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Conduction pathways in microtubules, biological quantum computation, and consciousness
Abstract
Technological computation is entering the quantum realm, focusing attention on biomolecular information processing systems such as proteins, as presaged by the work of Michael Conrad. Protein conformational dynamics and pharmacological evidence suggest that protein conformational states-fundamental information units ('bits') in biological systems-are governed by quantum events, and are thus perhaps akin to quantum bits ('qubits') as utilized in quantum computation. 'Real time' dynamic activities within cells are regulated by the cell cytoskeleton, particularly microtubules (MTs) which are cylindrical lattice polymers of the protein tubulin. Recent evidence shows signaling, communication and conductivity in MTs, and theoretical models have predicted both classical and quantum information processing in MTs. In this paper we show conduction pathways for electron mobility and possible quantum tunneling and superconductivity among aromatic amino acids in tubulins. The pathways within tubulin match helical patterns in the microtubule lattice structure, which lend themselves to topological quantum effects resistant to decoherence. The Penrose-Hameroff 'Orch OR' model of consciousness is reviewed as an example of the possible utility of quantum computation in MTs.
... These signals can include classical (ionic, protonic) as well as quantum (electronic, excitonic) modes of communication. Since the mid-1990s Stuart Hameroff and Roger Penrose have been developing the so-called "Orch OR" (Orchestrated Objective Reduction) theory regarding the quantum mechanical processes in MTs as a physical basis of consciousness (Hameroff, 2012;Hameroff et al., 2002;Penrose, 2014, 1996). Experimental validation of these predictions is a major challenge that has not been accomplished yet. ...
... Propagation Ion channels (Hodgkin and Huxley, 1952) microtubules Hameroff and Penrose, 2014;Rahnama et al., 2011) The lipid bilayer (Appali et al., 2012;Heimburg and Jackson, 2005) Processing Ion channels (Price and Wallace, 2001;Wallace, 2007) αβ-tubulin heterodimers (Craddock and Tuszynski, 2010;Hameroff et al., 2002;Hameroff and Penrose, 2014) G protein coupled receptors (GPCRs) (Kenakin, 2015) Storage In neurons, posttranslational modifications of ion channels and receptors and de novo synthesis of proteins (Kandel et al., 2014;Lisman, 1989;Zenke et al., 2015) Posttranslational modifications of αβ-tubulin heterodimer (Craddock et al., 2012) Diffusion of second messengers Soliton-like wave propagation along microtubules and the plasma membrane Chain of conformational changes in proteins of signaling pathway Decoding of electro-mechanical signal into biochemical signal voltage-, mechano-and thermo-sensitive signaling proteins of the plasma membrane signaling molecules associated with microtubules Outputs of the cellular "computer" (responses of the cell to the extra-cellular stresses) ...
... Information carried by electro-mechanical soliton-like wave along MTs should be decoded with activation/inactivation of classical signaling molecules (Fig. 8). It should be noted that there is a good number of both theoretical (Caligiuri and Musha, 2015;Freedman et al., 2010;Hameroff et al., 2002;Kumar et al., 2016;Kurian et al., 2017;Ostovari et al., 2014;Priel et al., 2005;Rahnama et al., 2011) and experimental (Priel et al., 2006(Priel et al., , 2008 works on propagation of various signals (electro-mechanical, electronic, photonic, ionic clouds) along MTs. On the other hand, there are reports on direct activation of such signaling Fig. 6. ...
Background:
Myriads of signaling pathways in a single cell function to achieve the highest spatio-temporal integration. Data are accumulating on the role of electromechanical soliton-like waves in signal transduction processes. Theoretical studies strongly suggest feasibility of both classical and quantum computing involving microtubules.
Aim:
A theoretical study of the role of the complex composed of the plasma membrane and the microtubule-based cytoskeleton as a system that transmits, stores and processes information.
Methods:
Theoretical analysis presented here is based on: (i) the Penrose-Hameroff theory of consciousness (Orchestrated Objective Reduction; Orch OR), (ii) the description of the centrosome as a reference system for construction of the 3D map of the cell proposed by Regolini, (iii) the Heimburg-Jackson model of the nerve pulse propagation along axons' lipid bilayer as soliton-like electro-mechanical waves.
Results and conclusion:
The ideas presented in this paper provide a qualitative model for the decision-making processes in a living cell undergoing a differentiation process.
Outlook:
This paper paves the way for the real-time live-cell observation of information processing by microtubule-based cytoskeleton and cell fate decision making.
... Different scenarios for interaction between the electromagnetic field and the cytoskeletal microtubules have been put forward such as the ferroelectric model of microtubules [13][14][15][16][17][18][19], the Penrose-Hameroff orchestrated objective reduction (Orch OR) model [12], and Porter's topological anyon microtubule model [20,21]. Careful consideration of the electromagnetic field strength in neurons reveals, however, ...
... This result was used to argue in favor of possible anyon formation within the microtubule inner or outer two-dimensional electron layers. Anyons have been found in nature and were speculated to be harnessed by microtubules [20,21]. Anyons are two-dimensional quasiparticles with partial spin made out of groups of electrons, which are suitable candidates for fault-tolerant quantum computation [58,59]. ...
... This change has been modeled to result in 27 • angle between the original line connecting the centers of the α and β monomers and the new center-to-center line [115]. These two conformational states and their associated dipole moments have been proposed as the basis for a binary system for information storage and manipulation [12,19,21,45,60,61,[116][117][118]. This model is biologically flawed because the associated conformational change α ↔ β could not be used for computation as it leads to microtubule destabilization and subsequent disassembly [119]. ...
To find out whether neuronal microtubules could translate and input the information carried by electric signals entering into the brain cortex, a detailed investigation of the local electromagnetic field structure is performed. The electric and magnetic field strengths in different neuronal compartments, including dendrites, soma, and axons, are assessed from reported electrophysiological measurements. The results show that the magnetic field is too weak to input information to microtubules and cannot support quantum Hall effect. Because the magnetic flux density of individual electric spikes is 3 orders of magnitude weaker than Earth's magnetic field, any information encoded in the magnetic signal will be suffocated by the surrounding noise. In contrast, the electric field carries biologically important information and acts upon transmembrane voltage-gated ion channels that govern the generation of neuronal action potentials. If the human mind is supported by subneuronal processing of information in the brain microtubules, then the microtubule interaction with the local electric field has to be the main source for input of sensory information. The intensity of the electric field inside the neuronal cytosol, however, is less than 500 V/m, which rules out any electric sensitivity of putative ferroelectric microtubules. Although the tubulin C-terminal tails are promising candidates for substrates that are both sensitive to electric signals and possess biologically useful intraneuronal functions, they lack physical means to affect back the electric output of neurons. Thus, voltage-gated ion channels incorporated into the neuronal plasma membranes appear to be best suited to support consciousness since they remain the only known biomolecular substrates that are capable of inputting, processing and outputting of electric signals.
... Это значит, что сохранившийся в памяти след существует в сознательной форме. То же самое можно сказать и о состоянии человека: под наркозом он временно находится без сознания, но после операции сознание вновь возвращается к нему [10]. ...
... Но они не раскрывают нейропсихологические операции, которые определяют изменения в структуре и функциях мозга. Открытие квантовых колебаний в микротрубочках внутри нейронов головного мозга, совершенное группой исследователей National Institute of Material Sciences в Цукубе (Япония), во главе с Anirban Bandyopadhyay, и Massachusetts Institute of Technology (2016), подтверждает теорию о том, что ритмы ЭЭГ также вытекают из колебаний микротрубочек [8,10]. Они предполагают, что лечение вибрацией цитоскелета может принести пользу при психических, неврологических и когнитивных расстройствах. ...
... ., Penrouse R., 2016). Принцип самоорганизации доказывает, что в исходно хаотической (неупорядоченной) среде, элементы которой способны взаимодействовать РИС. 1. Появление послеоперационной когнитивной дисфункции[9,10] ...
... Penrose and Hameroff proposed their theory because they remarked that evidence related to the "integrate and fire" network of neurons does not indicate how consciousness could arise from its activity [25][26][27][28][29]. ...
... Nonetheless, these protozoa have a cytoskeleton. Stuart Hameroff remarked that neurons also have an organized cytoskeleton, composed of microtubules and persuaded Roger Penrose to collaborate in the formulation of a theory linking quantum physics with brain function [25,28,29]. ...
The known theories discussing the essence of consciousness have been recently updated. This prompts an attempt to integrate these explanations concerning several distinct components of the consciousness phenomenon such as the ego, and qualia perceptions. Therefore, it is useful to consider the latest publications on the 'Orch OR' and 'cemi' theories, which assume that quantum processing occurs in microtubules and that the brain's endogenous electromagnetic field is important. The authors combine these explanations with their own theory describing the neural circuits realizing imagery. They try to present such an interdisciplinary, integrated theoretical model in a manner intuitively understandable to people with a typical medical education. In order to do this, they even refer to intuitively understandable metaphors. The authors maintain that an effective comprehension of consciousness is important for health care professionals because its disorders are frequent medical symptoms in emergencies, during general anesthesia and in the course of cogni-tive disorders in elderly people. The authors emphasize the current possibilities to verify these theses regarding the essence of consciousness thanks to the development of functional brain imaging methods-magnetoencephalography, transcranial magnetic stimulation-as well as clinical studies on the modification of perceptions and feelings by such techniques as mindfulness and the use of certain psychoactive substances, especially among people with self-awareness and identity disorders .
... It is well known that consciousness is inextricably linked to anesthesia. Hameroff et al. (2002) have conducted many complementary and engaging studies to refine their quantum theory of consciousness. Moreover, a series of mechanics of anesthetic agent function were proposed and included the following: (1) selective binding in hydrophobic pockets comprising non-polar amino acid groups in brain proteins [e.g., microtubule-associated proteins (MAPs); tubulin; and van der Waals (London dispersion) forces, which can inhibit the quantum process by impairing electron mobility]; (2) a specialized combination with "qubits, " fundamental information units that abide by quantum events that induce disruption of the quantum computation; (3) a concept of "quantum channels" that consist of tryptophan tings in tubulin that are olive-like, non-polar, and hydrophobic; (4) probability for π-electron resonant energy transfer through quantum channels and weakening of anesthetic agents that could therefore weaken this π-resonance energy transfer (a theorem that accounts for loss of consciousness); and (5) alterations of collective terahertz dipole oscillations in tubulins (Hameroff, 1998(Hameroff, , 2006Hameroff et al., 2002;Craddock et al., 2015Craddock et al., , 2017Mayner et al., 2018). ...
... Hameroff et al. (2002) have conducted many complementary and engaging studies to refine their quantum theory of consciousness. Moreover, a series of mechanics of anesthetic agent function were proposed and included the following: (1) selective binding in hydrophobic pockets comprising non-polar amino acid groups in brain proteins [e.g., microtubule-associated proteins (MAPs); tubulin; and van der Waals (London dispersion) forces, which can inhibit the quantum process by impairing electron mobility]; (2) a specialized combination with "qubits, " fundamental information units that abide by quantum events that induce disruption of the quantum computation; (3) a concept of "quantum channels" that consist of tryptophan tings in tubulin that are olive-like, non-polar, and hydrophobic; (4) probability for π-electron resonant energy transfer through quantum channels and weakening of anesthetic agents that could therefore weaken this π-resonance energy transfer (a theorem that accounts for loss of consciousness); and (5) alterations of collective terahertz dipole oscillations in tubulins (Hameroff, 1998(Hameroff, , 2006Hameroff et al., 2002;Craddock et al., 2015Craddock et al., , 2017Mayner et al., 2018). The systematic theory of "Orch OR" proposed that consciousness is constituted by discrete events that correspond with varying oscillation frequencies of distinct brain regions (Crick and Koch, 2003;Hameroff and Penrose, 2014;Li et al., 2018), which is similar with respect to the "snapshots, " which is one of the ten frameworks for consciousness proposed by Koch (Li et al., 2018). ...
The definition of consciousness remains a difficult issue that requires urgent understanding and resolution. Currently, consciousness research is an intensely focused area of neuroscience. However, to establish a greater understanding of the concept of consciousness, more detailed, intrinsic neurobiological research is needed. Additionally, an accurate assessment of the level of consciousness may strengthen our awareness of this concept and provide new ideas for patients undergoing clinical treatment of consciousness disorders. In addition, research efforts that help elucidate the concept of consciousness have important scientific and clinical significance. This review presents the latest progress in consciousness research and proposes our assumptions with regard to the network of consciousness.
