While some other theories assert that consciousness emerges as the complexity of thecomputations performed bycerebralneurons increases,[4][5] Orch OR posits that consciousness is based onnon-computablequantum processing performed byqubits formed collectively on cellular microtubules, a process significantly amplified in the neurons. The qubits are based on oscillatingdipoles formingsuperposed resonance rings in helical pathways throughout lattices of microtubules. The oscillations are either electric, due to charge separation fromLondon forces, or magnetic, due toelectron spin—and possibly also due tonuclear spins (that can remain isolated for longer periods) that occur ingigahertz,megahertz, andkilohertz frequency ranges.[2][6] Orchestration refers to the hypothetical process by which connective proteins, such asmicrotubule-associated proteins, influence or orchestrate qubitstate reduction by modifying the spacetime-separation of their superimposed states.[7] The latter is based onPenrose's objective-collapse theory for interpreting quantum mechanics, which postulates the existence of an objective threshold governing the collapse ofquantum states, related to the difference of thespacetime curvature of these states in the universe'sfine-scale structure.[8]
Orchestrated objective reduction has been criticized from its inception by mathematicians, philosophers,[9][10][11][12][13] and scientists.[14][15][16] These criticisms focus on three issues: Penrose's interpretation ofGödel's theorem; Penrose'sabductive reasoning, linking non-computability to quantum events; and the brain's unsuitability to host the quantum phenomena required by the theory, since it is considered too "warm, wet and noisy" to avoiddecoherence.
In 1931, mathematician and logicianKurt Gödel proved that anyeffectively generated theory capable of proving basic arithmetic cannot be bothconsistent andcomplete. In other words, a mathematically sound theory lacks the means to prove itself.[17] In his first book concerning consciousness,The Emperor's New Mind (1989),Roger Penrose argued that equivalent statements to "Gödel-type propositions" had recently been put forward.[18]
Partially in response to Gödel's argument, thePenrose–Lucas argument leaves the question of the physical basis of non-computable behavior open. Most physical laws are computable, and thus algorithmic. However, Penrose determined thatwave function collapse was a prime candidate for a non-computable process. Inquantum mechanics, particles are treated differently from the objects ofclassical mechanics. Particles are described bywave functions that evolve according to theSchrödinger equation. Non-stationary wave functions arelinear combinations of theeigenstates of the system, a phenomenon described by thesuperposition principle. When a quantum system interacts with a classical system—i.e., when anobservable is measured—the system appears tocollapse to a random eigenstate of that observable from a classical vantage point.
If collapse is truly random, then no process or algorithm can deterministically predict its outcome. This provided Penrose with a candidate for the physical basis of the non-computable process that he hypothesized to exist in the brain. However, he disliked the random nature of environmentally induced collapse, as randomness was not a promising basis for mathematical understanding. Penrose proposed that isolated systems may still undergo a new form of wave function collapse, which he called objective reduction (OR).[7]
Penrose sought to reconcilegeneral relativity and quantum theory using his own ideas about the possible structure ofspacetime.[18][page needed][19] He suggested that at thePlanck scale, curved spacetime is not continuous, but discrete. He further postulated that each separatedquantum superposition has its own piece ofspacetime curvature, a blister in spacetime. Penrose suggests that gravity exerts a force on these spacetime blisters, which become unstable above the Planck scale of and collapse to just one of the possible states. The rough threshold for OR is given by Penrose's indeterminacy principle:
where:
is the time until OR occurs,
is the gravitational self-energy or the degree of spacetime separation given by the superpositioned mass, and
Thus, the greater the mass–energy of the object, the faster it will undergo OR and vice versa.Mesoscopic objects could collapse on a timescale relevant to neural processing.[7][additional citation(s) needed]
An essential feature of Penrose's theory is that the choice of states when objective reduction occurs is selected neither randomly (as are choices following wave function collapse) nor algorithmically. Rather, states are selected by a "non-computable" influence embedded in thePlanck scale of spacetime geometry. Penrose claimed that such information isPlatonic, representing pure mathematical truths, which relates to Penrose's ideas concerning the three worlds: the physical, the mental, and the Platonic mathematical world. InShadows of the Mind (1994), Penrose briefly indicates that this Platonic world could also include aesthetic and ethical values, but he does not commit to this further hypothesis.[19]
