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<h1>Adaptive substance, creative regeneration: Mainstream science, repression, and creativity</h1>
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<a href="/"><img class="epic" src="/icons/chads/chad.png"></a>
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<p class="nav"><span class="nav-left">Listed under <a href="/ray-peat.html">Ray Peat</a>.</span><span class="nav-right"><a href="/theme.html">Theme</a></span></p>
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<p>From the <a href="https://raypeat.com/articles/articles/adaptive-substance.shtml" target="_blank">original article</a> in 2008. Author: <a href="https://raypeat.com/" target="_blank">Ray Peat</a>.</p>
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<blockquote>
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<strong><q>I
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intend to show you how neo-Darwinism has been invalidated within science
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itself, as an explanation of how life on earth has evolved and is evolving.
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It is nevertheless still perpetrated by the academic establishment,
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if only because it serves so well to promote genetic engineering, a
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technology that has the potential to destroy all life on earth. Furthermore,
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neo-Darwinism reinforces a worldview that undermines all moral values
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and prevents us from the necessary shift to holistic, ecological sciences
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that can truly regenerate the earth and revitalize the human spirit.</q></strong><br>
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Mae-Wan Ho
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<a href="http://www.i-sis.org.uk/paris.php" target="_blank">http://www.i-sis.org.uk/paris.php</a>
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</blockquote>
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<p>More
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than 50 years have been wasted in one of the most important and fundamental
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branches of science and medicine, for reasons that are highly ideological
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and political. Rather than studying the regeneration of organs and tissues,
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and recognizing its obvious importance in healing as well as in understanding
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the nature of life, much of the last century was devoted to the defamation
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of the researchers who were making real process in the field. Despite
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many demonstrations that regeneration can occur in adult mammals, students
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were taught that it happens only in lower vertebrates. I think it's
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important to look closely at the ideology responsible for this great
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loss.</p>
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<p>Warburg
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and Szent-Gyorgyi, in thinking about cancer, emphasized that growth
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is the primordial function of all cells, and that the differentiated
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functions of complex organisms involve restraints of that primitive
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function, imposed by a system that has developed through time. </p>
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<p>Seen
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with this orientation, regeneration is the spontaneous result of the
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disappearance of restraint. The reproduction of a whole plant from a
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twig, or clone, was a process known for thousands of years. Any part
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of the plant contains the information needed for making a whole plant.
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More than thirty years ago, cells from a tumor were added to the cells
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of a normal embryo, and the animal that matured from the embryo-tumor
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mix was normal, and had traits of both lineages, showing that the tumor
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cells had retained the genetic information of a complete healthy organism,
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and just needed a different environment in which to realize their full
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potential. </p>
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<p>One
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of the currents of medical thinking, from classical times through Paracelsus
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to homeopathy and naturopathy, has been a confidence in the capacity
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of the organism to heal itself. But "modern" medicine has
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arrogated to itself the "healing power," with terrible results,
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mitigated only by their occasional reluctant acceptance of fragments
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of sane organismic thinking, such as recognizing the importance of nutrition,
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or of keeping sewage out of the drinking water. Research into methods
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to support the organism's natural restorative powers has been ridiculed
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and suppressed.</p>
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<p>We
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are immersed in the propaganda of modern medicine, and part of that
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propaganda involves the confabulation of a history of science that supports
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their practice and their ideology. The real history of science won't
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be found in science textbooks.</p>
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<p>"I intend
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to show you how neo-Darwinism has been invalidated within science itself,
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as an explanation of how life on earth has evolved and is evolving.
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It is nevertheless still perpetrated by the academic establishment,
|
|
if only because it serves so well to promote genetic engineering, a
|
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technology that has the potential to destroy all life on earth. Furthermore,
|
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neo-Darwinism reinforces a worldview that undermines all moral values
|
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and prevents us from the necessary shift to holistic, ecological sciences
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that can truly regenerate the earth and revitalize the human spirit."
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Mae-Wan Ho
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<a href="http://www.i-sis.org.uk/paris.php" target="_blank">http://www.i-sis.org.uk/paris.php</a></p>
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<p>Mainstream
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medical treatments are based on some fundamentally absurd scientific
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ideas. The advent of experimental animal cloning and the industrialization
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of genetic engineering have undercut the most important biological doctrines
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of the 20th century, but the processes of critical thinking haven't
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made headway against most of the traditional medical stereotypes. Cloning
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shows that all cells are potential "stem cells," but this
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fact co-exists with the Hayflick doctrine, that says, essentially, that
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no cell is a stem cell.</p>
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<p>The
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ideology of culturally significant "intellectuals"--scientists,
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professors, neurobiologists, linguists, philosophers, oncologists, geneticists--in
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the US is deeply influenced by the dualism and mechanistic materialism
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of Rene DesCartes.</p>
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<p>The
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denial that animals can think or understand language, the claim that
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babies or animals don't feel pain, or that heart cells and brain cells
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can't divide, or that somatic cells lack the genetic capacity to be
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cloned, or that they are intrinsically mortal, limited to a maximum
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of 50 cell divisions--these absurdities of 20th century biology and
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medicine all resulted from an abject commitment to the mechanistic doctrine
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of matter and life promoted or invented by DesCartes.</p>
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<p>I
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doubt that DesCartes really invented anything, because, by the evidence
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of his writing, he wasn't an intelligent man, but he placed himself
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politically in such a way that his arguments were acceptable to many
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influential people, and they continue to be acceptable to authoritarian
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and elitist factions even today.</p>
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<p>In
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the 16th and 17th century the cultures of England, Holland, and France
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were increasingly dominated by business interests. People who had money
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to invest wanted to see the world as an orderly, predictable place,
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and they found that many of the ideas of the ancient Greeks were useful.
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Mathematics was needed to calculate interest rates, insurance premiums,
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and, for the military, the trajectories of missiles. In an orderly world,
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allowance for a little random variation helped to save the perfection
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of the general rule.</p>
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<p>In
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this environment, theological thinking began retrenching its doctrine,
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to make it more acceptable to the increasingly powerful commercial people.
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The clockwork universe of DesCartes' time, in which a perfect world
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that operated according to perfect natural laws had been divinely created,
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gradually became theologically acceptable during the 18th and 19th centuries.