... 2. Biochemical processes as described by Dennis Bray in his 2009 book, Wetware: A computer in every cell. 3. Various quantum processes including quantum coherence as described by Herbert Fröhlich; spin resonance as described by Mae Wan Ho and Emilio Del Giudice; biophotonic communications as described by Fritz Albert Popp (2000) and Marco Bischof (1995); and wavelike energy transfer that takes place in chloroplasts of green plants as documented by Fleming and colleagues (see Engel et al., 2007), and conduction pathways in microtubules (Hameroff, Nip, Porter, & Tuszynski, 2002). ...
... An average period of a resistance spike is 24 ns (2.4×10 −5 ), standard deviation 0.4 ns. The oscillations can be caused by electro-mechanical vibrations of the MT [29,35], shuttling of conformation changes [27], orientation transitions of dipole moments [54,8,14], and ionic waves [55,44,50]. The oscillations show a visual resemblance to spiking of a chattering neuron in Izhikevich model [32] (Fig. 7(b)), yet the oscillations time scale is different by several orders of magnitude. ...
We study electrical properties of Taxol-stabilised microtubule (MT) ensembles in a droplet of water. We demonstrate that the MT droplets act as electrical switches. Also, a stimulation of a MT droplet with a positive fast impulse causes oscillation of the droplet's resistance. The findings will pave a way towards future designs of MT-based sensing and computing devices, including data storage and featuring liquid state.
... Since microtubule stiffness variation can affect whole cell morphology 70 and intracellular transport, this could lead to changes in the timing of neuron firing and neuron function, resulting in a loss of coherence and ultimately anesthesia. Controversial theories have been suggested that relate such microtubule processes directly to neural coherence and consciousness [71][72][73] , but experimental confirmation is needed for validation of such claims. To date, understanding London dispersion and van der Waals interactions in complex systems relies mostly on theoretical concepts and the analysis of the results of computer modeling 74 . ...
Anesthesia blocks consciousness and memory while sparing non-conscious brain activities. While the exact mechanisms of anesthetic action are unknown, the Meyer-Overton correlation provides a link between anesthetic potency and solubility in a lipid-like, non-polar medium. Anesthetic action is also related to an anesthetic's hydrophobicity, permanent dipole, and polarizability, and is accepted to occur in lipid-like, non-polar regions within brain proteins. Generally the protein target for anesthetics is assumed to be neuronal membrane receptors and ion channels, however new evidence points to critical effects on intra-neuronal microtubules, a target of interest due to their potential role in post-operative cognitive dysfunction (POCD). Here we use binding site predictions on tubulin, the protein subunit of microtubules, with molecular docking simulations, quantum chemistry calculations, and theoretical modeling of collective dipole interactions in tubulin to investigate the effect of a group of gases including anesthetics, non-anesthetics, and anesthetic/convulsants on tubulin dynamics. We found that these gases alter collective terahertz dipole oscillations in a manner that is correlated with their anesthetic potency. Understanding anesthetic action may help reveal brain mechanisms underlying consciousness, and minimize POCD in the choice and development of anesthetics used during surgeries for patients suffering from neurodegenerative conditions with compromised cytoskeletal microtubules.
... Another possible source of sentience at the cellular and subcellular levels is the dynamic cytoskeleton. Especially microtubules are discussed as important in this respect [157] [140] [141] [142], representing quantum channels related to consciousness [158] [159] and terahertz oscillations in tubulin were reported to be affected by exposures to anesthetics [160]. Besides microtubules, also the actin filaments behave as excitable medium which transports ionic waves and mediates eukaryotic chemotaxis in response to diverse gradients [161] [162] [163] [164]. ...
The slime mould Physarum polycephalum has been used in developing unconventional computing devices for in which the slime mould played a role of a sensing, actuating, and computing device. These devices treated the slime mould rather as an active living substrate yet the slime mould is a self-consistent living creature which evolved for millions of years and occupied most part of the world, but in any case, that living entity did not own true cognition, just automated biochemical mechanisms. To "rehabilitate" the slime mould from the rank of a purely living electronics element to a "creature of thoughts" we are analyzing the cognitive potential of P. polycephalum. We base our theory of minimal cognition of the slime mould on a bottom-up approach, from the biological and biophysical nature of the slime mould and its regulatory systems using frameworks suh as Lyon's biogenic cognition, Muller, di Primio-Lengeler\'s modifiable pathways, Bateson's "patterns that connect" framework, Maturana's autopoetic network, or proto-consciousness and Morgan's Canon.
... Another possible source of sentience at the cellular and subcellular levels is the dynamic cytoskeleton. Especially microtubules are discussed as important in this respect [157] [140] [141] [142], representing quantum channels related to consciousness [158] [159] and terahertz oscillations in tubulin were reported to be affected by exposures to anesthetics [160]. Besides microtubules, also the actin filaments behave as excitable medium which transports ionic waves and mediates eukaryotic chemotaxis in response to diverse gradients [161] [162] [163] [164]. ...
The slime mould Physarum polycephalum has been used in developing un-conventional computing devices for in which the slime mould played a role of a sensing, actuating, and computing device. These devices treated the slime mould rather as an active living substrate yet the slime mould is a self-consistent living creature which evolved for millions of years and occupied most part of the world, but in any case, that living entity did not own true cognition, just automated biochemical mechanisms. To "rehabilitate" the slime mould from the rank of a purely living electronics element to a "crea-ture of thoughts" we are analyzing the cognitive potential of P. polycephalum. We base our theory of minimal cognition of the slime mould on a bottom-up approach, from the biological and biophysical nature of the slime mould and its regulatory systems using frameworks suh as Lyons biogenic cognition, Muller, di Primio-Lengeler´sLengeler´s modifiable pathways, Bateson's "patterns that connect" framework, Maturanas autopoetic network, or proto-consciousness and Morgans Canon.
... TIR processing, and the TCP which constitutes the GCM, is based upon a paradigm relatively new to computer science and information technology but not to quantum physics, molecular biology or neuroscience. Among examples in biology providing a basis for TIR are the studies of cellular membrane control of ion channels [7], biosolitons [8], and the microtubulin assemblies of the cytoskeleton in eukaryotic cells [9,10,11,12]. ...
NeoPlexus is a newly established permanent program of international collaborative scientific research and application development. It is focused upon the design, construction and application of a new architecture and family of computing machines that are adept at solving problems of control involving extreme complex systems (XCS) for which conventional numerical computing methods and machines are fundamentally inadequate. The GCM involves a different foundation of computing from classical Turing Machines including qubit-based quantum computers and it incorporates geometrical and specifically topological dynamics. The target for implementation is to construct molecular-scale platform using protein-polymer conjugates and MEMS-type microfluidics.
... Though FtsZ is a respective homolog of tubulin, the evolutionary distance between the two proteins is substantial and hence it has been suggested that an undiscovered species of bacteria or archaea could hold the evolutionary precursor of tubulin that could determine the true evolution of this protein. FtsZ could therefore be considered as the precursor for quantum computation resulting in the origination of quantum proto-consciousness (Barlow [1], Hameroff et al. [25]). This idea is supported by several theoretical models and simulations which suggest that conformational states of tubulins within microtubular lattices are influenced by quantum events (Hameroff and Watt [27], Tuszynski et al. [79], Pitkanen [57], Kukuljan [36], Faber et al. [18]). ...
Microorganisms demonstrate conscious-like intelligent behaviour, and this form of consciousness may have emerged from a quantum mediated mechanism as observed in cytoskeletal structures like the microtubules present in nerve cells which apparently have the architecture to quantum compute. This paper hypothesises the emergence of proto-consciousness in primitive cytoskeletal systems found in the microbial kingdoms of archaea, bacteria and eukarya. To explain this, we make use of the Subject–Object Model (SOM) of consciousness which evaluates the rise of the degree of consciousness to conscious behaviour in these systems supporting the hypothesis of emergence and propagation of conscious behaviour during the pre-Cambrian part of Earth’s evolutionary history. Consciousness as proto-consciousness or sentience computed via primitive cytoskeletal structures substantiates as a driver for the intelligence observed in the microbial world during this period ranging from single-cellular to collective intelligence as a means to adapt and survive. The growth in complexity of intelligence, cytoskeletal system and adaptive behaviours are key to evolution, and thus supports the progression of the Lamarckian theory of evolution driven by quantum mediated proto-consciousness to consciousness as described in the SOM of consciousness.
https://content.iospress.com/articles/journal-of-integrative-neuroscience/jin064
... Another possible source of sentience at the cellular and subcellular levels is the dynamic cytoskeleton. Especially microtubules are discussed as important in this respect [159] [142] A c c e p t e d M a n u s c r i p t [143] [144], representing quantum channels related to consciousness [160] [161] and terahertz oscillations in tubulin were reported to be affected by exposures to anesthetics [162]. Besides microtubules, also the actin filaments behave as excitable medium which transports ionic waves and mediates eukaryotic chemotaxis in response to diverse gradients [163] [164] [165] [166]. ...
The slime mould Physarum polycephalum has been used in developing unconventional computing devices for in which the slime mould played a role of a sensing, actuating, and computing device. These devices treated the slime mould rather as an active living substrate yet the slime mould is a self-consistent living creature which evolved for millions of years and occupied most part of the world, but in any case, that living entity did not own true cognition, just automated biochemical mechanisms. To "rehabilitate" the slime mould from the rank of a purely living electronics element to a "creature of thoughts" we are analyzing the cognitive potential of P. polycephalum. We base our theory of minimal cognition of the slime mould on a bottom-up approach, from the biological and biophysical nature of the slime mould and its regulatory systems using frameworks suh as Lyons biogenic cognition, Muller, di Primio-Lengelerś modifiable pathways, Bateson's "patterns that connect" framework, Maturanas autopoetic network, or proto-consciousness and Morgans Canon.
... The investigation of microtubules properties has become especially topical nowadays in relation to Orch OR Theory by Penrose and Hameroff (Penrose, 1994), who put forward a hypothesis that microtubules may play an important part in forming the phenomenon of consciousness. It is supposed that the phenomenon of consciousness could be understood in the context of coherent quantum mechanical effects Penrose, 1996, 2014;Hameroff, 1998;Hameroff et al., 2002;Craddock et al., 2015). ...
The paper investigates microtubules lattice properties taking into consideration elastic, dipole-dipole interaction of tubulins and viscosity. A microtubule is modeled as a system of bound tubulins, forming a skewed hexagonal two-dimensional lattice. Wave frequencies and group velocities have been calculated. Calculations have been performed for various directions of wave front propagation: helix, along the protofilament, and anti-helix. Three different wave polarization directions have been considered. It has been shown that the direction of the wave polarization influences the frequency and wave group velocity values in the lattice considerably. The impact of dipole-dipole interaction greatly depends on the direction of the wave polarization; thus, it is only moderate for the longitudinally (LA) polarized waves while it is sufficient for the transversely (TA), and out-of-plane (ZA) polarized waves. Moreover dipole-dipole interaction may result in the waves which are able to cause the rupture of microtubules. With viscosity considered, lattice oscillations become harmonically damped only over a certain wavelength range when longitudinal polarization occurs. Out of this range as well as for the other polarization directions, lattice deviations from equilibrium are dampened exponentially. Taking viscosity into consideration also results in a noticeable decrease in frequency and increase in the group wave velocity when the waves are longitudinally polarized. Reverse wave domains which may be associated with a possible phenomenon of negative refraction have been determined for hexagonal microtubule lattice.
... The importance of aromatic heterocycles for conductivity is highlighted by Hameroff (Stuart Hameroff, 2008, 2002 . This likely explains a similarity in conductivity in DNA and microtubules. ...
Although magnetism of DNA in strong fields is well established, it is not commonly considered magnetic in natural weak fields. SInce the behavior of strings of magnetic balls resembles some of DNA behaviors such as in replication and transcription, we hypothesize that DNA is magnetic and that DNA strands are magnetized in antiparallel orientation. We hypothesise that magnetism of DNA is based on ring currents of pi electrons in its bases. We hypothesize that ring currents are fueled by heat, enzymes or active forms of water. Accordingly, we proposed a helical model of magnetic lines in DNA. We also suggested a new way how the magnetic field in DNA may oscillate and that these oscillations will be sequence dependent. We suggest that collective oscillations of interspersed and periodic repetitive DNA sequences could contribute to electromagnetic communications between the cells and creation of Gurwitch morphogenic field. We suggest that primary cilium may be an antenna for sending and receiving electromagnetic oscillations by the genome.
