The Song of the Cell - Revision history

Rob: /* The Songs of the Cell */

2025-04-21T15:54:19Z

The Songs of the Cell

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	* Cellular engineering has already allowed us to rebuild parts of humans with reengineered cells. As our understanding grows, new medical and ethical conundrums will arise, intensifying and challenging the basic definition of who we are, and how much we wish to change ourselves.		* Cellular engineering has already allowed us to rebuild parts of humans with reengineered cells. As our understanding grows, new medical and ethical conundrums will arise, intensifying and challenging the basic definition of who we are, and how much we wish to change ourselves.
	[[Category:Science]]		[[Category:Science]]
			[[Category:Books]]

Rob: Rob moved page Cells to The Song of the Cell

2025-04-21T15:53:30Z

Rob moved page Cells to The Song of the Cell

← Older revision	Revision as of 15:53, 21 April 2025
(No difference)

Rob: /* The Songs of the Cell */

2025-04-21T15:51:28Z

The Songs of the Cell

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	* The capacity to build new humans out of our building blocks - cells - lies very much within ghe reach of medicine today. Cellular reengineering can ameliorate, or even reverse, cellular pathology.		* The capacity to build new humans out of our building blocks - cells - lies very much within ghe reach of medicine today. Cellular reengineering can ameliorate, or even reverse, cellular pathology.
	* Cellular engineering has already allowed us to rebuild parts of humans with reengineered cells. As our understanding grows, new medical and ethical conundrums will arise, intensifying and challenging the basic definition of who we are, and how much we wish to change ourselves.		* Cellular engineering has already allowed us to rebuild parts of humans with reengineered cells. As our understanding grows, new medical and ethical conundrums will arise, intensifying and challenging the basic definition of who we are, and how much we wish to change ourselves.
	[[Category:~~Consciousness~~]]		[[Category:Science]]

193.16.224.14 at 17:37, 16 February 2025

2025-02-16T17:37:01Z

← Older revision		Revision as of 17:37, 16 February 2025
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	* The capacity to build new humans out of our building blocks - cells - lies very much within ghe reach of medicine today. Cellular reengineering can ameliorate, or even reverse, cellular pathology.		* The capacity to build new humans out of our building blocks - cells - lies very much within ghe reach of medicine today. Cellular reengineering can ameliorate, or even reverse, cellular pathology.
	* Cellular engineering has already allowed us to rebuild parts of humans with reengineered cells. As our understanding grows, new medical and ethical conundrums will arise, intensifying and challenging the basic definition of who we are, and how much we wish to change ourselves.		* Cellular engineering has already allowed us to rebuild parts of humans with reengineered cells. As our understanding grows, new medical and ethical conundrums will arise, intensifying and challenging the basic definition of who we are, and how much we wish to change ourselves.
			[[Category:Consciousness]]

Rob at 20:24, 19 June 2024

2024-06-19T20:24:25Z

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	== The Selfish Cell (Cancer) ==		== The Selfish Cell (Cancer) ==

			* A cut on your hand shows homeostasis at work. Blood leaks out. Platelets and clotting factors, induced by the tissue damage, gather around the wound. Neutrophils, sensing a danger signal, accumulate at the site as first responders to infection. They stand guard to ensure that pathogens don't get a chance to breach the boundaries of the self. A clot forms, and the wound is temporarily plugged.
			* Then the healing begins. If the wound is shallow, the two ends of skin appose against themselves. If the wound is deep, fibroblasts from under the skin, crawl in to deposit a protein matrix underneath the wound. And then skin cells proliferate over the matrix to cover the wound, occasionally leaving a scar. Once they touch each other, the cells stop dividing. It takes a host of cells to coordinate this process. The wound has healed.

			* In cancel, cell division is dysregulated - jammed accelerator genes and snapped brakes. The cars speed through the traffic jam, piling up on each other and causing tumors. Or they frantically move into alternate routes, causing metastasis.
			* The jammed accelerators are called oncogenes. The snapped brakes are called tumor suppressors
			* Any individual specimen of cancer has a permutation of mutations that is unique to it.
			* The genetic programs that enable cancer cells to sustain malignant growth are shared, to some extent, with stem cells
			* A tiny fraction of the bulk of leukemia cells in the marrow are capable of regenerating the whole leukemia from scratch.

