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Pathol Res Pract. 2012 Jul 15;208(7):377-81. doi: 10.1016/j.prp.2012.04.006. Epub 2012 Jun 8.
The influence of physical activity in the progression of experimental lung cancer in mice
Renato Batista Paceli 1, Rodrigo Nunes Cal, Carlos Henrique Ferreira dos Santos, José Antonio Cordeiro, Cassiano Merussi Neiva, Kazuo Kawano Nagamine, Patrícia Maluf Cury
- PMID: 22683274
- DOI: 10.1016/j.prp.2012.04.006
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GRUPO_AF1 – GROUP AFA1 – Aerobic Physical Activity – Atividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
GRUPO AFAN 1 – GROUP AFAN1 – Anaerobic Physical Activity – Atividade Física Anaeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
GRUPO_AF2 – GROUP AFA2 – Aerobic Physical Activity – Atividade Física Aeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
GRUPO AFAN 2 – GROUP AFAN 2 – Anaerobic Physical Activity – Atividade Física Anaeróbia – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
Slides – mestrado – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
CARCINÓGENO DMBA EM MODELOS EXPERIMENTAIS
DMBA CARCINOGEN IN EXPERIMENTAL MODELS
Avaliação da influência da atividade física aeróbia e anaeróbia na progressão do câncer de pulmão experimental – Summary – Resumo – ´´My´´ Dissertation – Faculty of Medicine of Sao Jose do Rio Preto
Abstract
Lung cancer is one of the most incident neoplasms in the world, representing the main cause of mortality for cancer. Many epidemiologic studies have suggested that physical activity may reduce the risk of lung cancer, other works evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. The aim of this study was to evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Lung tumors were induced with a dose of 3mg of urethane/kg, in 67 male Balb – C type mice, divided in three groups: group 1_24 mice treated with urethane and without physical activity; group 2_25 mice with urethane and subjected to aerobic swimming free exercise; group 3_18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5-20% of body weight. All the animals were sacrificed after 20 weeks, and lung lesions were analyzed. The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5-3 (p=0.052). When comparing only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 as compared with group 1 (p=0.03) but not in relation to group 2. There were no metastases or other changes in other organs. The anaerobic physical activity, but not aerobic, diminishes the incidence of experimental lung tumors.
Copyright © 2012 Elsevier GmbH. All rights reserved.
´´Virtuality is the quality of having the attributes of something without sharing its (real or imagined) physical form.´´ https://en.wikipedia.org/wiki/Virtuality_(disambiguation) @ ´´Reality is the sum or aggregate of all that is real or existent within a system, as opposed to that which is only imaginary. The term is also used to refer to the ontological status of things, indicating their existence.[1] In physical terms, reality is the totality of a system, known and unknown.[2]´´https://en.wikipedia.org/wiki/Reality @ How to Submit research article for SPRINGER NATURE #Naturepublishing #Springer #SNAPPLIED SCIENCES – YouTube Video @ A closer look at the race to develop antibody drugs for COVID-19 – AUTHOR – Ben Fidler @BentheFidler PUBLISHED May 12, 2020 @ CGD NOTES – Leave No One Behind: Using a Benefit-Based Advance Market Commitment to Incentivise Development and Global Supply of COVID-19 Vaccines – MAY 7, 2020 @ Genetics of Covid-19 patients is focus of study – Research into the genetic code of Covid-19 patients could help predict severity of the disease. & MAY 12, 2020 5:51 AM PDT Share – Disabling Genes in Immune Cells Prevents Obesity – WRITTEN BY: Tara Fernandez ´´Obesity is a $1.7 trillion problem in the United States, a condition that leads to several chronic illnesses including heart disease, stroke and certain types of cancer.´´ @ Blood Factors Reverse Epigenetic Age by Half in Rats Steve Hill May 11, 2020 ´´Researchers have demonstrated that epigenetic age can be halved in rats by using signals commonly found in the blood.´´ https://www.lifespan.io/news/blood-factors-reverse-epigenetic-age-by-half-in-rats/
https://www.lifespan.io/news/blood-factors-reverse-epigenetic-age-by-half-in-rats/
https://www.labroots.com/trending/immunology/17561/disabling-genes-immune-cells-prevents-obesity
https://www.biopharmadive.com/news/coronavirus-antibody-drug-trials/577778/
https://en.wikipedia.org/wiki/Virtuality_(disambiguation)
https://en.wikipedia.org/wiki/Reality
Virtuality (disambiguation)
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Look up virtuality in Wiktionary, the free dictionary. |
Virtuality is the quality of having the attributes of something without sharing its (real or imagined) physical form.
Virtuality also may refer to:
Technology[edit]
- Virtuality (gaming), a family of virtual reality arcade machines.
- Virtuality (software design), a concept of software design proposed by Ted Nelson.
- Reality–virtuality continuum, a concept in computer science.
- Augmented virtuality, the merging of real-world objects into virtual worlds.
- Real Virtuality, a proprietary computer game engine developed by Bohemia Interactive.
Other[edit]
- Virtuality (philosophy)
- Virtuality (song), by Rush
- “Virtuality”, a song by VBirds
- Virtuality, a proposed science-fiction TV show by Ronald D. Moore for which a pilot was produced in 2009, but no series was ultimately commissioned
See also[edit]
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Reality
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Reality is the sum or aggregate of all that is real or existent within a system, as opposed to that which is only imaginary. The term is also used to refer to the ontological status of things, indicating their existence.[1] In physical terms, reality is the totality of a system, known and unknown.[2] Philosophical questions about the nature of reality or existence or being are considered under the rubric of ontology, which is a major branch of metaphysics in the Western philosophical tradition. Ontological questions also feature in diverse branches of philosophy, including the philosophy of science, philosophy of religion, philosophy of mathematics, and philosophical logic. These include questions about whether only physical objects are real (i.e., Physicalism), whether reality is fundamentally immaterial (e.g., Idealism), whether hypothetical unobservable entities posited by scientific theories exist, whether God exists, whether numbers and other abstract objects exist, and whether possible worlds exist.
Related concepts
World views and theories
A common colloquial usage would have reality mean “perceptions, beliefs, and attitudes toward reality”, as in “My reality is not your reality.” This is often used just as a colloquialism indicating that the parties to a conversation agree, or should agree, not to quibble over deeply different conceptions of what is real. For example, in a religious discussion between friends, one might say (attempting humor), “You might disagree, but in my reality, everyone goes to heaven.”
Reality can be defined in a way that links it to worldviews or parts of them (conceptual frameworks): Reality is the totality of all things, structures (actual and conceptual), events (past and present) and phenomena, whether observable or not. It is what a world view (whether it be based on individual or shared human experience) ultimately attempts to describe or map.
Certain ideas from physics, philosophy, sociology, literary criticism, and other fields shape various theories of reality. One such belief is that there simply and literally is no reality beyond the perceptions or beliefs we each have about reality. Such attitudes are summarized in the popular statement, “Perception is reality” or “Life is how you perceive reality” or “reality is what you can get away with” (Robert Anton Wilson), and they indicate anti-realism – that is, the view that there is no objective reality, whether acknowledged explicitly or not.
Many of the concepts of science and philosophy are often defined culturally and socially. This idea was elaborated by Thomas Kuhn in his book The Structure of Scientific Revolutions (1962). The Social Construction of Reality, a book about the sociology of knowledge written by Peter L. Berger and Thomas Luckmann, was published in 1966. It explained how knowledge is acquired and used for the comprehension of reality. Out of all the realities, the reality of everyday life is the most important one since our consciousness requires us to be completely aware and attentive to the experience of everyday life.
Western philosophy
Philosophy addresses two different aspects of the topic of reality: the nature of reality itself, and the relationship between the mind (as well as language and culture) and reality.
On the one hand, ontology is the study of being, and the central topic of the field is couched, variously, in terms of being, existence, “what is”, and reality. The task in ontology is to describe the most general categories of reality and how they are interrelated. If a philosopher wanted to proffer a positive definition of the concept “reality”, it would be done under this heading. As explained above, some philosophers draw a distinction between reality and existence. In fact, many analytic philosophers today tend to avoid the term “real” and “reality” in discussing ontological issues. But for those who would treat “is real” the same way they treat “exists”, one of the leading questions of analytic philosophy has been whether existence (or reality) is a property of objects. It has been widely held by analytic philosophers that it is not a property at all, though this view has lost some ground in recent decades.
On the other hand, particularly in discussions of objectivity that have feet in both metaphysics and epistemology, philosophical discussions of “reality” often concern the ways in which reality is, or is not, in some way dependent upon (or, to use fashionable jargon, “constructed” out of) mental and cultural factors such as perceptions, beliefs, and other mental states, as well as cultural artifacts, such as religions and political movements, on up to the vague notion of a common cultural world view, or Weltanschauung.
The view that there is a reality independent of any beliefs, perceptions, etc., is called realism. More specifically, philosophers are given to speaking about “realism about” this and that, such as realism about universals or realism about the external world. Generally, where one can identify any class of object, the existence or essential characteristics of which is said not to depend on perceptions, beliefs, language, or any other human artifact, one can speak of “realism about” that object.
One can also speak of anti-realism about the same objects. Anti-realism is the latest in a long series of terms for views opposed to realism. Perhaps the first was idealism, so called because reality was said to be in the mind, or a product of our ideas. Berkeleyan idealism is the view, propounded by the Irish empiricist George Berkeley, that the objects of perception are actually ideas in the mind. In this view, one might be tempted to say that reality is a “mental construct”; this is not quite accurate, however, since, in Berkeley’s view, perceptual ideas are created and coordinated by God. By the 20th century, views similar to Berkeley’s were called phenomenalism. Phenomenalism differs from Berkeleyan idealism primarily in that Berkeley believed that minds, or souls, are not merely ideas nor made up of ideas, whereas varieties of phenomenalism, such as that advocated by Russell, tended to go farther to say that the mind itself is merely a collection of perceptions, memories, etc., and that there is no mind or soul over and above such mental events. Finally, anti-realism became a fashionable term for any view which held that the existence of some object depends upon the mind or cultural artifacts. The view that the so-called external world is really merely a social, or cultural, artifact, called social constructionism, is one variety of anti-realism. Cultural relativism is the view that social issues such as morality are not absolute, but at least partially cultural artifact.