... Tryptophan is the most polarisable amino acid 15 , possessing a particular double ring (an 'indole ring')-a six-carbon ring joined to a five-carbon ring with one nitrogen and four carbons. The distance between the tryptophan residues in MTs is around 2 nm, a spacing that could facilitate electron hops 12 . ...
We report on the electrical behaviour of thin films of bovine brain microtubules (MTs). For samples in both their dried and hydrated states, the measured currents reveal a power law dependence on the applied DC voltage. We attribute this to the injection of space-charge from the metallic electrode(s). The MTs are thought to form a complex electrical network, which can be manipulated with an applied voltage. This feature has been exploited to undertake some experiments on the use of the MT mesh as a medium for computation. We show that it is possible to evolve MT films into binary classifiers following an evolution in materio approach. The accuracy of the system is, on average, similar to that of early carbon nanotube classifiers developed using the same methodology.
... The theory of microtubular signal transmission have been developed by Stuart Hameroff and coauthors for the last 30 years. [107][108][109][110] Hameroff proposed that microtubules in neurons contribute to creation of consciousness by transmitting, computing and storing information. He proposed that it is delocalized electrons of aromatic amino acids that are oscillating in microtubules. ...
We suggest that it is microtubules which serve as waveguides to transfer the electromagnetic signal from the nucleus through the cytoplasm. The theory of microtubular signal transmission have been developed by Stuart Hameroff and coauthors for the last 30 years.107–110 Hameroff proposed that microtubules in neurons contribute to creation of consciousness by transmitting, computing and storing information. He proposed that it is delocalized electrons of aromatic amino acids that are oscillating in microtubules. Stuart Hameroff and Anirban Bandyopadhyay proposed that oscillating are electron spins. We have noticed that microtubules radiating from the nucleus to cell periphery come close to the nucleus and to the cell wall and therefore we proposed that microtubules serve as waveguides connecting all the nuclei of the body and that they communicate electromagnetically across the cell wall with the DNA and across the cell membrane in cell junctions with the microtubules of the adjacent cells
... Priel, Tuszynski and Cantiello discussed how information processing could be implemented in actin-tubulin networks of neuron dendrites [151]. The hypothetical AF/MT information processing devices can transmit signals as travelling localised patterns of conformational changes [87,83], orientational transitions of dipole moments [201,24,28], and ionic waves [202,150,164]. While propagation of information along the cytoskeleton is well studied, in theoretical models, there are almost no experimental results on actual processing of information. ...
We propose a road-map to experimental implementation of cytoskeleton-based computing devices. An overall concept is described in the following. Collision-based cytoskeleton computers implement logical gates via interactions between travelling localisation (voltage solitons on AF/MT chains and AF/MT polymerisation wave fronts). Cytoskeleton networks are grown via programmable polymerisation. Data are fed into the AF/MT computing networks via electrical and optical means. Data signals are travelling localisations (solitons, conformational defects) at the network terminals. The computation is implemented via collisions between the localisations at structural gates (branching sites) of the AF/MT network. The results of the computation are recorded electrically and/or optically at the output terminals of the protein networks. As additional options, optical I/O elements are envisaged via direct excitation of the protein network and by coupling to fluorescent molecules.
... One of the first motivations is the set of ideas of Penrose and Hameroff (Penrose, 1989;Hameroff, 1994, 2003, Hameroff, Penrose, 2014, who suggested that mental processes are associated with the collapse of the wave function, which is caused by the effects of gravity. In this case, non-computability plays an important role in the processes of thinking. ...
In this study, a model is constructed in which the formation of new synaptic contacts and the tuning of synaptic weights are mediated by quantum nonlocal interactions. The interaction between biologically important molecules in the brain can be the basis of the quantum metalanguage, which controls the behavior of humans and animals. The dynamics of biologically important molecules must include their topological properties. Thus the work of the brain can only be consistently described using quantum mechanics.
... We suggest that it is microtubules which serve as waveguides to transfer the electromagnetic signal from the nucleus through the cytoplasm. The theory of microtubular signal transmission has been developed by Stuart Hameroff and coauthors for the last 30 years Hameroff, 1974;Hameroff et al., 2002;Sahu et al., 2013). Hameroff proposed that microtubules in neurons contribute to the creation of consciousness by transmitting, computing and storing information. ...
A possible role of DNA sequence-specific electromagnetic resonances in the formation of the morphogenic field is
discussed. It is proposed that the morphogenic field is formed by resonant oscillations of delocalized electron
and proton clouds in the base stack of the DNA. Models are proposed for DNA sequence-dependence of possible
electromagnetic resonance patterns. It is proposed that genomic repeats act as universal resonators providing the
bidirectional communication between the chromatin structure and the morphogenic field. It is proposed that genomic
repeats participate in two major functions - the morphogenic function and the brain function. It is proposed that
microtubules mediate the resonance communication between the action potential in axons and genomic repeats in
the nucleus. The existence of an algorithm is proposed responsible for the conversion of genomic information into the
shape of the body. Such an algorithm is named the DNA resonance code. It is proposed that the DNA resonance code
can be deciphered by targeted efforts in biophysics, spectroscopy, molecular modeling, and experimental genomics.
A possible resonance interaction between the DNA of neurons and neuronal firing is discussed and it is suggested that
deciphering the DNA resonance code may be of help to deciphering the neuronal coding in the brain. It is suggested that the
deciphering of the DNA resonance code would benefit medical applications related to morphogenesis and brain function
... We suggest that it is microtubules which serve as waveguides to transfer the electromagnetic signal from the nucleus through the cytoplasm. The theory of microtubular signal transmission has been developed by Stuart Hameroff and coauthors for the last 30 years Hameroff, 1974;Hameroff et al., 2002;Sahu et al., 2013). Hameroff proposed that microtubules in neurons contribute to the creation of consciousness by transmitting, computing and storing information. ...
... Using computer modeling, it has been demonstrated the anesthetic bind in hydrophobic channels within tubulin [48]. These hydrophobic channels associate with those in adjacent tubulins, to create macroscopic "quantum channels" and collective dipoles through microtubules and neurons [48,70]. In such quantum channels, anesthetics can inhibit electron mobility and disperse dipoles [25, 71,72], and these activities could stop cognitive activities essential to consciousness [73] (Fig. 2). ...
The mechanism by which general anesthetics prevent consciousness remains largely unknown because the mechanism by which brain physiology produces consciousness is yet unexplained. After its most evident goal, to allow surgery for million people in the world, the contribution of anesthesia to science is the unique and great opportunity to study consciousness.
... Actin filaments (AFs) and tubulin microtubules (MTs) represent the key components of cytoskeleton networks [13]. They have been experimentally demonstrated and modelled as ionic wave conducting biowires [18, 19, 23-25, 28, 31], and predicted to support conformational solitons [8,9,12], as well as orientational transitions of dipole moments [4,5,30]. These propagating localizations could carry information and transform it when interacting with one another. ...
Starting with an experimentally observed networks of actin bundles, we model their network structure in terms of edges and nodes. We then compute and discuss the main electrical parameters, considering the bundles as electrical wires. A set of equations describing the network is solved with several initial conditions. Input voltages, that can be considered as information bits, are applied in a set of points and output voltages are computed in another set of positions. We consider both an idealized situation, where point-like electrodes can be inserted in any points of the bundles and a more realistic one, where electrodes lay on a surface and have typical dimensions available in the industry. We find that in both cases such a system can implement the main logical gates and a finite state machine.
... One component of this cytoskeleton are thin hollow fibers, called microtubules that demonstrate coordinated vibrational beat frequencies that may produce quantum coherences (Hameroff and Penrose 2014). Along with other components of the cytoskeleton, these vibratory motions seem to enable quantum signaling that is the foundation of certain biological activities crucial to some animals, such as the magnetic sensitivities that permit bird migrations (Hameroff et al. 2002;Craddock et al. 2014;Friesen et al. 2015). ...
Our contemporary era permits a harnessing of fresh contemporary resources to evolutionary biology from the emerging fields of metagenomics (the direct study of genetic material from environmental samples), epigenomics (the complete range of epigenetic factors that influence gene expression), and hologenomics (the complete genetic complement of an organism, including its microbial fraction). None of these fields mattered or were even thought to exist within the twentieth century. With the productive application of critical research from these disciplines, evolutionary biology can now be explored from a vantage that was unavailable to Darwin and the myriad others that followed in the ensuing decades.
... One component of this cytoskeleton are thin hollow bers, called microtubules that demonstrate coordinated vibrational beat frequencies that may produce quantum coherences (Hameroff and Penrose 2014). Along with other components of the cytoskeleton, these vibratory motions seem to enable quantum signaling that is the foundation of certain biological activities crucial to some animals, such as the magnetic sensitivities that permit bird migrations (Hameroff et al. 2002;Craddock et al. 2014;Friesen et al. 2015). ...
The Singularity/Big Bang is believed to have instantiated the Universe 13.8 billion years ago, giving rise to everything in the cosmos, including the Earth and its biosphere (Hawking 1998). From this unitary beginning, a path opens from the first primitive unicell to consciousness as one continuous process of dualities (matter and energy existing as two complimentary parts) formed after the Big Bang (Gionti 2015), culminating in the vital mechanism of homeostasis (Torday and Rehan 2012). By regarding the narrative of the cosmos and consciousness as having common origins and epistemology, predictions emerge that can illuminate aspects of biology that have previously been considered dogmatic or enigmatic.
... One component of this cytoskeleton are thin hollow bers, called microtubules that demonstrate coordinated vibrational beat frequencies that may produce quantum coherences (Hameroff and Penrose 2014). Along with other components of the cytoskeleton, these vibratory motions seem to enable quantum signaling that is the foundation of certain biological activities crucial to some animals, such as the magnetic sensitivities that permit bird migrations (Hameroff et al. 2002;Craddock et al. 2014;Friesen et al. 2015). ...
Aside from the transfer of genetic material and a large array of bioactive molecules by endocytosis and other cellular mechanisms, there are many additional sources of information exchange among cells. The primary cilia are one such example. These slender projections on microbes and cells are an essential element for both their communication processes and mobility (Wheatley et al. 1996). They also serve an important sensory function that is part of the cell’s analysis of mechanical and chemical signals, which is a consequential part of their information space. As such, they are part of what is termed the “senome” of the cell. The “senome” represents the summation of all the sensory inputs of the cell derived through the use of all of its sensory apparatus and tools (Baluška and Miller 2018). This is the means by which the cognitive cell can assess its environment as it attempts to maintain homeostatic balance. Even bacteria show a high degree of sensory complexity linked to sensorimotor circuits that activate at the plasma membrane and ramify throughout the cell (Lyon 2015). These inputs feed adaptive behaviors. In effect, the senome is the cognitive gateway that receives information that can be channeled from the external environment into the interior of the organism to support homeostasis (Baluška and Miller 2018). How that information is used becomes a function of the cellular information management system (Miller 2016a, 2017; Miller and Torday 2018; Miller et al. 2019). Therefore, the senome is the biological nexus of the means by which an organism attaches to its informational matrix. Its sensory memory is then encoded within a variety of bioactive molecules as well as its genetic complement so that all aspects of the cell participate.
... One component of this cytoskeleton are thin hollow bers, called microtubules that demonstrate coordinated vibrational beat frequencies that may produce quantum coherences (Hameroff and Penrose 2014). Along with other components of the cytoskeleton, these vibratory motions seem to enable quantum signaling that is the foundation of certain biological activities crucial to some animals, such as the magnetic sensitivities that permit bird migrations (Hameroff et al. 2002;Craddock et al. 2014;Friesen et al. 2015). ...
In 2010, the evolutionary biologist, mathematician, and geneticist, Richard Lewontin noted that the standard narrative of evolution by natural selection does not explain the actual forms of life that have evolved. He further contended that there is an immense amount of biology that is missing from neo-Darwinism. Other scientists also agree (Pigliucci 2007; Baluška 2009; Witzany 2010; Shapiro 2011; Torday 2015a, b; Miller 2016b, 2017; Miller and Torday 2018). Therefore, it can be defended that the central tenets of the modern synthesis should be questioned. Of these areas of inquiry, the most pertinent is the exact role and limits of natural selection in any evolutionary process. If selection has primacy in evolutionary development, does it proceed according to strict gene frequencies? Is it propelled by random genetic mutations? Is Crick’s central dogma that asserts a unilateral direction of the flow of biological information from DNA to RNA still applicable in the twenty-first century? Certainly, there is no requirement that the correct answers have to be any exact antipode of prior beliefs. Nor must any contradictions be absolute. Therefore, even a substantial reformulation of evolutionary development need not be an unyielding negation of the past. Instead, it is tasked to incorporate the weighty thoughts of prior generations of scientists and direct them toward a fuller understanding of this complicated issue.
