

For the past 9 years Anirban Bandyopadhyay’s group at National Institutes of Material Sciences, in Tsukuba, Japan has found excitation and resonance in microtubules in terahertz, gigahertz, megahertz, kilohertz and hertz frequency ranges. The excitations occur in self-similar patterns which repeat every ~3 orders of magnitude as ‘triplets of triplets’, i.e. three peaks, each composed of 3 peaks.

The biological quantum vibrations apparently originate in terahertz quantum (van der Waals) dipole oscillations in and among aromatic amino acid rings of tryptophan, phenylalanine and tyrosine within each tubulin. This is the medium in which anesthesia acts to prevent consciousness, possibly by dampening quantum terahertz dipole oscillations.

Anirban’s group has also shown that gigahertz and megahertz oscillations in dendritic-somatic microtubules regulate axonal firings, and have detected gigahertz and megahertz from the scalp within the EEG, with self-similar ‘triplet-of-triplet’ patterns.

The brain should be viewed as a scale-invariant hierarchy, with 15 orders of magnitude of activities critical to consciousness and cognition extending inward, deeper, faster into microtubules inside neurons. And further still to fundamental spacetime geometry, according to Penrose OR.

Stuart Hameroff

Stuart Hameroff’s research pursued microtubule information processing and anesthetic action. In the mid-1990s he teamed with eminent British physicist and Nobel Laureate Sir Roger Penrose to develop a controversial quantum theory of consciousness (‘orchestrated objective reduction’, ‘Orch OR’) based on microtubule quantum computing. Harshly criticized initially, Orch OR is now supported by experimental results including anesthetic action. In 2017, with Sir Roger Penrose, James Tagg, Ivette Fuentes and Erik Viirre, Hameroff co-founded the Penrose Institute, intended to support research based on the various works of Sir Roger (cosmology, quantum mechanics, general relativity, black holes, geometry and consciousness).

Sir Roger Penrose

Roger Penrose Oxford University, Mathematics Dept. Born, 8 August 1931, Colchester Essex UK; 1st class mathematics degree at University College London; PhD at Cambridge UK: assistant lecturer, Bedford College London: Research Fellow St John’s College, Cambridge (now Honorary Fellow) post-doc at King’s College London; Cambridge; NATO Fellow at Princeton, Syracuse, and Cornell Universities, USA; 1-year appointment at University of Texas; Reader then full Professor at Birkbeck College, London; Rouse Ball Professor of Mathematics, Oxford University (during which, several 1/2-year periods as Mathematics Professor at Rice University, Houston, Texas) now Emeritus Rouse Ball Professor; Fellow, Wadham College, Oxford (now Emeritus Fellow). Many awards and honorary degrees, including knighthood, Fellow of Royal Society and of US National Academy of Sciences, De Morgan Medal of London Mathematical Society, Copley Medal of the Royal Society, Wolf Prize (shared with Stephen Hawking), Pomeranchuk Prize (Moscow). Designed many non-periodic tiling patterns including large paving at entrance of Andrew Wiles Mathematics Building, Oxford and Transbay Center, San Francisco

October 6, 2020 - The Royal Swedish Academy of Sciences awarded the Nobel Prize in Physics 2020 with one half to Roger Penrose for the discovery that black hole formation is a robust prediction of the general theory of relativity and the other half jointly to Reinhard Genzel and Andrea Ghez for the discovery of a supermassive compact object at the centre of our galaxy. Roger Penrose’s affiliation at the time of the Nobel award: University of Oxford, Oxford, United Kingdom - The Royal Swedish Academy of Sciences, Physics, 2020 - Scientific Background on the Nobel Prize in Physics 2020