A correspondence theory of knowledge about what exists claims that “true” knowledge of reality represents accurate correspondence of statements about and images of reality with the actual reality that the statements or images are attempting to represent. For example, the scientific method can verify that a statement is true based on the observable evidence that a thing exists. Many humans can point to the Rocky Mountains and say that this mountain range exists, and continues to exist even if no one is observing it or making statements about it.
Being
The nature of being is a perennial topic in metaphysics. For, instance Parmenides taught that reality was a single unchanging Being, whereas Heraclitus wrote that all things flow. The 20th century philosopher Heidegger thought previous philosophers have lost sight the question of Being (qua Being) in favour of the questions of beings (existing things), so that a return to the Parmenidean approach was needed. An ontological catalogue is an attempt to list the fundamental constituents of reality. The question of whether or not existence is a predicate has been discussed since the Early Modern period, not least in relation to the ontological argument for the existence of God. Existence, that something is, has been contrasted with essence, the question of what something is. Since existence without essence seems blank, it associated with nothingness by philosophers such as Hegel. Nihilism represents an extremely negative view of being, the absolute a positive one.
Perception
The question of direct or “naïve” realism, as opposed to indirect or “representational” realism, arises in the philosophy of perception and of mind out of the debate over the nature of conscious experience;[3][4] the epistemological question of whether the world we see around us is the real world itself or merely an internal perceptual copy of that world generated by neural processes in our brain. Naïve realism is known as direct realism when developed to counter indirect or representative realism, also known as epistemological dualism,[5] the philosophical position that our conscious experience is not of the real world itself but of an internal representation, a miniature virtual-reality replica of the world.
Timothy Leary coined the influential term Reality Tunnel, by which he means a kind of representative realism. The theory states that, with a subconscious set of mental filters formed from their beliefs and experiences, every individual interprets the same world differently, hence “Truth is in the eye of the beholder”. His ideas influenced the work of his friend Robert Anton Wilson.
Abstract objects and mathematics
The status of abstract entities, particularly numbers, is a topic of discussion in mathematics.
In the philosophy of mathematics, the best known form of realism about numbers is Platonic realism, which grants them abstract, immaterial existence. Other forms of realism identify mathematics with the concrete physical universe.
Anti-realist stances include formalism and fictionalism.
Some approaches are selectively realistic about some mathematical objects but not others. Finitism rejects infinite quantities. Ultra-finitism accepts finite quantities up to a certain amount. Constructivism and intuitionism are realistic about objects that can be explicitly constructed, but reject the use of the principle of the excluded middle to prove existence by reductio ad absurdum.
The traditional debate has focused on whether an abstract (immaterial, intelligible) realm of numbers has existed in addition to the physical (sensible, concrete) world. A recent development is the mathematical universe hypothesis, the theory that only a mathematical world exists, with the finite, physical world being an illusion within it.
An extreme form of realism about mathematics is the mathematical multiverse hypothesis advanced by Max Tegmark. Tegmark’s sole postulate is: All structures that exist mathematically also exist physically. That is, in the sense that “in those [worlds] complex enough to contain self-aware substructures [they] will subjectively perceive themselves as existing in a physically ‘real’ world”.[6][7] The hypothesis suggests that worlds corresponding to different sets of initial conditions, physical constants, or altogether different equations should be considered real. The theory can be considered a form of Platonism in that it posits the existence of mathematical entities, but can also be considered a mathematical monism in that it denies that anything exists except mathematical objects.
Properties
The problem of universals is an ancient problem in metaphysics about whether universals exist. Universals are general or abstract qualities, characteristics, properties, kinds or relations, such as being male/female, solid/liquid/gas or a certain colour,[8] that can be predicated of individuals or particulars or that individuals or particulars can be regarded as sharing or participating in. For example, Scott, Pat, and Chris have in common the universal quality of being human or humanity.
The realist school claims that universals are real – they exist and are distinct from the particulars that instantiate them. There are various forms of realism. Two major forms are Platonic realism and Aristotelian realism.[9] Platonic realism is the view that universals are real entities and they exist independent of particulars. Aristotelian realism, on the other hand, is the view that universals are real entities, but their existence is dependent on the particulars that exemplify them.
Nominalism and conceptualism are the main forms of anti-realism about universals.
Time and space
A traditional realist position in ontology is that time and space have existence apart from the human mind. Idealists deny or doubt the existence of objects independent of the mind. Some anti-realists whose ontological position is that objects outside the mind do exist, nevertheless doubt the independent existence of time and space.
Kant, in the Critique of Pure Reason, described time as an a priori notion that, together with other a priori notions such as space, allows us to comprehend sense experience. Kant denies that either space or time are substance, entities in themselves, or learned by experience; he holds rather that both are elements of a systematic framework we use to structure our experience. Spatial measurements are used to quantify how far apart objects are, and temporal measurements are used to quantitatively compare the interval between (or duration of) events. Although space and time are held to be transcendentally ideal in this sense, they are also empirically real, i.e. not mere illusions.
Idealist writers such as J. M. E. McTaggart in The Unreality of Time have argued that time is an illusion.
As well as differing about the reality of time as a whole, metaphysical theories of time can differ in their ascriptions of reality to the past, present and future separately.
- Presentism holds that the past and future are unreal, and only an ever-changing present is real.
- The block universe theory, also known as Eternalism, holds that past, present and future are all real, but the passage of time is an illusion. It is often said to have a scientific basis in relativity.
- The growing block universe theory holds that past and present are real, but the future is not.
Time, and the related concepts of process and evolution are central to the system-building metaphysics of A. N. Whitehead and Charles Hartshorne.
Possible worlds
The term “possible world” goes back to Leibniz’s theory of possible worlds, used to analyse necessity, possibility, and similar modal notions. Modal realism is the view, notably propounded by David Kellogg Lewis, that all possible worlds are as real as the actual world. In short: the actual world is regarded as merely one among an infinite set of logically possible worlds, some “nearer” to the actual world and some more remote. Other theorists may use the Possible World framework to express and explore problems without committing to it ontologically. Possible world theory is related to alethic logic: a proposition is necessary if it is true in all possible worlds, and possible if it is true in at least one. The many worlds interpretation of quantum mechanics is a similar idea in science.
Theories of everything (TOE) and philosophy
The philosophical implications of a physical TOE are frequently debated. For example, if philosophical physicalism is true, a physical TOE will coincide with a philosophical theory of everything.
The “system building” style of metaphysics attempts to answer all the important questions in a coherent way, providing a complete picture of the world. Plato and Aristotle could be said to be early examples of comprehensive systems. In the early modern period (17th and 18th centuries), the system-building scope of philosophy is often linked to the rationalist method of philosophy, that is the technique of deducing the nature of the world by pure a priori reason. Examples from the early modern period include the Leibniz‘s Monadology, Descartes‘s Dualism, Spinoza‘s Monism. Hegel‘s Absolute idealism and Whitehead‘s Process philosophy were later systems.
Other philosophers do not believe its techniques can aim so high. Some scientists think a more mathematical approach than philosophy is needed for a TOE, for instance Stephen Hawking wrote in A Brief History of Time that even if we had a TOE, it would necessarily be a set of equations. He wrote, “What is it that breathes fire into the equations and makes a universe for them to describe?”[10]
Phenomenological reality
On a much broader and more subjective level,[specify] private experiences, curiosity, inquiry, and the selectivity involved in personal interpretation of events shapes reality as seen by one and only one individual [11] and hence is called phenomenological. While this form of reality might be common to others as well, it could at times also be so unique to oneself as to never be experienced or agreed upon by anyone else. Much of the kind of experience deemed spiritual occurs on this level of reality.
Phenomenology is a philosophical method developed in the early years of the twentieth century by Edmund Husserl and a circle of followers at the universities of Göttingen and Munich in Germany. Subsequently, phenomenological themes were taken up by philosophers in France, the United States, and elsewhere, often in contexts far removed from Husserl’s work.
The word phenomenology comes from the Greek phainómenon, meaning “that which appears”, and lógos, meaning “study”. In Husserl’s conception, phenomenology is primarily concerned with making the structures of consciousness, and the phenomena which appear in acts of consciousness, objects of systematic reflection and analysis. Such reflection was to take place from a highly modified “first person” viewpoint, studying phenomena not as they appear to “my” consciousness, but to any consciousness whatsoever. Husserl believed that phenomenology could thus provide a firm basis for all human knowledge, including scientific knowledge, and could establish philosophy as a “rigorous science”.[12]
Husserl’s conception of phenomenology has been criticised and developed not only by himself, but also by his student and assistant Martin Heidegger, by existentialists, such as Maurice Merleau-Ponty, Jean-Paul Sartre, and by other philosophers, such as Paul Ricoeur, Emmanuel Levinas, and Dietrich von Hildebrand.[13]
Skeptical hypotheses
A brain in a vat that believes it is walking
Skeptical hypotheses in philosophy suggest that reality is very different from what we think it is; or at least that we cannot prove it is not. Examples include:
- The “Brain in a vat” hypothesis is cast in scientific terms. It supposes that one might be a disembodied brain kept alive in a vat, and fed false sensory signals, by a mad scientist. This is a premise of the film series, Matrix hypothesis.
- The “Dream argument” of Descartes and Zhuangzi supposes reality to be indistinguishable from a dream.
- Descartes’ Evil demon is a being “as clever and deceitful as he is powerful, who has directed his entire effort to misleading me.”
- The five minute hypothesis (or omphalos hypothesis or Last Thursdayism) suggests that the world was created recently together with records and traces indicating a greater age.
- The Matrix hypothesis or Simulated reality hypothesis suggest that we might be inside a computer simulation or virtual reality.
Jain philosophy
Jain philosophy postulates that seven tattva (truths or fundamental principles) constitute reality.[14] These seven tattva are:[15]
- Jīva – The soul which is characterized by consciousness.
- Ajīva – The non-soul.
- Asrava – Influx of karma.
- Bandha – The bondage of karma.
- Samvara – Obstruction of the inflow of karmic matter into the soul.
- Nirjara – Shedding of karmas.
- Moksha – Liberation or Salvation, i.e. the complete annihilation of all karmic matter (bound with any particular soul).