... One component of this cytoskeleton are thin hollow bers, called microtubules that demonstrate coordinated vibrational beat frequencies that may produce quantum coherences (Hameroff and Penrose 2014). Along with other components of the cytoskeleton, these vibratory motions seem to enable quantum signaling that is the foundation of certain biological activities crucial to some animals, such as the magnetic sensitivities that permit bird migrations (Hameroff et al. 2002;Craddock et al. 2014;Friesen et al. 2015). ...
Any attempt to provide a coherent alternative evolutionary narrative to standard Darwinian tenets should offer a brief overview of the progression of scholarly thought about evolutionary mechanisms. All narratives focus on Charles Darwin's seminal “On the Origin of Species” (Darwin 1859). When Darwin offered that influential work in 1859, he was unaware of the existence of genes. He was a naturalist with a gift for scrupulous observation. Based upon his studies, he proposed the major dictums that have since guided evolutionary thoughts. He offered two linked primary arguments. Evolution proceeded by a process of natural selection through the gradual modification of inherited variations. Notably, the concept of natural selection was not original to Darwin. In 1831, a Scottish horticulturalist, Patrick Matthew had proposed a theory of natural selection, and Darwin was acquainted with his work (Rampino 2010). Another English naturalist and explorer, Alfred Russel Wallace was in communication with Darwin prior to his publication of On the Origin of Species. His correspondence with Darwin had outlined a deliberate mechanism for evolution that incorporated the concept of natural selection. However, it was Darwin's considerable reputation in the scientific community that gave an effective voice to this explosively controversial theory and energized its broader intellectual scrutiny. In this manner, Darwin was substantially adding to an already existing and lively debate. The nineteenth century French naturalist, Jean-Baptiste Lamarck also believed in evolution, and argued that it proceeded through natural laws. He and his many advocates proposed that individuals could inherit characteristics from their ancestors based on the patterns of use of the various faculties (Bowler 2003). For example, the long necks of giraffes were thought to be due to the stretching of their necks to reach high branches of trees. Darwin did not specifically disagree. He had espoused a variant of Lamarckism that he termed “pangenesis” in his 1868 text, Variation in Plants and Animals Under Domestication. A German biologist, Ernst Haeckel, added his own form of support in the 1870s with his well-known “ontogeny recapitulates phylogeny” hypothesis (Bowler 2003). He proposed that the stages of development of an embryo conformed to successive stages of its ancestral evolutionary development. Further reinforcement for this position emerged in the latter part of the nineteenth century through Wilhelm Haeckel's proposal of “orthogenesis.” Strenuously promoted by the German zoologist Theodore Eimer, orthogenesis was the process by which an organism directed toward a determined course by internal forces. In that circumstance, variation is not random, and selection need not be preponderant since a species is carried forward automatically by inner dynamics (Fox and Wolf 2006). Although the concept that one biological mechanism builds upon another in a non-random manner fell into substantial disfavor in the twentieth century, its basic validity has been resurrected on the basis of modern research in cell–cell signaling (Torday and Miller Jr 2017). It can be seen, then, that evolution has been the subject of intense and longstanding debate. Vigorous controversies remain about the primacy of natural selection, the role of acquired characteristics, sources of variation, and whether or not the evolution is random.
... One component of this cytoskeleton are thin hollow fibers, called microtubules that demonstrate coordinated vibrational beat frequencies that may produce quantum coherences (Hameroff and Penrose 2014). Along with other components of the cytoskeleton, these vibratory motions seem to enable quantum signaling that is the foundation of certain biological activities crucial to some animals, such as the magnetic sensitivities that permit bird migrations (Hameroff et al. 2002;Craddock et al. 2014;Friesen et al. 2015). ...
The self-referential appraisal of information characterizes cells of all types whether they are prokaryotic bacteria or individual eukaryotic cells (Shapiro 2011; Trewavas and Baluška 2011; Miller 2013). Plainly then, the manner in which cellular organisms retrieve, assess, and deploy information to maintain homeostasis or to communicate with other organisms unites the organizational structure that exists among all living organisms (Trewavas and Baluška 2011; Gamow 1955). It follows that these are linked and complex actions which require systematic ordering. Plainly then, any such ordering function must be under the control of a form of systematic information management. Every aspect of cellular life is directed toward information assessment and cell–cell communications to support homeostatic equipoise. It can be asserted that the exquisite coordination that cells exhibit in these tasks requires the presence of an information management apparatus (Miller 2017; Miller et al. 2019).
... One component of this cytoskeleton are thin hollow bers, called microtubules that demonstrate coordinated vibrational beat frequencies that may produce quantum coherences (Hameroff and Penrose 2014). Along with other components of the cytoskeleton, these vibratory motions seem to enable quantum signaling that is the foundation of certain biological activities crucial to some animals, such as the magnetic sensitivities that permit bird migrations (Hameroff et al. 2002;Craddock et al. 2014;Friesen et al. 2015). ...
For his entire life, Einstein retained a steadfast commitment to determinism. He believed that there is an objective reality that can be observed and accurately measured. If there was sufficient understanding and measuring capacity, any of the apparent indeterminacies of quantum mechanics would eventually be shown to be deterministic (Landsman 2009). His contemporary, the brilliant astronomer, mathematician, and physicist, Arthur Eddington, supposed differently. He had concluded that beyond any conceivable measuring, there is both more and less to any physical object. He sensed that the actual natural state always remains hidden within indeterminate variables (Durham 2003). Certainly, quantum theory points toward indeterminism, as it is underpinned by Heisenberg Uncertainty (the exact position and the exact speed of an object cannot be known simultaneously) and the Born Rule (an essential law within quantum mechanics giving the probability that a measurement on a quantum system will yield a given result) (Landsman 2009). Based on these within any quantum system, the outcome of any event is probabilistic and uncertain. When the Nobel Prize winners, Prigogine and Monod, attempted to scale these principles to biological systems, they argued for indeterminism (Prigogine and Stengers 1997; Merlin 2015). It is proposed that when biology is properly considered in the context of informational ambiguity and cell–cell communication across levels, there can be a productive unification of biology and quantum physics.
... Priel, Tuszynski and Cantiello discussed how information processing could be implemented in actin-tubulin networks of neuron dendrites [148]. The hypothetical AF/MT information processing devices can transmit signals as travelling localised patterns of conformational changes [86,82], orientational transitions of dipole moments [198,24,28], and ionic waves [199,147,161]. While propagation of information along the cytoskeleton is well studied, in theoretical models, there are almost no experimental results on actual processing of information. ...
Actin and tubulin are key structural elements of Eukaryotes’ cytoskeleton. The networks of actin filaments and tubulin microtubules are substrates for cells’ motility and mechanics, intra-cellular transport and cell-level learning. Ideas of information processing taking place on a cytoskeleton network, especially in neurons, have been proposed by Stuart. Hameroff and Steen. Rasmussen in the late 1980s in their designs of tubulin microtubules automata and a general framework of cytoskeleton automata as sub-cellular information processing networks. The cytoskeleton protein networks propagate signals in the form of ionic solitons, travelling conformation transformations and breathers generated through electrical and mechanical vibrations. A collision-based, or dynamical, computation employs mobile compact finite patterns, mobile self-localised excitations or simply localisations, in an active non-linear medium. These localisations travel in space and perform computation when they collide with each other. Memristor is a device whose resistance changes depending on the polarity and magnitude of a voltage applied to the device’s terminals and the duration of the voltage’s application.
... One component of this cytoskeleton are thin hollow fibers, called microtubules that demonstrate coordinated vibrational beat frequencies that may produce quantum coherences (Hameroff and Penrose 2014). Along with other components of the cytoskeleton, these vibratory motions seem to enable quantum signaling that is the foundation of certain biological activities crucial to some animals, such as the magnetic sensitivities that permit bird migrations (Hameroff et al. 2002;Craddock et al. 2014;Friesen et al. 2015). ...
In previous chapters, a differing point of initiation for evolutionary development has been introduced through concepts of information management and cell–cell communication. It has been emphasized that evolution proceeds quite differently than it had been supposed. Instead of random genetic variations based on intermittent replication errors, evolution can now be understood as a continuous self-referential process of self-modification in response to environmental stresses through natural cellular engineering and niche construction. Yet, to further comprehend how the modern synthesis must be altered, an accurate perception of the endpoint of all evolutionary processes must be explained. It is now known that all multicellular macro-organisms are holobionts. Taking ourselves as an example, it is currently estimated that there are many trillions of microbes—bacteria, viruses, fungi, and others—that are in us and on us (Sender et al. 2016). They outnumber our eukaryotic cells by a factor estimated by some to be up to 10 to 1 or more (Turnbaugh et al. 2007). When the total genetic complement of this microbial fraction is considered, the full genetic cohort of the associated microbiome outnumbers our innate genetic complement by perhaps as much as 100 to 1 (Bäckhed et al. 2005).
... An average period of a resistance spike is 24 ns (2.4×10 −5 ), standard deviation 0.4 ns. The oscillations can be caused by electro-mechanical vibrations of the MT [30,36], shuttling of conformation changes [28], orientation transitions of dipole moments [55,7,15], and ionic waves [56,46,52]. Those faster oscillations could be the result of the much higher stiffness of MT bundles in Taxol-stabilised solutions. ...
Hypothesis:
Tubulin is a key protein of the cytoskeleton, forming networks of microtubules (MTs). These networks are vital for many aspects of a cell, including intra-cellular transport. It has been suggested by others that this network could be responsible for sub-cellular information processing, which naturally raises the question of whether such a system could be exploited for more artificial constructs. In this endeavour, this paper studies the electrical properties of Taxol-stabilised MT ensembles.
Experiments:
Electrical experiments were conducted on samples containing MTs. Measurements were made using iridium-coated needle electrodes on a droplet. Cyclic voltammetry was performed, by sweeping through a DC voltage range of [-1.2,+1.2] V. AC measurements were also taken, between 1 kHZ and 10 MHz, and with a DC bias. Separately, pulse train stimulation were conducted, with an amplitude of 0.5 V and duration of 1 ms.
Findings:
Cyclic voltammetry experiments reveal that the MT droplets act as electrical switches, under the experimental conditions. This is partly revealed in a substantial hysteresis. The stimulation of a MT droplet with a positive fast-impulse resulted in oscillation of the droplet's resistance, not observed in control experiments. Taxol-stabilised MT samples proved to be mem-resistive/mem-inductive, therefore the history of their electrical characterisation is able to change their response and behaviour. If the history of electrical stimuli is the same, so is the response. These findings pave a way towards future designs of MT-based sensing and computing devices, including data storage featuring liquid states.
Ketamine is a common anaesthetic that works through complex neural mechanisms, including multiple molecular and circuitry targets. Importantly, it promotes analgesia, though it also induces undesirable effects, such as agitation, disorientation, hallucinations and nausea. Thus, there is an ongoing search for novel ketamine analogues that influence a similar repertoire of brain targets as ketamine, whose beneficial effects are potentiated. The present project, utilizing rats as an animal model, focused on examining functional properties of the ester-analogue of ketamine, R5, whose potentially beneficial profile had been suggested by preliminary studies. First, brain activation patterns following R5 compared to ketamine (and another ester-analogue control compound, R1) were assessed by employing immunohistochemical detection of an immediate-early gene product, c-Fos. R5 produced a somewhat similar pattern of activity as ketamine, whereas more profound differences in c-Fos were detected after R1. It was particularly striking in areas related to pain and addiction, including the anterior insular cortex (AIC) and paraventricular nucleus (PVN). Therefore, in the subsequent set of experiments, effects of R5 on pain- and addiction-related behavioral parameters were assessed in rats injected with R5 intracerebroventricularly (ICV) or intraparenchymally. It was found that BaCl attenuated ICV R5-induced analgesia. AIC administration of R5 produced modest analgesia in the tail-flick test. Finally, PVN R5 reduced naltrexone-precipitated exercise-induced withdrawal. In sum, R5 shows an analgesic effect similar to ketamine, most likely by targeting a similar subset of brain sites, which suggests that this particular ester-analogue can be considered as a good candidate for conceptualizing future pain management strategies.
