- 2957 - BIOLOGY - the physics of living matter? This is hard review to get through. Life is complicated. Biology is complicated. Physics and math have rules I can learn. Life has rules that are still secrets. If you make it through this review you will need a coffee break to recover. There has always been a contradiction between physics and biology. One is alive and the other is not. Where does the line cross between the two sciences?
----------------------------- 2957 - BIOLOGY - the physics of living matter
- The physics of living matter seems like a counter diction? Living is biology. Physics is math and science of non-living stuff. However, does new physics lurk inside living matter? Can the two sciences be combined?
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- The link between information and physics has been implicit since James Clerk Maxwell introduced his famous “demon“. “Information” in the scientific sense is now emerging as a key concept to merge physics and biology.
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- To a physicist, life looks like magic. Living things accomplish feats so dazzling, so mysteriously, that it’s easy to forget they are made of ordinary atoms. But if the secret of life is not the stuff of which living things are made, then what is it?
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- What gives organisms that distinctive trait that sets them apart as remarkable and special? That was the question posed by Erwin Schrödinger in a famous series of lectures delivered in Dublin, Ireland, in 1943, and published in his book titled “What Is Life?”
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- Schrödinger was a giant of theoretical physics and one of the founders of “quantum mechanics“, the most successful scientific theory ever conceived, both in terms of applications and accuracy.
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- When applied to the electromagnetic field, quantum mechanics correctly predicts the anomalous magnetic moment of the electron to better than 10 significant figures. Almost at a stroke, quantum mechanics explained the nature of inanimate matter, from subatomic particles, through atoms and molecules, to stars.
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- But, it didn’t explain living matter. And despite spectacular advances in biology in the intervening decades, life and biology remain a mystery. Nobody can say for sure what it is or how it began.
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- In the 1930s many of the architects of quantum mechanics, most notably Niels Bohr, Eugene Wigner, and Werner Heisenberg, had a hunch that there is indeed something new and different in the physics of living matter.
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- Schrödinger was undecided, but open to the possibility. “One must be prepared to find a new kind of physical law prevailing in it,” he conjectured. But he didn’t say what that might be.
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- A central goal of astrobiology is to seek traces of life beyond Earth, but without a definition of life it is hard to know precisely what to look for.
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- NASA is planning a mission to fly through the plume of material spewing from fissures in the icy crust of Enceladus, a moon of Saturn known to contain organic molecules. What would convince a skeptic that the material includes life, or the detritus of once-living organisms, as opposed to some form of pre-life? “Detritus” would be the waste or debris of any kind of life.
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- Unlike the measurement of, say, a magnetic field, scientists lack any sort of “life meter” that can quantify the progress of a chemical mixture toward known life, still less an alien form of life.
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- Most astrobiologists focus on signatures of life as we know it. NASA’s Viking mission to Mars in the 1970s sought signs of carbon metabolism using a broth of nutrients palatable to terrestrial organisms.
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- Another much-discussed biosignature is “homochirality“, the presence of only one enantiomer. “Enantiomer” is a pair of molecules that are a mirror image of each other. “Chirality” is handedness like left and right handedness in humans. Something that can not be superimposed on its mirror image.
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- Although the laws of physics are indifferent to left–right inversion, known life uses left-handed amino acids and right-handed sugars. But inorganic soil chemistry can mimic metabolism, and “homochirality” can be generated by iterated chemical cycles without life being involved, so those considered biosignatures are not definitive.
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- The problem of identifying life is doubly hard on another planet. Astrobiologists have pinned their hopes on detecting oxygen in the atmospheres of extrasolar planets, but again, atmospheric oxygen is not an unambiguous signature of photosynthesis, because nonbiological processes can also create oxygenated atmospheres.
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- What we lack is any general definition of “living” independent of the biochemical substrate in which life is instantiated. Are there any deep, universal principles that would manifest identifiable biosignatures, even of life as we don’t know it?
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- The gulf between physics and biology is more than a matter of complexity; a fundamental difference in conceptual framework exists. Physicists study life using concepts such as energy, entropy, molecular forces, and reaction rates.
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- Biologists offer a very different narrative, with terms such as signals, codes, transcription, and translation, or the “language of information“. The burgeoning field of “biophysics” seeks to bridge the conceptual gulf by modeling patterns of information flow and storage in various biological control networks.
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- Life is invested in information storage and processing at all levels, not just in DNA. Genes, or DNA sequences that serve as encrypted instruction sets can switch other genes on or off using chemical messengers, and they often form complex networks. Those chemical circuits resemble electronic or computing components, sometimes constituting modules or gates that enact logical operations. Wow!
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- At the cellular level, a variety of physical mechanisms permit signaling and can lead to cooperative behavior. Slime molds provide a striking example. They are aggregations of single cells that can self-organize into striking shapes and sometimes behave coherently as if they were a single organism.
