Elemental ‘particle physics‐iology’; the Big Bang behind being human

Abstract

In a previous editorial, I introduced the concept of quantum 'physics-iology', highlighting the nascent union between physics and physiology, a concept born out of the fact that we humans are, after all, merely a collection of atoms arranged in a curiously obliging manner, complemented by an array of subatomic particles that consist primarily of nuclei and electrons that ultimately conform to the fundamentally indeterministic and frequently counterintuitive laws of quantum mechanics (QM) (Bailey, 2019b). By transcending the traditional boundaries imposed by 'classical' mechanics, a deeper appreciation of the 'quantum quirkiness' of a particle, especially that of the enigmatic electron, the first in the extended family of particles to be discovered, might provide unique insight into aspects of physiological function that might have otherwise gone unnoticed or, at the very least, remain unresolved (see later; Bailey, 2019d). No longer relegated to the ranks of science fiction, which challenges our natural understanding of reality and space–time, a world notorious for its puzzles and paradoxes, where electrons can be in two places at once and exist in different states both as particle and wave (superposition), pass through impenetrable barriers (tunnelling) and be connected instantaneously over vast distances (entanglement) has offered tantalizing new insight into complex biological phenomena as diverse as magnetoreception, vision, olfaction, ion channel function, protein folding, polymerase dynamics, DNA bonding, photosynthesis, mitochondrial bioenergetics, neuronal processing/information transfer, ageing, cognition and the perennial puzzles of evolution and consciousness, among others (reviewed by Marais et al., 2018; McFadden & Al-Khalili, 2018; Melkikh & Khrennikov, 2015). Life, in its relentless quest to optimize energy, charge and information transfer, might well exploit 'non-trivial' QM (i.e. not simply because we are composed of atoms that 'blindly' conform to the quantum theory of atomic structure) for selective advantage, outperforming the very best classical analogues. In this editorial, I would like to extend the discussion by explaining precisely where electrons and the rest of our 'subatomic stuff' comes from, how it got here and into us and where it is going from a physiological perspective. 'Particle physics-iology' provides yet another twist in this ongoing quantum tale, because it is an 'elemental' fact that we can thank our lucky (albeit dying) stars for the particles that make us human. But before exploring the functional quantum links of the electron with physiology, it is necessary to provide some context by going back in time, in fact, to the very dawn of time itself, focusing purely on astrophysical events to appreciate the origins of the particles that we are made of. The majority of theoretical physicists believe that all matter in the universe was formed ∼13.82 billion years ago in a single turbulent event, the 'Big Bang' or, more aptly termed, 'Everywhere Stretch' (Figure 1a), nature's ultimate particle accelerator (first described by Lemaître, 1927; most recently modified by Nguyen, van de Vis, Sfakianakis, Giblin, & Kaiser, 2019). Current experiments can take us back to ∼10−43 s after this event (Planck epoch), although how and why it occurred remain a mystery. At this point in time, the universe was hot and infinitesimally compact (less than ∼10−24 the size of a single atom), allowing the four fundamental forces, gravity, electromagnetism and the strong/weak nuclear forces, to morph into one. A bubbling primordial soup of jostling particles careered into one another at close to the speed of light, releasing energy in a never-ending cycle of creation and destruction before the universe underwent 'breakneck' expansion (Cosmic inflation). Within ∼10−36 s, while running at extraordinarily high energies, the four fundamental forces were forced apart, giving birth to a family of elementary particles best described by the Standard Model (Figure 1b). First came the exotic particles, followed by the more familiar electrons, neutrinos, gluons and quarks; and thus began the link to physiology, far older than is traditionally given credit! Within 10−4 s, the universe had cooled sufficiently to allow the strong nuclear force to squeeze the (up/down-flavoured) quarks into two separate groups of three, forming the first composite particles that