Orchestrated objective reduction (Orch OR) is a biological theory of mind that postulates that consciousness originates at the quantum level inside neurons, rather than the conventional view that it is a product of connections between neurons. The mechanism is held to be a quantum process called objective reduction that is orchestrated by cellular structures called microtubules. It is proposed that the theory may answer the hard problem of consciousness and provide a mechanism for free will.^{} The hypothesis was first put forward in the early 1990s by theoretical physicist Roger Penrose and anaesthesiologist and psychologist Stuart Hameroff. The hypothesis combines approaches from molecular biology, neuroscience, quantum physics, pharmacology, philosophy, quantum information theory, and quantum gravity.^{}^{}

While mainstream theories assert that consciousness emerges as the complexity of the computations performed by cerebral neurons increases,^{}^{} Orch OR posits that consciousness is based on non-computable quantum processing performed by qubits formed collectively on cellular microtubules, a process significantly amplified in the neurons.^{} The qubits are based on oscillating dipoles forming superposed resonance rings in helical pathways throughout lattices of microtubules. The oscillations are either electric, due to charge separation from London forces, or magnetic, due to electron spin—and possibly also due to nuclear spins (that can remain isolated for longer periods) that occur in gigahertz, megahertz and kilohertz frequency ranges.^{}^{} Orchestration refers to the hypothetical process by which connective proteins, such as microtubule-associated proteins (MAPs), influence or orchestrate qubit state reduction by modifying the spacetime-separation of their superimposed states.^{} The latter is based on Penrose’s objective-collapse theory for interpreting quantum mechanics, which postulates the existence of an objective threshold governing the collapse of quantum-states, related to the difference of the space-time curvature of these states in the universe’s fine-scale structure.^{}

Orch OR has been criticized from its inception by mathematicians, philosophers,^{}^{}^{}^{} and scientists,^{}^{}^{}^{}^{} prompting the authors to revise and elaborate many of the theory’s peripheral assumptions, while retaining the core hypothesis.^{} The criticism concentrated on three issues: Penrose’s interpretation of Gödel’s theorem; Penrose’s abductive reasoning linking non-computability to quantum processes; and the brain’s unsuitability to host the quantum phenomena required by the theory, since it is considered too “warm, wet and noisy” to avoid decoherence. In other words, there is a missing link between physics and neuroscience in the pursuit of a theory of everything.^{} However, some evidence has been produced in recent years.

In 1931, mathematician and logician Kurt Gödel proved that any effectively generated theory capable of proving basic arithmetic cannot be both consistent and complete. In other words, a mathematically sound theory lacks the means to prove itself. An analogous statement has been used to show that humans are subject to the same limits as machines.^{} However, in his first book on consciousness, *The Emperor’s New Mind* (1989), Roger Penrose argued that Gödel-unprovable results are provable by human mathematicians.^{} He takes this disparity to mean that human mathematicians are not describable as formal proof systems, and are therefore running a non-computable algorithm.

If correct, the Penrose–Lucas argument leaves the question of the physical basis of non-computable behaviour open. Most physical laws are computable, and thus algorithmic. However, Penrose determined that wave function collapse was a prime candidate for a non-computable process. In quantum mechanics, particles are treated differently from the objects of classical mechanics. Particles are described by wave functions that evolve according to the Schrödinger equation. Non-stationary wave functions are linear combinations of the eigenstates of the system, a phenomenon described by the superposition principle. When a quantum system interacts with a classical system—i.e. when an observable is measured—the system appears to collapse 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).^{}

Penrose sought to reconcile general relativity and quantum theory using his own ideas about the possible structure of spacetime.^{}^{} He suggested that at the Planck scale curved spacetime is not continuous, but discrete. He further postulated that each separated quantum superposition has its own piece of spacetime curvature, a blister in spacetime. Penrose suggests that gravity exerts a force on these spacetime blisters, which become unstable above the Planck scale and collapse to just one of the possible states.

Thus, the greater the mass-energy of the object, the faster it will undergo OR and vice versa. Atomic-level superpositions would require 10 million years to reach OR threshold, while an isolated 1 kilogram object would reach OR threshold in 10^{−37}s. Objects somewhere between these two scales could collapse on a timescale relevant to neural processing.

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 the Planck scale of spacetime geometry. Penrose claimed that such information is Platonic, representing pure mathematical truth, aesthetic and ethical values at the Planck scale. This relates to Penrose’s ideas concerning the three worlds: the physical, the mental, and the Platonic mathematical world.

The Penrose–Lucas argument was criticized by mathematicians,^{}^{}^{}^{}^{} computer scientists,^{} and philosophers,^{}^{}^{}^{}^{} and the consensus among experts in these fields is that the argument fails,^{}^{}^{} with different authors attacking different aspects of the argument.^{}^{} Minsky 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.^{} Feferman 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.