Physical sciences
Scientific realism
Scientific realism is, at the most general level, the view that the world described by science (perhaps ideal science) is the real world, as it is, independent of what we might take it to be. Within philosophy of science, it is often framed as an answer to the question “how is the success of science to be explained?” The debate over what the success of science involves centers primarily on the status of entities that are not directly observable discussed by scientific theories. Generally, those who are scientific realists state that one can make reliable claims about these entities (viz., that they have the same ontological status) as directly observable entities, as opposed to instrumentalism. The most used and studied scientific theories today state more or less the truth.
Realism and locality in physics
Realism in the sense used by physicists does not equate to realism in metaphysics.[16] The latter is the claim that the world is mind-independent: that even if the results of a measurement do not pre-exist the act of measurement, that does not require that they are the creation of the observer. Furthermore, a mind-independent property does not have to be the value of some physical variable such as position or momentum. A property can be dispositional (or potential), i.e. it can be a tendency: in the way that glass objects tend to break, or are disposed to break, even if they do not actually break. Likewise, the mind-independent properties of quantum systems could consist of a tendency to respond to particular measurements with particular values with ascertainable probability.[17] Such an ontology would be metaphysically realistic, without being realistic in the physicist’s sense of “local realism” (which would require that a single value be produced with certainty).
A closely related term is counterfactual definiteness (CFD), used to refer to the claim that one can meaningfully speak of the definiteness of results of measurements that have not been performed (i.e. the ability to assume the existence of objects, and properties of objects, even when they have not been measured).
Local realism is a significant feature of classical mechanics, of general relativity, and of electrodynamics; but quantum mechanics has shown that quantum entanglement is possible. This was rejected by Einstein, who proposed the EPR paradox, but it was subsequently quantified by Bell’s inequalities.[18] If Bell’s inequalities are violated, either local realism or counterfactual definiteness must be incorrect; but some physicists dispute that experiments have demonstrated Bell’s violations, on the grounds that the sub-class of inhomogeneous Bell inequalities has not been tested or due to experimental limitations in the tests. Different interpretations of quantum mechanics violate different parts of local realism and/or counterfactual definiteness.
Role of the observer in quantum mechanics
The quantum mind–body problem refers to the philosophical discussions of the mind–body problem in the context of quantum mechanics. Since quantum mechanics involves quantum superpositions, which are not perceived by observers, some interpretations of quantum mechanics place conscious observers in a special position.
The founders of quantum mechanics debated the role of the observer, and of them, Wolfgang Pauli and Werner Heisenberg believed that it was the observer that produced collapse. This point of view, which was never fully endorsed by Niels Bohr, was denounced as mystical and anti-scientific by Albert Einstein. Pauli accepted the term, and described quantum mechanics as lucid mysticism.[19]
Heisenberg and Bohr always described quantum mechanics in logical positivist terms. Bohr also took an active interest in the philosophical implications of quantum theories such as his complementarity, for example.[20] He believed quantum theory offers a complete description of nature, albeit one that is simply ill-suited for everyday experiences – which are better described by classical mechanics and probability. Bohr never specified a demarcation line above which objects cease to be quantum and become classical. He believed that it was not a question of physics, but one of philosophy.
Eugene Wigner reformulated the “Schrödinger’s cat” thought experiment as “Wigner’s friend” and proposed that the consciousness of an observer is the demarcation line which precipitates collapse of the wave function, independent of any realist interpretation. Commonly known as “consciousness causes collapse“, this interpretation of quantum mechanics states that observation by a conscious observer is what makes the wave function collapse.
Multiverse
The multiverse is the hypothetical set of multiple possible universes (including the historical universe we consistently experience) that together comprise everything that exists: the entirety of space, time, matter, and energy as well as the physical laws and constants that describe them. The term was coined in 1895 by the American philosopher and psychologist William James.[21] In the many-worlds interpretation (MWI), one of the mainstream interpretations of quantum mechanics, there are an infinite number of universes and every possible quantum outcome occurs in at least one universe.
The structure of the multiverse, the nature of each universe within it and the relationship between the various constituent universes, depend on the specific multiverse hypothesis considered. Multiverses have been hypothesized in cosmology, physics, astronomy, religion, philosophy, transpersonal psychology and fiction, particularly in science fiction and fantasy. In these contexts, parallel universes are also called “alternative universes”, “quantum universes”, “interpenetrating dimensions”, “parallel dimensions”, “parallel worlds”, “alternative realities”, “alternative timelines”, and “dimensional planes”, among others.
Scientific theories of everything
A theory of everything (TOE) is a putative theory of theoretical physics that fully explains and links together all known physical phenomena, and predicts the outcome of any experiment that could be carried out in principle. The theory of everything is also called the final theory.[22] Many candidate theories of everything have been proposed by theoretical physicists during the twentieth century, but none have been confirmed experimentally. The primary problem in producing a TOE is that general relativity and quantum mechanics are hard to unify. This is one of the unsolved problems in physics.
Initially, the term “theory of everything” was used with an ironic connotation to refer to various overgeneralized theories. For example, a great-grandfather of Ijon Tichy, a character from a cycle of Stanisław Lem‘s science fiction stories of the 1960s, was known to work on the “General Theory of Everything”. Physicist John Ellis[23] claims to have introduced the term into the technical literature in an article in Nature in 1986.[24] Over time, the term stuck in popularizations of quantum physics to describe a theory that would unify or explain through a single model the theories of all fundamental interactions and of all particles of nature: general relativity for gravitation, and the standard model of elementary particle physics – which includes quantum mechanics – for electromagnetism, the two nuclear interactions, and the known elementary particles.
Current candidates for a theory of everything include string theory, M theory, and loop quantum gravity.
Technology
Virtual reality and cyberspace
Virtual reality (VR) is a computer-simulated environment that can simulate physical presence in places in the real world, as well as in imaginary worlds.
Reality-Virtuality Continuum.
The Virtuality Continuum is a continuous scale ranging between the completely virtual, a Virtuality, and the completely real: Reality. The reality-virtuality continuum therefore encompasses all possible variations and compositions of real and virtual objects. It has been described as a concept in new media and computer science, but in fact it could be considered a matter of anthropology. The concept was first introduced by Paul Milgram.[25]
The area between the two extremes, where both the real and the virtual are mixed, is the so-called Mixed reality. This in turn is said to consist of both Augmented Reality, where the virtual augments the real, and Augmented virtuality, where the real augments the virtual. Cyberspace, the world’s computer systems considered as an interconnected whole, can be thought of as a virtual reality; for instance, it is portrayed as such in the cyberpunk fiction of William Gibson and others. Second life and MMORPGs such as World of Warcraft are examples of artificial environments or virtual worlds (falling some way short of full virtual reality) in cyberspace.
“RL” in internet culture
On the Internet, “real life” refers to life in the real world. It generally references life or consensus reality, in contrast to an environment seen as fiction or fantasy, such as virtual reality, lifelike experience, dreams, novels, or movies. Online, the acronym “IRL” stands for “in real life”, with the meaning “not on the Internet”.[26] Sociologists engaged in the study of the Internet have determined that someday, a distinction between online and real-life worlds may seem “quaint”, noting that certain types of online activity, such as sexual intrigues, have already made a full transition to complete legitimacy and “reality”.[27] The abbreviation “RL” stands for “real life”. For example, one can speak of “meeting in RL” someone whom one has met in a chat or on an Internet forum. It may also be used to express an inability to use the Internet for a time due to “RL problems”.
See also
Notes
- ^ “reality | Definition of reality in English by Oxford Dictionaries”. Oxford Dictionaries | English. Retrieved 2017-10-28.
- ^ Saridakis E. (2016). “Information, reality, and modern physics”. International Studies in the Philosophy of Science. 30 (4): 327–341. doi:10.1080/02698595.2017.1331980.
- ^ Lehar, Steve. (2000). The Function of Conscious Experience: An Analogical Paradigm of Perception and Behavior, Consciousness and Cognition.
- ^ Lehar, Steve. (2000). Naïve Realism in Contemporary PhilosophyArchived 2012-08-11 at the Wayback Machine, The Function of Conscious Experience.
- ^ Lehar, Steve. RepresentationalismArchived 2012-09-05 at the Wayback Machine
- ^ Tegmark, Max (February 2008). “The Mathematical Universe”. Foundations of Physics. 38(2): 101–150. arXiv:0704.0646. Bibcode:2008FoPh…38..101T. doi:10.1007/s10701-007-9186-9.
- ^ Tegmark (1998), p. 1.
- ^ Loux (2001), p. 4
- ^ Price (1953), among others, sometimes uses such Latin terms
- ^ as quoted in [Artigas, The Mind of the Universe, p.123]
- ^ Present-time consciousness Francisco J. Varela Journal of Consciousness Studies 6 (2-3):111-140 (1999)
- ^ Joseph Kockelmans (2001). Edmund Husserl’s phenomenology (2 ed.). Purdue UniversityPress. pp. 311–314. ISBN1-55753-050-5.
- ^ Steven Galt Crowell (2001). Husserl, Heidegger, and the space of meaning: paths toward transcendental phenomenology. Northwestern University Press. p. 160. ISBN0-8101-1805-X.
- ^ S.A. Jain 1992, p. 6.
- ^ S.A. Jain 1992, p. 7.
- ^ Norsen, Travis (26 February 2007). “Against ‘Realism‘“. Foundations of Physics. 37 (3): 311–340. arXiv:quant-ph/0607057. Bibcode:2007FoPh…37..311N. doi:10.1007/s10701-007-9104-1.
- ^ Thompson, Ian. “Generative Science”. http://www.generativescience.org.
- ^ “Local realism and the crucial experiment”. bendov.info.
- ^ Juan Miguel Marin (2009). “‘Mysticism’ in quantum mechanics: the forgotten controversy”. European Journal of Physics. 30 (4): 807–822. Bibcode:2009EJPh…30..807M. doi:10.1088/0143-0807/30/4/014.link, summarized here [1]Archived 2011-06-06 at the Wayback Machine
- ^ John Honner (2005). “Niels Bohr and the Mysticism of Nature”. Zygon: Journal of Religion & Science. 17–3: 243–253.
- ^ James, William, The Will to Believe, 1895; and earlier in 1895, as cited in OED‘s new 2003 entry for “multiverse”: “1895 W. JAMES in Internat. Jrnl. Ethics 6 10 Visible nature is all plasticity and indifference, a multiverse, as one might call it, and not a universe.”
- ^ Weinberg (1993)
- ^ Ellis, John (2002). “Physics gets physical (correspondence)”. Nature. 415 (6875): 957. Bibcode:2002Natur.415..957E. doi:10.1038/415957b. PMID11875539.