constitute the nuclei of atoms, i.e. protons and neutrons (baryons). After ∼3 min of continued cooling, protons and neutrons coalesced into nuclei of the light elements (Big Bang nucleosynthesis), and within ∼380,000 years electrons eventually bound to nuclei, forming the first neutral atoms, mostly hydrogen (H) and helium (He) with a smattering of lithium (Li), the lightest elements in the periodic table (Recombination). Much thanks to free electrons, no charged particles were left that could easily interact with photons, and the universe became transparent to light, visible for the very first time. Gravity eventually took hold ∼100 million years after the Big Bang, forging H gas into burning stars and galaxies (Still, 2017). In an attempt to understand the infinitesimally small and recreate the particle primordial soup that made up the early universe, experimentalists rely on particle accelerators to smash protons at close to the speed of light (Figure 1c). Increasingly higher collision energies have progressively uncovered the entire spectrum of Standard Model particles, vindicating what the theorists predicted some six decades or so earlier through the mathematical power of pure physics, the cornerstone of science! Although the hot dense Big Bang gifted the cosmos with the lightest elements that still make up 98% of the universe today (73% H, 25% He) and, in the case of H, the oldest part of our very own physiology (see later), the remaining 2% of the heavy elements has come from stars that live, burn and die, more specifically supernova remnants (SRs); a small but nonetheless crucially important contribution (Cowan & Sneden, 2006). Leftovers from when stars explode, SRs contain the essential elements for life, the primordial precursors to the particles from which we are made. NASA's Chandra X-ray Observatory has focused intensively on one such SR (Type IIb), Cassiopeia A (Cas A), the youngest discovered to date, thought to have originated only 340 years ago from the internal collapse and violent explosion of a red supergiant ∼16 times the mass of the Sun (Figure 2a). Nucleosynthesis fused lighter elements into heavier ones, eventually causing the star to implode and form a dense stellar core known as a neutron star and blasting a shockwave that jettisoned material into interstellar space at ∼50 million km h−1, equivalent to travelling from Earth to the Moon within 30 s. Chandra identified that Cas A ejected a colossal 106 Earth masses (EM; each equivalent to ∼5.9736 × 1024 kg) worth of oxygen (O), 7 × 104 EM of iron (Fe), 2 × 104 EM of silicon (Si) and 104 EM of sulphur (S), notwithstanding lesser albeit huge quantities of nitrogen (N), carbon (C), H, calcium (Ca) and phosphorus (P) (Tananbaum, Weisskopf, Tucker, Wilkes, & Edmonds, 2014); in short, all the essential (CHNOPS) ingredients needed to create DNA. Precisely how these biogenic elements were transported across the galaxy to spark complex life, giving rise to ribonucleic acid on infant Earth, remains the Holy Grail for exobiologists, with asteroids, comets and interstellar dust and gas driven by galactic winds considered among the primary prebiotic candidates (National Research Council (US) Committee on Planetary Biology and Chemical Evolution, 1990; Szostak, 2018; Figure 2a). Ironically, it is precisely this stardust that prevents any breathable molecular O (O2) from forming in space; individual O atoms are bound so tightly that they simply cannot join together (He, Shi, Hopkins, Vidali, & Kaufman, 2015). Indeed, interstellar O2 is so rare that it has only ever been detected in two places, the Orion Nebula and the Rho Ophiuchi cloud. In stark contrast, and with the advent of oxygenic photosynthesis, atmospheric levels of molecular oxygen (O2) increased rapidly during the Proterozoic aeon of the Precambrian period, with each 'whiff' sparking an explosion in Earth's biota, including the evolution of complex, multicellular life (Figure 2b; Bailey, 2019d). Yet when you delve deep into the (subatomic) 'universe' of O2, its' first-generation leptons, the 'indivisible' electrons that still cannot be split apart by man-made accelerators (Figure 1b), reveal something of a quantum paradox that we would not typically associate with a gas traditionally considered the 'elixir of life'. In its most stable ground state, O2 exists in air as a potentially toxic, mutagenic free radical gas courtesy of two unpaired electrons with the same spin quantum number (parallel spin) in opposing π*2p