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In the 18th century, the Deists were the most famous embodiment of the
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idea, and then in the 19th century their place was taken by the Catastrophists,
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who claimed that the fossils which seemed to show evolutionary change
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of species actually represented species that had been created along
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with those now existing, but that had been destroyed by catastrophes,
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such as Noah's flood. By the end of the 19th century, the president
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of an American university recognized that theological compromises could
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prevent his undergraduates from rejecting religion entirely, and forbade
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sermons against evolution.</p>
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<p>There
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were many biologists who insisted that evolution of new species was
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analogous to the development of an individual, and that both revealed
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an adaptive capacity of the living substance. In this view, the adaptive
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growth of an individual in a new environment revealed novel solutions
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to new problems, and showed an innate inventiveness and intelligence
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in the process of growth and adaptation. The appearance of new species
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was thought to represent the same sorts of adaptive processes.</p>
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<p>Erasmus
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Darwin (grandfather of Charles) was an evolutionist of this sort, but
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because of political and theological pressure, he kept relatively quiet
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about his beliefs. There was an underground culture, in which an evolutionary
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view of the world was accepted, but these views were seldom published,
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because of increasingly stringent censorship. Because of censorship,
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poetry, letters, and diaries, rather than academic and scholarly works,
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give us the true picture of 18th century and early 19th century scientific
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culture.</p>
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<p>The
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scientists who wanted their work to be acceptable to those in power
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found ways to work with the Cartesian mechanical view of the world,
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building on the Deists' compromise, which had succeeded in removing
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the supernatural from nature. As the fossil evidence of evolution became
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inescapable, around the time of Charles Darwin's work, those who wanted
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to bring evolution into the mainstream of culture found that the Catastrophism
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of the creationists could be adapted to their purposes, with only slight
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modification. </p>
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<p>The
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doctrine of Thomas Malthus, who argued that war, famine, and disease
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were beneficial for those who survived, by decreasing the competition
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for limited resources, became a near equivalent to the catastrophic
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floods that the creationists had invoked to explain the geological record
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that contained evidence of many extinct animals. <strong>The doctrine of
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Malthus, like that of the Catastrophists, made loss, deletion, and destruction
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into a central device for explaining the history of the world.</strong></p>
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<p>Both
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of the Darwins had accepted the idea that many biological changes were
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adaptive, rather than random, but the new practical compromise doctrine
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introduced the idea that changes were just "random variations."
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The essentially mechanical nature of the world was preserved, because
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"chance" occurrences could be dealt with, and didn't involve
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anything supernatural. <strong>The function of the environment wasn't to
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add anything to life (that would have been to assert that there were
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creative powers other than those of the Creator), but simply to eliminate
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the inferior individuals that appeared as the result of random changes.</strong></p>
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<p>Gregor
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Mendel applied the principle of chance to explaining the inheritance
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of certain traits, and showed that "traits" were passed on
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unchanged, even when they weren't visible. His ideas were published
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and were acceptable to the scientific mainstream of his time. Traits
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were determined by "factors" that were passed on, unchanged,
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from parents, and biological variation was explained by varied mixing
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of factors which in themselves were unaffected by the organism or the
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environment. Genetic determinism was safely compatible with creationism. </p>
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<p>Shortly
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after Mendel's death, August Weismann began a campaign to put a stop
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to the claims of those who, like the Darwins and Lamarck, saw adaptive
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development of organisms as an essential part of the evolution of species.</p>
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<p>Weismann
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was essentially a propagandist, and his first fame was the result of
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"disproving" Lamarck by cutting the tails off more than 1500
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mice, and observing that their offspring were born with tails. The reason
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the inheritance of acquired traits was impossible, he said, was that
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the "germ line" was perfectly isolated from the rest of the
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organism. The differentiated tissues of the body were produced by the
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selective loss of information from the nuclei of cells in the embryo.
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The cells of the germ line were immortal and contained all the information
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needed to produce an organism, but no other cell of the organism was
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complete. </p>
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<p>Complexity
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was produced by deletion, and this was the basis for arguing that, if
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even the development of an individual was nothing but a passive unfolding
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of inherited properties, much like unpacking a trunkful of clothes,
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then there could be no adaptively acquired traits, and certainly no
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inheritance of something which didn't exist. Changes in an individual
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were simply accidents, such as having a tail amputated, and so the whole
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issue of the origin of complexity was safely left to a primordial creation. </p>
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<p>Weismann
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and his arguments were famous in Europe and the US, and formed the background
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for the ideas known as neo-Darwinism. His "isolation of the germ
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line" was the earliest version of the Central Dogma of molecular
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biology, namely, that information flows only from DNA to RNA to protein.
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His doctrine, of complexification through deletion, is the epitome of
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the greatest dogma of modern times, expressed in doctrines from Catastrophism
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through the second law of thermodynamics and the theory of the Big Bang,
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down to Hayflick's Doctrine of the mortality of somatic cells. All these
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are consequences of the Cartesian and Deistic separation of intelligence
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from matter.</p>
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<p>Regeneration
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is one of the most vivid examples of the intelligence of living substance.</p>
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<p>Given
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a natural tendency of cells to multiply, the interesting thing about
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regenerative healing is the question of why the new growth of tissue
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sometimes differentiates to fit appropriately into its surroundings,
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but sometimes fails to differentiate, becoming a tumor.</p>
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<p>With