Peer-reviewed publications — Orch OR

• Aarat P. Kalra, Alfy Benny, Sophie M. Travis, Eric A. Zizzi, Austin Morales-Sanchez, Daniel G. Oblinsky, Travis J. A. Craddock, Stuart R. Hameroff, M. Bruce MacIver, Jack A. Tuszynski, Sabine Petry, Roger Penrose, Gregory D. Scholes. Electronic Energy Migration in Microtubules, Aug 22, 2022. arXiv:2208.10628
• Hameroff, S. Consciousness, Cognition and the Neuronal Cytoskeleton — A New Paradigm Needed in Neuroscience. Front Mol Neurosci. 2022 Jun 16;15:869935. PubMed · doi
• Hameroff, S. ‘Orch OR’ is the most complete, and most easily falsifiable theory of consciousness. 2020. Cognitive Neuroscience, Published online: 24 Nov 2020. doi
• Kalra, A. P., Hameroff, S., Tuszynski, J., Dogariu, A., Nicolas, Sachin, & Gross, P. J. 2022, August 14. Anesthetic gas effects on quantum vibrations in microtubules – Testing the Orch OR theory of consciousness. OSF
• Editorial Views. “Anesthetic action and ‘quantum consciousness’: A match made in olive oil.” Hameroff, SR., 2018. Anesthesiology, 8(129):228-231. Anesthesiology
• Craddock TJA, Kurian P, Preto J, Sahu K, Hameroff SR, Klobukowski M, Tuszynski JA. Anesthetic Alterations of Collective Terahertz Oscillations in Tubulin Correlate with Clinical Potency: Implications for Anesthetic Action and Post-Operative Cognitive Dysfunction. Scientific Reports, 2017. PubMed · Newswise
• Hameroff, Stuart R., Penrose, Roger. Consciousness in the Universe: An Updated Review of the “Orch OR” Theory. In Biophysics of Consciousness: A Foundational Approach, eds. Poznanski, Tuszynski, Feinberg. World Scientific, 2016, Chapter 14. World Scientific
• Hameroff, S. “Change the Music: Psychotherapy and Brain Vibrations.” The Neuropsychotherapist 2016. Vol 4(4). 31-35. Link
• Craddock, Travis J.A., Stuart R. Hameroff, Ahmed T. Ayoub, Mariusz Klobukowski, & Jack A. Tuszynski. “Anesthetics act in quantum channels in brain microtubules to prevent consciousness.” Current Topics in Medicinal Chemistry 2015 Vol 15:6, 523-533. PubMed
• Hameroff, S. Commentary on Stuart Kauffman’s Quantum Criticality at the Origins of Life. Phys.org, Apr 15, 2015. phys.org
• Hameroff, S. Anesthesia Points to Deeper Level ‘Quantum Channels’. Newswise, March 23, 2015. Newswise
• Craddock, Travis John Adrian, Douglas Friesen, Jonathan Mane, Stuart Hameroff, & Jack A. Tuszynski. “The Feasibility of Coherent Energy Transfer in Microtubules.” Journal of the Royal Society Interface, 2014 11(100). Royal Society
• Hameroff, SR., Craddock TJ, & Tuszynski JA. Quantum effects in the understanding of consciousness. 2014. J Integr Neurosci. 13 June (2):229-52. PubMed
• Hameroff, S. Comment on L Turin et al, Proc. Nat. Acad. Sci., “Electron spin change during general anesthesia.” Aug. 11, 2014. PNAS
• Hadlington, Simon. “Knock-out theory puts new spin on general anaesthesia.” Chemistry World Review, 2014, August 11. Chemistry World
• Luca Turin, Efthimios M. C. Skoulakis, Andrew P. Horsfield. “Electron spin changes during general anesthesia in Drosophila.” Proc. Nat. Acad. Sci., 2014. PNAS
• Hameroff, SR. 2006. “The entwined mysteries of anesthesia and consciousness: Is there a common underlying mechanism?” Anesthesiology 105(2):400–412. Anesthesiology
• Hameroff, S., & Roger Penrose. “Consciousness in the universe: A review of the ‘Orch OR’ theory.” Physics of Life Reviews, 2014 March 11(1):39-78. PubMed
• Hameroff, S., & Penrose R. Reply to Seven Commentaries on “Consciousness in the Universe: Review of the ‘Orch OR’ theory.” Physics of Life Reviews, 2014 11:94–100. ScienceDirect
• Hameroff, S., & Penrose, R. Reply to Criticism of the ‘Orch OR qubit’ – Orchestrated objective reduction is scientifically justified. Physics of Life Reviews, 2014 11(1):104-112. ScienceDirect
• Hameroff, Stuart. Consciousness, Microtubules and “Orch-OR”: A ‘Space-time’ Odyssey. Journal of Consciousness Studies, Imprint Academic. 2014 Vol 21, 3-4, 126-153. IngentaConnect
• Hameroff, S. Quantum walks in brain microtubules — a biomolecular basis for quantum cognition? Top Cogn Sci., 2014 January; 6(1):91-7. PubMed
• Discovery of quantum vibrations in ‘microtubules’ corroborates theory of consciousness. Phys.org, 16 January 2014. phys.org
• Hameroff, SR. Quantum mathematical cognition requires quantum brain biology: the “Orch OR” theory. Behav Brain Sci, 2013. June; 36(3):287-90. PubMed
• Hameroff, S. Comment on: “Dissipation of ‘dark energy’ by cortex in knowledge retrieval” by Capolupo, Freeman and Vitiello. Phys Life Rev. 2013 March; 10(1):95-6; discussion 112-6. PubMed
• Hameroff, S, Trakas M, Duffield C, Annabi E, Gerace MB, Boyle P, Lucas A, Amos Q, Buadu A, Badal JJ. Transcranial ultrasound (TUS) effects on mental states: a pilot study. Brain Stimul, 2013; May;6(3):409-15. PubMed
• Hameroff, S. How quantum brain biology can rescue conscious free will. Front Integr Neurosci, 2012; 6:93, Oct 12. PubMed
• Craddock TJ, St. George Marc, Freedman Holly, Barakat Khaled, Damaraju Sambasivarao, Hameroff Stuart, Tuszynski Jack A. Computational Predictions of Volatile Anesthetic Interactions with the Microtubule Cytoskeleton. PLoS One, 2012; June 25. PLoS One
• Hameroff S. Quantum brain biology complements neuronal assembly approaches to consciousness: Comment on “Consciousness, biology and quantum hypotheses” by Baars and Edelman. Phys Life Rev. 2012 Sep;9(3):303-5; discussion 306-7. PubMed
• Craddock T, Tuszynski J, & Hameroff S. Cytoskeletal Signaling: Is Memory Encoded in Microtubule Lattices by CaMKII Phosphorylation? PLoS Comput Biology, 2012; March 8. PLoS Comput Biol
• Craddock TJ, Tuszynski JA, Chopra D, Casey N, Goldstein LE, Hameroff SR, Tanzi RE. The Zinc Dyshomeostasis Hypothesis of Alzheimer’s Disease. PLoS One, 2012; Mar 23 7(3). PLoS One
• Penrose, R., & Hameroff, S.R. “Consciousness in the Universe: Neuroscience, Quantum Space-Time Geometry and Orch OR Theory.” Journal of Cosmology, 2011, Vol 14. PDF

Full list of publications and citations available via the Bio / CV / Press link.