The Penrose–Lucas argument has been criticized by mathematicians,[20][21][22] computer scientists,[12] and philosophers,[23][24][9][10][11] and the consensus among experts in these fields is that the argument fails,[25][26][27] with different authors attacking various aspects of it.[27][28]Marvin Minsky has argued that because humans can believe false ideas to be true, human mathematical understanding need not be consistent, and consciousness may easily have a deterministic basis.[29]Solomon Feferman has argued that mathematicians do not progress by mechanistic search through proofs, but by trial-and-error reasoning, insight, and inspiration, and that machines do not share this approach with humans.[21]
Penrose outlined a predecessor to Orch OR inThe Emperor's New Mind, coming to the problem from a mathematical viewpoint and in particular Gödel's theorem, but it lacked a detailed proposal for how quantum processes could be implemented in the brain.Stuart Hameroff separately worked in cancer research andanesthesia, which gave him an interest in brain processes. Hameroff read Penrose's book and suggested to him thatmicrotubules within neurons were suitable candidate sites for quantum processing, and ultimately for consciousness.[30][31] Throughout the 1990s, the two collaborated on the Orch OR theory, which Penrose published inShadows of the Mind (1994).[19]
Hameroff's contribution to the theory derived from his study of the neuralcytoskeleton, and particularly on microtubules.[31] As neuroscience has progressed, the role of the cytoskeleton and microtubules has assumed greater importance. In addition to providing structural support, microtubule functions includeaxoplasmic transport and control of the cell's movement, growth, and shape.[31]
Orch OR combines the Penrose–Lucas argument with Hameroff's hypothesis on quantum processing in microtubules. It proposes that when condensates in the brain undergo an objective wave function reduction, their collapse connects noncomputational decision-making to experiences embedded in spacetime's fundamental geometry. The theory further proposes that the microtubules both influence and are influenced by the conventional activity at the synapses between neurons.
Hameroff proposed that microtubules were suitable candidates for quantum processing.[31] Microtubules are made up oftubulin protein subunits. The tubulin proteindimers of the microtubules havehydrophobic pockets that may contain delocalizedπ electrons. Tubulin has other, smaller non-polar regions, for example eighttryptophans per tubulin, which contain π electron-richindole rings distributed throughout tubulin with separations of roughly 2 nm. Hameroff claims that this is close enough for the tubulin π electrons to becomequantum entangled.[32] During entanglement, particle states become inseparably correlated.
Hameroff originally suggested in the fringeJournal of Cosmology that the tubulin-subunit electrons would form aBose–Einstein condensate.[33] He then proposed aFrohlich condensate, a hypothetical coherent oscillation of dipolar molecules. However, this too was rejected by Reimers's group.[34] Hameroff and Penrose contested the conclusion, noting that Reimers's microtubule model was oversimplified.[35]
Hameroff then proposed that condensates in microtubules in oneneuron can link with microtubule condensates in other neurons andglial cells via thegap junctions ofelectrical synapses.[36][37] He proposed that the gap between the cells is sufficiently small that quantum objects cantunnel across it, allowing them to extend across a large area of the brain. He further postulated that the action of this large-scale quantum activity is the source of 40 Hzgamma waves, building upon the much less controversial theory that gap junctions are related to gamma oscillation.[38]
In a study Hameroff was part of,Jack Tuszyński of theUniversity of Alberta demonstrated that anesthetics hasten the duration of a process called delayed luminescence, in which microtubules and tubulinsre-emit trapped light. Tuszyński suspects that the phenomenon has a quantum origin, withsuperradiance being investigated as one possibility (in a 2024 study, superradiance was confirmed to occur in networks oftryptophans, which are found in microtubules).[39][40] Tuszyński toldNew Scientist that "We're not at the level of interpreting this physiologically, saying 'Yeah, this is where consciousness begins,' but it may."[41]