^{}Orch OR

Penrose outlined a predecessor to Orch OR in *The Emperor’s New Mind*, coming to the problem from a mathematical viewpoint and in particular Gödel’s theorem, but lacked a detailed proposal for how quantum processes could be implemented in the brain. Stuart Hameroff separately worked in cancer research and anesthesia, which gave him an interest in brain processes. Hameroff read Penrose’s book and suggested to him that microtubules within neurons were suitable candidate sites for quantum processing, and ultimately for consciousness.^{}^{} Throughout the 1990s, the two collaborated on the Orch-OR theory, which Penrose published in *Shadows of the Mind* (1994).^{}

Hameroff’s contribution to the theory derived from his study of the neural cytoskeleton, and particularly on microtubules.^{} As neuroscience has progressed, the role of the cytoskeleton and microtubules has assumed greater importance. In addition to providing structural support, microtubule functions include axoplasmic transport and control of the cell’s movement, growth and shape.^{}

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.^{} Microtubules are made up of tubulin protein subunits. The tubulin protein dimers of the microtubules have hydrophobic pockets that may contain delocalized π electrons. Tubulin has other, smaller non-polar regions, for example 8 tryptophans per tubulin, which contain π electron-rich indole rings distributed throughout tubulin with separations of roughly 2 nm. Hameroff claims that this is close enough for the tubulin π electrons to become quantum entangled.^{} During entanglement, particle states become inseparably correlated.

Hameroff originally suggested in the fringe *Journal of Cosmology* that the tubulin-subunit electrons would form a Bose–Einstein condensate.^{} He then proposed a Frohlich condensate, a hypothetical coherent oscillation of dipolar molecules. However, this too was rejected by Reimers’ group.^{} Hameroff then responded to Reimers. “Reimers et al have most definitely NOT shown that strong or coherent Frohlich condensation in microtubules is unfeasible. The model microtubule on which they base their Hamiltonian is not a microtubule structure, but a simple linear chain of oscillators.” Hameroff reasoned that such condensate behavior would magnify nanoscopic quantum effects to have large scale influences in the brain.

Hameroff proposed that condensates in microtubules in one neuron can link with microtubule condensates in other neurons and glial cells via the gap junctions of electrical synapses.^{}^{} Hameroff proposed that the gap between the cells is sufficiently small that quantum objects can tunnel 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 Hz gamma waves, building upon the much less controversial theory that gap junctions are related to the gamma oscillation.

^{}**Evidence**

In 1998, Hameroff made eight probable assumptions and 20 predictions to test the proposal.^{} In 2013, Anirban Bandyopadhyay of the Japanese National Institute for Materials Science detected quantum states in microtubules.^{}^{} Penrose and Hameroff reported that Bandyopadhyay’s experiments supported six out of the 20 theses, while invalidating none of the others. They subsequently responded to several critiques.^{}^{}^{}^{}^{}

In 2015, physicist Matthew Fisher of the University of California, Santa Barbara proposed that the nuclear spins in phosphorus atoms could become entangled, preventing the information loss of decoherence and enabling quantum computation within the brain.^{} The FELIX experiment has also been suggested to evaluate and measure the criterion of orchestrated objective reduction.

^{}**Criticism**

Orch OR was criticized both by physicists^{}^{}^{}^{}^{} and neuroscientists^{}^{}^{}^{} who considered it to be a poor model of brain physiology.

**Decoherence in living organisms**

In 2000 Tegmark claimed that any quantum coherent system in the brain would undergo effective wave function collapse due to environmental interaction long before it could influence neural processes (the *“warm, wet and noisy”* argument, as it was later came to be known).^{} He determined the decoherence timescale of microtubule entanglement at brain temperatures to be on the order of femtoseconds, far too brief for neural processing. Christof Koch and Klaus Hepp also agreed that quantum coherence does not play, or does not need to play any major role in neurophysiology.^{}^{} 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’.”*^{}

In response to Tegmark’s claims, Hagan, Tuszynski and Hameroff^{}^{} claimed that Tegmark 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 25 ms. Hameroff’s group also suggested that the Debye layer of counterions could screen thermal fluctuations, and that the surrounding actin 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 for quantum error correction, a means of resisting quantum decoherence.