	== The Songs of the Cell ==		== The Songs of the Cell ==

			* All cells come from cells.
			* The first human cells gives rise to all human tissues. Every cell in the human body can be produced, in principle, from an embryonic cell (or stem cell)
			* Although cells vary widely in their form and function, there are deep physiological similarities that run through them.
			* These similarities can be repurposed by cells for specialized functions. An immune cell uses its molecular apparatus for ingestion to eat microbes; a glial cell uses similar pathways to prune synapses in the brain.
			* Systems of cells with specialized functions, communicating with each other through short and long-range messages, can achieve powerful physiological functions that individual cells cannot achieve - for example, the healing of wounds, the signaling of metabolic states, sentience, cognition, homeostasis, immunity. The human body functions as a citizenship of cooperating cells. The disintegration of this citizenship tips us from wellness to disease.
			* Cellular physiology is thus the basis for human physiology, and cellular pathology is the basis for human pathology.
			* The process of decay, repair, and rejuvenation in individual organs are idiosyncratic. Specialized cells in some organs are responsible for consistent repair and rejuvenation (blood rejuvenates through human adulthood, albeit at diminished rates), but other organs lack such cells (nerve cells rarely rejuvenate). The balance between injury/decay and repair/rejuvenation ultimately results in the integrity or defeneration of an organ.
			* Beyond understanding cells in isolation, deciphering the internal laws of cellular citizenship - tolerance, communication, specialization, diversity, boundary-formation, cooperation, niches, ecological relationships - will ultimately result in the birth of a new kind of cellular medicine.
			* The capacity to build new humans out of our building blocks - cells - lies very much within ghe reach of medicine today. Cellular reengineering can ameliorate, or even reverse, cellular pathology.
			* Cellular engineering has already allowed us to rebuild parts of humans with reengineered cells. As our understanding grows, new medical and ethical conundrums will arise, intensifying and challenging the basic definition of who we are, and how much we wish to change ourselves.

Rob at 16:20, 19 June 2024

2024-06-19T16:20:27Z

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	== The Renewing Cell (Stem Cells) ==		== The Renewing Cell (Stem Cells) ==
			* On the one hand, a stem cell must generate functional "differentiated" cells; a blood stem cell, for instance, must divide to give rise to the cells that form the mature elements of blood - white cells, red cells, platelets. But it must also divide to replenish itself, ie a stem cell
			* A totipotent cell can give rise to all types of cells
			* A pluripotent cell can five rise to nearly all cell types
			* A multipotent cell can give rise to all cell types in a particular kind of tissue.
			* A single stem cell can produce billions of mature red and white cells - and an entire organ system of an animal.
			* Human embryonic stem cells (h-ES cells) come from embryos discarded from IVF procedures.
			* In 1998, James Thomson extracted cells from inside these embryos and grew five human cell lines - three "males" and two "females". One of these, H-9, a female, has become the standard ES cell, grown in thousands of incubators in undreds of labs around the planet, and subject to tens of thousands of experiments.
			* In 2001, Bush restricted federal funding to research involving ES cells that had already been derived (such as H-9)
			* There are now iPS cells (induced pluripotent stem cells) changed, using generic manipulations, from mature fibroblasts into induced pluripotent cells. The ides is you take your own cell, from your skin or blood and make it crawl backward in time and transfom it into an iPS cell, from which you can make any cell - cartilage, neurons, T cells, pancreatic beta call, without any problems of histocompatibility, because they are your own cells.