The 2024 study, called "Ultraviolet Superradiance from Mega-Networks of Tryptophan in Biological Architectures" and published inThe Journal of Physical Chemistry, confirmed superradiance in networks of tryptophans.[39][40] Large networks of tryptophans are a warm and noisy environment, in which quantum effects typically are not expected to take place.[39] The results of the study were theoretically predicted and then experimentally confirmed by the researchers.[39][40]Majed Chergui, who led the experimental team, stated that "It's a beautiful result. It took very precise and careful application of standard protein spectroscopy methods, but guided by the theoretical predictions of our collaborators, we were able to confirm a stunning signature of superradiance in a micron-scale biological system."[39]Marlan Scully, a physicist known for his work in the field of theoretical quantum optics, said, "We will certainly be examining closely the implications for quantum effects in living systems for years to come."[39] The study states that "by analyzing the coupling with the electromagnetic field of mega-networks of Trp present in these biologically relevant architectures, we find the emergence of collective quantum optical effects, namely, superradiant and subradiant eigenmodes. ... our work demonstrates that collective and cooperative UV excitations in mega-networks of Trp support robust quantum states in protein aggregates, with observed consequences even under thermal equilibrium conditions."[40]
Microtubule quantum vibration theory of anesthetic action
In an experiment,Gregory D. Scholes and Aarat Kalra ofPrinceton University used lasers to excite molecules within tubulins, causing a prolonged excitation to diffuse through microtubules farther than expected, which did not occur when repeated under anesthesia.[42] However, diffusion results have to be interpreted carefully, since even classical diffusion can be very complex due to the wide range of length scales in the fluid-filled extracellular space.[43]
At high concentrations (~5MAC), the anesthetic gashalothane causes reversible depolymerization of microtubules.[44] This cannot be the mechanism of anesthetic action, however, because human anesthesia is performed at 1MAC. (Neither Penrose or Hameroff claim that depolymerization is the mechanism of action for Orch OR.)[45][46] At ~1 MAC halothane, reported minor changes in tubulin protein expression (~1.3-fold) in primary cortical neurons after exposure to halothane and isoflurane are not evidence that tubulin directly interacts with general anesthetics, but rather shows that the proteins controlling tubulin production are possible anesthetic targets.[47] Further proteomic study reports 0.5 mM [14C]halothane binding to tubulin monomers alongside three dozens of other proteins.[48] In addition, modulation of microtubule stability has been reported duringanthracene general anesthesia of tadpoles.[49] The study, called "Direct Modulation of Microtubule Stability Contributes to Anthracene General Anesthesia" claims to provide "strong evidence that destabilization of neuronal microtubules provides a path to achieving general anesthesia".[49]
Computer modeling of tubulin's atomic structure[50] found that anesthetic gas molecules bind adjacent to amino acid aromatic rings of non-polarπ-electrons and that collective quantum dipole oscillations among all π-electron resonance rings in each tubulin showed a spectrum with a common mode peak at 613THz.[51] Simulated presence of eight different anesthetic gases abolished the 613 THz peak, whereas the presence of two different nonanesthetic gases did not affect the 613 THz peak, from which it was speculated that this 613 THz peak in microtubules could be related to consciousness and anesthetic action.[51]
Another study that Hameroff was a part of claims to show that "anesthetic molecules can impair π-resonance energy transfer and exciton hopping in 'quantum channels' of tryptophan rings in tubulin, and thus account for selective action of anesthetics on consciousness and memory".[52]
In a study published in August 2024, an undergraduate group led by aWellesley College professor found that rats givenepothilone B, a drug that binds to microtubules, took over a minute longer to fall unconscious when exposed to an anesthetic gas.[53]
David Chalmers has argued against quantum consciousness, discussing instead how quantum mechanics may relate todualistic consciousness.[61] He has expressed skepticism that any new physics can resolve thehard problem of consciousness[62][63][64] and argued that quantum theories of consciousness suffer from the same weakness as more conventional theories. Just as he has argued that there is no particular reason why specific macroscopic physical features in the brain should give rise to consciousness, he also holds that there is no particular reason why a specific quantum feature, such as the EM field in the brain, should give rise to consciousness.[64]