- ^ Ellis, John (1986). “The Superstring: Theory of Everything, or of Nothing?”. Nature. 323(6089): 595–598. Bibcode:1986Natur.323..595E. doi:10.1038/323595a0.
- ^ Milgram, Paul; H. Takemura; A. Utsumi; F. Kishino (1994). “Augmented Reality: A class of displays on the reality-virtuality continuum”(PDF). Proceedings of Telemanipulator and Telepresence Technologies. pp. 2351–34. Archived from the original(PDF) on 2006-10-04. Retrieved 2007-03-15.
- ^ “AcronymFinder.com search for IRL”.
- ^ Don Slater (2002). “Social Relationships and Identity On-line and Off-line”. In Leah, Sonia, Lievrouw, and Livingstone (eds.). Handbook of New Media: Social Shaping and Consequences of ICTs. Sage Publications Inc. pp. 533–543. ISBN0-7619-6510-6.
References
- Berger, Peter L.; Luckmann, Thomas (1966). The Social Construction of Reality: A Treatise in the Sociology of Knowledge. New York: Anchor Books. pp. 21–22.
- Jain, S. A. (1992). Reality. Jwalamalini Trust. Archived from the original on 2015.
Not in Copyright
Further reading
- George Musser, “Virtual Reality: How close can physics bring us to a truly fundamental understanding of the world?”, Scientific American, vol. 321, no. 3 (September 2019), pp. 30–35. “Physics is… the bedrock of the broader search for truth…. Yet [physicists] sometimes seem to be struck by a collective imposter syndrome…. Truth can be elusive even in the best-established theories. Quantum mechanics is as well tested a theory as can be, yet its interpretation remains inscrutable. [p. 30.] The deeper physicists dive into reality, the more reality seems to evaporate.” [p. 34.]
External links
Definitions from Wiktionary
Media from Wikimedia Commons
News from Wikinews
Quotations from Wikiquote
Texts from Wikisource
Textbooks from Wikibooks
Resources from Wikiversity
- Miller, Alexander. “David Lewis”. In Zalta, Edward N. (ed.). Stanford Encyclopedia of Philosophy.
- C.D. Broad on Reality
- Video: Animated version of the above with Dr Quantum – Flatland
- Phenomenology Online: Materials discussing and exemplifying phenomenological research
- The Matrix as Metaphysics by David Chalmers
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xDEEP DIVE
A closer look at the race to develop antibody drugs for COVID-19
A vaccine is likely what will stop the new coronavirus, so it’s no surprise that the dozens of programs speeding through testing are getting so much attention.
Even at the unprecedented pace vaccines are moving, the first might not be available until next year. And it’ll likely take much longer than that for enough people to be vaccinated that the U.S. achieves ‘herd immunity,’ and can more definitively curb the spread of SARS-CoV-2.
That’s why many experts believe the efforts of a group of companies developing antibody drugs are so vital. Regeneron, Eli Lilly, Amgen and Vir Biotechnology are leading an increasingly competitive race to develop therapies that could give people short-term protection from the coronavirus, or help treat those who are exposed or infected. And they could be more potent than the current standard of care, Gilead’s antiviral drug remdesivir, which seems to help hasten recovery from COVID-19 but only modestly so.
“These medicines may be the best chance for a meaningful near-term success,” former FDA commissioner Scott Gottlieb recently wrote in an op-ed in the Wall Street Journal.
Still, even if successful — which is no guarantee — these injectable biologic drugs won’t solve the pandemic. Their effects are temporary, for instance, and manufacturing will also be a challenge.
But many believe there is a good chance that they could get through clinical testing and be available for use before vaccines arrive. In combination with mass testing and tracing measures, they could, then, be a critical tool in helping keep the disease in check.
“Can you turn this into something where we can take the distancing requirements down in a significant way?” said Ronny Gal, a biotech analyst at Bernstein, in an interview.
The first clinical tests of COVID-19 antibodies should start next month. With those trials approaching, BioPharma Dive spoke with the developers of these drugs and some outside observers about what lies ahead.
What are antibody therapies for coronavirus, and how do they work?
When fighting off foreign invaders, our bodies make antibodies specifically produced for the task. The reason vaccines provide such long-lasting protection is they train the immune system to recognize a pathogen, so immune cells remember and are ready to attack the virus when it appears.
Monoclonal antibodies for coronavirus would take the place of the ones our bodies might produce to fight the disease. Specifically engineered to act like coronavirus-fighting immune cells, the manufactured antibodies would be infused into the body to either tamp down an existing infection, or to protect someone who has been exposed to the virus.
This approach has proven effective against infectious diseases before. A major study in the Democratic Republic of the Congo, for instance, showed a cocktail of antibodies developed by Regeneron reduced the risk of death from Ebola compared to two other treatments. That success has fueled hopes of a repeat, both for Regeneron and for other companies, too.
“Antibodies are the treatments that turned out to be most useful for Ebola. That may or may not be the case with coronavirus,” said Diane Griffin, a professor of infectious diseases and of neurology at the Johns Hopkins University School of Medicine, in an interview.
“But it at least brings to the fore the possibility that antibodies could be an important component for treatment.”
Effectively, these drugs are synthetic versions of the convalescent plasma treatments that rely on antibodies from people who have recovered from infection. But the engineered versions are easier to scale because they’re manufactured in vats, rather than from plasma donors.
The biggest problem with antibody treatments, however, is their staying power. Their effects only last as long as the antibodies are alive — likely a month or more. As Gal puts it, “the weakness is that they’re not a solution.”
Why care about antibodies if vaccines are the real solution?
First, it’s risky to count on vaccines being developed at an historic pace — testing normally takes many years — and be an immediate panacea. There are many other uncertainties ahead, too. No vaccine has ever been successfully developed for any type of coronavirus, and the most advanced prospects rely on new, unproven technologies that have never been made at the kind of global scale needed to fight a pandemic.
What’s more, some vaccines are only effective for a portion of people. Among the hardest to help are elderly people with weaker immune systems — the kind that are most prone to serious complications from coronavirus disease. Vaccine’s effects also take time; they don’t kick in immediately.
“We don’t know if the vaccines will work, when they will work, or how well they will work,” said Vir CEO George Scangos in an interview. “I hope it will be the case, but I don’t believe it will be the case that vaccines provide universal protection for everyone.”
Vaccines aside, the cupboard of drugs that doctors can use to treat infected patients right now is nearly bare. The only treatments granted emergency use by the FDA thus far are the antiviral remdesivir and the generic malaria pill hydroxychloroquine. But remdesivir must be infused over either 5 or 10 days and has only shown it may help shorten hospital stays for people with severe disease. It’s unclear what, if any, benefit hydroxychloroquine has.
Social distancing has, thus far, helped to keep case numbers from rising exponentially and reduce strain on the healthcare system. But some states are already reducing such measures or soon will, and the economic pressure to open has grown by the day. That will likely lead to a spike in new cases or, perhaps, a second wave in the fall, experts predict. There is a huge need for a temporary solution that can help people until a vaccine arrives.
“We need something to bridge that gap,” said Andrew Adams, Eli Lilly’s chief scientific officer of RNA therapeutics in an interview. Adams also works on antibodies.
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Monoclonal antibodies could help. They’re being made with well-known technologies that are used to make many marketed drugs for cancer and autoimmune diseases — and have become effective medicines for other infections like respiratory syncytial virus. Their effects kick in immediately, which means that they can be tested in people with live infections quickly.
Select antibodies in development for COVID-19
| Company | Approach | Modifying antibodies? | Target trial start |
|---|---|---|---|
| Regeneron | Cocktail | No | June |
| Vir | Monotherapy | Yes | Summer |
| Amgen/Adaptive | Not disclosed | Not disclosed | Not disclosed |
| Eli Lilly/AbCellera/Junshi | Looking at both options | Not disclosed | June |
SOURCE: Companies
How would antibody drugs be used?
What makes antibodies unique, compared to vaccines or antiviral drugs, is their potential to both treat and protect against viral infections. They could work as a “short-term preventative” for healthcare workers who are at “exceptionally high risk” of contracting COVID-19, or as a treatment for people who are sick, said Ray Deshaies, Amgen’s senior vice president of global research, in an interview.
Proving antibodies can treat patients with existing disease will be much faster and easier than showing a preventive benefit. As with vaccines, antibodies would have to succeed in much longer tests to fully show they can prevent infections. And it’s up to the developers to figure out exactly when, in a disease course, the best time is to intervene with an antibody drug.
Scangos, for instance, said Vir plans to test its antibody candidate in multiple scenarios: in people who are either already hospitalized, newly diagnosed with disease but yet to have respiratory problems, or who have just been exposed to the virus.
“How it would be used depends on which one of those” works best, he said.
Would antibodies be for everybody, or only select groups?
The quickest path to success for an antibody is likely through a drug that has to be given intravenously in a hospital or clinic, rather than through an auto-injector a patient could self-administer, said Amgen’s Deshaies. They’re also complex to manufacture, transport and supply in massive quantities. Taken together, “it’s going to be difficult to use them on the general population,” he said.
More realistically, antibodies will provide the most value for the people at the highest risk, like healthcare workers or people who are old or immuno-compromised.
The latter group, in particular, might not even be helped by a vaccine or if they are, only after awhile, said Christos Kyratsous, Regeneron’s vice president of infectious disease research and viral vector technologies, in an interview. “There is a huge question mark if this population will respond to a vaccine,” he said, “so I don’t think monoclonal antibodies are just bridging until a vaccine [gets here].”
Still, it’s unknown, as of yet, what the real demand will be for antibodies should they succeed and whether they’d be able to meet it. Executives from each four firms said they are manufacturing their drugs “at risk,” before it’s known whether they’ll work. Their capabilities may depend on how large of a dose is needed and whether multiple antibodies are needed in each of them — which would make them harder to produce.
“These factors are clearly going to affect how the product is going to be used,” Kyratsous said.
What other challenges do antibodies face?
Bernstein analyst Gal believes there’s a good chance antibodies will succeed in clinical trials because multiple efforts are underway using technologies that have produced treatments for other infectious diseases, like Ebola.
The way they work is also “fairly straightforward,” he said. Generally speaking, the idea is that an antibody drug will bind to the “spike” protein SARS-CoV-2 uses to crack open cells, and prevent the virus from entering.