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aging, the regenerative process declines, and the process of tissue
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rebuilding slows. Against a background of reduced regenerative ability,
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tissue growth sometimes produces tumors, rather than renewed healthy
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tissue. When tumors are grafted onto the amputated tail stump of
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a salamander, which has good regenerative ability, the tumor is transformed
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into a tail, by its envirornment, or morphogenic field. The "cancer
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problem" is essentially the problem of understanding the organizing
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forces of the organism. The aging problem is another aspect of the same
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problem.</p>
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<p>Traditionally,
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biologists had studied anatomy, physiology, embryology or development,
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and taxonomy or the classification of organisms. The growth of knowedge
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early in the 20th century was suddenly seeming to confirm the physiological,
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adaptive view of organisms that Lamarck had held. C.M. Child, Joseph
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Needham, Alexander Gurwitsch, and L.V. Polezhaev were demonstrating
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the primacy of a formative process in biology. Polezhaev and Vladimir
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Filatov were studying practical means of stimulating regeneration as
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a medical technique. </p>
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<p>Until
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the beginning of the second world war, the study of regeneration and
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the pattern-forming processes in embryology were the liveliest parts
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of biological research. Gestalt psychology was being developed at the
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same time, with a similar emphasis on patterns and wholes.</p>
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<p>But
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Weismannism and neo-Darwinism, largely embodied in the person of the
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geneticist T.H. Morgan, deliberately set out to kill that line of biological
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research. Gestalt psychology was similarly eliminated by the Behaviorists.</p>
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<p>One
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of Morgan's closest associates, his student and colleague A.H. Sturtevant,
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said that "Morgan's objectives, what he was trying to get at in
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general in his biological work was to produce mechanistic interpretations
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of biological phenomena. One of the things that irritated him most was
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any suggestion of purpose in biological interpretation. He always had
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some reservations about the idea of natural selection, because it seemed
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to him to open the door to interpretations of biological phenomena in
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terms of purpose. He could be talked into the conclusion that there
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was nothing that wasn't strictly mechanistic about this interpretation,
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but he never liked it. And you had to talk him into it again every few
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months." (Sturtevant, A. H., <em>Genetics, Vol. 159,</em> 1-5, September
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2001, Copyright 2001, Reminiscences of T. H. Morgan.)</p>
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<p>Whatever
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his motives, Morgan was known to have prevented his students (including
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C.M. Child) from publishing work that supported a holistic view of the
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organism. After Morgan's death, there was an intense and widespread
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campaign to suppress any approach to biology other than the "new
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synthesis," neo-Darwinism, with its doctrine of mechanistic genetic
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determinism and its doctrine of random variation. A developmental biologist,
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J.M. Opitz (1985), commented that <strong>"in one of the most astounding
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developments in Western scientific history, the gradient-field, or epimorphic
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field concept, as embodied in normal ontogeny and as studied by experimental
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embryologists, seems to have simply vanished from the intellectual patrimony
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of Western biologists."</strong><strong> </strong></p>
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<p>Formative
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processes are necessarily multidimensional, and that makes calculation
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and analysis very complex. To a great extent, the geneticists were motivated
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to study bacterial genes, rather than vertebrate embryos, by the principle
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that motivated the drunk to look for his car keys under the street lamp,
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even though that wasn't where he lost them, because the light made it
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easier to look there. </p>
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<p>Bacteria
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are easy to study because they lack the complexity that makes it hard
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to study an embryo or an animal. The language used in genetics textbooks
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shows not only that bacteria are treated by geneticists as if they were
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one or two dimensional, but that the concepts developed for bacterial
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genetics have been extrapolated to use in describing complex organisms:
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"<strong>Genes interact</strong> to establish the body axis in Drosophila.
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Homeotic <strong>Genes control</strong> pattern formation along the anterior-posterior
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body axis." (<em>Essentials of Genetics,</em> M. Cummings and W.
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Klug, Prentice Hall, 2004.)</p>
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<p>One
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of the basic distinctions in embryology is in the way the cells divide
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after the egg is fertilized. Oysters and earthworms have spiral cleavage,
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sea urchins and people have radial cleavage. Several decades ago an
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experimenter was transferring a nucleus from an egg of an animal with
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radial cleavage, I think a sea urchin, into the enucleated egg of a
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snail, with spiral cleavage. The nucleus transplanted across such a
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great difference in phyla didn't sustain maturation of the animal, but
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it did permit development to proceed for several rounds of cell division,
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and the pattern of cell division, or cleavage, and embryonic development
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always followed the pattern of the phylum to which the egg cytoplasm
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belonged, never the pattern of the phylum from which the nucleus was
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derived. The genes in the nucleus, obviously, weren't directing the
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basic pattern formation of the embryo.</p>
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<p>One-dimensional
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bacterial genetics can be used to "explain" multidimensional
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systems, but it can't be expected to make useful predictions. </p>
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<p>The
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idea of complexity, or of multidimensionality, has often been analyzed
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in terms of "fields," by analogy with a magnetic field, as
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some property, or properties, that extend beyond any individual part,
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giving some coherence to the parts. Lamarck was concerned with understanding
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ensembles of particles and cells, but in his time electricity and heat
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were the only principles that physics provided that helped to illuminate
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the nature of living organisms. At the end of the 19th century, though,
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the physicist J.C. Bose was noticing that all of the properties of life
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that had interested Lamarck and Buffon--irritability, sensation, contraction,
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memory, etc.--had their close analogs in non-living substances. Bose,
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who invented the radio detector that was the core of Marconi's apparatus,
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found that, in the presence of an electromagnetic field, particles of
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a substance, such as finely powdered metal filings, cohered into a unified
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whole. An otherwise invisible, undetectable "field" which
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in Lamarck's time might have been known as one of the "subtle fluids,"