In 2000,Max Tegmark claimed that any quantum coherent system in the brain would undergo effectivewave function collapse due to environmental interaction long before it could influence neural processes (the "warm, wet and noisy" argument, as it later came to be known).[14] He determined the decoherence timescale of microtubule entanglement at brain temperatures to be on the order offemtoseconds, far too brief for neural processing.Christof Koch andKlaus Hepp also agreed thatquantum coherence does not play, or does not need to play, any major role inneurophysiology.[15][16] Koch and Hepp concluded that "The empirical demonstration of slowly decoherent and controllable quantum bits in neurons connected by electrical or chemical synapses, or the discovery of an efficient quantum algorithm for computations performed by the brain, would do much to bring these speculations from the 'far-out' to the mere 'very unlikely'".[15]
In response to Tegmark's claims, Hagan, Tuszynski, and Hameroff claimed that he did not address the Orch OR model but instead a model of his own construction. This involved superpositions of quanta separated by 24 nm rather than the much smaller separations stipulated for Orch OR. As a result, Hameroff's group claimed a decoherence time seven orders of magnitude greater than Tegmark's, although still far below 25ms. Hameroff's group also suggested that theDebye layer ofcounterions could screen thermal fluctuations, and that the surroundingactin gel might enhance the ordering of water, further screening noise. They also suggested that incoherent metabolic energy could further order water, and finally that the configuration of the microtubule lattice might be suitable forquantum error correction, a means of resisting quantum decoherence.[65][66]
In 2009, Reimers et al. and McKemmish et al. published critical assessments. Earlier versions of the theory had required tubulin-electrons to form eitherBose–Einsteins orFrohlich condensates, and the Reimers group noted the lack of empirical evidence that such could occur. Additionally, they calculated that microtubules could only support weak 8 MHz coherence. McKemmish et al. argued thataromatic molecules cannot switch states, because they are delocalized, and that changes in tubulin protein-conformation driven byGTP conversion would result in a prohibitive energy requirement.[54][34][55]
In 2022, a group of Italian physicists conducted several experiments that failed to observe spontaneous radiation emissions predicted by theDiósi–Penrose collapse model, but that "Penrose's original collapse model, unlike Diósi's, did not predict spontaneous radiation, so has not been ruled out."[67][68]
Endogenous ferritin quenches microtubule radiance, which may prevent generation of ultraviolet biophotons
While some of the studies mentioned above purport to show superradiance and an influence of anesthetics on decreasing excitation diffusion through microtubules, those studies were performed under artificial conditions that failed to include proteins associated with microtubules likeferritin,[69] which quenches microtubule superradiance.[70] Evidence published prior to those studies establishes that ferritin interacts with microtubules in vivo and is essential for microtubule stability and function.[71] For instance, those studies overlooked that:
Studies of biophotons in the human body fail to find any evidence ofultraviolet (UV)biophotons.[72] In contrast, at least one of the studies cited above that is relied on as evidence of microtubule superradiance in support of Orch-OR relies on earlier studies of UV biophotons measured in single-celled organisms likeE. coli and respiratory deficient yeast as the basis for its contention that such biophotons are present in cells.[73][74] That study also usedUV-vis equipment with a light source that can generate 1020 photons per second, which is not representative of neurons' environment.
Ferritin in the human body absorbs UV from external sources at least in the skin and in the cornea, where the levels of UV photons are much higher than measured biophoton levels of UV even inE. coli and yeast.[75][76] Endogenous ferritin in neurons would absorb UV biophotons that might be emitted from chemical processes (at levels that are too low to measure), and those UV biophotons would not even reach microtubules to cause superradiance or energy transport.
Ferritin contains tryptophan residues, the same material in microtubules that is supposed to cause microtubule superradiance.[77] According to one of the studies cited above, microtubule superradiance is based on special configurations of tryptophan residues. The failure of that study to consider additional ferritin tryptophan residues in the vicinity of microtubule tryptophan residues means that the study is not relevant to cellular environments that include ferritin (which is basically every cell). As noted above, ferritin perturbs tubulin in the vicinity of tryptophan residues, which invalidates ana priori assumption of that study.
Ferritin has stronger ionic interaction with microtubules than the anesthetics that were used in one of the studies cited above and has electrical and magnetic properties that those anesthetics lack.[78][79][80] Even if anesthetics interact with microtubules, ferritin has stronger interactions with microtubules, which may explain why ferritin is able to quench microtubule fluorescence.