The paper investigates quantum dynamics of a system of microtubule tubulins electric dipole moments. Electric dipoles represent two-level pseudo-spin systems, with one of the two polarized tubulin states corresponding to each of a pseudo-spin one. The pseudo-spin system behavior with time has been analyzed on basis of the Born–Markov formalism. The decoherence and dissipation processes caused by pseudo-spin – boson interaction have been considered. The problem of a possible signal propagation mechanism in the microtubule dipole–dipole system, which can be exclusively quantum in nature, has been discussed. It has been determined that the decoherence time depends considerably on dissipative processes in microtubules. Thus, the decoherence time in case of weak dissipation or absence of it equals 10−11−10−10 s. The decoherence time in the presence of dissipation process has been found to be 1.86⋅10−13 s. The temperature dependence of decoherence process has been considered. It has been stated that temperature values are the major factor influencing the dissipation-less decoherence time. The results obtained in the paper make it possible to describe the microtubule as a system in which quantum relaxation processes are important and comparable in time with those occurring in bio systems.
Neural therapy is a non-conventional medical practice in which the injection of local anesthetics (procaine and lidocaine) in concentrations in the range of 1 - 10 mg/ml, in quantities between 1-10 cm3 , is applied in different parts of the body with therapeutical but not anesthetics purposes. The mechanism of action of local anesthetics in this therapy is not known. The possible remote action and the electrical effect of procaine on the signal transport and on the membrane is normal potential recovery are very important issues in neural therapy, and a physico-chemical explanation of these phenomena is required. In this paper we propose that the propagation of signals in neural microtubules could be involved in the mechanism of action of procaine in neural therapy. We suggest some experimental studies in order to find a more rigorous scientific interpretation of the reported observations and of the remote effects that are assigned to the injection of procaine in neural therapy.
Biosensors based on the principle of surface plasmon resonance (SPR) detection were used to measure biomolecular interactions in sarcomeres and changes in the dielectric constant of tubulin samples with varying concentration. At SPR, photons of laser light efficiently excite surface plasmons propagating along a metal (gold) film. This resonance manifests itself as a sharp minimum in the reflection of the incident laser light and occurs at a characteristic angle. The dependence of the SPR angle on the dielectric permittivity of the sample medium adjacent to the gold film allows the monitoring of molecular interactions at the surface. We present results of measurements of cross-bridge attachment-detachment within intact mouse heart muscle sarcomeres and measurements on bovine tubulin molecules pertinent to cytoskeletal signal transduction models.
Microtubules lattice equal-frequency maps are obtained in the paper. Microtubule vibrational properties depending on their elastic properties, tubulins’ dipole–dipole interaction and the surrounding solution viscosity are analyzed in detail. Calculations have been made for different elastic constant values, damping coefficients and for different dipole moment directions. The relief of equal-frequency maps has also been investigated in accordance with a wave polarization direction. The dynamics of equal-frequency map relief changes have been analyzed. Its considerable dependence on viscosity, the direction of tubulins’ dipole–dipole moment and polarization has been demonstrated. The dynamics of changing the maps areas corresponding to damping harmonic oscillations and exponential damping law has been considered. Possible factors contributing to the microtubule’s structural damage are analyzed.
Consciousness and reality are related through the “measurement problem” in quantum mechanics, i.e., why we do not consciously perceive particles as quantum superpositions of multiple possibilities, as they appear to be when unobserved, but rather perceive them consciously as being in definite states or locations. Quantum pioneers Niels Bohr, John von Neumann, Eugene Wigner, and Henry Stapp concluded that subjective conscious observation causes quantum state reduction (“subjective reduction” (SR)), that “consciousness collapses the wavefunction.” However, Sir Roger Penrose suggested instead that quantum state reduction occurs spontaneously due to an objective threshold property (“objective reduction” (OR)) in fundamental spacetime geometry, collapsing the wave function and causing moments of conscious experience (“collapse causes consciousness,” or “collapse is consciousness”). Penrose OR would be occurring ubiquitously and randomly in the environment (“decoherence”) resulting in ubiquitous proto-conscious moments. The Penrose–Hameroff “Orch OR” model of orchestrated objective reduction suggests that microtubules inside brain neurons “orchestrate” quantum computations which “halt” by Orch OR to produce moments of a full, rich conscious experience.
General anesthetics, able to reversibly suppress all conscious brain activity, have baffled medical science for decades, and little is known about their exact molecular mechanism of action. Given the recent scientific interest in the exploration of microtubules as putative functional targets of anesthetics, and the involvement thereof in neurodegenerative disorders, the present work focuses on the investigation of the interaction between human tubulin and four volatile anesthetics: ethylene, desflurane, halothane and methoxyflurane. Interaction sites on different tubulin isotypes are predicted through docking, along with an estimate of the binding affinity ranking. The analysis is expanded by Molecular Dynamics simulations, where the dimers are allowed to freely interact with anesthetics in the surrounding medium. This allowed for the determination of interaction hotspots on tubulin dimers, which could be linked to different functional consequences on the microtubule architecture, and confirmed the weak, Van der Waals-type interaction, occurring within hydrophobic pockets on the dimer. Both docking and MD simulations highlighted significantly weaker interactions of ethylene, consistent with its far lower potency as a general anesthetic. Overall, simulations suggest a transient interaction between anesthetics and microtubules in general anesthesia, and contact probability analysis shows interaction strengths consistent with the potencies of the four compounds.
Communicated by Ramaswamy H. Sarma
Filaments of the cellular protein actin can form bundles, which can conduct ionic currents as well as mechanical and voltage solitons. These inherent properties can be utilized to generate computing circuits solely based on self-assembled actin bundle structures. Starting with experimentally observed networks of actin bundles, we model their network structure in terms of edges and nodes. We compute and discuss the main electrical parameters, considering the bundles as electrical wires with either low or high filament densities. A set of equations describing the network is solved with several initial conditions. Input voltages, which can be considered as information bits, are applied in a set of points and output voltages are computed in another set of positions. We consider both an idealized situation, where pointlike electrodes can be inserted in any points of the bundles and a more realistic case, where electrodes lay on a surface and have typical dimensions available in the industry. We find that in both cases such a system can implement the main logical gates and a finite state machine.
A prior series of peer-reviewed journal articles (Torday and Rehan 2007; Torday 2013, 2015a, b, 2018a, b) and monographs (Torday and Rehan 2012; Torday et al. 2017) have elucidated how cell–cell signaling for form and function during embryologic development can be exploited to determine the evolution of such processes. This is particularly true when the mechanisms of development are identified as the source of phylogenetic changes in physiologic traits such as the lung, kidney, skin, and bone (Torday and Rehan 2012, 2017).
Biologic organisms act like fields. Hypothetically, pleiotropy results from the systematic re-purposing of genes over the course of the evolutionary history of the organism as pre-adaptations or exaptations. Mechanistically, pleiotropic genes are selected for during the process of evolution with reference to the First Principles of Physiology (FPP). Under stress conditions, pleiotropic genes will act as a functional network to cohesively maintain allostasis. There are strong homologies between Quantum Mechanics and the FPP. The homology between the Quantum states of the electron and cell may be due to the self-organizing principle that underlies both, hypothetically emanating from the Big Bang that formed the Universe some 13.8 billion years ago. The identification of the common origins and principles of physics and biology offers a cohesive explanation for origins and evolution of life.
Being observed when completing physical and mental tasks alters how successful people are at completing them. This has been explained in terms of evaluation apprehension, drive theory, and due to the effects of stress caused by being observed. In three experiments, we explore how being observed affects participants’ ability to recognise faces as it relates to the aforementioned theories — easier face recognition tasks should be completed with more success under observation relative to harder tasks. In Experiment 1, we found that being observed during the learning phase of an old/new recognition paradigm caused participants to be less accurate during the test phase than not being observed. Being observed at test did not affect accuracy. We replicated these findings in an line-up type task in Experiment 2. Finally, in Experiment 3, we assessed whether these effects were due to the difficulty of the task or due to the physiological stress being observed caused. We found that while observation caused physiological stress, it did not relate to accuracy. Moderately difficult tasks (upright unfamiliar face recognition and inverted familiar face recognition) were detrimentally affected by being observed, whereas easy (upright familiar face recognition) and difficult tasks (inverted unfamiliar face recognition) were unaffected by this manipulation. We explain these results in terms of the direct effects being observed has on task performance for moderately difficult tasks and discuss the implications of these results to cognitive psychological experimentation.
Consciousness is a multidisciplinary problem that has puzzled all human beings since the origin of human life. Being defined in various pointcuts by philosophers, biologists, physicists, and neuroscientists, the definitive explanation of consciousness is still suspending. The nature of consciousness has taken great evolution by centering on the behavioral and neuronal correlates of perception and cognition, for example, the theory of Neural Correlates of Consciousness, the Global Workspace Theory, the Integrated Information Theory. While tremendous progress has been achieved, they are not enough if we are to understand even basic facts-how and where does the consciousness emerge. The Quantum mechanics, a thriving branch of physics, has an inseparable relationship with consciousness (e.g., observer effect) since Planck created this subject and its derived quantum consciousness theory can perfectly fill this gap. In this review, we briefly introduce some consciousness hypotheses derived from quantum mechanics and focus on the framework of orchestrated objective reduction (Orch-OR), including its principal points and practicality.
YinYang bipolar relativity leads to an equilibrium-based logically complete quantum theory which is presented and discussed in this chapter. It is shown that bipolar quantum entanglement and bipolar quantum computing bring bipolar relativity deeper into microscopic worlds. The concepts of bipolar qubit and YinYang bipolar complementarity are proposed and compared with Niels Bohr’s particle-wave complementarity. Bipolar qubit box is compared with Schrödinger’s cat box. Since bipolar quantum entanglement is fundamentally different from classical quantum theory (which is referred to as unipolar quantum theory in this book), the new approach provides bipolar quantum computing with the unique features: (1) it forms a key for equilibrium-based quantum controllability and quantum-digital compatibility; (2) it makes bipolar quantum teleportation theoretically possible for the first time without conventional communication between Alice and Bob; (3) it enables bitwise encryption without a large prime number that points to a different research direction of cryptography aimed at making prime-number-based cryptography and quantum factoring algorithm both obsolete; (4) it shows potential to bring quantum computing and communication closer to deterministic reality; (5) it leads to a unifying Q5 paradigm aimed at revealing the ubiquitous effects of bipolar quantum entanglement with the sub theories of logical, physical, mental, social, and biological quantum gravities and quantum computing.
The DNA double helix, containing a n-stacked array of base pairs in its core, represents a unique and efficient medium for long-range charge transport. DNA assemblies have been constructed containing tethered metallointercalators, and these provide chemically well-defined systems through which to probe the DNA n-stack. Using both spectroscopy and chemical assays of reactivity, we find electron transfer reactions mediated by the DNA base pairs to occur over long molecular distances. The structure of DNA facilitates chemistry at a distance. Importantly, these long-range reactions depend sensitively upon base pair stacking, and hence are modulated by and report on the characteristic stacking within the double helix.
General anesthetics produce a widespread neurodepression in the central nervous system by enhancing inhibitory neurotransmission and reducing excitatory neurotransmission. However, the action mechanisms of general anesthetics are not completely understood. Moreover, the general anesthetic state comprises multiple components (amnesia, unconsciousness, analgesia, and immobility), each of which is mediated by different receptors and neuronal pathways. Recently, neurotransmitter- and voltage-gated ion channels have emerged as the most likely molecular targets for general anesthetics. The gamma-aminobutyric acid type A (GABA(A)) receptors are leading candidates as a primary target of general anesthetics. This review summarizes current knowledge on how anesthetics modify GABA(A) receptor function.
Chromatin is thought to be structurally discontinuous because it is packaged into morphologically distinct chromosomes that appear physically isolated from one another in metaphase preparations used for cytogenetic studies. However, analysis of chromosome positioning and movement suggest that different chromosomes often behave as if they were physically connected in interphase as well as mitosis. To address this paradox directly, we used a microsurgical technique to physically remove nucleoplasm or chromosomes from living cells under isotonic conditions. Using this approach, we found that pulling a single nucleolus or chromosome out from interphase or mitotic cells resulted in sequential removal of the remaining nucleoli and chromosomes, interconnected by a continuous elastic thread. Enzymatic treatments of interphase nucleoplasm and chromosome chains held under tension revealed that mechanical continuity within the chromatin was mediated by elements sensitive to DNase or micrococcal nuclease, but not RNases, formamide at high temperature, or proteases. In contrast, mechanical coupling between mitotic chromosomes and the surrounding cytoplasm appeared to be mediated by gelsolin-sensitive microfilaments. Furthermore, when ion concentations were raised and lowered, both the chromosomes and the interconnecting strands underwent multiple rounds of decondensation and recondensation. As a result of these dynamic structural alterations, the mitotic chains also became sensitive to disruption by restriction enzymes. Ion-induced chromosome decondensation could be blocked by treatment with DNA binding dyes, agents that reduce protein disulfide linkages within nuclear matrix, or an antibody directed against histones. Fully decondensed chromatin strands also could be induced to recondense into chromosomes with pre-existing size, shape, number, and position by adding anti-histone antibodies. Conversely, removal of histones by proteolysis or heparin treatment produced chromosome decondensation which could be reversed by addition of histone H1, but not histones H2b or H3. These data suggest that DNA, its associated protein scaffolds, and surrounding cytoskeletal networks function as a structurally-unified system. Mechanical coupling within the nucleoplasm may coordinate dynamic alterations in chromatin structure, guide chromosome movement, and ensure fidelity of mitosis. J. Cell. Biochem. 65:114–130. © 1997 Wiley-Liss, Inc.