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was able to organize a myriad of inert particles into a unified whole.</p>
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<p>In
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the early 1920s, Bungenberg de Jong and A.I. Oparin showed how solutions
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of organic substances could spontaneously organize themselves into complex
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systems, with differentiated parts. A Russian embryologist, Alexander
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Gurwitsch, found that the parts of an organ or embryo could exert their
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stimulating or organizing influence on other cells even through a piece
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of glass, and by using different types of filter, he identified ultraweak
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ultraviolet rays as a medium of communication between cells. F.-A. Popp
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and others are currently studying the integrating functions of ultraweak
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light signals. Guenter Albrecht-Buehler (who has an interesting website
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called Cell Intelligence) is investigating the role of pulsed infrared
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signals in cell communication.</p>
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<p>Electrical
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fields produced by cells, tissues, and organisms have been shown to
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influence cellular metabolism and physiology, and to influence growth
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patterns. Closely associated with cellular electrical fields are fields
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or gradients of pH and osmolarity, and all of these fields are known
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to affect the activity of enzymes, and so to create environments or
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fields of particular chemical concentrations.</p>
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<p>A
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phenomenon that was well known in the 1930s, when developmental fields
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were still a familiar part of scientific discussion, was the "cancer
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field." Before a cancer developed in a particular area, the area
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showed progessive changes, away from normal function and structure,
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toward the cancer physiology.</p>
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<p>In
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the embryonic state, damaged tissues regenerate quickly. The metabolism
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of an embryo or fetus is highly oxidative, converting glucose rapidly
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to carbon dioxide and water. Both carbon dioxide and water are important
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regulators of cellular metabolism and function, and the concentrations
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of both of them decrease systematically with maturity and aging. Both
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are involved with the most basic aspects of cellular sensitivity, responsiveness,
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and organization.</p>
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<p>To
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resume the scientific tradition that has "simply vanished,"
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I think we have to recover our ability to think about organisms generally,
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leaving aside as many of the concepts of genetics as possible (such
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as "gene," "operon," "receptor"; "the
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gene" has never been more than an ideological artifact), because
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they so often falsify the most important issues. The organization of
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tissues and organs, and their functional properties, should be the focus
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of attention, as they were for Lamarck around 1800, and for Johanes
|
|
Muller, who in 1840 saw cancer as a problem on the level of tissue,
|
|
rather than cells. For Lamarck, sensitivity and movement were the essential
|
|
properties of the living substance, and J. C. Bose showed reasons for
|
|
believing that the characteristics of life were built on related properties
|
|
of matter itself.</p>
|
|
<p>Sensitivity,
|
|
the ability to respond appropriately to the environment, is probably
|
|
a missing factor in the development of a tumor. The ability to become
|
|
quiescent, to quietly participate in the ensemble of cells, is an essential
|
|
feature of the sensitivity and responsiveness of the cells of complex
|
|
organisms. The factors that support organized appropriate functioning
|
|
are the factors that help cells to inhibit the excitatory state. If
|
|
the keys of an accordion or organ didn't spring back after the musician
|
|
pressed them, the instrument would be unplayable. In extreme physiological
|
|
states, such as epilepsy or malignant hyperthermia, nerves or muscles
|
|
become incapable of relaxing. Insomnia and muscle cramps are milder
|
|
degrees of a defective relaxation process. Excitoxicity and inflammation
|
|
describe less generalized cases of a similar process, in which there
|
|
is an imbalance between excitation and the restorative ability to stop
|
|
the excitation. Prolonged excitation, resulting in excessive fatigue,
|
|
can cause a cell to disintegrate, in the process of cell death called
|
|
apoptosis, "falling away." </p>
|
|
<p>In
|
|
the experiments of Polezhaev and Filatov, the products of cell disintegration
|
|
were found to stimulate the birth of new cells (possibly by blocking
|
|
a signal that restrains cell division). This process has been found
|
|
in every organ that has been examined appropriately. It amounts to a
|
|
"streaming regeneration" of the organism, analogous to the
|
|
progressive creation of Lamarck's view. G. Zajicek has demonstrated
|
|
an orderly "streaming" renewal in several organs, and even
|
|
the oocytes (which in the Weismannian dogma were formed at a very early
|
|
stage during embryonic development, and were perfectly isolated from
|
|
the cells of the mature body) have recently been shown to be continually
|
|
regenerated in adult ovaries. </p>
|
|
<p>"Stem"
|
|
cells turn out to be ubiquitous, and the failure of regeneration and
|
|
restoration seems to be situational. In the 1950s a magazine article
|
|
described the regeneration of a finger-tip when the wound was kept enclosed.
|
|
Decades later, friends (one a child, the other a man in his forties)
|
|
had accidental amputations of a finger-tip, down to the cuticle so that
|
|
no visible nail remained. The boy's mother fitted his finger with the
|
|
tube from a ballpoint pen, and the man used an aluminum cigar tube as
|
|
his "bandage." Within a few weeks, their fingers had regenerated
|
|
to their normal shape and length. I think the closed environment allows
|
|
the healing tissues to be exposed to a high concentration of carbon
|
|
dioxide, in equilibrium with the carbon dioxide in the capillaries,
|
|
and to a humid atmosphere, regulated by the osmotic or vapor pressure
|
|
of the living tissues.</p>
|
|
<p>Under
|
|
ordinary conditions, the creation of cells and the dissolution of cells
|
|
should be exactly balanced. The coordination of these processes requires
|
|
a high degree of coherence in the organism.</p>
|
|
<p>Simple
|
|
increase of water in the vicinity of a cell increases its tendency to
|
|
multiply, as well as its excitability, and hypertonicity restrains cell
|
|
division, and reduces excitability. Carbon dioxide, besides helping
|
|
proteins to release water, appears to increase the ability of proteins
|
|
and cells to respond to morphogenetic fields. Carbon dioxide is the
|
|
most universal agent of relaxation, restoration, and preservation of
|
|
the ability of cells to respond to signals. Progesterone is another
|
|
very general agent of restorative inhibition.</p>
|
|
<p>The
|
|
study of regeneration and "stem cells" is helping to illuminate
|
|
the general process of aging, and to provide very practical solutions
|
|
for specific degenerative diseases, as well as providing a context for
|
|
more appropriate treatment of traumatic tissue injury.</p>
|
|
<p>In
|
|
aging, the growth and regenerative processes are slowed. There is some
|
|
evidence that even cell death is slower in old age, at least in some
|
|
tissues. Since animals with the highest metabolic rate live the longest,
|
|
the slowing rate of metabolism during aging probably accounts for those
|
|
changes in the rate of cell renewal. The continually streaming regeneration
|
|
of tissues is part of the adaptive process, and it is probably intensified
|
|
by stress.</p>
|
|
<p>The
|
|
ability to sleep deeply decreases in old age, as a generalized inflammatory,
|
|
excitatory state of stress develops. With progressive weakening of restorative
|
|
cellular relaxation (inhibition), cells become more susceptible to disintegration.
|
|
It's well established that bone loss occurs almost entirely during the
|
|
night, and since the catabolic hormones generally affect soft tissues
|
|
as well as bones, the atrophy of soft tissues ("sarcopenia")
|
|
of aging is also probably a process that occurs mostly during the night.
|
|
Mediators of inflammation are at their highest during the night (Cutolo
|
|
and Masi, 2005). But during the period of growth, the length of bones
|
|
seems to increase mostly during the night (Noonan, et al., 2004). My
|
|
interpretation of this is that the stress of darkness accelerates biological
|
|
processes, whether the process is mainly constructive or mainly destructive. </p>
|
|
<p>The
|
|
effect of light supports efficient oxidative energy production, which
|
|
supports the protective inhibitory processes, by increasing ATP and
|
|
CO2, and decreases the inflammatory mediators that intensify stress.
|
|
If organized cellular luminescence is required for a proper balance,
|
|
then the random luminescence produced by lipid peroxidation (which may
|
|
be more intense at night--Diaz-Munoz, et al., 1985), might be an important
|
|
factor in disrupting the balanced streaming of regeneration. Free radicals,
|
|
whatever their source, absorb a broad spectrum of radiation, and would
|
|
block luminous signals of all frequencies. Isoprene, produced mainly
|
|
at night (Cailleux and Allain, 1989), is another ultraviolet absorber
|
|
that might account for nocturnal regulatory disorders.</p>
|
|
<p>The
|
|
age pigment, lipofuscin, is known to contribute to degenerative diseases,
|
|
but the nature of its toxicity has never been established. Its absorptive
|
|
and fluorescent properties would be very likely to interfere with mitogenetic
|
|
and morphogenetic radiation. Polyunsaturated fats are the main component
|
|
of lipofuscin, and these fats in themselves can absorb ultraviolet light.