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- Social insects such as ants and bees exchange complex information and engage in collective decision making. And, human brains are information processing systems of staggering complexity. Is life a computer?
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- The informational basis of life has led some scientists to pronounce the informal dictum, Life = Matter + Information. For that linking equation to acquire a real explanation and predictive power a formal theoretical framework is necessary that couples “information to matter“. It couples the computer program to DNA.
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- In 1867, in a letter to a friend, Scottish physicist James Clerk Maxwell imagined a tiny being that could perceive individual molecules in a box of gas as they rushed around. By manipulating a screen and shutter, the “demon“;, as the diminutive being soon came to be known, could direct all the fast molecules to the left of the box and the slow ones to the right.
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- Maxwell’s demon was a box of gas divided into two chambers by a screen with a small aperture through which molecules may pass one by one. The aperture is blocked by a shutter. It’s controlled by the 1867 brainchild of James Clerk Maxwell, a tiny demon who observes the randomly moving molecules and can open and close the shutter to allow fast molecules to travel from the right-hand chamber to the left, and slow molecules to travel in the opposite direction.
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- The mechanism could then be used to convert disorganized molecular motion into directed mechanical motion. The demon lay like an “inconvenient truth” at the heart of physics for decades, mostly dismissed as a mere “theoretical puzzle“.
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- A 100 years after Maxwell envisaged that thought experiment, a real “demon” was made in a laboratory in Edinburgh, the city of Maxwell’s birth. The experiment consisted of a molecular ring that could slide back and forth on a rod with stoppers at the end.
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- In the middle of the rod sat another molecule that could exist in two conformations, one that blocks the ring and one that allows it to pass. The molecule thus serves as a gate, akin to Maxwell’s original conception of a movable shutter.
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- Following that lead, a cottage industry in demonic devices emerged, including an information-powered refrigerator.
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- In the refrigerator, the role of the gas molecule is played by a single electron confined to a two-sided nanoscale box that is coupled to a heat bath. The cooling cycle exploits the existence of two degenerate box states for a certain electron energy.
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- The cycle begins with the electron in a definite, non-degenerate state. An external electric field raises the electron energy to the degenerate level, where the electron can reside with equal probability in either of the two states.
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- That introduction of “uncertainty” represents an “increase in the entropy” of the electron and a corresponding decrease in the entropy, and thus the temperature, of the bath.
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- At this point the demon, played by another single-electron box coupled to the first, detects which of the two states the electron is in and autonomously feeds the information to the driving field, which uses it to rapidly return the electron to its initial non-degenerate state and complete the cooling cycle.
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- The researchers found that the creation of one bit of information per cycle, which state the electron is in, could extract heat from the bath with an average efficiency of about 75%. Maxwell was right. Information really can serve as a type of fuel that controls the process.
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- Because molecular speed is a measure of temperature, the demon would, in effect, use information about molecules to create a heat gradient inside the box. An engineer could then tap that gradient to extract energy and perform useful work.
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- On the face of it, Maxwell had designed a “perpetual motion machine“, powered by pure information, in defiance of the “second law of thermodynamics“.
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- To resolve the paradox, information must be quantified and formally incorporated into the laws of thermodynamics. The basis for modern information theory was laid down by Claude Shannon in the late 1940s. Shannon defined “information” as reduction in uncertainty, for example, by inspecting the outcome of a coin toss.
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- The familiar binary digit, or bit, is the information gained by determining heads or tails from flipping a coin. The synthesis of Shannon’s information theory and thermodynamics led to the identification of “information” as “negative entropy“.
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- Any information acquired by the demon to gain a thermodynamic advantage must be paid for by a rise in entropy at some stage, for example, when the demon’s memory store is erased and reset so the demon can repeat the cycle.
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- Maxwell conceived of his demon as a thought experiment, but advances in nanotechnology now permit experimental realizations of the basic idea. Yet life has been making and using varieties of demons for billions of years.
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- Our bodies are replete with them. Molecular machines that copy DNA, transport cargo along fibers, or pump protons through cell membranes operate very close to the ideal thermodynamic limit. They play the margins of the second law to gain an energy advantage.
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- The human brain uses in its wiring a type of demon, “voltage-gated ion channels“, to propagate electrical signals. Those ion channels enable the brain to run on the energy equivalent of a dim light bulb even though it has the power of a megawatt supercomputer.
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- The “demon” is the contextual nature of biological information. Demonics is merely the tip of life’s informational iceberg. “Biological information” goes far beyond optimizing the energy budget; it often acts as a type of energy manager.