But there are reasons to be skeptical. It’s still unproven, in humans, whether a drug that binds to the spike protein will protect an infection or stop one from spreading. Even approved antibodies for infectious diseases don’t work for everyone — AstraZeneca’s (and now Sobi’s) RSV drug Synagis, for example, reduces hospitalizations about 50% of the time.
Jen Heemstra, an associate professor of chemistry at Emory University, noted that it’s unknown whether engineered antibodies will grab hold of target viral protein “as tightly as planned,” in part because of how they’re designed and made. Additionally, while an antibody is supposed to temporarily mimic the effects of a vaccine, it’s “unlikely to work with that level of efficacy,” she said in an interview.
“There is cautious optimism that they will be beneficial in treating the disease,” she said. “But that is tempered with a realization that no single therapy is likely to work for all patients and all stages of infection and that there is still much we don’t understand about the virus that can undermine even the most well-planned approaches.”
Deshaies added one other potentially significant concern: Examples in past research of antibodies “exacerbating” the effects of other members of the coronavirus family. “That’s certainly in the back of our minds and the minds of others that are taking this approach,” he said.
How do the antibodies being developed differ?
Regeneron, Amgen, Vir and Eli Lilly are each using different methods to screen for and develop their antibodies. And those initial experiments may lead to different types of products: One type of antibody versus a cocktail of two or three, for example, or antibodies designed to mimic the ones our bodies make, versus those that are modified in some way to improve their properties.
These choices come with pros and cons. More antibodies means more ways to attack a pathogen, and account for potential mutations – at the possible cost of not being able to ramp up a dose to higher levels. Modifying an antibody could help it last longer, but make it look more foreign to the immune system, which could lead to potential problems.
Regeneron is going forward with a cocktail of two synthetic versions of natural antibodies, “We don’t like messing with a solution that nature has evolved for millions of years,” Kyratsous said.
Vir is modifying its antibodies to make their effects last for multiple months, and with at least one of its prospects, making a change in an attempt to boost its effectiveness. Scangos believes fears those changes could lead to potentially deleterious effects are “overblown.”
Amgen and Lilly are still thinking through their approaches. “It’s something that we continue to discuss all day,” Lilly’s Adams said. They’re each working in tandem with smaller companies — Amgen with Adaptive Biotechnologies, Lilly with AbCellera and Junshi Biosciences.
Regeneron and Lilly plan to start human tests next month. Vir expects to start trials in the summer. Amgen hasn’t been as specific. “We’re working as fast as we can,” Amgen’s Deshaies said. But those timelines mean meaningful data will likely be produced by multiple companies by the fall.
Griffin, from Johns Hopkins, cautions each developer to make sure it knows what it has before moving forward at such speed.
“Just be a little bit humble about your antibody and knowing what it does,” she said, “and that it’s going to be protective rather than make things worse.”
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Leave No One Behind: Using a Benefit-Based Advance Market Commitment to Incentivise Development and Global Supply of COVID-19 Vaccines
Executive Summary
Theglobal effort to control the COVID-19 pandemic has seen an exceptional allocation of public and philanthropic funds to advance the development of diagnostics, therapeutics, and vaccines as quickly as possible. While critical, even these significant commitments represent only a “down payment” on a price tag that could eventually exceed $50 billion just to scale the production of vaccines to control this global pandemic—amounts that cannot be raised through traditional donor and philanthropic commitments.
High-income countries (HICs) can afford to compete for products, and if their taxpayers are willing to contribute, traditional donor funding approaches can help low-income countries (LICs) through mechanisms such as the GAVI-proposed Advance Market Commitment (AMC). However, billions of poor people who live in middle-income countries (MICs) ineligible for donor funding are at risk of being left out. Any exclusion will undermine the effort to control the virus. Further, MICs are key actors in the global supply and production chain, and we will require an unprecedented level of collaboration between governments and with industry to develop and rapidly manufacture global supplies of a vaccine. No country has all the science, equipment, and capacity on its own soil to research, develop, manufacture, and supply a vaccine to all its citizens, let alone the whole world.
The world is certain to experience other pandemics—it is a matter of when, not if. The important question now is whether the battle against COVID-19 will strengthen or exhaust our ability to respond again in the future. The world faces a unique challenge, but it also has a unique opportunity to craft solutions that not only address the challenge of providing effective vaccines against COVID-19 but also are replicable and sustainable. To do so will require us to abandon the binary distinction of health goods as “market driven” or “charitable.” Instead, we must create incentives and pathways for governments to work together and with the private sector to tap its enormous reserve of capital, talent, and technology.
In this note we propose a new mechanism that would address these challenges. The Market-Driven Value-Based Advance Commitment (MVAC) is designed to pull in money from the private sector to help fund the R&D and manufacturing scale up by explicitly monetizing future expected demand from HICs and MICs. The MVAC differentiates the price according to efficacy, thereby incentivizing development and use of vaccines with higher rates of disease prevention, while ensuring that vaccines are available at manufacturing cost for LICs. By pooling commitments and pre-agreeing vaccination priorities, countries avoid destructive beggar-thy-neighbour policies to pre-empt supplies, instead sending clear signals to market entrants.
Without consideration of value, HICs and MICs risk getting locked into purchasing inferior or cost-ineffective products that divert scarce resources from other potential COVID-19 responses, including potential therapies, non-pharmaceutical interventions like testing and contact tracing, and superior vaccines. If all the funding flows to the first entrant, the second or third entrants may be boxed out of the market—even if their product is of better value or more efficacious.
Given the importance of having enough manufacturing capacity to supply successful vaccines, a complementary advance purchase mechanism that operates alongside the MVAC could be set up with donors and governments entering into contracts with potential manufacturers who would receive licenses from the innovator, with an initial contract component entering into force immediately to build and hold manufacturing capacity before a vaccine has come to market.
By rewarding performance, the MVAC can increase the likelihood that all the world’s citizens gain access to effective vaccines that all countries, regardless of income level, have a stake in.
Context
Over 100 vaccines are under development against COVID-19 today but unless we take international action to ensure that most of the world’s population have access, we cannot realize the global goal of controlling the pandemic. Where a circulating virus anywhere poses the threat of reintroduction everywhere, timely introduction and broad coverage are not just issues of equity but are critical to an effective response.
The first challenge to global and timely access is the paucity of public funding for financing an issue of this magnitude. In support of the recently launched Access to COVID-19 Tools (ACT) Accelerator, philanthropies and governments have committed nearly $8 billion to support the development of diagnostics, therapies, and vaccines, but they recognize that this is only a “down payment.” Even when we have an effective vaccine, tens of billions of dollars will be required to scale up the manufacturing of doses needed. Biopharmaceutical companies are nervous about the reliability of future markets and respect of IP rights, and are reluctant to front the capital investments needed,[1] and there is no credible public-only alternative through which to coordinate vaccine development, manufacture, and distribution.
A second challenge is the pressure governments face to prioritize their own citizens over a globally coordinated allocation plan, even if thatglobal allocation might better serve the global goal of controlling the virus. The capabilities and resources to develop vaccines are concentrated in just a few HICs and MICs, where governments, under immense public pressure, may adopt both financial and legislative measures to restrict global access to vaccines, or vaccine components, manufactured in their jurisdictions. Without legal constraints, pre-approval manufacturing agreements or domestic export policies can still restrict international availability.[2] To overcome the instinct and public pressure to prioritize national self-interest, governments need to assure their public (and themselves) that a coordinated plan will better meet their priorities, be that volumes, price, or something else.
The third challenge is that many MICs and LICs are at risk of being deprioritized for supplies even as global leaders are committed to leaving no one behind. Most countries are not funding their own vaccine candidates, have no or only limited manufacturing capacity, do not offer an attractive financial market, and are underrepresented at the global tables. A sustainable solution that recognizes and responds to the different circumstances and needs of HICs, MICs, and LICs is needed.
A Public-Private Disconnect?
At the heart of this problem is the fact that there is no coherent path to align public and private investment along the vaccine development value chain from laboratory to global market. Public and private efforts to fund and collaborate are more aligned in upstream R&D, where the main risks are scientific. As the products advance, many complementary efforts are required to accelerate the development and manufacture of accessible and desirable vaccines, and to realize the optimal distribution needed to control the pandemic as quickly as possible. However, without credible market pulls that includes explicit expectations with regard to global access and for whom, companies that might have the capital to resolve the funding bottlenecksare likely to wait for more push funding, unable to see a pathway to a reasonable return between the high-costs of development and manufacturing to global scale and the volatile and politically charged market.
To sustainably resolve this, we need to create mechanism(s) to improve the predictability of the companies’ market returns so as to mobilize their investment in development and manufacturing capacity. And, in tandem, we need a mechanism(s) to mobilize additional suppliers to prepare to scale manufacturing to global demand in parallel with the innovators.
Does a Solution Exist?
In 2019, we proposed aMarket-Driven, Value-Based Advance Commitment (MVAC) to incentivize private sector investment for a universal drug regimen for tuberculosis (TB), a condition that is mostly prevalent in MICs and LICs. A modified version of this MVAC, that includes HICs, offers a potential global solution for the current crisis, incentivizing COVID-19 vaccine innovators to make investments by improving the credibility and predictability of all the markets. With more certainty about returns in HICs and MICs, companies are more likely to agree to offer the LICs the lowest tier subsidised prices either directly or via voluntary licenses to local manufacturers through conduits such as the Medicine Patent Pool. A parallel and linked advance purchase agreement could help mobilize those license recipient suppliers to invest early in expanded manufacturing capacity.[3]
Incentives for accelerated development and commercialization
TheMVAC is based on the AMC—a concept piloted with pneumococcal vaccines in 2009—with some important adaptations. The advance commitments in the MVAC case are built on value assessments done by national payers that are indexed to their ability to pay for a new product. Countries make a commitment to purchase—without having to put up the money now—with their contributions scaling as a function of the value of the vaccine to their health system and ability to pay. The poorest countries would pay the least—possibly zero—and their contributions could be met with full or partial donor support through an organization like GAVI.
Assuming more than one vaccine proves sufficiently efficacious, the vaccine that best meets the preferred product characteristics (as detailed in theWHO Target Product Profile or TPP) would receive a greater share of the total revenue commitment. However, the mechanism would allow inclusion of more than one product meeting minimal TPP requirements. As was the case with the pneumo AMC, provision will be made for a product offering more suitable characteristics for implementation in different contexts and populations. It also takes account of the likelihood that the first vaccine to get a product license may not meet all needed criteria (in terms of overall efficacy, or method of administration) and multiple vaccines may ultimately be necessary to address challenges of efficacy and tolerability in sub populations or to address field conditions.