|
|
When those fats are present in the skin, exposure to ultraviolet light
|
|
accelerates the aging of the skin. Free fatty acids often increase during
|
|
the night, under the influence of hormones such as adrenaline and growth
|
|
hormone.</p>
|
|
<p>A
|
|
single night of poor sleep probably causes significant anatomical damage
|
|
to the streaming cellular systems that will be repaired over the next
|
|
few days if a high level of energy metabolism can be combined with a
|
|
sufficient amount of deep sleep. The things that optimize energy and
|
|
sleep form the background for supporting the restorative processes.
|
|
Salt, glycine, carbon dioxide, progesterone, thyroid hormone and sugar
|
|
all contribute to preserving the organism's energetic reserves by reducing
|
|
inappropriate excitation. </p>
|
|
<p>Lamarck's
|
|
idea that organs developed or regressed according to their use or disuse
|
|
was often attacked by followers of the Weismann-Morgan genetic dogma.
|
|
In their view, the influence of the environment was limited to either
|
|
preventing or permitting the realization of "the genetic potential."
|
|
Once that predefined potential had been unfolded, the finite and mortal
|
|
nature of the somatic cells didn't allow for any significant changes,
|
|
except for depletion and death. One of the high points of Weismannian
|
|
biology came with the publication of an article in Science, around 1970,
|
|
that proposed to explain learning in terms of the lifelong loss of brain
|
|
cells, beginning in humans around the age of 18 months, with a daily
|
|
loss of 100,000 cells, which would record experience by selective deletion,
|
|
the way punching holes in cards had been used to enter data into computers.
|
|
I was present to witness "world class biologists" taking that
|
|
idea very seriously.</p>
|
|
<p>As
|
|
Sturtevant mentioned in the quotation above, T.H. Morgan couldn't accept
|
|
any attribution of purposefulness to organisms. In his genetic dogma,
|
|
changes were only random, and people who denied that were denounced
|
|
as "teleological" (or metaphysical) thinkers. Changes occurred
|
|
by deletion, not by meaningful addition.</p>
|
|
<p>One
|
|
of Pavlov's students, P.K. Anokhin, developed the concept of the Functional
|
|
System in the 1930s, to explain the purposive behavior of animals. In
|
|
the 1950s, Anokhin integrated the endocrinology of stress and adaptation
|
|
into the concept, and F.Z. Meerson continued the work, concentrating
|
|
on the metabolic and structural changes that protect the heart during
|
|
stress. The simplest view of the conditional reflex involves the adaptation
|
|
of an animal to an external signal, identifying it as the occasion for
|
|
a particular action. Analyzing the Functional System starts with the
|
|
need of the animal, for example for food, and examines the processes
|
|
that are involved in satisfying that need, including nerve cells, a
|
|
sense of hunger, knowledge of what things are edible, the muscles needed
|
|
to get the food, and the digestive apparatus for assimilating it. </p>
|
|
<p>When
|
|
an understanding of stress physiology is combined with the idea of functional
|
|
systems, the adaptive meaning of the use or disuse of certain organs
|
|
is given a concrete basis. Cortisol mobilizes amino acids from muscles
|
|
that are idle, and makes them available for the synthesis of proteins
|
|
in the muscles, nerves, or glands that are activated in adapting to
|
|
the stress. The London taxi drivers whose hippocampus grows as they
|
|
learn the locations of the streets are very good examples of the processes
|
|
described by Meerson, Anokhin, and Lamarck, in which the use of an organ
|
|
in meeting a need contributes to the development of that organ. The
|
|
balance between growth and regression is shifted during adaptive behavior.</p>
|
|
<p>Exercise
|
|
physiologists, without mentioning functional systems, have recently
|
|
discovered some principles that extend the discoveries of Meerson and
|
|
Anokhin. They found that "concentric" contraction, that is,
|
|
causing the muscle to contract against resistance, improves the muscle's
|
|
function, without injuring it. (Walking up a mountain causes concentric
|
|
contractions to dominate in the leg muscles. Walking down the mountain
|
|
injures the muscles, by stretching them, forcing them to elongate while
|
|
bearing a load; they call that eccentric contraction.) Old people, who
|
|
had extensively damaged mitochondrial DNA, were given a program of concentric
|
|
exercise, and as their muscles adapted to the new activity, their mitochondrial
|
|
DNA was found to have become normal. </p>
|
|
<p>There
|
|
are probably the equivalents of constructive "concentric"
|
|
activity and destructively stressful "eccentric" activity
|
|
in the brain. For example, "rote learning" is analogous to
|
|
eccentric muscle contraction, and learning by asking questions is "concentric."
|
|
"No bird soars too high, if he soars with his own wings."