anti-bonding orbitals, rendering it 'spin restricted' (Bailey, 2007, d). Its oxidizing power, originating from this peculiar quantum configuration, makes O2 the perfect terminal electron acceptor that ultimately gave rise to oxidative phosphorylation in mitochondria, providing more efficient, regulated metabolic support in the form of ATP combined with the new-found ability of the cell safely to 'harness' a gas otherwise capable of wreaking molecular havoc if left unchecked (Bailey, 2003, 2018, 2019b,d; Figure 2b). This metabolic revolution is likely to have provided the bioenergetic gunpowder for the development of more complex structures, including the early ectodermal nerve net/CNS in the ancestral bilaterian, the predecessor to the modern human brain that has evolved with an unprecedented reliance on O2 and relentless constancy of mitochondrial electron flow (Bailey, 2019c, d). Keeping this gas within 'safe limits' is underscored by a complex armoury of cellular O2-sensing machinery that has become increasingly more sophisticated over the course of vertebrate evolution in tandem with more elaborate O2 transport systems and increasing atmospheric O2 concentrations (Taylor & McElwain, 2010). Indeed, this ability to 'sense' O2 is considered to be one of the most important roles of the CNS and probably represented a major driving force in the evolution of the human brain, providing a selective advantage (Bailey, 2019c). The fact that this year's Nobel Prize in Physiology or Medicine was awarded jointly to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza for 'discoveries of how cells sense and adapt to O2 availability' stands testament to the fundamental significance of this evolutionarily conserved mechanism (Johnson, 2019). Nonetheless, discoveries do not simply stop with a Nobel Prize; a deeper understanding of the quantum quirkiness of the electron, by moving beyond the deterministic constraints imposed by classical mechanics, has the potential to offer new ways of thinking in physiology (Bailey, 2019a,b,d). Indeed, emerging evidence suggests that cerebral O2 sensing is subject to redox regulation, relying specifically on the mitochondrial formation of the superoxide anion to trigger stabilization of hypoxia-inducible factor-1α (reviewed by Smith, Waypa, & Schumacker, 2017). The fact that the brain readily exploits and does not simply suffer at the hands of these (unpaired) electrons to good effect is perhaps not surprising, because this ancestral univalent reductant of O2 has been present since the last universal common ancestor ∼3.8 billion years ago (Briehl, 2015; Slesak, Slesak, & Kruk, 2012). The application of QM to further our understanding of life is not new. Indeed, it was Niels Bohr, the father of atomic theory, who first posed this question (Bohr, 1933), later immortalized in Erwin Schrödinger's book, 'What is Life?' (Schrödinger, 1944), who also puzzled over the ability of life somehow to buck the second law of thermodynamics and achieve 'order-from-(degenerative) disorder'. And why shouldn't QM have something to offer? After all, it is the most successful scientific theory ever conceived, combined with the fact that physiologists are mostly concerned with the dynamics of energy, charge and information transfer that collectively rely on electrons, protons and ions. The original scepticism, levelled at life being awash with disorder and simply too 'warm, wet and messy' for coherence/phasing to endure, appears unfounded; wave patterns can and, indeed, do stay in step and are not solely confined to controlled laboratory settings held under vacuum at ultra-low cryogenic temperatures within the nanometre range. Furthermore, the fact that particles can engage in such quantum trickery as tunnelling, superposition and entanglement suggests that the (physiological) possibilities, including the aforementioned free radical basis of mitochondrial O2 sensing (Bailey, 2019b), are potentially endless; we need look only as far as Young's 'double slit' interference experiment (Figure 2b; Aharonov et al., 2017), arguably the most famous physics experiment conducted to date, to appreciate (if not understand) the complexities and potential of QM best described by the late Nobel Laureate Richard Feynman: 'We choose to examine a phenomenon which is impossible, absolutely impossible, to explain in any classical way, and which has in it the heart of quantum mechanics. In reality, it contains the only mystery' (Feynman, Leighton, & Sands, 