In summary, experiments trying to demonstrate microtubule superradiance involved unrealistic levels of UV light and artificial environments, and excluded cellular substances that would prevent microtubule superradiance and energy transport.
Biology-based criticisms have been offered, including a lack of explanation for the probabilistic release ofneurotransmitters from presynapticaxon terminals[81][82][83] and an error in the calculated number of the tubulin dimers per cortical neuron.[84]
In 2014, Penrose and Hameroff published responses to some criticisms and revisions to many of the theory's peripheral assumptions, while retaining the core hypothesis.[2][6]
^abcHameroff, Stuart; Penrose, Roger (2014). "Reply to seven commentaries on "Consciousness in the universe: Review of the 'Orch OR' theory"".Physics of Life Reviews.11 (1):94–100.Bibcode:2014PhLRv..11...94H.doi:10.1016/j.plrev.2013.11.013.
^abHameroff, Stuart; Penrose, Roger (2014). "Reply to criticism of the 'Orch OR qubit' – 'Orchestrated objective reduction' is scientifically justified".Physics of Life Reviews.11 (1):104–112.Bibcode:2014PhLRv..11..104H.doi:10.1016/j.plrev.2013.11.014.
^abDavis, Martin (September 1993). "How subtle is Gödel's theorem? More on Roger Penrose".Behavioral and Brain Sciences.16 (3):611–612.doi:10.1017/S0140525X00031915.S2CID144018337.
^Hofstadter 1979, pp. 476–477,Russell & Norvig 2003, p. 950,Turing 1950 under "The Argument from Mathematics", where he writes, "although it is established that there are limitations to the powers of any particular machine, it has only been stated, without sort of proof, that no such limitations apply to the human intellect".
^In an article at"King's College London – Department of Mathematics". Archived fromthe original on 25 January 2001. Retrieved22 October 2010., L.J. Landau at the Mathematics Department of King's College London writes that "Penrose's argument, its basis and implications, is rejected by experts in the fields which it touches."
^abPrinceton Philosophy professor John Burgess writes inOn the Outside Looking In: A Caution about Conservativeness (published in Kurt Gödel: Essays for his Centennial, with the following comments found onpp. 131–132) that "the consensus view of logicians today seems to be that the Lucas–Penrose argument is fallacious, though as I have said elsewhere, there is at least this much to be said for Lucas and Penrose, that logicians are not unanimously agreed as to where precisely the fallacy in their argument lies. There are at least three points at which the argument may be attacked."
^Marvin Minsky. "Conscious Machines". Machinery of Consciousness, Proceedings, National Research Council of Canada, 75th Anniversary Symposium on Science in Society, June 1991.
^Pan, Jonathan Z.; Xi, Jin; Tobias, John W.; Eckenhoff, Maryellen F.; Eckenhoff, Roderic G. (2007). "Halothane binding proteome in human brain cortex".Journal of Proteome Research.6 (2):582–592.doi:10.1021/pr060311u.PMID17269715.
^Craddock, T. J.; Hameroff, S. R.; Ayoub, A. T.; Klobukowski, M.; Tuszynski, J. A. (2015). "Anesthetics act in quantum channels in brain microtubules to prevent consciousness".Current Topics in Medicinal Chemistry.15 (6):523–533.doi:10.2174/1568026615666150225104543.PMID25714379.
^abReimers, Jeffrey R.; McKemmish, Laura K.; McKenzie, Ross H.; Mark, Alan E.; Hush, Noel S. (2014). "The revised Penrose–Hameroff orchestrated objective-reduction proposal for human consciousness is not scientifically justified".Physics of Life Reviews.11 (1):101–103.Bibcode:2014PhLRv..11..101R.doi:10.1016/j.plrev.2013.11.003.PMID24268490.
^Villatoro, Francisco R. (17 June 2015)."On the quantum theory of consciousness".Mapping Ignorance. University of the Basque Country. Retrieved18 August 2018.Hameroff's ideas in the hands of Penrose have developed almost to absurdity.