A two-dimensional quantum system with anyonic excitations can be considered as a quantum
computer. Unitary transformations can be performed by moving the excitations around
each other. Measurements can be performed by joining excitations in pairs and observing the
result of fusion. Such computation is fault-tolerant by its physical nature.
Orch OR ("Orchestrated Objective Reduction") is a theory of consciousness put forth in the mid-1990s by British physicist Sir Roger Penrose and American anesthesiologist Stuart Hameroff. Whereas most theories assume consciousness emerges from complex computation at the level of synapses among brain neurons, Orch OR involves a specific form of quantum computation which underlies these neuronal synaptic activities. The proposed quantum computations occur in structures inside the brain's neurons called microtubules.
The stability of living organisms is of kinetic nature. It is the stability of a whirlwind and not of a static structure. A continuous flood-tide of molecules circulates in the organism. Consequently its unity is not to be sought at the molecular level but at the level of a kinetic structure.
We report in this article that the retraction of PC 12 neurites, unlike that of other cultured neurons, is due to tension within the neurite. Retraction is rapid and independent of metabolic energy. Transection of one arm of a branched neurite immediately causes the remaining arm to take up a new equilibrium position between attachment points. Similarly, detachment of one growth cone of a cell causes the cell body to move to a new equilibrium position between the remaining neurites. These observations provide direct evidence for the suspension of the cell soma among a network of tensioned neurites. We used retraction as an assay for neurite tension to examine the role of actin filaments and microtubules in neurite support and elongation. Our data suggest that microtubules (MTs) within PC 12 neurites are under compression, supporting tension within the actin network. Treatment of cells with drugs that disrupt actin networks, cytochalasin D or erythro-9-[3-(2-hydroxynonyl)]adenosine eliminates retraction regardless of the absence of MTs, lack of adhesion to the substratum, or integrity of the neurite. Conversely, stimulation of actin polymerization by injection of phalloidin causes retraction of neurites. Treatments that depolymerize MTs, nocodazole or cold, cause retraction of neurites, which suggests that microtubules support this tension, i.e., are under compression. Stabilization of MTs with taxol stabilizes neurites to retraction and under appropriate circumstances can drive neurite extension. Taxol-stimulated neurite extension is augmented by combined treatment with anti-actin drugs. This is consistent with the actin network's normally exerting a force opposite that of MT assembly. Cytochalasin and erythro-9-[3-(2-hydroxynonyl)] adenosine were found to increase slightly the dose of nocodazole required for MT depolymerization. This is consistent with the postulated balance of forces and also suggests that alteration of the compression borne by the microtubules could serve as a local regulator for MT polymerization during neurite outgrowth.
Microtubule (MT) networks, subneural paracrystalline cytoskeletal structures, seem to play a fundamental role in the neurons. We cast here the complicated MT dynamics in the form of a (1 + 1)-dimensional noncritical string theory, thus enabling us to provide a consistent quantum treatment of MTs, including environmental friction effects. We suggest, thus, that the MTs are the microsites, in the brain, for the emergence of stable, macroscopic quantum coherent states, identifiable with the preconscious states. Quantum space-time effects, as described by noncritical string theory, trigger then an organized collapse of the coherent states down to a specific or conscious state. The whole process we estimate to take script O sign(1 sec), in excellent agreement with a plethora of experimental/observational findings. The microscopic arrow of time, endemic in noncritical string theory, and apparent here in the self-collapse process, provides a satisfactory and simple resolution to the age-old problem of how the, central to our feelings of awareness. sensation of the progression of time is generated. In addition, the complete integrability of the stringy model for MT we advocate in this work proves sufficient in providing a satisfactory solution to memory coding and capacity. Such features might turn out to be important for a model of the brain as a quantum computer.
Structure, occurrence, and functions of microtubules are reviewed. The theoretical principles of bioholography are outlined and the neuronal microtubular system is offered as an anatomical substrate for such a mechanism. This entails microtubules acting as coherency inducing, dielectric wave guides and resonators for atmospheric ultraviolet radiation which is refracted by the stratum corneum and other tissues. The proposed corporeal energy and its pathways are correlated with Ch'i, the ancient Chinese life energy and medium of acupuncture.
We examined the anesthetic and convulsant properties of 16 unfluorinated to completely fluorinated aromatic compounds, having six to nine carbon atoms (e.g., benzene to 1,3,5-tris(trifluoromethyl)benzene), and four cycloalkanes (cyclopentane to cyclooctane). Benzene, fluorobenzene, toluene, p-xylene, ethylbenzene, and cyclopentane caused excitation (twitching, jerking, and hyperactivity), and three aromatic compounds (perfluorotoluene, p-difluorotoluene and 1,3,5-tris(trifluoromethyl)benzene) and three cycloalkanes (cyclohexane, cycloheptane, and cyclooctane) produced convulsions. Cyclooctane and 1,3,5-tris(trifluoromethyl)benzene were nonanesthetics. Except for nonanesthetics and perfluorotoluene (too toxic to test for anesthetic potency), all compounds produced anesthesia or decreased the minimum alveolar anesthetic concentration of desflurane. Aromatic compounds were more potent and lipid-soluble than n-alkanes (data from previous report) and cycloalkanes. All three series increasingly disobeyed the Meyer-Overton hypothesis as molecular size increased. For a particular number of carbons (e.g., cyclohexane, n-hexane, and benzene), the deviation was cycloalkanes >or=to normal alkanes > aromatic compounds. These results suggest that molecular shape (including "bulkiness") and size provide limited clues to the structure of the anesthetic site of action. (Anesth Analg 1996;83:1097-104)
The mathematical description of B.E. (Bose-Einstein) condensation is generalized so as to be applicable to a system of interacting particles. B.E. condensation is said to be present whenever the largest eigenvalue of the one-particle reduced density matrix is an extensive rather than an intensive quantity. Some transformations facilitating the practical use of this definition are given. An argument based on first principles is given, indicating that liquid belium II in equilibrium shows B.E. condensation. For absolute zero, the argument is based on properties of the ground-state wave function derived from the assumption that there is no "long-range configurational order." A crude estimate indicates that roughly 8% of the atoms are "condensed" (note that the fraction of condensed particles need not be identified with ρsρ). Conversely, it is shown why one would not expect B.E. condensation in a solid. For finite temperatures Feynman's theory of the lambda-transition is applied: Feynman's approximations are shown to imply that our criterion of B.E. condensation is satisfied below the lambda-transition but not above it.
We discuss the occurence of self-focusing of Fröhlich electric vibrations in living cells by investigating the Kerr activity of actin solutions. This process could provide a dynamical support of the filamentous microstructure of cell cytoplasm.
Potential features of quantum computation could explain enigmatic aspects of consciousness. The Penrose—Hameroff model (orchestrate objective reduction: ‘Orch OR’) suggests that quantum superposition and a form of quantum computation occur in microtubules—cylindrica protein lattices of the cell cytoskeleton within the brain's neurons. Microtubules couple to and regulate neural–level synapti functions, and they may be ideal quantum computers because of dynamical lattice structure, quantum–level subunit states an intermittent isolation from environmental interactions. In addition to its biological setting, the Orch OR proposal differ in an essential way from technologically envisioned quantum computers in which collapse, or reduction to classical outpu states, is caused by environmental decoherence (hence introducing randomness). In the Orch OR proposal, reduction of microtubul quantum superposition to classical output states occurs by an objective factor: Roger Penrose's quantum gravity threshol stemming from instability in Planck–scale separations (superpositions) in spacetime geometry. Output states following Penrose' objective reduction are neither totally deterministic nor random, but influenced by a non–computable factor ingrained in fundamenta spacetime. Taking a modern pan–psychist view in which protoconscious experience and Platonic values are embedded in Planck–scal spin networks, the Orch OR model portrays consciousness as brain activities linked to fundamental ripples in spacetime geometry.
Cell BiologyA team of cell biologists has demonstrated that mammalian cells are densely "hard-wired" with force-carrying connections that reach all the way from the membrane through the cytoskeleton to the genome. The group combined micromanipulation, video microscopy, and molecular adhesives to show that tugging on particular receptors at the cell surface triggers nearly instantaneous rearrangements in the nucleus. The demonstration supports the idea that cytoskeletal connections could transmit regulatory information throughout the cell.
Nonlinear electrodynamic theories predict dynamic organization of biomolecular activities at all cellular levels: DNA, membranes, extracelluular glycoproteins, and the interconnecting cytoskeletal lattice. 1–5 Cytoskeletal lattice proteins including microtubules are particularly involved in dynamic regulation of intracellular movements and activities.6, 7This paper considers possibilities and implications of biological information processing due to coupling of Davydov solitons, Frohlich coherent oscillations and other nonlinear electrodynamic phenomena to conformational states of the grid-like polymer subunits of cytoskeletal microtubules.
Microtubules have been the subject of intense research in the last ten
years in particular as speculation has grown surrounding their
involvement in a diverse range of biological and cognitive functions. In
this context, this thesis focuses on microtubules with a view to develop
simple models of electromagnetic effects in this important biological
polymer. The goal of the work is to provide insight into fundamental
questions of microtubule structure and function. My modelling began with
considering the ferroelectric properties of an individual microtubule.
Each tubulin dimer of which the microtubule is comprised has an
associated dipole which changes with conformational changes of the
dimer. I have studied the conditions under which the interdimer
dipole-dipole interactions are sufficient to result in a
ferroelectrically ordered polymer. I find that the microtubule may adopt
a conformation of ferroelectrically or antiferroelectrically ordered
alternating protofilaments depending upon its lattice type. I have
further studied whether defects introduced upon the lattice can
propagate and constitute a form of intracellular signalling. The
investigation demonstrates that such defects will indeed propagate in
the presence of an action potential which is required to provide
directionality. I next studied the possibility of electrical conduction
by microtubules and determined that their conductivity is strongly
related to the relative and absolute hopping parameters in each of the
three lattice directions. The microtubule can indeed have
semi-conducting properties if the protofilament-protofilament
interactions are sufficiently strong due to the triangular nature of its
lattice. Lastly, I have tried to unite the latest structural data on the
atomic structure of tubulin with the microtubule structure, their
assembly properties and their functions. The conclusion is that the
electrostatics play a large role in the behaviour of microtubules.
Grush and Churchland (1995) attempt to address aspects of the proposal that we have been making concerning a possible physical mechanism underlying the phenomenon of consciousness. Unfortunately, they employ arguments that are highly misleading and, in some important respects, factually incorrect. Their article `Gaps in Penrose's Toilings' is addressed specifically at the writings of one of us (Penrose), but since the particular model they attack is one put forward by both of us (Hameroff and Penrose, 1995; 1996), it is appropriate that we both reply; but since our individual remarks refer to different aspects of their criticism we are commenting on their article separately. The logical arguments discussed by Grush and Churchland, and the related physics are answered in Part 1 by Penrose, largely by pointing out precisely where these arguments have already been treated in detail in Shadows of the Mind (Penrose, 1994). In Part 2, Hameroff replies to various points on the biological side, showing for example how they have seriously misunderstood what they refer to as `physiological evidence' regarding effects of the drug colchicine. The reply serves also to discuss aspects of our model `orchestrated objective reduction in brain microtubules - Orch OR' which attempts to deal with the serious problems of consciousness more directly and completely than any previous theory.
The paper begins with a general introduction to the nature of human consciousness and outlines several different philosophical approaches. A critique of traditional reductionist and dualist positions is offered and it is suggested that consciousness should be viewed as an emergent property of physical systems. However, although consciousness has its origin in distributed brain processes it has macroscopic properties - most notably the `unitary sense of self', non-deterministic free will, and non-algorithmic `intuitive' processing - which can best be described by quantum-mechanical principles.