	== The Repairing Cell (Bone) ==		== The Repairing Cell (Bone) ==
			* The skeleton grows to a point, and then knows when to stop growing. It heals itself continuously throughout adult life and repairs itself acutely after injury. It responds with sensitivity to hormones; it potentially even synthesizes its own hormones.
			* It might look like a chunk of hardened calcium, but bone is in fact made of a multiplicity of cells:
			** Cartilage cells - chondrocytes
			** Osteoblast - deposits calcium and other proteins to form a calcified matrix in layers, and then get trapped in its own deposit to form new bone. It is the bone-making, bone-depositing cell.
			** OSteoclast -are large cells with multiple nuclei that are bone eaters. They chew away on the matrix, or puch holes in it, removing and remodeling bone like constanly pruning gardeners
			* There are cells at the ends of a bone - but not in its middle - that generate new cells that lengthen it.
			* How does bone grow during adolescence? A special population of cells, sitting at the growth plate at the two ends of bone, shoots off cartilage and osteoblasts that allows bone to lengthen. And why does it stop growing? Because this population diminishes over time, until early adulthood, when very few are left.
			* Why doesn't cartilage in joints get repaired, just as a bone fracture does, in adults? Because the repairing cells die during the injury.
			* There are other organs where damage, once done, is permanent. Neurons in the brain and the spinal cord, once they've stopped dividing, don't divide to regenerate neurones (they are post-mitotic, ie no longer able to divide).

	== The Selfish Cell (Cancer) ==		== The Selfish Cell (Cancer) ==

Rob at 17:17, 15 June 2024

2024-06-15T17:17:09Z

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	* When we turn the DBS on, patients want to move again, but the activities that they want to do involve cleaning out rooms. Taking the trash out of the kitchen. Washing dishes.		* When we turn the DBS on, patients want to move again, but the activities that they want to do involve cleaning out rooms. Taking the trash out of the kitchen. Washing dishes.

	== The Orchestrating Cell ==		== The Orchestrating Cell (Pancreas, Kidney, Liver + Hormones) ==

			* There must be a means for one part of the body to "meet" a distant part of the bodfy. We call these signals "hormones" from the Greek hormon - to impel, or to set some actions into motion. In a sense, they impel the body to act as a whole.
			* Hormones are molecules that are produced by endocrine glands, including the hypothalamus, pituitary gland, adrenal glands, gonads, (i.e., testes and ovaries), thyroid gland, parathyroid glands, and pancreas.
			* The pancreas is a gland that releases juices into the digestive system, where they break down complex food molecules into simple ones. It contains the islets of Langerhans, which produce a range of hormones, including glucagon, somatostatin, and ghrelin.
			* Insulin is the master regulator of sugar metabolism. It is synthesized in the pancreatic beta cells, and its secretion is stimulated by the presence of glucose in the blood. It then travels all over the body. Virtually every tissue responds to insulin: the presence of sugar means that the extraction of energy, and everything that flows from energy - the synthesis of proteins and fats, the storage of chemicals for future use, the firing of neurons, the growth of cells - can proceed. It is, perhaps, among the most important of the "long range" messages that acts as a central coordinator and orchestrates metabolism all through the body.
			* Type 1 diabetes is a disease in which immune cells attack the beta-islet-cells of the pancreas. Without insulin, the body cannot sense the presence of sugar. The cells in e body, imagining that the body has no sugar, begin to scramble around for other forms of fuel. The sugar, meanwhile, spikes threateningly in the blood, and spills into the urine - cellular starvation in the presence of plenty.
			* The pancreas is the central coordinator of metabolism, the maker of the hormone to which all tissues respond.

			After dinner at a pizzeria:

			* The carbohydrates from the bread and rigatoni are digested into sugars - ultimately into glucose. The glucose is packed up from the intestines, absorbed into blood and moved into circulation. When the blood reaches the pancreas, it sense the spike in glucose, and sends out insulin. The insulin, in turn, moves the sugar from the blood into all the cells of your body, where it can be stored, if needed, or used for energy, as needed. The brain is the ultimate recipient of these signals: if the sugar drops too low, it reacts by sending out converse signals. Yet other hormones, secreted by different cells, send signals to release stored sugars into the blood. The stores come from liver cells, which respond, at least transiently, by releasing their stockpiles of stored glucose to restore equilibrium.