|
|
Any activity that seems "programmed" probably stifles cellular
|
|
energy and cellular intelligence.</p>
|
|
<p>When
|
|
activity is meaningful, and is seen to be meeting a felt need, the catabolic
|
|
and anabolic systems support and strengthen the components of the functional
|
|
system that has been activated. Everything we do has an influence on
|
|
the streaming renewal of the adaptive living substance.</p>
|
|
<p>There
|
|
are many therapeutic techniques that could be improved by organized
|
|
research, for example, investigating the interactions of increasing
|
|
carbon dioxide, reducing atmospheric pressure, supplementing combinations
|
|
of salt and other minerals, balancing amino acids and sugars, and varying
|
|
light exposure and types of activity. The dramatic results that have
|
|
occasionally been demonstrated (and then suppressed and forgotten) are
|
|
just a hint of the possibilities.</p>
|
|
<p>If
|
|
we keep our thoughts on the living substance, the pervasive ideologies
|
|
lose their oppressive power.</p>
|
|
<h2>References</h2>
|
|
<small>
|
|
<p>Chronobiol
|
|
Int. 2004;21(6):937-47. <strong>Postprandial metabolic profiles following
|
|
meals and snacks eaten during simulated night and day shift work.</strong>
|
|
Al-Naimi S, Hampton SM, Richard P, Tzung C, Morgan LM. "We have
|
|
previously shown that both simulated and real shift workers showed relatively
|
|
impaired glucose and lipid tolerance if a single test meal was consumed
|
|
between 00:00-02:00 h (night shift) compared with 12:00-14:00 h (day
|
|
shift). The objective of the present study was to extend these observations
|
|
to compare the cumulative metabolic effect of consecutive snacks/meals,
|
|
as might normally be consumed throughout a period of night or day shift
|
|
work." "There was a trend toward an effect of shift for plasma
|
|
glucose, with higher plasma glucose at night (p = 0.08), and there was
|
|
a time-shift interaction for plasma insulin levels (p < 0.01). NEFA
|
|
levels were unaffected by shift." "These findings confirm
|
|
our previous observations of raised postprandial TAG and glucose at
|
|
night, and show that sequential meal ingestion has a more pronounced
|
|
effect on subsequent lipid than carbohydrate tolerance."</p>
|
|
<p>
|
|
Anokhin P.K. <strong><em>System mechanisms of higher nervous activity.</em></strong>
|
|
Moscow, Nauka, 1979. (In Russian).</p>
|
|
<p>Life
|
|
Sci. 1989;44(24):1877-80. <strong>Isoprene and sleep.</strong> Cailleux A, Allain
|
|
P. Isoprene is one of the main constituents of endogenous origin in
|
|
exhaled human breath. The concentration of isoprene seems to vary with
|
|
states of sleep and wakefulness, <strong>increasing during sleep and decreasing
|
|
sharply just after awakening.</strong> Thus, isoprene may be involved in
|
|
in sleep upholding.</p>
|
|
<p>Exp
|
|
Neurol. 1978 May 15;60(1):41-55. Evidence of normal mitosis with complete
|
|
cytokinesis in central nervous system neurons during sustained depolarization
|
|
with ouabain. Cone CD Jr, Cone CM.</p>
|
|
<p>Nat
|
|
New Biol. 1973 Nov 28;246(152):110-1. Stimulation of DNA synthesis in
|
|
CNS neurones by sustained depolarisation. Stillwell EF, Cone CM, Cone
|
|
CD Jr.</p>
|
|
<p>J
|
|
Natl Cancer Inst. 1971 Mar;46(3):655-63. Intercellular transfer of toxic
|
|
components after laser irradiation. May JF, Rounds DE, Cone CD.</p>
|
|
<p>J
|
|
Theor Biol. 1971 Jan;30(1):151-81. <strong>Unified theory on the basic mechanism
|
|
of normal mitotic control and oncogenesis.</strong> Cone CD Jr.</p>
|
|
<p>Oncology.
|
|
1971;25(2):168-82. <strong>Control of somatic cell mitosis by simulated changes
|
|
in the transmembrane potential level.</strong> Cone CD Jr, Tongier M Jr.</p>
|
|
<p>Acta
|
|
Cytol. 1969 Oct;13(10):576-82. <strong>Autosynchrony and self-induced mitosis
|
|
in sarcoma cell networks.</strong> Cone CD Jr.</p>
|
|
<p>Ann
|
|
N Y Acad Sci. 1980;339:115-31. <strong>Ionically mediated induction of mitogenesis
|
|
in CNS neurons.</strong> Cone CD Jr.</p>
|
|
<p>Science.
|
|
1976 Apr 9;192(4235):155-8. <strong>Induction of mitosis in mature neurons
|
|
in central nervous system by sustained depolarization.</strong> Cone CD Jr,
|
|
Cone CM. DNA synthesis and mitosis have been induced in vitro in fully
|
|
differentiated neurons from the central nervous system by depolarization
|
|
with a variety of agents that produce a sustained rise in the intracellular
|
|
sodium ion concentration and a decrease in the potassium ion concentration.
|
|
Depolarization was followed in less than 1 hour by an increase in RNA
|
|
synthesis and in 3 hours by initiation of DNA synthesis. Apparently
|
|
normal nuclear mitosis ensued, but cytokinesis was not completed in
|
|
most cells; this resulted in the formation of binucleate neurons. The
|
|
daughter nuclei each contained the same amount of DNA as the diploid
|
|
preinduction parental neurons; this implies that true mitogenic replication
|
|
was induced.</p>
|
|
<p>Ann
|
|
N Y Acad Sci. 1974;238:420-35. <strong>The role of the surface electrical
|
|
transmembrane potential in normal and malignant mitogenesis</strong>. Cone
|
|
CD Jr.</p>
|
|
<p>Ann
|
|
N Y Acad Sci. 1974;238:451-6. <strong>Panel discussion: The role of electrical
|
|
potential at the cellular level in growth and development.</strong> Becker
|
|
RO, Cone CD, Jaffe LF, Parsegian VA, Pohl HA, Weiss L.</p>
|
|
<p>J
|
|
Cell Physiol. 1973 Dec;82(3):373-86. <strong>Contact inhibition of division:
|
|
involvement of the electrical transmembrane potential.</strong> Cone CD Jr,
|
|
Tongier M Jr.</p>
|
|
<p>J
|
|
Theor Biol. 1971 Jan;30(1):183-94. <strong>Maintenance of mitotic homeostasis
|
|
in somatic cell populations.</strong> Cone CD Jr.</p>
|
|
<p>Oncology.
|
|
1970;24(6):438-70. <strong>Variation of the transmembrane potential level
|
|
as a basic mechanism of mitosis control.</strong> Cone CD Jr.</p>
|
|
<p>Trans
|
|
N Y Acad Sci. 1969 Apr;31(4):404-27. <strong>Electroosmotic interactions
|
|
accompanying mitosis initation in sarcoma cells in vitro. </strong>
|
|
Cone CD Jr.</p>
|
|
<p>Rheum
|
|
Dis Clin North Am. 2005 Feb;31(1):115-29, ix-x. <strong>Circadian rhythms
|
|
and arthritis. </strong>Cutolo M, Masi AT.</p>
|
|
<p>Neuroscience.
|
|
1985 Dec;16(4):859-63. <strong>Day-night cycle of lipid peroxidation
|
|
in rat cerebral cortex and their relationship to the glutathione cycle
|
|
and superoxide dismutase activity.</strong> Diaz-Munoz M, Hernandez-Munoz
|
|
R, Suarez J, Chagoya de Sanchez V. Lipoperoxidation, glutathione cycle
|
|
components and superoxide dismutase activity show a day-night rhythm
|
|
in the cerebral cortex of the rat. <strong>The highest lipoperoxidative activity
|
|
is observed during the night (20.00-04.00 h). </strong>
|
|
The enhancement in lipoperoxidation occurs concurrently with a decrease
|
|
in glutathione peroxidase activity, an increase in superoxide dismutase
|
|
activity and an increase in the double bonds in the brain cortex lipid
|
|
fraction. The changes described in this paper seem to be related to
|
|
a succession of light and dark periods, or to fasting and feeding periods.