What is consciousness? Some philosophers have contended that "qualia," or an experiential medium from which consciousness is derived, exists as a fundamental component of reality. Whitehead, for example, described the universe as being comprised of "occasions of experience." To examine this possibility scientifically, the very nature of physical reality must be re-examined. We must come to terms with the physics of space-time--as is described by Einstein's general theory of relativity--and its relation to the fundamental theory of matter--as described by quantum theory. This leads us to employ a new physics of objective reduction: " OR" which appeals to a form of quantum gravity to provide a useful description of fundamental processes at the quantum/classical borderline. Within the OR scheme, we consider that consciousness occurs if an appropriately organized system is able to develop and maintain quantum coherent superposition until a specific "objective" criterion (a threshold related to quantum gravity) is reached; the coherent system then self-reduces (objective reduction: OR). We contend that this type of objective self-collapse introduces non-computability, an essential feature of consciousness. OR is taken as an instantaneous event--the climax of a self-organizing process in fundamental space-time--and a candidate for a conscious Whitehead "occasion" of experience. How could an OR process occur in the brain, be coupled to neural activities, and account for other features of consciousness? We nominate an OR process with the requisite characteristics to be occurring in cytoskeletal microtubules within the brain's neurons. In this model, quantum-superposed states develop in microtubule subunit proteins ("tubulins"), remain coherent and recruit more superposed tubulins until a mass-time-energy threshold (related to quantum gravity) is reached. At that point, self-collapse, or objective reduction (OR) abruptly occurs. We equate the pre-reduction, coherent superposition ("quantum computing") phase with pre-conscious processes, and each instantaneous (and non-computable) OR, or self-collapse, with a discrete conscious event. Sequences of OR events give rise to a "stream" of consciousness. Microtubule-associated-proteins can "tune" the quantum oscillations of the coherent superposed states; the OR is thus self-organized, or "orchestrated" ("Orch OR"). Each Orch OR event selects (non-computably) microtubule subunit states which regulate synaptic/neural functions using classical signaling. The quantum gravity threshold for self-collapse is relevant to consciousness, according to our arguments, because macroscopic superposed quantum states each have their own space-time geometries. These geometries are also superposed, and in some way "separated," but when sufficiently separated, the superposition of space-time geometries becomes significantly unstable, and reduce to a single universe state. Quantum gravity determines the limits of the instability; we contend that the actual choice of state made by Nature is non-computable. Thus each Orch OR event is a self-selection of space-time geometry, coupled to the brain through microtubules and other biomolecules. If conscious experience is intimately connected with the very physics underlying space-time structure, then Orch OR in microtubules indeed provides us with a completely new and uniquely promising perspective on the hard problem of consciousness.
Microtubules, which play many diverse and important roles in biological systems, are usually made up of 13 nearly axial protofilaments formed from individual tubulin molecules. In this paper, a nonlinear dynamic model has been developed to elucidate the mechanism of the internal motion occurring during the assembly of microtubules. The results derived from the model indicate that such internal motion is associated with a solitary wave, or kink, excited by the energy released from the hydrolysis of GTP ⟹ GDP in microtubular solutions. As the kink moves forward, the individual tubulin molecules involved in the kink undergo motions that can be likened to the dislocation of atoms within the crystal lattice. Thus, the dynamic instability of microtubules may be characterized by a series of dislocation motions of the tubulin molecules. An energy estimate shows that a kink in the system possesses about 0.36–0.44 eV, which is quite close to but smaller than the 0.49 eV of energy released from the hydrolysis of GTP. Therefore, the relevant energy derived from our model is fully consistent with experimental observations; this finding also suggests that the hydrolysis energy may be responsible for exciting the solitary wave, or kink, leading to tubulin dislocation in microtubules.Our model, and its intrinsic properties, i.e., dynamic nonlinearity, thermodynamic irreversibility, as well as an energy input from a sustained source, implies that the growth of microtubules is a typical dissipative process and that their structure in vivo is typical of dissipative structures. © 1994 John Wiley & Sons, Inc.
The mathematical description of B.E. (Bose-Einstein) condensation is generalized so as to be applicable to a system of interacting particles. B.E. condensation is said to be present whenever the largest eigenvalue of the one-particle reduced density matrix is an extensive rather than an intensive quantity. Some transformations facilitating the practical use of this definition are given. An argument based on first principles is given, indicating that liquid belium II in equilibrium shows B.E. condensation. For absolute zero, the argument is based on properties of the ground-state wave function derived from the assumption that there is no "long-range configurational order." A crude estimate indicates that roughly 8% of the atoms are "condensed" (note that the fraction of condensed particles need not be identified with rhosrho). Conversely, it is shown why one would not expect B.E. condensation in a solid. For finite temperatures Feynman's theory of the lambda-transition is applied: Feynman's approximations are shown to imply that our criterion of B.E. condensation is satisfied below the lambda-transition but not above it.
We define an extremal computer as one which uses physical resources as effectively as possible for computation. As far as presently understood, extremal computers should be molecular computers. A number of computing mechanisms at the cellular level are considered, including word processing, kinetic mechanisms, conformational mechanisms, control processes in the membrane, diffusional mechanisms, and mechanisms involving sound waves. The hypothesis is put forward that the cyclic nucleotide system of intraneuronal information processing serves both as an analog diffusional mechanism and as a link between extremal (molecular) computing processes and macroscopic computing processes involving the nerve impulse. According to this hypothesis the computing power of the brain is primarily based on intracellular processes. The describability of nature by (computable) physical laws is limited by the extreme of computing which is possible in the physical universe. The paradox of molecular computing is that the unpredictable features exhibited by an object system which is not computable by an extremal computer could not be distinguished from new computing primitives which would allow more extremal computing. The authors present separate possible resolutions of this paradox. But under any interpretation the limits on the describability of nature imposed by the physical limits of computing imply that macromolecular processes of the type which occur in living systems provide a more fundamental foundation stone for the structure of science and of nature than previously thought.
Electronic-conformational interactions allow for a speedup of biomolecular structure formation that derives from the quantum mechanical superposition principle. Changing phase relationships among electronic states of different energy lead to perturbative interactions between non Born-Oppenheimer electrons and atomic nuclei that can have a self-amplifying (positive feedback) character. Conformations that satisfy the conditions for such an interaction are inherently unstable. The term “conformational soliton” refers to nuclear configurational changes that ripple through macromolecular lattices in a manner that preserves informational integrity. The model suggests that such states of ordered conformational motions are genetic to polymacromolecular organizations of the type that occur in biological cells.
Features of consciousness difficult to understand in terms of conventional neuroscience have evoked application of quantum theory, which describes the fundamental behavior of matter and energy. In this paper we propose that aspects of quantum theory (e.g. quantum coherence) and of a newly proposed physical phenomenon of quantum wave function “self-collapse” (objective reduction: OR - Penrose, 1994) are essential for consciousness, and occur in cytoskeletal microtubules and other structures within each of the brain's neurons. The particular characteristics of microtubules suitable for quantum effects include their crystal-like lattice structure, hollow inner core, organization of cell function and capacity for information processing. We envisage that conformational states of microtubule subunits (tubulins) are coupled to internal quantum events, and cooperatively interact (compute) with other tubulins. We further assume that macroscopic coherent superposition of quantum-coupled tubulin conformational states occurs throughout significant brain volumes and provides the global binding essential to consciousness. We equate the emergence of the microtubule quantum coherence with pre-conscious processing which grows (for up to 500 ms) until the mass-energy difference among the separated states of tubulins reaches a threshold related to quantum gravity. According to the arguments for OR put forth in Penrose (1994), superpositioned states each have their own space-time geometries. When the degree of coherent mass-energy difference leads to sufficient separation of space-time geometry, the system must choose and decay (reduce, collapse) to a single universe state. In this way, a transient superposition of slightly differing space-time geometries persists until an abrupt quantum → classical reduction occurs. Unlike the random, “subjective reduction” (SR, or R) of standard quantum theory caused by observation or environmental entanglement, the OR we propose in microtubules is a self-collapse and it results in particular patterns of microtubule-tubulin conformational states that regulate neuronal activities including synaptic functions. Possibilities and probabilities for post-reduction tubulin states are influenced by factors including attachments of microtubule-associated proteins (MAPs) acting as “nodes” which tune and “orchestrate” the quantum oscillations. We thus term the self-tuning OR process in microtubules “orchestrated objective reduction” (“Orch OR”), and calculate an estimate for the number of tubulins (and neurons) whose coherence for relevant time periods (e.g. 500 ms) will elicit Orch OR. In providing a connection among (1) pre-conscious to conscious transition, (2) fundamental space-time notions, (3) non-computability, and (4) binding of various (time scale and spatial) reductions into an instantaneous event (“conscious now”), we believe Orch OR in brain microtubules is the most specific and plausible model for consciousness yet proposed.
What kind of physical structure could most plausibly be associated with consciousness? It is argued from the unity and complexity of states of consciousness that no classical physical system could play the role. Among quantum systems a Bose-Einstein condensate has the right properties. The brain probably contains one and only one system of this kind—a pumped phonon system described by Fröhlich—which is hypothesized to be the substrate of human consciousness. Some experimental tests and implications of the hypothesis are discussed.
Age-old battle lines over the puzzling nature of mental experience are shaping a modern resurgence in the study of consciousness. On one side are the long-dominant `physicalists' who view consciousness as an emergent property of the brain's neural networks. On the alternative, rebellious side are those who see a necessary added ingredient: proto-conscious experience intrinsic to reality, perhaps understandable through modern physics (panpsychists, pan-experientialists, `funda-mentalists'). It is argued here that the physicalist premise alone is unable to solve completely the difficult issues of consciousness and that to do so will require supplemental panpsychist/pan-experiential philosophy expressed in modern physics. In one scheme proto-conscious experience is a basic property of physical reality accessible to a quantum process associated with brain activity. The proposed process is Roger Penrose's `objective reduction' (OR), a self-organizing `collapse' of the quantum wave function related to instability at the most basic level of space-time geometry. In the Penrose–Hameroff model of `orchestrated objective reduction' (Orch OR), OR quantum computation occurs in cytoskeletal microtubules within the brain's neurons. The basic thesis is that consciousness involves brain activities coupled to self-organizing ripples in fundamental reality.
It is proposed that ciliary microtubules are actively involved in the reception and transduction of sensory information from the distal portion of the dendrite to the basal body area of the receptor cell. Environmental stimuli may cause stimulus-specific conformational changes in the tubulin protein molecule. This characteristic change may then be propagated along the tubulin polymer filaments. Once this coded information has reached the cell body, classical ion flux mechanisms are thought to further amplify the stimulus energy and transmit its patterned information (generator potential) to the action potential generating sites of the cell. Morphological and biochemical evidence for this point of view is presented.
Cytoskeletal microtubules structurally organize interiors of living eukaryotic cells. As polymers of subunit proteins (“tubulin”), which are each dipoles, microtubules are thus lattices of oriented dipoles. In general, three types of arrangements of dipoles in lattices may occur: (i) random, (ii) ferroelectric (parallel-aligned) and (iii) an intermediate weakly ferroelectric phase, which is length-dependent. Because of involvement in dynamical cell activities (movement, growth, mitosis, differentiation, etc.), models of microtubule signaling and information processing have been proposed. In these, tubulin units are assumed to represent informational “bit states” and to be coupled to intra-tubulin dipoles. In the present paper, we consider microtubules as lattice arrays of coupled local dipole states that interact with their immediate neighbors. Depending on the values of assumed model parameters, the system may exhibit “frustration”: conflict in satisfying all dipole couplings. Such systems have properties suitable for efficient information processing and computation. By slightly altering temperature and external field (both within physiological conditions), microtubule dipole lattices may assume a ferroelectric phase with long-range order and alignment with capabilities to propagate kink-like excitations. The ferroelectric phase appears to be optimal for microtubule signaling and assembly/disassembly. Microtubules may organize cell activities by operating in different modes suitable for information processing and computation (intermediate phase) or signaling and assembly/disassembly (ferroelectric phase).
“Neural network” models of brain function assume neurons and their synaptic connections to be the fundamental units of information processing, somewhat like switches within computers. However, neurons and synapses are extremely complex and resemble entire computers rather than switches. The interiors of the neurons (and other eucaryotic cells) are now known to contain highly ordered parallel networks of filamentous protein polymers collectively termed the cytoskeleton. Originally assumed to provide merely structural “bone-like” support, cytoskeletal structures such as microtubules are now recognized to organize cell interiors dynamically. The cytoskeleton is the internal communication network for the eucaryotic cell, both by means of simple transport and by means of coordinating extremely complicated events like cell division, growth and differentiation. The cytoskeleton may therefore be viewed as the cell's “nervous system”. Consequently the neuronal cytoskeleton may be involved in molecular level information processing which subserves higher, collective neuronal functions ultimately relating to cognition. Numerous models of information processing within the cytoskeleton (in particular, microtubules) have been proposed. We have utilized cellular automata as a means to model and demonstrate the potential for information processing in cytoskeletal microtubules. In this paper, we extend previous work and simulate associative learning in a cytoskeletal network as well as assembly and disassembly of microtubules. We also discuss possible relevance and implications of cytoskeletal information processing to cognition.