			* The kidney contains the nephron, which is the site where the blood and kidney cells meet, and the first drops of urine are generated. The circulation of blood carries the excess salt, dissolved in plasma to the kidneys.
			* The excess sodium causes a hormonal system, regulated by the kidney and the adrenal gland, which sits just above the kidney, to decrease its signal. The cells in the tubule respond to these changes by excreting the excess sodium into urine, thereby discarding the salt and returning the sodium level to normal. The salt is also detected by specialized cells in the brain that monitor the overall concentration of salts in the blood, a property called osmolality.*
			* The non-waste products? The sugar and other essential products are reabsorbed into the body by the cells in the collecting duct through special channels. We generate excess, and the pare it back to restore normalcy.

			* The alcohol is treated by the cells of the liver - hepatocytes. Liver cells are specialized for both storage and waste disposal, secretion, protein syntheses, etc.
			* We think of metabolism as a mechanism to generate energy. But it's also a mechanism to generate waste. The kidney dispenses some of this through urine, but the kidney is not a detoxifying plant: its master plan for waste is to merely wash it away down a sewer.
			* Liver cells, in contrast, have evolved dozens of mechanisms to detoxyfy and dispense waste. Alcohol is detoxified in a series of reactions, until it is broken down into a harmless chemical

			* The pancreatic cell maintains metabolic constancy, the kidneys salt constancy, the liver chemical constancy.
			* The liver, pancreas, brain, and kidney are four of the principal organs of homeostasis. The pancreatic beta cells control metabolic homeostasis through the hormone insulin. The kidney's nephrons control salt and water, maintaining a constant level of salinity in the blood. The liver, among many of its functions, prevents us from being soused in toxic products, including ethanol. The brain coordinates this activity by sensing levels, sending out hormones, and acting as a master orchestrator of balance-restoration.

Rob at 17:40, 14 June 2024

2024-06-14T17:40:18Z

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	* It has invented a system of identification cards to recognize its citizens and eject intruders (T cells) and an army to guard itself from invaders (B cells).		* It has invented a system of identification cards to recognize its citizens and eject intruders (T cells) and an army to guard itself from invaders (B cells).
	* It has evolved language, organization, memory, architecture, subcultures, and self-recognition. Perhaps we might think of it as a cellular civilization		* It has evolved language, organization, memory, architecture, subcultures, and self-recognition. Perhaps we might think of it as a cellular civilization

			== The Pandemic ==

			* The gene TLR7 (Toll-Like Receptor 7) is one of the key detectors of viral invasion.
			* The virus was most deadly when it infected a host whose early antiviral response had been functionally paralyzed - like a raider that had come into an unlocked house. The pathogenicity of SARS_COV2 perhaps lay precisely in its ability to dupr cells into believing that it is not pathogenic.
			If you mount a robust innate immune response during the early phase of infection, you control the virus and have a mild disease. If you don't, you have uncontrolled virus replication in the lung that fuels the fire of inflammation leading to severe disease.

			* Cellular specialization and citizenship - the hallmark of the cell biology of an organ - result in the profound "emergent" properties of human physiology - ie properties that can only emerge when multiple cells coordinate their functions and work together. A heartbeat. A thought. And the restoration of constancy - the orchestration of homeostasis.

			== The Citizen Cell (Heart) ==

			* The heart will beat more than 2bn times over an average person's life.
			* The heart is two pumps:
			** The right-sided pump (veins to heart to lung) collects blood from the veins of the body. Exhausted and depleted, having delivered oxygen and nutrients to the organs, "venous" blood (often darker red than bright crimson) pours into the upper right chamber called the right atrium. It then passes through a valve and is moved into the pumping chamber, the right ventricle. A powerful heave from the right ventricle pumps the blood to the lungs.
			** The lungs, having received blood from the right side of the heart, oxygenate the blood and clear the carbon dioxide. Replete with oxygen and cleansed, blood, nos a vivid crimson, moves to the left side. It collects in the left atrium of the heart. It si then pushed into the left ventricle. It is this left ventricle, perhaps the most tireless muscle in the body, that ejects te blood forcefully into the wide arc of the aorta, the major blood vessel that carries oxygenated blood to the body, and to the brain.