|
|
We propose that those fluctuations could act as a physiological oscillator
|
|
with an important role in modulating the membrane properties of the
|
|
nerve cell. </p>
|
|
<p>Brain
|
|
Res. 1977 Mar 4;123(1):137-45. <strong>Daily variations of various parameters
|
|
of serotonin metabolism in the rat brain.</strong> <strong>II. Circadian variations
|
|
in serum and cerebral tryptophan levels: lack of correlation with 5-HT
|
|
turnover. </strong>Hery F, Chouvet G, Kan JP, Pujol JF, Glowinski J. Rats
|
|
submitted to regular 12 h cycles of light and darkness for three weeks
|
|
were sacrificed at various times of the day. 5-HT, 5-HIAA and tryptophan
|
|
levels were estimated in the fronto-parietal cerebral cortex. Tyrosine
|
|
and free and total tryptophan levels in serum were estimated in parallel.
|
|
Significant circadian variations in 5-HT and 5-HIAA levels were found
|
|
in cerebral tissues. The peaks of 5-HIAA levels were dectected during
|
|
the lignt and dark periods respectively, the maximal fluctuations being
|
|
seen between 17.00 h and 21.00 h, two times separating the light off.
|
|
Important significant circadian variations in free and total <strong>serum
|
|
tryptophan</strong> levels were also observed<strong>. In both cases, the maximal
|
|
levels were found during the middle of the dark phase</strong> after the
|
|
peak of 5-HIAA levels. The circadian rhythm of tyrosine levels in serum
|
|
was in opposite phase with that of tryptophan (free or total). The diurnal
|
|
changes in tryptophan content in cerebral tissues seemed thus related
|
|
to those found in serum. Taking in consideration results obtained in
|
|
previous studies 16,17 carried out in similar experimental conditions,
|
|
it was concluded that the parallel increase in serum free tryptophan
|
|
and in tissues 5-HIAA levels seen during the night were not related
|
|
to a stimulation of 5-HT turnover. Indeed 5-HT synthesis is minimal
|
|
at this time16.</p>
|
|
<p>Kryukov
|
|
V.I. <strong>An attention model based on the principle of dominanta</strong> <strong>
|
|
// <em>Proceedings in Nonlinear Science. Neurocomputers and Attention.
|
|
I: Neurobiology, Synchronization, and Chaos.</em></strong> 1989. Ed. by A.Y.
|
|
Holden and V.I. Kryukov, pp. 319-351.</p>
|
|
<p>Endocrinol
|
|
Exp. 1976 Jun;10(2):131-7. <strong>Diurnal variation in the effect of melatonin
|
|
on plasma and muscle free fatty acid levels in the pigeon.</strong> John
|
|
TM, George JC. Pigeons maintained on standard diet and held under 12
|
|
h daily photo-period in a controlled environmental room, were given
|
|
intravenous injections of melatonin. A low dose (1.25 mg/kg body weight)
|
|
of melatonin when given in the middle of the scotophase, produced a
|
|
significant increase in plasma FFA when estimated at 20 min and 90 min
|
|
post-injection, whereas no significant change was seen with injections
|
|
given in the middle of the photophase. No significant change in muscle
|
|
FFA level was obtained either during the photophase or the scotophase
|
|
when estimated at 90 min postinjection. <strong>With
|
|
a higher dose (5 mg/kg body weight) of melatonin given in the scotophase,
|
|
on the other hand, a significant increase in both plasma as well as
|
|
muscle FFA levels was obtained at 90 min post-injection but there was
|
|
no effect on plasma FFA at 20 min or 90 min</strong> post-injection in the
|
|
photophase and at 20 min in the scotophase. It is concluded that <strong>
|
|
melatonin has a lipid mobilizing action in the pigeon when administered
|
|
during the scotophase.</strong></p>
|
|
<p>Exp
|
|
Brain Res. 2001 Feb;136(3):313-20. <strong>Enhanced neurogenesis after transient
|
|
global ischemia in the dentate gyrus of the rat.</strong> Kee NJ, Preston
|
|
E, Wojtowicz JM. "Certain insults such as epileptic seizures and
|
|
ischemia are known to enhance the rate of neuronal production. We analyzed
|
|
this phenomenon using the temporary occlusion of the two carotid arteries
|
|
combined with arterial hypotension as a method to induce ischemia in
|
|
rats. We measured the rate of cell production and their state of differentiation
|
|
with a mitotic indicator, bromodeoxyuridine (BrdU), in combination with
|
|
the immunohistochemical detection of neuronal markers. One week after
|
|
the ischemic episode, the cell production in dentate gyrus was increased
|
|
two- to threefold more than the basal level seen in control animals. <strong>
|
|
Two weeks after ischemia, over 60% of these cells became young neurons
|
|
as determined by colabeling with BrdU and a cytoplasmic protein (CRMP-4)
|
|
involved in axonal guidance during development. Five weeks after the
|
|
ischemia, over 60% of new neurons expressed calbindin, a calcium-binding
|
|
protein normally expressed in mature granule neurons.</strong> In addition
|
|
to more cells being generated, a greater proportion of all new cells
|
|
remained in the differentiated but not fully mature state during the
|
|
2- to 5-week period after ischemia." "The results support
|
|
the hypothesis that survival of dentate gyrus after ischemia is linked
|
|
with enhanced neurogenesis. Additional physiological stimulation after
|
|
ischemia may be exploited to stimulate maturation of new neurons and
|
|
to offer new therapeutic strategies for promoting recovery of neuronal
|
|
circuitry in the injured brain."</p>
|
|
<p>Am
|
|
J Cardiol. 1998 Dec 17;82(12A):24U-28U; discussion 39U-41U. <strong>Clinical
|
|
profiles of plain versus sustained-release niacin (Niaspan) and the
|
|
physiologic rationale for nighttime dosing.</strong> Knopp RH. Niacin is
|
|
the oldest and most versatile agent in use for the treatment of dyslipidemia.
|
|
It has beneficial effects on low-density lipoprotein cholesterol; high-density
|
|
lipoprotein cholesterol; the apolipoproteins B and A-I constituting
|
|
these fractions; triglyceride; and lipoprotein(a). Together, these benefits
|
|
lead to a diminished incidence of coronary artery disease among niacin
|
|
users. The chief constraints against niacin use have been flushing,
|
|
gastrointestinal discomfort, and metabolic effects including hepatotoxicity.
