GABA

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/GABA 

γ-Aminobutyric acid

Names
Pronunciation	/ˈɡæmə əˈmiːnoʊbjuːˈtɪrɪk ˈæsɪd/, /ˈɡæbə/ (GABA)
Preferred IUPAC name 4-Aminobutanoic acid
Other names γ-Aminobutanoic acid 4-Aminobutyric acid 3-Carboxypropylamine Piperidic acid Piperidinic acid

Properties
Chemical formula	C4H9NO2
Molar mass	103.121 g·mol−1
Appearance	white microcrystalline powder
Density	1.11 g/mL
Melting point	203.7 °C (398.7 °F; 476.8 K)
Boiling point	247.9 °C (478.2 °F; 521.0 K)
Solubility in water	130 g/100 ml
log P	−3.17
Acidity (pKa)	4.031 (carboxyl; H2O) 10.556 (amino; H2O)

GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.

GABA is sold as a dietary supplement in many countries. It has been traditionally thought that exogenous GABA (i.e., taken as a supplement) does not cross the blood–brain barrier, but data obtained from more recent research (2010s) in rats describes the notion as being unclear.

The carboxylate form of GABA is γ-aminobutyrate.

Function

Neurotransmitter

Two general classes of GABA receptor are known:

• GABA_A in which the receptor is part of a ligand-gated ion channel complex
• GABA_B metabotropic receptors, which are G protein-coupled receptors that open or close ion channels via intermediaries (G proteins)

Release, reuptake, and metabolism cycle of GABA

Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate. Medium spiny cells are a typical example of inhibitory central nervous system GABAergic cells. In contrast, GABA exhibits both excitatory and inhibitory actions in insects, mediating muscle activation at synapses between nerves and muscle cells, and also the stimulation of certain glands. In mammals, some GABAergic neurons, such as chandelier cells, are also able to excite their glutamatergic counterparts. In addition to fast-acting phasic inhibition, small amounts of extracellular GABA can induce slow timescale tonic inhibition on neurons.

GABA_A receptors are ligand-activated chloride channels: when activated by GABA, they allow the flow of chloride ions across the membrane of the cell. Whether this chloride flow is depolarizing (makes the voltage across the cell's membrane less negative), shunting (has no effect on the cell's membrane potential), or inhibitory/hyperpolarizing (makes the cell's membrane more negative) depends on the direction of the flow of chloride. When net chloride flows out of the cell, GABA is depolarising; when chloride flows into the cell, GABA is inhibitory or hyperpolarizing. When the net flow of chloride is close to zero, the action of GABA is shunting. Shunting inhibition has no direct effect on the membrane potential of the cell; however, it reduces the effect of any coincident synaptic input by reducing the electrical resistance of the cell's membrane. Shunting inhibition can "override" the excitatory effect of depolarising GABA, resulting in overall inhibition even if the membrane potential becomes less negative. It was thought that a developmental switch in the molecular machinery controlling the concentration of chloride inside the cell changes the functional role of GABA between neonatal and adult stages. As the brain develops into adulthood, GABA's role changes from excitatory to inhibitory.

Brain development

GABA is an inhibitory transmitter in the mature brain; its actions were thought to be primarily excitatory in the developing brain. The gradient of chloride was reported to be reversed in immature neurons, with its reversal potential higher than the resting membrane potential of the cell; activation of a GABA-A receptor thus leads to efflux of Cl⁻ ions from the cell (that is, a depolarizing current). The differential gradient of chloride in immature neurons was shown to be primarily due to the higher concentration of NKCC1 co-transporters relative to KCC2 co-transporters in immature cells. GABAergic interneurons mature faster in the hippocampus and the GABA machinery appears earlier than glutamatergic transmission. Thus, GABA is considered the major excitatory neurotransmitter in many regions of the brain before the maturation of glutamatergic synapses.

In the developmental stages preceding the formation of synaptic contacts, GABA is synthesized by neurons and acts both as an autocrine (acting on the same cell) and paracrine (acting on nearby cells) signalling mediator. The ganglionic eminences also contribute greatly to building up the GABAergic cortical cell population.

GABA regulates the proliferation of neural progenitor cells, the migration and differentiation the elongation of neurites and the formation of synapses.