			* There are two systems of interconnected fibers inside a muscle cell: actin and myosin
			* Each muscle cell has thousand of ropes - bands of actin in parallel with bands of myosin. As the ropes, lines side by side, slide against each other - clutch, pull, release - the edges of the cell are also yanked, and the cell is dragged into a contraction. The process requires energy, of course, and every heart cell and muscle cell is chock-full of mitochondria to supply the energy required for the two fibers to slide.
			* There are three fundamental types of muscle cells:
			** cardiac muscle
			** skeletal muscle (that moves your arms on command)
			** smooth muscle (that moves involuntarily, but consistently, allowing say liquid in the intestines to keep moving
			* Heart cells are connected to each other through minuscule molecular channels, called gap junctions. Every cell is inherently designed to communicate with the rest. Although many, they behave as one. When a stimulus to contract is generated in one cell, it automatically travels to the next cell, resulting in its stimulation, and ultimately resulting in contraction in unison.

			== The Contemplating Cell (Neuron) ==

			* Neurons possess a cell body - the some - from which sprout dozens, hundreds, or even thousands of branch-like projections called dendrites. And they possess an outflow tract - an "axon" - that extends to the next cell, which is separated from the second neuron by an intervening speace - the synapse. The nervous system is wired, but the wires consist of cells connected to cells connected to cells with intervening spaces between them.
			* Information travels unidirectionally. The dendrites receive the impulse, which is then moved through the cell body, out through the axon, through the synapse to the next nerve cell
			* Nerve cells chatter with each other - collecting inputs via dendrites and generating outputs via the axon, and this intercellular chatter gives rise to the profound properties of the nervous system: sentience, sensation, consciousness, memory, thinking, and feeling.
			* Chemical transmitters are stored in vesicles (membrane-bound sacs) at the end of the axon.
			* The synapse can not just excite the neuron to fire, but can also be an inhibitory synapse, making the next neuron less prone to excitation. A single neuron can thus have positive inputs and negative inputs from other neurons. Its job is to integrate these inputs and his integrated total of excitatory and inhibitory inputs determines whether a neuron will fire or not.

			* Glial cells are present all over the nervous system - in about the same number as neurons. They don't generate electrical impulse but they are extraordinarily diverse in structure and function.
			* Synaptic pruning is thought to involve the paring back of structures, eliminating the synaptic connection at that site - akin to removing, or cutting the soldering joint between two wires. Our brains make connections in vast excess, and then we pare back the excess
			* The secret of learning is the systematic elimination of excess. We grow mostly by dying. We are hardwired not to be hardwired, and this anatomical plasticity may be the key to the plasticity in our minds.
			* Specialized cells known as microglia - spidery and many-fingered - had been seen crawling around the brain, scrounging for debris, and their role in eliminating pathogens and cellular waster had been known for decades. But they are also found coiled around synapses that have been marked for elimination. They nibble at the synaptic connections between neurons and pare them away. They are the brain's constant gardeners.
			* Microgiglia use proteins and processes to mark synapses to be nibbled and ingest the bits of a neuron involved in the synaptic connections. The very proteins and pathways that are used to clear pathogens in the body have been repurposed to fine-tune connections between neurons. Microglia have evolved to "eat " pieces of our own brain.
			* Synapses compete against each other and the strongest synapse wins.
			* Dysfunctions in glial pruning may be related to schizophrenia - a disease where pruning doesn't occur appropriately. Maybe also Alzheimers, multiple sclerosis, and autism.