|
|
Time-release niacin has been developed in part to limit flushing, and
|
|
now a nighttime formulation (Niaspan) has been developed that assists
|
|
in containing this untoward effect. In a pivotal metabolic study, bed-time
|
|
administration of 1.5 g time-release niacin was shown to have the same
|
|
beneficial effects as 1.5 g plain niacin in 3 divided doses and to be
|
|
well tolerated. <strong>Previous studies suggest that bedtime niacin administration
|
|
diminishes lipolysis and release of free fatty acids</strong> to the liver;
|
|
this, in turn, leads to an abolition of the usual diurnal increase in
|
|
plasma triglyceride, which may result in diminished formation and secretion
|
|
of triglyceride in the very-low-density lipoprotein fraction.</p>
|
|
<p>J
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|
Pediatr Orthop. 2004 Nov-Dec;24(6):726-31. <strong>Growing pains: are they
|
|
due to increased growth during recumbency as documented in a lamb model? </strong>
|
|
Noonan KJ, Farnum CE, Leiferman EM, Lampl M, Markel MD, Wilsman NJ.</p>
|
|
<p>Cell
|
|
Tissue Kinet. 1977 Nov;10(6):557-68. <strong>Circadian rhythms of presumptive
|
|
stem cells in three different epithelia of the mouse.</strong> Potten CS,
|
|
Al-Barwari SE, Hume WJ, Searle J.</p>
|
|
<p>Physiol
|
|
Res. 1995;44(4):249-56. <strong>Circadian and circaannual oscillations of
|
|
tissue lipoperoxides in rats.</strong> Solar P, Toth G, Smajda B, Ahlers
|
|
I, Ahlersova E. Circadian and circaannual oscillations of tissue lipid
|
|
peroxides (LPO) were studied in young male Wistar rats. The concentration
|
|
of malondialdehyde, one of LPO degradation products, was measured at
|
|
3-h intervals during 24 hours in rats, adapted to light:dark 12:12 h
|
|
regimen in the course of the year. LPO in the liver, thymus and bone
|
|
marrow oscillated rhythmically in the course of the day and year. Circadian
|
|
oscillations in all tissues were two-peaked, with zeniths at various
|
|
times of the light and dark parts of the day. In the liver and thymus, <strong>the highest mesors were found during
|
|
the winter</strong>, in the bone marrow during the spring. The same holds
|
|
for amplitude values, with the exception of the bone marrow which exhibited
|
|
the highest values during the summer. The reason for the LPO oscillations
|
|
is probably resulting from the changing ratio of pro- and anti-oxidative
|
|
capacities in various tissues during the day and the year. </p>
|
|
<p>Biofizika.
|
|
1976 Jul-Aug;21(4):688-91. <strong>[Circadian rhythms of ultraweak chemiluminescence
|
|
of bean roots]</strong> Sul'tsman FM, Petrusevich IuM, Tarusov BN. Circadian
|
|
rhythms of ultra-weak chemoluminescence of bean roots were investigated.
|
|
It was found that under periodical change of light and darkness and
|
|
without subsequent illumination a periodical change of spontaneous chemoluminescence
|
|
of bean roots was observed. (The study of antiradical activity of the
|
|
substances extracted from the root showed the dependence of this activity
|
|
on illumination conditions.</p>
|
|
<p>Ukr
|
|
Biokhim Zh. 1977 Sep-Oct;49(5):64-9. [Effect of "carbostimulin",
|
|
vitamin D 3 and their mixture on bone tissue regeneration] [Article
|
|
in Ukrainian] Taran TT, Guly MF, Mykhajlovskyj VO, Dvornykova PD, Fanak
|
|
MM, Vorobjov NA. "Healing of the bone injury in rabbits was studied
|
|
as affected by carbostimulin and its mixture with vitamin D3. Some biochemical
|
|
indexes: the content of sialic acids, calcium and citric acid in blood
|
|
serum of the animals, intensity of 14C incorporation from NaH14CO3 into
|
|
the regenerated bone tissue and its proteins as well as histological
|
|
studies, data, evidence for a positive effect of the mentioned preparations
|
|
on the bone substance regeneration in the animals under experiment." </p>
|
|
<p>Biofizika.
|
|
1961;6(4):490-2. <strong>[Study on ultra-weak spontaneous luminescence of
|
|
animal cells.]</strong> Tarusov BN, Polivoda AI, Zhuravlev AI.</p>
|
|
<p>Biofizika.
|
|
1961;6(4):83-5. <strong>Study of the faint spontaneous luminescence of animal
|
|
cells.</strong> Tarusov BN, Polivoda AI, Zhuravlev AI.</p>
|
|
<p>Vopr
|
|
Med Khim. 1977 May-Jun;(3):375-81. <strong>[Free fatty acids and cholesterol
|
|
as possible participants in lipid oxidation radical reactions in animal
|
|
tissues]</strong> [Article in Russian] Terekhova SF, Burlakova EB, Elizarova
|
|
TI. Alterations in concentration of free fatty acids, free cholesterol,
|
|
native antioxidants as well as in the antioxidative activity were studied
|
|
in lipids of mice liver tissue and small intestinal mucosa. The intensity
|
|
of free radical reactions in lipids of animal tissues was affected directly
|
|
by administration of synthetic inhibitors of the reactions. The inverse
|
|
correlation was observed between the alteration in concentrations of
|
|
native antioxidants and free fatty acids as well as between the antioxidative
|
|
activity of lipids and amount of free cholesterol in them. <strong>Free fatty
|
|
acids appears to be the constant participants in the system of free
|
|
radical oxidation of lipids, while cholesterol can center the system
|
|
under distinct level of these reactions intensity.</strong></p>
|
|
<p>Ukhtomsky
|
|
A.A. <strong><em>Dominanta as factor of behavior // Collected works.</em></strong>
|
|
Leningrad, 1950. Vol.1, pp.293-315. </p>
|
|
<p>Biofizika.
|
|
1974 Mar-Apr;19(2):295-9.<strong> [Formation of pigments of lipid nature
|
|
in animal tissues during neoplastic growth and irradiation] </strong>
|
|
Vertushkov VT, Ivanov II, Tarusov BN.</p>
|
|
<p>Biofizika.
|
|
1967 Jul-Aug;12(4):739-41. <strong>[Antioxidative activity of blood serum
|
|
fractions during malignant degeneration studied by inhibition of chemiluminescence] </strong>
|
|
Zakarian AE, Tarusov BN.</p>
|
|
<p>Biofizika.
|
|
1966;11(5):919-21. <strong>[Inhibition of chemiluminescence of the blood
|
|
plasma in malignant growth]</strong> [Article in Russian] Zakarian AE, Tarusov
|
|
BN.</p>
|
|
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