^Chalmers, David J. (1997).The Conscious Mind: In Search of a Fundamental Theory (Paperback ed.). New York: Oxford University Press.ISBN978-0-19-511789-9.
^Derakhshani, Maaneli; Diósi, Lajos; Laubenstein, Matthias; Piscicchia, Kristian; Curceanu, Catalina (1 September 2022). "At the crossroad of the search for spontaneous radiation and the Orch OR consciousness theory".Physics of Life Reviews.42:8–14.Bibcode:2022PhLRv..42....8D.doi:10.1016/j.plrev.2022.05.004.PMID35617922.S2CID248868080.
^Hasan, Mohammad Rubayet; Koikawa, Sayaka; Kotani, Susumu; Miyamoto, Shigeaki; Nakagawa, Hiroyuki (July 2006). "Ferritin forms dynamic oligomers to associate with microtubules in vivo: Implication for the role of microtubules in iron metabolism".Experimental Cell Research.312 (11):1950–1960.doi:10.1016/j.yexcr.2006.02.023.ISSN0014-4827.PMID16603154.
^Ghosh, Subhajit; Mohapatra, Saswat; Thomas, Anisha; Bhunia, Debmalya; Saha, Abhijit; Das, Gaurav; Jana, Batakrishna; Ghosh, Surajit (4 November 2016). "Apoferritin Nanocage Delivers Combination of Microtubule and Nucleus Targeting Anticancer Drugs".ACS Applied Materials & Interfaces.8 (45):30824–30832.Bibcode:2016AAMI....830824G.doi:10.1021/acsami.6b11798.ISSN1944-8244.PMID27782381.Intrinsic Trp fluorescence of tubulin is quenched upon binding of Apf with tubulin and indicates that its binding with tubulin perturbs tubulin conformation in the vicinity of Trp residues
^Rourk, Christopher (29 May 2025). "The interaction of ferritin with microtubules in vivo will inhibit microtubule superradiance and electronic energy migration through microtubules".doi.org.doi:10.31219/osf.io/qujne_v3.
^Tilbury, R. N.; Quickenden, T. I. (January 1988). "Spectral and Time Dependence Studies of the Ultra Weak Bioluminescence Emitted by the BacteriumEscherichia coli".Photochemistry and Photobiology.47 (1):145–150.doi:10.1111/j.1751-1097.1988.tb02704.x.ISSN0031-8655.
^Applegate, Lee Ann; Scaletta, Corinne; Panizzon, Renato; Frenk, Edgar (July 1998). "Evidence That Ferritin is UV Inducible in Human Skin: Part of a Putative Defense Mechanism".Journal of Investigative Dermatology.111 (1):159–163.doi:10.1046/j.1523-1747.1998.00254.x.ISSN0022-202X.PMID9665404.
^Kumar, Karuppannan Senthil; Pasula, Rupali Reddy; Lim, Sierin; Nijhuis, Christian A. (28 December 2015). "Long-Range Tunneling Processes across Ferritin-Based Junctions".Advanced Materials.28 (9):1824–1830.doi:10.1002/adma.201504402.ISSN0935-9648.PMID26708136.
^Hasan, Mohammad R.; Morishima, Daisuke; Tomita, Kyoko; Katsuki, Miho; Kotani, Susumu (13 January 2005). "Identification of a 250 kDa putative microtubule-associated protein as bovine ferritin".The FEBS Journal.272 (3):822–831.doi:10.1111/j.1742-4658.2004.04520.x.ISSN1742-464X.PMID15670162.
^Sahu, Satyajit; Ghosh, Subrata; Ghosh, Batu; Aswani, Krishna; Hirata, Kazuto; Fujita, Daisuke; Bandyopadhyay, Anirban (September 2013). "Atomic water channel controlling remarkable properties of a single brain microtubule: Correlating single protein to its supramolecular assembly".Biosensors and Bioelectronics.47:141–148.doi:10.1016/j.bios.2013.02.050.ISSN0956-5663.PMID23567633.
^Beck, Friedrich; Eccles, John C. (1998). "Quantum processes in the brain: A scientific basis of consciousness".Cognitive Studies: Bulletin of the Japanese Cognitive Science Society.5 (2):95–109.doi:10.11225/jcss.5.2_95.