GABA also regulates the growth of embryonic and neural stem cells. GABA can influence the development of neural progenitor cells via brain-derived neurotrophic factor (BDNF) expression. GABA activates the GABA_A receptor, causing cell cycle arrest in the S-phase, limiting growth.

Beyond the nervous system

mRNA expression of the embryonic variant of the GABA-producing enzyme GAD67 in a coronal brain section of a one-day-old Wistar rat, with the highest expression in subventricular zone (svz)

Besides the nervous system, GABA is also produced at relatively high levels in the insulin-producing beta cells (β-cells) of the pancreas. The β-cells secrete GABA along with insulin and the GABA binds to GABA receptors on the neighboring islet alpha cells (α-cells) and inhibits them from secreting glucagon (which would counteract insulin's effects).

GABA can promote the replication and survival of β-cells and also promote the conversion of α-cells to β-cells, which may lead to new treatments for diabetes.

Alongside GABAergic mechanisms, GABA has also been detected in other peripheral tissues including intestines, stomach, fallopian tubes, uterus, ovaries, testicles, kidneys, urinary bladder, the lungs and liver, albeit at much lower levels than in neurons or β-cells.

Experiments on mice have shown that hypothyroidism induced by fluoride poisoning can be halted by administering GABA. The test also found that the thyroid recovered naturally without further assistance after the fluoride had been expelled by the GABA.

Immune cells express receptors for GABA and administration of GABA can suppress inflammatory immune responses and promote "regulatory" immune responses, such that GABA administration has been shown to inhibit autoimmune diseases in several animal models.

In 2018, GABA has shown to regulate secretion of a greater number of cytokines. In plasma of T1D patients, levels of 26 cytokines are increased and of those, 16 are inhibited by GABA in the cell assays.

In 2007, an excitatory GABAergic system was described in the airway epithelium. The system is activated by exposure to allergens and may participate in the mechanisms of asthma. GABAergic systems have also been found in the testis and in the eye lens.

Structure and conformation

GABA is found mostly as a zwitterion (i.e., with the carboxyl group deprotonated and the amino group protonated). Its conformation depends on its environment. In the gas phase, a highly folded conformation is strongly favored due to the electrostatic attraction between the two functional groups. The stabilization is about 50 kcal/mol, according to quantum chemistry calculations. In the solid state, an extended conformation is found, with a trans conformation at the amino end and a gauche conformation at the carboxyl end. This is due to the packing interactions with the neighboring molecules. In solution, five different conformations, some folded and some extended, are found as a result of solvation effects. The conformational flexibility of GABA is important for its biological function, as it has been found to bind to different receptors with different conformations. Many GABA analogues with pharmaceutical applications have more rigid structures in order to control the binding better.

History

In 1883, GABA was first synthesized, and it was first known only as a plant and microbe metabolic product.

In 1950, Washington University School of Medicine researchers Eugene Roberts and Sam Frankel used newly-developed techniques of chromatography to analyze protein-free extracts of mammalian brain and discovered that GABA is produced from glutamic acid and accumulates in the mammalian central nervous system.

There was not much further research into the substance until seven years later, Canadian researchers identified GABA as the mysterious component (termed Factor I by its discoverers in 1954) of brain and spinal cord extracts which inhibited crayfish neurons.

By 1959, it was shown that at an inhibitory synapse on crayfish muscle fibers GABA acts like stimulation of the inhibitory nerve. Both inhibition by nerve stimulation and by applied GABA are blocked by picrotoxin.

Biosynthesis

GABAergic neurons which produce GABA

GABA is primarily synthesized from glutamate via the enzyme glutamate decarboxylase (GAD) with pyridoxal phosphate (the active form of vitamin B6) as a cofactor. This process converts glutamate (the principal excitatory neurotransmitter) into GABA (the principal inhibitory neurotransmitter).

GABA can also be synthesized from putrescine by diamine oxidase and aldehyde dehydrogenase.

Historically it was thought that exogenous GABA did not penetrate the blood–brain barrier, but more current research describes the notion as being unclear pending further research.

Metabolism

GABA transaminase enzymes catalyze the conversion of 4-aminobutanoic acid (GABA) and 2-oxoglutarate (α-ketoglutarate) into succinic semialdehyde and glutamate. Succinic semialdehyde is then oxidized into succinic acid by succinic semialdehyde dehydrogenase and as such enters the citric acid cycle as a usable source of energy.