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- Consider the way an embryo develops from a fertilized egg. It is supervised at every stage by information networks finely tuned to a multitude of physical and chemical processes, all arranged so that the complex final form emerges with the right architecture and morphology. How does a baby get born starting from a few cells? This is way beyond my imagination to ponder.
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- Attempts to model “embryogenesis” using information flow in gene regulatory networks have been remarkably successful. Eric Davidson at Caltech worked out the entire wiring diagram, chemically speaking, for the gene network that regulates the sea urchin’s early-stage development.
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- By tracking the information flow, the group programmed a computer to simulate the network dynamics step by step. At each stage they compared the computer model of the state of the circuit with the observed stage of the sea urchin’s development and obtained an impressive match.
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- The Caltech researchers also considered the effects of chemically silencing specific genes in the computer model to predict what would happen to the mutant embryo; again, their modeling matched the experimental observations.
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- A group at Princeton University has been investigating the early stages of fruit fly development, how distinctive morphological features first appear. During development, cells need to know their location relative to other cells in three-dimensional space.
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- How do they obtain that positional information? It has long been known that cells exhibit a type of GPS based on chemical gradients that are, in turn, regulated by the expression levels of specific genes.
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- The Princeton group recently zeroed in on four so-called “gap genes” that lay the foundations for patterning the embryo by creating gaps, or bands, in the body plan. They found that cells were extracting optimal positional information from the gene expression levels by exploiting Bayesian probabilities, and thereby achieving an astonishing 1% accuracy.
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- The researchers were able to apply a Bayesian optimization model to mutant strains and correctly predict their modified morphology too. Those analyses raise a crucial philosophical question that goes to the heart of the conceptual mismatch between physics and biology. “Morphology” is a branch of biology that deals with the relationship between living structures.
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- Studies of gene regulatory networks and the application of Bayesian algorithms are currently treated as phenomenological models in which “information” is a convenient surrogate or label for generating a lifelike simulation of a real organism. “Phenomenological models” are those not derived from theories.
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- The lesson of Maxwell’s demon is that information is actually a physical quantity that can profoundly affect the way that matter behaves. Information, as defined by Shannon, is more than an informal parameter; it is a fundamental physical variable that has a defined place in the laws of thermodynamics.
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- Shannon stressed that his information theory dealt purely with the efficiency and capacity of information flow; it said nothing about the meaning of the information communicated.
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- In biology, communicating information meaning or context is critical. How might one capture mathematically that property of instructional or supervisory or contextual information?
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- One approach is “molecular biology’s” so-called central dogma is that information flows in one direction, from DNA to the machinery that makes proteins and thence to the organism. One might term that a “bottom-up” flow.
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- Today, information transfer in biology is known to be a two-way process, involving feedback loops and top-down information flow. If cells cultured to grow in a Petri dish get too crowded, they stop dividing, a phenomenon known as “contact inhibition“.
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- Experiments with microbes on the International Space Station have shown that bacteria may express different genes in a zero-gravity environment than they do on Earth. Evidently, system-level physical forces affect gene expression operating at the molecular level.
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- The work of Michael Levin at Tufts University, provides an arresting example of top-down information flow. Levin’s group is exploring how system-wide electrical patterning can be as important as mechanical forces or chemical patterning in controlling the growth and morphology of some organisms.
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- Healthy cells are electrically polarized. They maintain a potential difference of a few tens or hundreds of millivolts across the cell walls by pumping out ions. Cancer cells, by contrast, tend to be depolarized.
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- Levin’s group has found that in multicellular organisms, cell polarization patterns across tissues play a key role in growth and development, wound healing, and organ regeneration. By disrupting those electrical patterns chemically, the group can produce novel morphologies to order.
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- A species of flatworm provides a convenient experimental subject. If a normal worm is chopped in two, the head grows a new tail and the tail grows a new head, making two complete worms. But by modifying the electrical polarization state near the wound, one can make two-headed or two-tailed worms.
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- This two-headed worm was created by manipulating electrical polarity. The worm reproduces other two-headed worms when bisected, as if it is a different species, even though it has the same DNA as normal one-headed worms. Somehow the information about the global body plan is passed on to the progeny “epigenetically“.
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- Amazingly, if those monsters are in turn chopped in two, they do not revert to the normal phenotype. Rather, the two-headed worms make more two-headed worms, and likewise with two-tailed worms. Despite all having identical DNA, the worms look like different species.
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- The DNA system’s morphological information must be getting stored in a distributed way in the truncated tissue and guiding the appropriate regeneration at the gene level. But how does that happen? Does an encrypted electrical code operate alongside the genetic code?
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- The term “epigenetic” refers to the phenotype-determining factors, such as gross physical forces, that lie beyond the genes. Very little is known about the mechanisms of epigenetic information storage, processing, and propagation, but their role in biology is critical.