The value assessment element of MVAC allows for the same product or indeed different products to command different prices and hence market share across different country contexts as they may meet local needs at differing levels (perhaps because of a differential safety profile; their effect on younger vs elderly multi-morbid populations; the need for cold chain; or administration complexity). In addition to accommodating population heterogeneity through subgroup analysis, such an integrated health economic and dynamic disease transmission model[4] would also allow for comparisons to be made against future counterfactuals of different levels of herd immunity or more effective treatment regimens coming about, when assessing the future value of a vaccine.
An MVAC for a COVID-19 vaccine would have the following attributes:
- Early health technology assessment (HTA), (building on countries’ existing national and regional HTA processes, such as UK’s NICE, Australia’s PBAC, or Thailand’s HITAP), would be used to understand how helpful a vaccine would be in different country contexts and determine the ability of each country to pay. The results would then be adjusted downwards for relevant push funding and “locked in” to provide overall market predictability.
- MVAC could use a financial intermediary like a multilateral development bank for MICs or HICs’ national bank reserves or holdings of government bonds, to underwrite countries’ own value-based advance market commitments, so countries do not need to put scarce resources aside until an effective product comes to market.
- All countries could participate in the mechanism to guarantee a large total market commitment, but their contributions to the total market would vary based on their respective ability to pay and population sizes.
- Governments would construct the MVAC to offer multiple value-based entry market commitments (country-specific tiered prices for guaranteed volumes) to multiple developers that meet the minimum effectiveness threshold (as per the WHO TPP) as an incentive to keep many different potential innovators in the game post launch. This would hedge risk against late failure of one or more early candidates and against the possibility of safety risks after widespread deployment requiring restricted use or withdrawal from the market of the first entrant.
- As a condition of accessing this guaranteed market, governments would require the successful innovator(s) to license their vaccines out to other suppliers at low or zero cost, helping facilitate widespread scale-up across all countries, but in particular in LICs.[5]
Incentives for scaling manufacturing
In anticipation of a widely licensed vaccine, an advance purchase mechanism that complements the MVAC could be set up with donors and governments entering a two-part contract with potential manufacturers with licenses from the innovator.
The first part of the contract would enter into force immediately to build and hold manufacturing capacity for production of a vaccine (at a flat rate possibly determined through an auction mechanism), before a vaccine has come to market. Public monies can fund this, and such public investment will be reflected in a discounted price. The mechanism could solicit potential suppliers through open bidding to ensure they receive manufacturing capacity at competitive prices. It will require careful hedging of investment to align to different vaccine platforms that might be most easily adaptable if the front runners fail. While this might be more straightforward for conventional vaccine platforms, it may require significant additional upfront investment to build up large-scale production of innovative nucleic acid vaccines. High-quality manufacturing, meeting standards agreed by regulators, geographically distributed, and the innovator company—and vigorously enforced by regulators—would be a key requisite.
The second part of the contract would enter into force once a vaccine is approved and licensed and the reserved manufacturing capacity is put into use on a competitive pricing basis. This is a cost which could be internalised by the participating innovators (as per conventional contract manufacturing organization [CMO] contracts) and reflected, this time as a positive, in the final value-based price.
How to distribute manufacturing plants and manufacturing supplies globally, including across sub-Saharan Africa, to ensure seamless and efficient transport and access would also need to be explored.
MVAC for a COVID-19 Vaccine
The MVAC de-risks the commercial market, encourages voluntary licensing early to crowd in additional suppliers, and offers an avenue for widespread, rapid uptake across countries with divergent abilities to pay. It incorporates flexibilities to reward value—and ensures we continue to incentivize investments in the best (and safest) possible products.
The MVAC signals to industry that the market values their up-front investments and those investments have the potential to pay off down the line in a way that reflects the value of their product.
Perhaps most importantly, the MVAC differentiates the price according to efficacy, drawing on countries’ established HTA capacities, and incentivizing development and use of vaccines with higher rates of disease prevention, while ensuring that vaccines are available at manufacturing cost for LICs.
Without consideration of value, countries risk getting locked into competing to purchase inferior or cost-ineffective products that divert scarce resources from other potential COVID-19 responses, including potential therapies, non-pharmaceutical interventions like testing/contact tracing, and later, superior vaccines that may be boxed out of the market if all funding immediately flows to a first, poor-value or minimally efficacious entrant.
Finally, beyond the immediate challenge at hand, a MVAC for COVID-19 vaccine could set a sustainable precedent for how to combat future emerging challenges, demonstrating to developers how a market could exist for high-value innovations and encouraging them to invest aggressively to tackle global challenges, crowding in private capital that governments may find hard to raise alone. Recent fundraising cycles to tackle antimicrobial resistance and now COVID-19 have shown this to be a challenge.
Next steps
A flurry of activity is already underway to address the vaccine financing, manufacturing scale up, and allocation issues for COVID-19, but none are taking a value/health benefit-based approach. With an AMC being discussed for LICs, and nationalistic and protectionist tendencies across HICs and some MICs, it is urgent we send coordinated and clear incentive signals to the public and private actors who we need invested in the research, development, manufacture, and delivery of COVID-19 vaccines.
We call on governments, philanthropic organisations, and key international bodies to work together with the private and nonprofit sectors to design and implement a benefit-based AMC based on our MVAC mechanism.
These unprecedented times require novel solutions and bold, unprecedented action.
[1] “If the industry does not know if there will be a market in 18 months, [it] cannot carry all [the costs]. Industry alone can’t provide all the investment needed now for billions of doses,” David Loew, EVP, Sanofi-Pasteur, FT April 20, 2020.
[2] “The danger is that richer nations will buy up the supply for their own use or prevent exports of vaccines developed within their borders as countries scramble to protect their citizens or stockpile for future outbreaks. Another concern is that manufacturers might restrict sales to the highest bidder.” Seth Berkeley, NYT Op-ed, April 29, 2020.
[3] We propose explicit accommodations for the LIC market be incorporated into the MVAC but a complementary and separate GAVI AMC developed to service LICs could be an alternative approach to consider.
[4] For examples of health economic evaluation using dynamic disease models see here for dengue vaccine introduction and here and here for a more general exposition of the issues.
[5] The LIC commitments could be paid for by global donors through Gavi/IFFIm and maybe cost plus AMC. Donors might offer further support for delivery within countries with weak health systems
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Genetics of Covid-19 patients is focus of study
Research into the genetic code of Covid-19 patients could help predict severity of the disease.
Researchers are to study the genetic blueprints of severely ill Covid-19 patients to find out why the disease affects some more seriously than others and suggest potential treatments.
A UK-wide initiative will sequence the genetic makeup – the whole genome – of patients to identify the specific genes that cause a predisposition to the disease.
The study hopes to explain one of the biggest mysteries about Covid-19: why some people get no symptoms at all, while others become critically ill, or die.
The project, led by Dr Kenneth Baillie from the Roslin Institute, is a collaboration between Genomics England, the NHS, and the GenOMICC (Genetics of Susceptibility and Mortality in Critical Care) consortium – a global consortium to study genetics in critical illness.
This new partnership will allow whole genome sequencing to take place across the NHS involving up to 20,000 people currently or previously in an intensive care unit with Covid-19, and 15,000 individuals who have mild symptoms.
All critically ill patients
GenOMICC – which was launched by Dr Baillie in 2016 – is already active in more than 170 intensive care units across the UK and has signed up more than one thousand patients for the study.
The team aim to recruit every Covid-19 patient on a ventilator in the UK. The group have now been funded to sequence the entire genomes of patients with Covid-19 in collaboration with Genomics England and Illumina.
By discovering why some people are predisposed to developing life-threatening symptoms, scientists will be able to identify treatments for clinical trials and potentially highlight people at extreme risk.
The results will also inform global strategic planning for possible later waves of Covid-19 and for future pandemics.
Global collaboration
GenOMICC is an open, global consortium of intensive care clinicians to understand genetic factors that influence outcomes in intensive care from diseases such as SARS, influenza and sepsis. It is designed to enable rapid research in the event of outbreaks like the current pandemic.
It is funded by the charity Sepsis Research (FEAT), the Intensive Care Society, Wellcome, UKRI and Scotland’s Chief Scientist Office.
This new work has been enabled by £28 million of funding from Genomics England, UK Research and Innovation, the Department of Health and Social Care and the National Institute for Health Research.
I am delighted to be announcing this further major programme in the UK’s fight against Covid-19. As a nation, we are determined to harness the UK’s leadership in genomics to understand its role in viral response and whether we can use this information to identify those at greatest risk and improve their treatment.
Our genes play a role in determining who becomes desperately sick with infections like Covid-19. Understanding these genes will help us to choose treatments for clinical trials. The GenOMICC study was launched before this outbreak and it is recruiting in 145 ICUs across the country with tremendous support from the critical care community. We are excited to work with Genomics England to tackle this new and complex disease.
For the first time in a generation, we face a global viral pandemic that is life threatening for some people, yet others have a mild infection. By reading the whole genome we may able to identify variation that affects response to Covid-19 and discover new therapies that could reduce harm, save lives and even prevent future outbreaks.
** The Roslin Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies. **
Contact
Edd McCracken, Press and PR Office, University of Edinburgh
07557502823, edd.mccracken@ed.ac.uk
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Obesity impacts on Covid-19 recovery prospect
£5m Covid-19 study seeks to understand virus impact
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Disabling Genes in Immune Cells Prevents Obesity
Obesity is a $1.7 trillion problem in the United States, a condition that leads to several chronic illnesses including heart disease, stroke and certain types of cancer. For many, this results in preventable, premature death. Unsurprisingly, identifying clinical strategies to prevent obesity from a pharmacological, or even a genetic standpoint have been in the research spotlight for decades.
Scientists at the Washington University School of Medicine are exploring the possibility of targeting obesity on a genetic level. By switching off a specific gene in immune cells of mice, they successfully stopped mice fed a high-fat diet from becoming obese. The study was published in The Journal of Clinical Investigation.