1965). Last, but not least, there are certainly enough particles to warrant our undivided attention; there are an estimated (∼2.3 ×) 1028 electrons contained within discrete orbitals, whose exact trajectories are indeterminate thanks to the Heisenberg uncertainty principle, locked inside our ∼7 × 1027 atoms (Figure 2b; Freitas, 1999). By mass, >99% of these are confined to no more than six elements, with O being the most abundant at ∼61%, followed by C, H, N, Ca and P, and with the remainder being a sparse sampling of trace elements from the periodic table (Haynes, 2012). And here's the twist (in the tale); they were borne almost exclusively from the remnants of blown-up stars or, in the case of H, as ancient as the Big Bang itself! (Figures 2 and 3). Having established the stellar origins of our 'particulate physiology', mounting evidence suggests that life makes explicit use of non-trivial quantum phenomena to improve its physiological 'lot', with advances in ultrafast/single-molecule spectroscopy, time-resolved microscopy and single-particle imaging leading to some remarkable discoveries, pioneered mostly by the quantum biologists (Marais et al., 2018). Long-lived (quantum) coherence during the transport of exciton energy in photosynthesis (Engel et al., 2007) and electron/proton tunnelling in catalysis (Page, Moser, Chen, & Dutton, 1999) are among the most celebrated examples, and these discoveries have helped to resolve the extraordinary efficiency of energy/charge transfer that were originally considered thermodynamically impossible by classical standards. Other, more theoretical, examples include entanglement in magnetoreception/metabolism via spin-correlated (free) radical pairs that confer signalling properties, tunnelling in olfaction/adaptive mutation and coherence in cognition and consciousness (McFadden & Al-Khalili, 2018). The need to explore complementary ideas that can be woven into the integrative framework of physiology is eminently justified, because there is general agreement that traditional coarse-grained classical (physics) and overly reductionist systems (biology) approaches have consistently failed to account adequately for a multitude of life's complex processes, including our understanding and treatment of human disease (Joyner & Pedersen, 2011; Marais et al., 2018; Noble, Tasaki, Noble, & Noble, 2019). To what extent QM could help to tackle some of the more intractable questions posed by traditional physiology, including (for example) those related to the origin of life and evolution, systems biology, cell signalling, stem cell and regenerative medicine, gene regulation, ageing, disease pathophysiology and benefits of physical activity, cellular bioenergetics, cognition and consciousness (Bennett, 2019; Dev, 2015; Gabriel & Zierath, 2017; Hunter, 2017; Melkikh & Khrennikov, 2015; Paterson, 2016), remain to be established given that this is an emerging discipline, barely a decade old, complicated by unique philosophical, conceptual and technical challenges (Figure 2b; Koch & Hepp, 2006). Although it clearly defies (classical) logic, 'particle physics-iology', the union between particle physics and physiology, should not be considered simply 'off' limits; instead, it is an evolving integrative discipline, 'without' limits. It is important to remind ourselves that although the ∼50 × 1012 to 75 × 1012 cells in the human body undergo repair and replacement over the short term, ranging from days to years (Willyard, 2016), we are made up of much older 'subatomic stuff', with electrons 'ballroom dancing' around atomic nuclei filled full of fields and forces that are governed ultimately by the laws of QM best described by the Standard Model. Our physiology consists of fundamental particles, 'cosmic relics' of elements forged within the nuclear furnaces of stars that live, burn and, ultimately, die. Even in death, our particles will be repurposed, less orderly but never lost, consistent with another immutable law, albeit of classical (Newtonian) physics, the law of conservation of energy. This deeper understanding has the potential to offer new and complementary ways of thinking in physiology that warrant consideration if we are to continue to evolve as a discipline. As the late astrophysicist and science communicator Carl Sagan once remarked, 'We are star stuff which has taken its destiny into its own hands. The beauty of a living thing is not the atoms that go into it, but the way those atoms are put together' (Sagan, 1980).