Pharmacology

Drugs that act as allosteric modulators of GABA receptors (known as GABA analogues or GABAergic drugs), or increase the available amount of GABA, typically have relaxing, anti-anxiety, and anti-convulsive effects (with equivalent efficacy to lamotrigine based on studies of mice). Many of the substances below are known to cause anterograde amnesia and retrograde amnesia.

In general, GABA does not cross the blood–brain barrier, although certain areas of the brain that have no effective blood–brain barrier, such as the periventricular nucleus, can be reached by drugs such as systemically injected GABA. At least one study suggests that orally administered GABA increases the amount of human growth hormone (HGH). GABA directly injected to the brain has been reported to have both stimulatory and inhibitory effects on the production of growth hormone, depending on the physiology of the individual. Consequently, considering the potential biphasic effects of GABA on growth hormone production, as well as other safety concerns, its usage is not recommended during pregnancy and lactation.

GABA enhances the catabolism of serotonin into N-acetylserotonin (the precursor of melatonin) in rats. It is thus suspected that GABA is involved in the synthesis of melatonin and thus might exert regulatory effects on sleep and reproductive functions.

Chemistry

Although in chemical terms, GABA is an amino acid (as it has both a primary amine and a carboxylic acid functional group), it is rarely referred to as such in the professional, scientific, or medical community. By convention the term "amino acid", when used without a qualifier, refers specifically to an alpha amino acid. GABA is not an alpha amino acid, meaning the amino group is not attached to the alpha carbon. Nor is it incorporated into proteins as are many alpha-amino acids.

GABAergic drugs

GABA_A receptor ligands are shown in the following table.

Activity at GABAA	Ligand
Orthosteric agonist	Muscimol, GABA, gaboxadol (THIP), isoguvacine, progabide, piperidine-4-sulfonic acid (partial agonist)
Positive allosteric modulators	Barbiturates, benzodiazepines, neuroactive steroids, niacin/niacinamide, nonbenzodiazepines (i.e., z-drugs, e.g., zolpidem), etomidate, alcohol (ethanol), methaqualone, propofol, stiripentol, and anaesthetics (including volatile anaesthetics)
Orthosteric (competitive) antagonist	bicuculline, gabazine, thujone, flumazenil
Uncompetitive antagonist (e.g., channel blocker)	cicutoxin
Negative allosteric modulators	furosemide, oenanthotoxin, amentoflavone

GABAergic pro-drugs include chloral hydrate, which is metabolised to trichloroethanol, which then acts via the GABA_A receptor.

The plant kava contains GABAergic compounds, including kavain, dihydrokavain, methysticin, dihydromethysticin and yangonin.

Other GABAergic modulators include:

• GABA_B receptor ligands.
  • Agonists: baclofen, propofol, GHB, phenibut.
  • Antagonists: phaclofen, saclofen.
• GABA reuptake inhibitors: deramciclane, hyperforin, tiagabine.
• GABA transaminase inhibitors: gabaculine, phenelzine, valproate, vigabatrin, lemon balm (Melissa officinalis).
• GABA analogues: pregabalin, gabapentin, picamilon, progabide

4-Amino-1-butanol is a biochemical precursor of GABA and can be converted into GABA by the actions of aldehyde reductase (ALR) and aldehyde dehydrogenase (ALDH) with γ-aminobutyraldehyde (GABAL) as a metabolic intermediate.

In plants

GABA is also found in plants. It is the most abundant amino acid in the apoplast of tomatoes. Evidence also suggests a role in cell signalling in plants.

Vestigiality

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Vestigiality

In humans, the vermiform appendix is sometimes called a vestigial structure as it has lost much of its ancestral digestive function.

Vestigiality is the retention, during the process of evolution, of genetically determined structures or attributes that have lost some or all of the ancestral function in a given species. Assessment of the vestigiality must generally rely on comparison with homologous features in related species. The emergence of vestigiality occurs by normal evolutionary processes, typically by loss of function of a feature that is no longer subject to positive selection pressures when it loses its value in a changing environment. The feature may be selected against more urgently when its function becomes definitively harmful, but if the lack of the feature provides no advantage, and its presence provides no disadvantage, the feature may not be phased out by natural selection and persist across species.

Examples of vestigial structures (also called degenerate, atrophied, or rudimentary organs) are the loss of functional wings in island-dwelling birds; the human vomeronasal organ; and the hindlimbs of the snake and whale.