			* An electrical impulse arrives at the end of the neuron - the axon terminal - and causes the release of chemical neurotransmitters into the synapse. These chemicals, in turn, open channels in the next neuron, and ions surge in, reinitiating the impulse. This is the fast electrical brain.
			* But the chemical signals also create a cascade of slow signals in the neuron. Neuronal signaling instigates profound biochemical and metabolic changes in the recipient cell causing alterations in metabolism, in gene expression, and in the nature and concentration of chemical transmitters that are secreted into the synapse. And these slow changes in turn alter the electrical conduction of an impulse from nerve to nerve.
			* We might divide the pathologies of the brain into those that affect the fast electrical signals, those that impact the slow biochemical cascades, and those that fall in between
			* In the 1950s, there was the idea that depression was caused by a lack of serotonin in the synapse so that the electrical circuits don't get enough stimulation. But not everyone responds to SSRIs.
			* The Brodmann area 25 (BA25) is an area of the brain that seems to regulate emotional tone, anxiety, motivation, drive, self-reflection, and sleep - all of which are dysregulated by depression.
			* When this area is stimulated with Deep Brain Stimulation (DBS) patients spontaneously reported acute effects including sudden calmness or lightness, disappearance of the void, sense of heightened awareness, increased interest, connectedness and sudden brightening of the room. One woman described her illness as a complete incapacity to feel emotional, or even sensory connections.
			* When we turn the DBS on, patients want to move again, but the activities that they want to do involve cleaning out rooms. Taking the trash out of the kitchen. Washing dishes.

			== The Orchestrating Cell ==


			== The Renewing Cell (Stem Cells) ==


			== The Repairing Cell (Bone) ==


			== The Selfish Cell (Cancer) ==


			== The Songs of the Cell ==

Rob at 16:48, 13 June 2024

2024-06-13T16:48:23Z

@@ Line 204: / Line 204: @@
 * Ultimately the B cell matures into a cell so single-mindedly dedicated to antibody production that its structure and metabolism are altered to facilitate the process. It is now a cell dedicated to making antibodies - a plasma cell. Some of these plasma cells also become long lived and retain the memory of the infection.
-== The Discerning Cell (T Cells) ==
+* The thymus is a gland that sits above the heart.
 == The Tolerant Cell (T Cells II) ==

Rob at 16:09, 13 June 2024

2024-06-13T16:09:17Z

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	== The Defending Cell (B Cells) ==		== The Defending Cell (B Cells) ==

			* The terms "antitoxin" and "antibody" coined in 1890s. An antibody was a body - a protein - that locked on to another substance. And an antigen was a substance that generated an antibody.
			* Our bodies produce B cells primarily in the bone marrow, which then mature in the lymph nodes.
			* If the structure of antibodies was malleable then the genes that encoded them must also be malleable - by mutation.
			* In cell biology and genetics - in fact in most of the biological world - learning and memory typically happen by mutation, not instruction or aspiration.
			* When the connection is made, and a particular lymphocyte with a particular receptor is brought into the presence of the particular antigen, one of the greatest small spectacles in nature occurs. The cell enlarges, begins making new DNA at a great rate and turns into what is termed, appropriately, a blast. It then begins dividing, replicating itself into a new colony of identical cells all labeled with the same receptor. In the end, the dominant B cell clones, displaying the "right" receptor (the one that best binds the antigen) blast away, outgrowing all others. It is a Darwinian process, much like the finch with the right beak is "chosen" by natural selection.
			* These blasts now begin to secrete the receptor into the blood. Freed from the B cell's membrane and now floating in the blood, the receptor "becomes" the antibody. And when the antibody is bound to its target, it can summon a cascade of proteins to poison the microbe and can recruit macrophage to devour, or phagocytose, it. Decades later, researchers demonstrated that some of the activated B cells don't simply peter out. They persist in the body in the form of memory cells. The new cluster of cells stimulated by the antigen is a memory, no less. Once the fulminant infection has ceased and the microbe cleared, some of these B cells become more quiescent, but they persist - finches huddled in the cave. When the body encounters the antigen again, the memory B cell is reactivated. It arises out of dormancy into active division to mature into an antibody-making plasma cell, thereby encoding an immunological memory. The locus of immunological memory, in summary, is not a protein that persists. It is a B cell, previously stimulated, that bears the memory of the prior exposure.
			* Ultimately the B cell matures into a cell so single-mindedly dedicated to antibody production that its structure and metabolism are altered to facilitate the process. It is now a cell dedicated to making antibodies - a plasma cell. Some of these plasma cells also become long lived and retain the memory of the infection.