Obesity and inflammation are intricately linked. The number of macrophages in adipose, or fat tissue, differs depending on an individual’s metabolic status. Lean humans have around 10 percent of macrophages in adipose tissues, while obese people have up to 40 percent. Experts believe that this increased number and activity of macrophages could be linked to metabolic perturbations and the onset of associated chronic diseases in obese individuals.
By disabling the ASXL2 gene in macrophages, the researchers hypothesized that this would curb chronic low-grade inflammation in fat tissues and in turn, help resist excess weight gain in spite of high-fat diets. Their experimental model involved either genetically modifying macrophages in obese mice, or injecting them with nanoparticles that specifically target and shut off ASXL2.
Interestingly, despite being fed a high calorie diet, the treated mice burnt 45 percent more calories than mice with active macrophage ASXL2.
Principal investigator of the study, Steven L. Teitelbaum, MD, said, “These mice consumed high-fat diets, but they didn’t get fatty livers. They don’t get type 2 diabetes. It seems that limiting the inflammatory effects of their macrophages allows them to burn more fat, which keeps them leaner and healthier.”
Sources: The Journal of Clinical Investigation, Washington University in St. Louis.
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Tara Fernandez has a PhD in Cell Biology and has spent over a decade uncovering the molecular basis of diseases ranging from skin cancer to obesity and diabetes. She currently works on developing and marketing disruptive new technologies in the biotechnology industry. Her areas of interest include innovation in molecular diagnostics, cell therapies, and immunology. She actively participates in various science communication and public engagement initiatives to promote STEM in the community.
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Researchers have demonstrated that epigenetic age can be halved in rats by using signals commonly found in the blood.
Epigenetic changes
One of the proposed reasons we age are the changes to gene expression that our cells experience as we get older; these are commonly called epigenetic alterations. These alterations harm the fundamental functions of our cells and can increase the risk of cancer and other age-related diseases.
Gene expression is modified by the addition of epigenetic markers to the DNA, which change the pattern of gene expression in a cell, suppressing or enhancing the expression of certain genes in a cell as the situation demands.
You might think of DNA as the building blocks and epigenetics as the instruction manual that explains how to assemble those blocks in order to make a certain structure to suit a particular situation.
This is how a cell in the liver knows that it needs to be a liver cell: the epigenetic instructions make sure that it is given the right guidance to become the correct cell type. At a basic level, these epigenetic instructions make sure that the genes needed to develop into a liver cell are turned on while the instructions specific to other types of cells are turned off.
However, as we age, our cells are exposed to damage from environmental factors and are subject to negative genomic changes through epigenetic mechanisms. Such changes accumulate over time and have been correlated with the decline observed in aging cells.
Epigenetic alterations in aging include changes to methylation patterns, and, in general, these correlate with a decrease in the amount of heterochromatin and an increase in chromosome fragility and transcriptional alterations (variance in gene expression), remodeling of chromatin (a DNA support structure that assists or impedes its transcription), and transcriptional noise.
Some researchers believe that these harmful epigenetic alterations could be reset to youthful levels in humans and, in doing so, reverse some aspects of aging, particularly improving the repair and rejuvenation of tissues and organs. There are a number of potential ways we might achieve this; today, we are going to focus on resetting the epigenetic age of cells using the signal molecules in our blood.
The internet of the body
Like the internet, the bloodstream is an information superhighway; it transmits signals between cells across huge distances, allowing remote parts of the body to communicate and regulate their activities. This network of blood vessels delivers nutrients, oxygen, and various kinds of cellular signals around the body to cells, so it is highly likely that it is a principal regulator of aging on a systemic level.
Researchers such as Dr. Dongsheng Cai have long proposed that certain elements of aging are controlled by the hypothalamus, a small area of the brain located at the base of the brain near the pituitary gland. While it’s very small, the hypothalamus plays a crucial role in many important functions, including releasing hormones and regulating body temperature. Dr. Cai and his team have discovered evidence that specialized stem cells living in the hypothalamus regulate systemic aging via secreted miRNAs [1].
As we age, these specialized cells die off and the hypothalamus becomes increasingly dysfunctional and unable to properly control the various functions it once did, in this manner, stem cell exhaustion in the hypothalamus seems to accelerate aging. This then leads to it secreting signals that are either not enough or too much, depending on the type. This then contributes to the shift in the environment of the bloodstream, as do other sources of harmful signaling, such as senescent cell secretions, changing it to a pro-aging rather than pro-youthful environment.
As we get older, there is typically a build-up of pro-inflammatory signals known as cytokines, which in low levels are helpful in healing and regeneration but when present in excessive amounts harm tissue upkeep and repair by blocking stem cell activity, cause immune cells to become dysfunctional, and contribute to a rise in systemic inflammation levels that support the onset of various age-related diseases. Typical cytokines that increase in concentration in the blood as we age are transforming growth factor beta 1 (TGF-ß1), interleukin 6 (IL6), and tumour necrosis factor alpha (TNFa).
Resetting epigenetic age with blood factors
Drs. Irina and Michael Conboy have long suggested with their research that certain elements of aging and tissue rejuvenation can be spurred by the calibration of signaling molecules in the blood. Indeed, their experiments have shown that youthful tissue function can be restored in aged mice by selectively reducing the level of key cytokines in the blood [2]. Doing so has the result of releasing stem cells, normally blocked from working by inflammatory signals typically present in old age, and allowing them to resume their activity. This return to activity allows the stem cells to begin repairing tissue and creating replacement cells as they do when the host is young.
Other researchers, such as Dr. Amy Wagers, Dr. Tony Wyss-Coray, and Dr. Hanadie Yousef, have also conducted research that strongly supports the idea that the epigenetic element of aging might at least be partially reset to a youthful level by calibrating, removing, or adding various signaling factors in blood.
While there are likely hundreds of factors in blood that may play a role in aging, the evidence is increasingly supporting the idea that a handful of key factors sit at the top of the process and regulate the hundreds of factors below. In other words, targeting these key factors may reverse epigenetic aging and restore youthful tissue function in aged individuals.
The results from a new study in rats suggest once again that the rejuvenation of aged organs and tissues is possible by resetting the epigenetic state of old cells back to a more youthful one using blood factors. It should be noted at this point that the results have been published as a preprint on bioRxiv, a site on which authors are able to make their research immediately available to the scientific community and receive feedback from their colleagues before they are submitted to journals for peer review and publication. With that caveat out of the way, let’s take a look at the data.
The researchers delivered Elixir, an undisclosed mixture of plasma fractions presumably isolated from young rat plasma, to aged rats. They state that their technique is based on heterochronic parabiosis but forgoes the need to physically join an old and young animal together so that they share circulatory systems.
The researchers claim that their results are averaged based on measurements taken using multiple epigenetic clocks.
Crucially, plasma treatment of the old rats reduced the epigenetic ages of blood, liver and heart by a very large and significant margin, to levels that are comparable with the young rats. According to the six epigenetic clocks, the plasma fraction treatment rejuvenated liver by 73.4%, blood by 52%, heart by 52%, and hypothalamus by 11%. The rejuvenation effects are even more pronounced if we use the final versions of our epigenetic clocks: liver 75%, blood 66%, heart 57%, hypothalamus 19%. According to the final version of the epigenetic clocks, the average rejuvenation across four tissues was 54.2%.
If these results are correct, then the epigenetic age of these rats has essentially been halved and returned to a level seen in young rats. On top of these epigenetic clock measurements, a number of other aging biomarkers saw improvement:
- Pro-inflammatory cytokines IL-6 and TNFa were reset to a lower, more youthful, level
- Blood triglycerides were reduced to a youthful level
- HDL cholesterol were increased to a youthful level
- Blood glucose levels dropped to more youthful levels
- Cognition became more youthful according to tests in a Barnes Maze
- Glutathione (GSH), superoxide dismutase (SOD), and some other antioxidant levels were reset to more youthful levels
Unanswered questions
These impressive results were apparently achieved with just four injections; however, it remains to be seen if these changes are persistent and for how long.
Given that there are many feedback loops in the system; it could be the case that once reset, the changes will persist for considerable time; after all, it takes decades for your system to break down and reach the point where aging becomes apparent.
There is also the question with blood factor-based rejuvenation experiments as to if it is what you put into aged blood or what you take out that is key to rejuvenation.
The Conboys have, in the past, suggested that reducing the excessive levels of proinflammatory cytokines in aged blood is likely more critical than adding anything found in young blood. In other words, it’s more about calibration of aged blood and the cytokines therein rather than there being any “special sauce” in young blood that spurs rejuvenation.
Of course, if could just as easily be both, and the past results of the Conboys, which showed that reduced levels of TGF-ß1 resulted in tissue rejuvenation, support this notion. Equally, there have been other experiments by researchers such as Dr. Amy Wagers and Dr. Tony Wyss-Coray in which factors found in young blood were added to aged blood and nothing was removed, which also spurred some level of rejuvenation.
In this particular experiment, the researchers only added replacement young blood plasma factors without removing anything, which suggests that what they did was enough to have a significant effect. It does appear in this case that whatever was added was able to encourage some level of rejuvenation in the context of epigenetic age. This could be more effective than the calibration and removal of harmful cytokines via filtering as proposed by the Conboys.
It could be that adding enough key factors is enough to spur rejuvenation without the need to carefully calibrate factors in aged blood. That remains to be seen, and at this early stage, it is too soon to say if what you take out is more important than what you put in or even if doing both will produce an even better result.
Conclusion
What needs to happen next is a lifespan study to see if resetting epigenetic age in this manner leads to an increase in healthy lifespan in rats. Also, this experiment used a small number of rats, so a greater number of rats used in such a follow-up lifespan study would be ideal. It would also be interesting to see if these results can be replicated in mice as a step towards moving this to human trials.
Taken as a whole, these results and similarly focused studies further support that methylation patterns in nuclear DNA are not merely the hands of a clock indicating cellular age but are also the workings of that clock. This is further evidence that epigenetic aging is one of the primary reasons we age and that its reversal could have big ramifications for human aging and healthy longevity if successfully translated.
Literature
[1] Zhang, Y., Kim, M. S., Jia, B., Yan, J., Zuniga-Hertz, J. P., Han, C., & Cai, D. (2017). Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature, 548(7665), 52-57.
[2] Yousef, H., Conboy, M. J., Morgenthaler, A., Schlesinger, C., Bugaj, L., Paliwal, P., … & Schaffer, D. (2015). Systemic attenuation of the TGF-ß pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget, 6(14), 11959.