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- To make progress, we need to discover how different types of informational patterns, electrical, chemical, and genetic codes, interact to produce a regulatory framework that manages the organization of living matter and translates it into specific phenotypes.
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- Thinking about the physics of living matter in informational terms rather than purely molecular terms is analogous to the difference between software and hardware in a computer.
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- Just as a full understanding of a particular computer application, PowerPoint, for example, requires a grasp of the principles of software engineering as much as the physics of computer circuitry, so life can only be understood when the principles of biological information dynamics are fully understood.
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- This is new concept of dynamics in physics. Since the time of Isaac Newton, a fundamental dualism has pervaded physics. Although physical states evolve with time, the underlying laws of physics are normally regarded as immutable.
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-That “immutable” assumption underlies “Hamiltonian dynamics“, “trajectory integrability“, and “periodicity“. But immutable laws are a poor fit for biological systems, in which dynamical patterns of information couple to time-dependent chemical networks and where expressed information, the switching on of genes, can depend on global or systemic physical forces as well as local chemical signaling.
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- “Biological evolution“, with its open-ended variety, novelty, and lack of predictability, also stands in stark contrast to the way that nonliving systems change over time. Yet biology is not chaos: Many examples of rules at work can be found.
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- Take the universal genetic code. The nucleotide triplet “CGT” codes for the amino acid arginine. Although no known exceptions to that rule exist, it would be wrong to think of it as a law of nature, like the fixed law of gravity. Almost certainly, the CGT-to-arginine assignment emerged, millions of years ago, from some earlier and simpler rule. Biology is full of cases like that.
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- Life is on the quantum edge If biology deploys new physics, such as state-dependent dynamical rules, then at what point between simple molecules and living cells does it emerge?
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- “CA” models may be instructive, but they are cartoons, not physics; they tell us nothing about where to look for new emergent phenomena. As it happens, standard physics already contains a familiar example of state-dependent dynamics. It is called “quantum mechanics“.
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- Left in isolation, a pure quantum state described by a coherent wavefunction evolves predictably according to a well-understood mathematical prescription known as unitary evolution. But when a measurement is made, the state changes abruptly—a phenomenon often called the collapse of the wavefunction.
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- In an ideal measurement, the jump projects the system into one possible “eigenstate” corresponding to the observable being measured. For that step, the “unitary evolution rule” is replaced by the “Born rule“, which predicts the relative probabilities of the measurement outcomes and introduces into quantum mechanics the element of indeterminism or uncertainty.
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- That marks the transition from the quantum to the classical domain. Could quantum mechanics therefore point us to what makes life tick?
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- Schrödinger appealed to quantum mechanics to explain the stability of genetic-information storage. Before Crick and Watson had defined the structure of DNA, Schrödinger deduced that the information must be stored at the molecular level in what he termed “an aperiodic crystal,” a perceptive description of what nucleic acid polymers turned out to be.
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- Left open was the possibility that quantum phenomena might play a more pervasive role in living organisms. In the intervening decades, a general assumption prevailed that in the warm, noisy environment of living matter, quantum phenomena would be smothered and classical ball-and-stick chemistry would suffice to explain life.
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- In the past decade interest has grown in the possibility that non-trivial quantum phenomena, such as superposition, entanglement, and tunneling, might be important for life after all.
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- The new field of “quantum biology” is now under intensive investigation. Research has focused on topics as diverse as “coherent energy transport in photosynthesis“, the “avian magnetic compass“, and the “olfactory response of flies“.
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- Investigating the quantum properties of living matter on the nanoscale presents significant challenges. Systems that are critical to the operation of life may involve few degrees of freedom, are far from thermodynamic equilibrium, and are strongly coupled to their thermal environment.
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- In the field of “non-equilibrium quantum statistical mechanics“, that the emergence of new physics might be expected. One set of experiments of possible relevance is the measurement of electron conductance through organic molecules.
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- The major progress in science stems more from the clash of ideas than from the steady accumulation of facts. Biophysics lies at the intersection of two great domains of science: the physical sciences and the life sciences. Each domain comes with its own vocabulary, but also with its own distinctive conceptual framework, the former being rooted in mechanical concepts, the latter in informational concepts.
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- The ensuing clash presages a new frontier of science in which information, now understood formally as a physical quantity occupies a central role and thereby serves to unify physics and biology.
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- The huge advances in molecular biology of the past few decades may be largely attributed to the application of mechanical concepts to bios stems, physics infiltrating biology.
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- The reverse is now happening. Many physicists, particularly those working on foundational questions in quantum mechanics, advocate placing information at the heart of physics, while others conjecture that new physics lurks in the remarkable and baffling world of biological organisms.
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- Biology is shaping up to be the next great frontier of physics. Go figure?
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December 31, 2020 BIOLOGY - the physics of living matter 2955
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