Overview

The Darwin-tubercle (left) is a vestigial form of the ear tip (right) in the mammalian ancestors of humans—here shown in a crab-eating macaque.

Vestigial features may take various forms; for example, they may be patterns of behavior, anatomical structures, or biochemical processes. Like most other physical features, however functional, vestigial features in a given species may successively appear, develop, and persist or disappear at various stages within the life cycle of the organism, ranging from early embryonic development to late adulthood.

Vestigial hindlegs (spurs) in a boa constrictor

Vestigiality, biologically speaking, refers to organisms retaining organs that have seemingly lost their original function. Vestigial organs are common evolutionary knowledge. In addition, the term vestigiality is useful in referring to many genetically determined features, either morphological, behavioral, or physiological; in any such context, however, it need not follow that a vestigial feature must be completely useless. A classic example at the level of gross anatomy is the human vermiform appendix, vestigial in the sense of retaining no significant digestive function.

Similar concepts apply at the molecular level—some nucleic acid sequences in eukaryotic genomes have no known biological function; some of them may be "junk DNA", but it is a difficult matter to demonstrate that a particular sequence in a particular region of a given genome is truly nonfunctional. The simple fact that it is noncoding DNA does not establish that it is functionless. Furthermore, even if an extant DNA sequence is functionless, it does not follow that it has descended from an ancestral sequence of functional DNA. Logically such DNA would not be vestigial in the sense of being the vestige of a functional structure. In contrast pseudogenes have lost their protein-coding ability or are otherwise no longer expressed in the cell. Whether they have any extant function or not, they have lost their former function and in that sense, they do fit the definition of vestigiality.

Vestigial structures are often called vestigial organs, although many of them are not actually organs. Such vestigial structures typically are degenerate, atrophied, or rudimentary, and tend to be much more variable than homologous non-vestigial parts. Although structures commonly regarded "vestigial" may have lost some or all of the functional roles that they had played in ancestral organisms, such structures may retain lesser functions or may have become adapted to new roles in extant populations.

It is important to avoid confusion of the concept of vestigiality with that of exaptation. Both may occur together in the same example, depending on the relevant point of view. In exaptation, a structure originally used for one purpose is modified for a new one. For example, the wings of penguins would be exaptational in the sense of serving a substantial new purpose (underwater locomotion), but might still be regarded as vestigial in the sense of having lost the function of flight. In contrast Darwin argued that the wings of emus would be definitely vestigial, as they appear to have no major extant function; however, function is a matter of degree, so judgments on what is a "major" function are arbitrary; the emu does seem to use its wings as organs of balance in running. Similarly, the ostrich uses its wings in displays and temperature control, though they are undoubtedly vestigial as structures for flight.

Vestigial characters range from detrimental through neutral to favorable in terms of selection. Some may be of some limited utility to an organism but still degenerate over time if they do not confer a significant enough advantage in terms of fitness to avoid the effects of genetic drift or competing selective pressures. Vestigiality in its various forms presents many examples of evidence for biological evolution.

History

The blind mole rat (Spalax typhlus) has tiny eyes completely covered by a layer of skin.

Vestigial structures have been noticed since ancient times, and the reason for their existence was long speculated upon before Darwinian evolution provided a widely accepted explanation. In the 4th century BC, Aristotle was one of the earliest writers to comment, in his History of Animals, on the vestigial eyes of moles, calling them "stunted in development" due to the fact that moles can scarcely see. However, only in recent centuries have anatomical vestiges become a subject of serious study. In 1798, Étienne Geoffroy Saint-Hilaire noted on vestigial structures:

Whereas useless in this circumstance, these rudiments... have not been eliminated, because Nature never works by rapid jumps, and She always leaves vestiges of an organ, even though it is completely superfluous, if that organ plays an important role in the other species of the same family.

His colleague, Jean-Baptiste Lamarck, named a number of vestigial structures in his 1809 book Philosophie Zoologique. Lamarck noted "Olivier's Spalax, which lives underground like the mole, and is apparently exposed to daylight even less than the mole, has altogether lost the use of sight: so that it shows nothing more than vestiges of this organ."