Since the 1990s numerous counter-observations to the “warm, wet and noisy” argument existed at ambient temperatures, *in vitro*^{}^{} and *in vivo* (i.e. photosynthesis, bird navigation). For example, Harvard researchers achieved quantum states lasting for 2 sec at room temperatures using diamonds.^{}^{} Plants routinely use quantum-coherent electron transport at ambient temperatures in photosynthesis.^{} In 2014, researchers used theoretical quantum biophysics and computer simulations to analyze quantum coherence among tryptophan π resonance rings in tubulin. They claimed that quantum dipole coupling among tryptophan π resonance clouds, mediated by exciton hopping or Forster resonance energy transfer (FRET) across the tubulin protein are plausible.^{}

In 2007, Gregory S. Engel, Professor in Chemistry at The University of Chicago, claimed that all arguments concerning the brain being “too warm and wet” have been dispelled, as multiple “warm and wet” quantum processes have been discovered.^{}^{}

In 2009, Reimers *et al.* and McKemmish *et al.,* published critical assessments.^{}^{}^{} Earlier versions of the theory had required tubulin-electrons to form either Bose–Einsteins or Frohlich condensates, and the Reimers group claimed that these were experimentally unfounded. Additionally they claimed that microtubules could only support ‘weak’ 8 MHz coherence. The first argument was voided by revisions of the theory that described dipole oscillations due to London forces and possibly due to magnetic and/or nuclear spin cloud formations.^{} On the second issue the theory was retrofitted so that 8 MHz coherence is sufficient to support the whole Orch-OR hypothesis.

McKemmish *et al.* made two claims: that aromatic molecules cannot switch states because they are delocalised; and that changes in tubulin protein-conformation driven by GTP conversion would result in a prohibitive energy requirement. Hameroff and Penrose responded to the first claim by stating that they were referring to the behaviour of two or more electron clouds, inherently non-localised. For the second claim they stated that no GTP conversion is needed since (in that version of the theory) the conformation-switching is not necessary, replaced by oscillation due to the London forces produced by the electron cloud dipole states.

**Neuroscience**

The presented neuronal reconstrucions illustrate Hameroff’s miscalculation of the number of tubulins per neuron upon which he based Orch OR. ^{}Hameroff frequently writes: “*A typical brain neuron has roughly 10 ^{7} tubulins (Yu and Baas, 1994),*” yet this is Hameroff’s own invention, which should not be attributed to Yu and Baas.

^{}Hameroff apparently misunderstood that Yu and Baas actually “

*reconstructed the microtubule (MT) arrays of a 56 μm axon from a cell that had undergone axon differentiation*” and this reconstructed axon “

*contained 1430 MTs … and the total MT length was 5750 μm.*“

^{}A direct calculation shows that 10

^{7}tubulins (to be precise 9.3 × 10

^{6}tubulins) correspond to this MT length of 5750 μm inside the 56 μm axon.

Hameroff’s 1998 hypothesis required that cortical dendrites contain primarily ‘A’ lattice microtubules,^{} but in 1994 Kikkawa *et al.* showed that all *in vivo* microtubules have a ‘B’ lattice and a seam.^{}^{}

Orch OR also required gap junctions between neurons and glial cells,^{} yet Binmöller *et. al.* proved in 1992 that these don’t exist in the adult brain.^{} In vitro research with primary neuronal cultures shows evidence for electrotonic (gap junction) coupling between *immature* neurons and astrocytes obtained from rat embryosextracted prematurely through Cesarean section,^{} however, the Orch-OR claim is that *mature* neurons are electrotonically coupled to astrocytes in the adult brain. Therefore, Orch OR contradicts the well-documented *electrotonic decoupling* of neurons from astrocytes in the process of neuronal maturation, which is stated by Fróes *et al.* as follows: “junctional communication may provide metabolic and electrotonic interconnections between neuronal and astrocytic networks at early stages of neural development and such interactions are weakened as differentiation progresses.”^{}

In 2001, Hameroff further proposed that microtubule coherence spreads between different neurons via dendritic lamellar bodies (DLBs) that are connected directly with gap junctions.^{} De Zeeuw *et al.* had already proved this to be impossible in 1995,^{} by showing that DLBs are located micrometers away from gap junctions.^{}

In 2014, Bandyopadhyay *et. al.* speculated that microtubule-based quantum coherence can extend between different neurons if their notion of wireless transmission of information globally across the entire brain is proven. ^{}Hameroff and Penrose doubt whether such a wireless transmission would be capable of transmitting superimposed quantum-states and stick to their original gap junction proposal.^{}

Hameroff speculated that visual photons in the retina are detected directly by the cones and rods instead of decohering and subsequently connect with the retinal glia cells via gap junctions,^{} but this too was falsified.^{}

Other biology-based criticisms have been offered.^{} Papers by Georgiev point to problems with Hameroff’s proposals,^{}^{} including a lack of explanation for the probabilistic release of neurotransmitter from presynaptic axon terminals^{}^{}^{} and an error in the calculated number of the tubulin dimers per cortical neuron. ^{}Hameroff insisted in a 2013 interview that those falsifications were invalid, but did not provide any explanation where the falsifications fail.^{}