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This seems quite promising. Thanks for summarizing the study. Your conclusions are thoughtful. I wonder if the researchers have any conflicts of interests. I believe some have started companies who seek to offer treatments of blood factors. I also wonder if Peer Review will reveal other weaknesses in the study. Promising nonetheless. Looking forward to many more studies on this, including human clinical trials!
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When I read Friday’s paper I felt that “this makes sense.” I had interviewed the Conboys for my new aging film and came away feeling they were onto something. This feels like a parallel or next step. I’m aware of Aubrey and Reason’s theory of damage being the cause. My guess is that there is more than one road to Rome.
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Konrad Kleinknecht
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Konrad Kleinknecht (* 23. April 1940 in Ravensburg) ist ein deutscher Physiker.
Inhaltsverzeichnis
Leben und Werk[Bearbeiten | Quelltext bearbeiten]
Kleinknecht studierte von 1958 bis 1963 Physik an den Universitäten München und Heidelberg. 1966 wurde er in Heidelberg zum Dr. rer. nat. promoviert. Anschließend war er bis 1969 wissenschaftlicher Angestellter am CERN in Genf, dann bis 1972 wissenschaftlicher Assistent an der Universität Heidelberg, wo er sich 1971 habilitierte. 1972 wurde er auf einen Lehrstuhl an der Universität Dortmund berufen, wo er die Fachrichtung Teilchenphysik aufbaute und Dekan, Prodekan sowie Institutsleiter wurde. 1985 wechselte er an die Universität Mainz. Von 1989 bis 1992 war er Vorsitzender des Fachverbandes Teilchenphysik der Deutschen Physikalischen Gesellschaft (DPG) und 1997 bis 1999 Vorstandsmitglied der DPG. Von 2000 bis 2008 beriet er den Vorstand der DPG als Beauftragter für den Klimaschutz.
Kleinknecht arbeitet auf dem Gebiet der experimentellen Elementarteilchenphysik, besonders zur Schwachen Wechselwirkung, zur Neutrinophysik und zur Verletzung der Materie-Antimaterie-Symmetrie. Durch Entwicklungen auf dem Gebiet der Teilchendetektoren gelangen ihm Präzisionsexperimente, insbesondere zur Verletzung der CP-Symmetrie im System neutraler Kaonen. 1988 konnte die NA31 Kollaboration am CERN, deren Mitglied er war, unter Leitung von Heinrich Wahl erste Anzeichen für direkte CP-Verletzung bei Kaonen liefern.[1]
Seit Ende 2012 ist Kleinknecht Gründungsvorsitzender der Heisenberg-Gesellschaft.[2]
Auszeichnungen[Bearbeiten | Quelltext bearbeiten]
- 1984 Neutrino-Medaille der Eötvös-Society (Ungarische physikalische Gesellschaft)
- 1990 Gottfried-Wilhelm-Leibniz-Preis (Deutsche Forschungsgemeinschaft)
- 2001 Gentner-Kastler-Preis (Société française de physique und Deutsche Physikalische Gesellschaft)
- 2005 High Energy and Particle Physics prize (European Physical Society) als Mitglied der NA31 Kollaboration*
- 2008 Stern-Gerlach-Medaille (Deutsche Physikalische Gesellschaft)
* Zur Hälfte an Heinrich Wahl, zur anderen Hälfte an NA31[3]
Veröffentlichungen[Bearbeiten | Quelltext bearbeiten]
Kleinknecht publizierte mehr als 500 wissenschaftliche Arbeiten und teilweise Sachbücher, darunter
- Interferenz zwischen den {\displaystyle \pi ^{+}\pi ^{-}}-Zerfällen der KS und KL-Mesonen und die KS-KL-Massendifferenz. Dissertation, Heidelberg 1966
- Detektoren für Teilchenstrahlung. Teubner Verlag, Stuttgart 1984, ISBN 978-3-519-03058-4, 4. Auflage: Teubner, Wiesbaden 2005, ISBN 3-8351-0058-0
- Detectors for Particle Radiation. Cambridge University Press, Cambridge 1998, 2nd edition
- K. Kleinknecht und T. D. Lee (Hrsg.): Particles and Detectors. Festschrift für Jack Steinberger. Springer, Berlin [u. a.] 1986 (= Springer tracts in modern physics, Band 108), ISBN 3-540-16265-8.
- Uncovering CP Violation. Experimental Clarification in the Neutral K Meson and B Meson Systems. Springer, Berlin [u. a.] 2003 (= Springer Tracts in Modern Physics, Band 195), ISBN 978-3-540-40333-3.
- Wer im Treibhaus sitzt. Piper Verlag München, 2007, ISBN 978-3-492-05011-1
- Quanten, Herausgeber Konrad Kleinknecht, Schriften der Heisenberg-Gesellschaft, Hirzel Verlag Stuttgart, Erstausgabe 2013, Folgebände in den nachfolgenden Jahren ebenfalls im Hirzel Verlag.
- Risiko Energiewende : Wege aus der Sackgasse, Springer Spektrum Verlag, 2015, ISBN 978-3-662-46887-6.
- Einstein und Heisenberg, Begründer der modernen Physik, Kohlhammer Verlag Stuttgart 2017
- Einstein and Heisenberg, The Controversy over Quantum Physics, Springer Nature Publ., 2019, ISBN 978-3-030-05264-5
- Werner Heisenberg – Ordnung der Wirklichkeit, Herausgeber Konrad Kleinknecht, Springer Spektrum Verlag, 2019, ISBN 978-3-662-59529-9
- Werner Heisenberg – Reality and its Order, Konrad Kleinknecht (ed.), Springer Nature Publ., 2019, ISBN 978-3-030-25696-8
- Einstein et Heisenberg, la controverse quantique, 2020
Einzelnachweise[Bearbeiten | Quelltext bearbeiten]
- ↑ NA31 Collaboration: First Evidence for Direct CP Violation. In: Physical Letters B. Band 206, 1988, S. 169.
- ↑ Die Gründung des Vereins. Heisenberg-Gesellschaft e.V., abgerufen am 21. März 2016.
- ↑ Prizes reward high-energy physics. physicsworld, abgerufen am 4. Mai 2019.
Literatur[Bearbeiten | Quelltext bearbeiten]
- Kürschners Deutscher Gelehrten-Kalender. 2007, S. 1793f., ISBN 3-598-23616-6
Weblinks[Bearbeiten | Quelltext bearbeiten]
- Prof. Dr. Konrad Kleinknecht auf uni-mainz.de
- Literatur von und über Konrad Kleinknecht im Katalog der Deutschen Nationalbibliothek
- Arbeiten von Konrad Kleinknecht auf SPIRES
Normdaten (Person): GND: 12847906X | LCCN: n84182940 | VIAF: 93522384 | Wikipedia-PersonensucheKategorien:
- Physiker (20. Jahrhundert)
- Physiker (21. Jahrhundert)
- Hochschullehrer (Technische Universität Dortmund)
- Hochschullehrer (Johannes Gutenberg-Universität Mainz)
- Gentner-Kastler-Preisträger
- Leibnizpreisträger
- Deutscher
- Geboren 1940
- Mann
- Person (CERN)
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Einstein and Heisenberg: The Controversy over Quantum Physics
21 March 2020
Einstein and Heisenberg: The Controversy over Quantum Physics, by Konrad Kleinknecht, Springer
This attractive and exciting book gives easy access to the history of the two main pillars of modern physics of the first half of the 20th century: the theory of relativity and quantum mechanics. The history unfolds along the parallel biographies of the two giants in these fields, Albert Einstein and Werner Heisenberg. It is a fascinating read for everybody interested in the science and culture of their time.
At first sight, one could think that the author presents a twin biography of Einstein and Heisenberg, and that’s all. However, one quickly realises that there is much more to this concise and richly illustrated text. Einstein and Heisenberg’s lives are embedded in the context of their time, with emphasis given to explaining the importance and nature of their interactions with the physicists of rank and name around them. The author cites many examples from letters and documents for both within their respective environments, which are most interesting to read, and illustrate well the spirit of the time. Direct interactions between both heroes of the book were quite sparse though.
At several stages throughout the book, the reader will become familiar with the personal life stories of both protagonists, who were, in spite of some commonalities, very different from each other. Common to both, for instance, was their devotion to music and their early interest and outstanding talent in physics as boys at schools in Munich, but on the contrary they were very different in their relations with family and partners, as the author discusses in a lively way. Many of these aspects are well known, but there are also new facets presented. I liked the way this is done, and, in particular, the author does not shy away from also documenting the perhaps less commendable human aspects, but without judgement, leaving the reader to come to their own conclusion.
Topics covering a broad spectrum are commented on in a special chapter called “Social Affinities”. These include religion, music, the importance of family, and, in the case of Einstein, his relation to his wives and women in general, the way he dealt with his immense public reputation as a super scientist, and also his later years when he could be seen as “scientifically an outsider”. In Heisenberg’s case, one is reminded of his very major contributions to the restoration of scientific research in West Germany and Europe after World War II, not least of course in his crucial founding role in the establishment of CERN.
Do not expect a systematic, comprehensive introduction to relativity and quantum physics; this is not a textbook. Its great value is the captivating way the author illustrates how these great minds formed their respective theories in relation to the physics and academic world of their time. The reader learns not only about Einstein and Heisenberg, but also about many of their contemporary colleagues. A central part in this is the controversy about the interpretation of quantum mechanics among Heisenberg’s colleagues and mentors, such as Schrödinger, Bohr, Pauli, Born and Dirac, to name just a few.
Another aspect of overriding importance for the history of that time was of course the political environment spanning the time from before World War I to after World War II. Both life trajectories were influenced in a major way by these external political and societal factors. The author gives an impressive account of all these aspects, and sheds light on how the pair dealt with these terrible constraints, including their attitudes and roles in the development of nuclear weapons.
A special feature of the book, which will make it interesting to everybody, is the inclusion of various hints as to where relativity and quantum mechanics play a direct role in our daily lives today, as well as in topical contemporary research, such as the recently opened field of gravitational-wave astronomy.
This is an ambitious book, which tells the story of the birth of modern physics in a well-documented and well-illustrated way. The author has managed brilliantly to do this in a serious, but nevertheless entertaining, way, which will make the book a pleasant read for all.
Peter Jenni Albert Ludwig University of Freiburg and CERN
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