SOME time ago it was proposed that the energy produced in biological
activities is partly stored in various materials through excitation of
coherent electrical vibrations (polarization waves). If strong enough,
such excitations can be stabilized through non-linear effects leading to
various types of deformations1,2. R. Ferreira (personal
communication) has suggested that such considerations might be of
importance for an understanding of the action of enzymes. In fact the
properties of a model which I have considered recently (unpublished)
seems to support this idea.
A flash-quench method has been employed to probe electron-transfer reactions from peptides to DNA. The photoexcited intercalators [Ru(phen)(2)(dppz)](2+) (phen = 1,10-phenanthroline; dppz = dipyridophenazine) and [Ru(phen)(bpy')(dppz)](2+) (bpy' = 4-(4'-methyl-2,2'-bipyridyl)valerate) are quenched by a nonintercalating and weakly bound electron-transfer quencher to generate the corresponding DNA-bound Ru(III) complexes in situ. Both Ru(III) complexes are powerful ground-state oxidants, capable of oxidizing guanine in DNA or DNA-bound tryptophan of the intercalating peptide, Lys-Trp-Lys. In mixed-sequence oligonucleotide duplexes containing [Ru(phen)(bpy')(dppz)](2+) tethered at one end, damage to distant guanines is observed by gel electrophoresis, consistent with the mobility of the electron through the DNA duplex. This damage at guanines is observed in both the presence and absence of Lys-Trp-Lys, but the presence of the peptide affects the distribution. in flash-quench experiments using mixed-sequence oligonucleotides or poly(dG.dC) in the presence of Lys-Trp-Lys, transient absorption spectroscopy reveals a signal at lambda = 510 nm assigned to the tryptophan radical; it decays on the time scale of 60-250 mu s. The final peptide product of this electron-transfer reaction has been described by UV/vis spectroscopy and mass spectrometry. No DNA-peptide adducts were detected. Significantly, the tryptophan radical is not observed in reactions with Ru(III) bound to poly(dA.dT), an observation that suggests the intermediacy of the guanine radical cation in generating the tryptophan radical. These results indicate that charge migration from tryptophan to [Ru(phen)(bpy')(dppz)](3+) occurs to produce the tryptophan radical and that this process is DNA mediated. This work establishes methodology to probe tryptophan intercalation in DNA by protein or peptides. Moreover, this methodology demonstrates an electron-transfer event between peptides and DNA and suggests the consideration of such events within the cell.
The interaction of contiguous proteins is explored in microtubules, rosettes, and membranes based on the well established molecular phenomena of cooperativity and allosterism. It is proposed that conformational gradients in protein arrays cause the formation of gradions by nearest-neighbor interactions. Gradions are repeating functional molecular sequences that contain several conformational forms of one or more proteins, with the result that different reactive sites can exist in the same molecular architecture at any one time. Gradionators are small controlling molecules that may be microscopically visible as layers of linkages, but could alse be smaller. Some of the presently available supporting evidence and its functional implications are discussed, including the possibility that the raison d'etre for membrane-particle arrays is to enhance the regulation and amplification capabilities of cell systems.
Octanol-water partition coefficients (log P) were determined for a series of substituted psychotomimetic phenethylamine derivatives. A relationship was established between log P, steric bulk in the paraposition and the ability to stimulate serotonin (5-HT) receptors in an sheep umbilical artery preparation. It appears that Log P values and activity in this preparation.may be useful in predicting hallucinogenic potency in man.
From very general theoretical considerations it is concluded that many biomolecules (i) should have metastable excited states with very high dipole moment, and (ii) should be capable of strongly excited giant dipole vibrations with frequencies near 10(11) Hz. Experimental evidence available so far seems to support these postulates. It is suggested that the two postulates should be of importance for the action of enzymes, and relevant experiments are proposed.
THERE is increasing evidence that several cell functions are controlled by the state of polymerisation of microtubules (MTs) and by the interaction of MTs with membranes. For example, previous studies in our laboratory have shown that colchicine-sensitive structures, presumably MTs, determine the topographical organisation of cell membrane components1-3. Conditions for the polymerisation of MTs in vitro have been described4. The MT subunit has been identified by centrifugation studies as a 6S dimer of approximately 110,000 daltons5. An additional 36S component is required for MT assembly6. The established procedures used, however, to record MT polymerisation (light scattering and viscosity measurements supplemented by negative staining and electron microscopy) do not reveal details of the interactions between subunits undergoing polymerisation and cannot be applied in the presence of elements such as membranes that contribute separately to light scatter and viscosity.
The relationship of brain activity to conscious intentions is considered on the basis of the functional microstructure of the cerebral cortex. Each incoming nerve impulse causes the emission of transmitter molecules by the process of exocytosis. Since exocytosis is a quantal phenomenon of the presynaptic vesicular grid with a probability much less than 1, we present a quantum mechanical model for it based on a tunneling process of the trigger mechanism. Consciousness manifests itself in mental intentions. The consequent voluntary actions become effective by momentary increases of the probability of vesicular emission in the thousands of synapses on each pyramidal cell by quantal selection.
The hypothesis of the origin of consciousness is built upon the unique properties of the mammalian neocortex. The apical dendrites of the pyramidal cells bundle together as they ascend to lamina I to form neural receptor units of approximately 100 apical dendrites plus branches receiving hundreds of thousands of excitatory synapses, the collective assemblage being called a dendron. It is proposed that the whole world of consciousness, the mental world, is microgranular, with mental units called psychons, and that in mind-brain interaction one psychon is linked to one dendron through quantum physics. The hypothesis is that in mammalian evolution dendrons evolved for more effective integration of the increased complexity of sensory inputs. These evolved dendrons had the capacity for interacting with psychons that came to exist, so forming the mental world and giving the mammal conscious experiences. In Darwinian evolution, consciousness would have occurred initially some 200 million years ago in relation to the primitive cerebral cortices of evolving mammals. It would give global experiences of a surrounding world for guiding behavior beyond what is given by the unconscious operation of sensory cortical areas per se. So conscious experiences would give mammals evolutionary advantage over the reptiles, which lack a neocortex giving consciousness. The Wulst of the avian brain needs further investigation to discover how it could give birds the consciousness that they seem to have.
This chapter discusses the role of cytoskeleton in genome regulation and cancer. It describes two-tiered theory of regulation of the mammalian genome to the problem of cancer. Cancer represents a distortion of normal metabolic regulation. Cancer cells exhibit a loss of differentiation properties and a concomitant loss of growth control. The phenomenon of reverse transformation offers a unique opportunity to study the molecular nature of cancer. The cancer cells revert to the normal phenotype in the presence of cell-specific agonists and return to their original malignant behavior on its removal. The two-tiered scheme for the regulation of the mammalian genome accounts for the mode of action of genes that are differentiation specific in the mammalian organism. The first step in the activation of such tissue-specific genes is their conversion from the sequestered to the exposed state. This involves transfer of the appropriate DNA from the interior of the nucleus to the region of the nuclear periphery and the necessary conformational changes and specific protein interactions that render such DNA susceptible to hydrolysis by DNase I. The second step, which resembles the corresponding process in bacteria, is activation or inactivation of the exposed genes as a result of interaction with appropriate effector molecules in the surrounding medium. The restoration of cytoskeletal control of nuclear function in reverse transformation allows increased genome exposure and access of DNA to specific transcriptional regulators.
In this symposium I will present our studies about the molecular architecture and function of the cytomatrix of the nerve cells. The nerve cell is a highly polarized cell composed of highly branched dendrites, cell body, and a single long axon along the direction of the impulse propagation. Each part of the neuron takes characteristic shapes for which the cytoskeleton provides the framework. The neuronal cytoskeletons play important roles on neuronal morphogenesis, organelle transport and the synaptic transmission. In the axon neurofilaments (NF) form dense arrays, while microtubules (MT) are arranged as small clusters among the NFs. On the other hand, MTs are distributed uniformly, whereas NFs tend to run solitarily or form small fascicles in the dendrites Quick freeze deep etch electron microscopy revealed various kinds of strands among MTs, NFs and membranous organelles (MO). These structures form major elements of the cytomatrix in the neuron. To investigate molecular nature and function of these filaments first we studied molecular structures of microtubule associated proteins (MAP1A, MAP1B, MAP2, MAP2C and tau), and microtubules reconstituted from MAPs and tubulin in vitro. These MAPs were all fibrous molecules with different length and formed arm like projections from the microtubule surface.
The kinetic pathway of microtubule depolymerization at 0 degrees C has been examined. Microtubules made of MAP-containing and MAP-free tubulins were depolymerized at 0 degree C in the presence of [3H]GDP or [3H]GTP or of trace amounts of 125I dimeric tubulin. The products of depolymerization were separated on a column, their structures were identified by electron microscopy, and the time course of incorporation of 3H or 125I labels in the different components of the system was determined. Two predominant assembly states of tubulin found in the nonmicrotubule state were alpha-beta dimers and double rings. Kinetic data indicate that ring formation from disassembling microtubules does not occur by direct coiling of protofilaments as previously thought, but disassembling GDP subunits are in very rapid equilibrium with curved oligomers that are kinetic intermediates in the isodesmic assembly of GDP-tubulin. The formation of oligomers and rings from dimers, at concentrations as low as 10 microM, is much faster than nucleotide exchange on alpha-beta-tubulin. Disassembly of double rings, in contrast, is slower than nucleotide exchange on alpha-beta-tubulin, by 1 order of magnitude in the absence of MAPs and 2 orders of magnitude in the presence of MAPs. These results support the model proposed previously to explain spontaneous oscillations in microtubule assembly. They are consistent with the existence of an equilibrium between two conformations of tubulin, "straight", i.e., microtubule forming, and "curved", i.e., ring forming, under the allosteric control of bound nucleotide. The straight conformation requires the presence of two ionizable hydroxyls on the gamma-phosphate in GTP or GDP-Pi.
We report in this article that the retraction of PC 12 neurites, unlike that of other cultured neurons, is due to tension within the neurite. Retraction is rapid and independent of metabolic energy. Transection of one arm of a branched neurite immediately causes the remaining arm to take up a new equilibrium position between attachment points. Similarly, detachment of one growth cone of a cell causes the cell body to move to a new equilibrium position between the remaining neurites. These observations provide direct evidence for the suspension of the cell soma among a network of tensioned neurites. We used retraction as an assay for neurite tension to examine the role of actin filaments and microtubules in neurite support and elongation. Our data suggest that microtubules (MTs) within PC 12 neurites are under compression, supporting tension within the actin network. Treatment of cells with drugs that disrupt actin networks, cytochalasin D or erythro-9-[3-(2-hydroxynonyl)]adenosine eliminates retraction regardless of the absence of MTs, lack of adhesion to the substratum, or integrity of the neurite. Conversely, stimulation of actin polymerization by injection of phalloidin causes retraction of neurites. Treatments that depolymerize MTs, nocodazole or cold, cause retraction of neurites, which suggests that microtubules support this tension, i.e., are under compression. Stabilization of MTs with taxol stabilizes neurites to retraction and under appropriate circumstances can drive neurite extension. Taxol-stimulated neurite extension is augmented by combined treatment with anti-actin drugs. This is consistent with the actin network's normally exerting a force opposite that of MT assembly. Cytochalasin and erythro-9-[3-(2-hydroxynonyl)] adenosine were found to increase slightly the dose of nocodazole required for MT depolymerization. This is consistent with the postulated balance of forces and also suggests that alteration of the compression borne by the microtubules could serve as a local regulator for MT polymerization during neurite outgrowth.
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Two membranes from brain lipids were formed in the presence of brain tubulin and their electrical potentials were simultaneously measured. When electrical pulses were applied across one of them, displacements of the potential of the other membrane were found even when the membranes were not in contact. This effect was observed only in the presence of polymerized tubulin. It was not found in the presence of depolymerized tubulin or in other control experiments. The findings suggest that the microtubule fiber networks may serve as an interconnecting system between membranes or membrane bounded compartments.