Charles Darwin was familiar with the concept of vestigial structures, though the term for them did not yet exist. He listed a number of them in The Descent of Man, including the muscles of the ear, wisdom teeth, the appendix, the tail bone, body hair, and the semilunar fold in the corner of the eye. Darwin also noted, in On the Origin of Species, that a vestigial structure could be useless for its primary function, but still retain secondary anatomical roles: "An organ serving for two purposes, may become rudimentary or utterly aborted for one, even the more important purpose, and remain perfectly efficient for the other.... [A]n organ may become rudimentary for its proper purpose, and be used for a distinct object."

In the first edition of On the Origin of Species, Darwin briefly mentioned inheritance of acquired characters under the heading "Effects of Use and Disuse", expressing little doubt that use "strengthens and enlarges certain parts, and disuse diminishes them; and that such modifications are inherited". In later editions he expanded his thoughts on this, and in the final chapter of the 6th edition concluded that species have been modified "chiefly through the natural selection of numerous successive, slight, favorable variations; aided in an important manner by the inherited effects of the use and disuse of parts".

In 1893, Robert Wiedersheim published The Structure of Man, a book on human anatomy and its relevance to man's evolutionary history. The Structure of Man contained a list of 86 human organs that Wiedersheim described as, "Organs having become wholly or in part functionless, some appearing in the Embryo alone, others present during Life constantly or inconstantly. For the greater part Organs which may be rightly termed Vestigial." Since his time, the function of some of these structures have been discovered, while other anatomical vestiges have been unearthed, making the list primarily of interest as a record of the knowledge of human anatomy at the time. Later versions of Wiedersheim's list were expanded to as many as 180 human "vestigial organs". This is why the zoologist Horatio Newman said in a written statement read into evidence in the Scopes Trial that "There are, according to Wiedersheim, no less than 180 vestigial structures in the human body, sufficient to make of a man a veritable walking museum of antiquities."

Common descent and evolutionary theory

Further information: Evidence of common descent

Vestigial structures are often homologous to structures that are functioning normally in other species. Therefore, vestigial structures can be considered evidence for evolution, the process by which beneficial heritable traits arise in populations over an extended period of time. The existence of vestigial traits can be attributed to changes in the environment and behavior patterns of the organism in question. Through an examination of these various traits, it is clear that evolution had a hard role in the development of organisms. Every anatomical structure or behavior response has origins in which they were, at one time, useful. As time progressed, the ancient common ancestor organisms did as well. Evolving with time, natural selection played a huge role. More advantageous structures were selected, while others were not. With this expansion, some traits were left to the wayside. As the function of the trait is no longer beneficial for survival, the likelihood that future offspring will inherit the "normal" form of it decreases. In some cases, the structure becomes detrimental to the organism (for example the eyes of a mole can become infected). In many cases the structure is of no direct harm, yet all structures require extra energy in terms of development, maintenance, and weight, and are also a risk in terms of disease (e.g., infection, cancer), providing some selective pressure for the removal of parts that do not contribute to an organism's fitness. A structure that is not harmful will take longer to be 'phased out' than one that is. However, some vestigial structures may persist due to limitations in development, such that complete loss of the structure could not occur without major alterations of the organism's developmental pattern, and such alterations would likely produce numerous negative side-effects. The toes of many animals such as horses, which stand on a single toe, are still evident in a vestigial form and may become evident, although rarely, from time to time in individuals.

The vestigial versions of the structure can be compared to the original version of the structure in other species in order to determine the homology of a vestigial structure. Homologous structures indicate common ancestry with those organisms that have a functional version of the structure. Douglas Futuyma has stated that vestigial structures make no sense without evolution, just as spelling and usage of many modern English words can only be explained by their Latin or Old Norse antecedents.

Vestigial traits can still be considered adaptations. This is because an adaptation is often defined as a trait that has been favored by natural selection. Adaptations, therefore, need not be adaptive, as long as they were at some point.

Examples

Non-human animals

Letter c in the picture indicates the undeveloped hind legs of a baleen whale.

Vestigial characters are present throughout the animal kingdom, and an almost endless list could be given. Darwin said that "it would be impossible to name one of the higher animals in which some part or other is not in a rudimentary condition."

The wings of ostriches, emus and other flightless birds are vestigial; they are remnants of their flying ancestors' wings. These birds go through the effort of developing wings, even though most birds are too large to use the wings successfully. Seeing vestigial wings in birds is also common when they no longer need to fly to escape predators, such as birds on the Galapagos Islands. The eyes of certain cavefish and salamanders are vestigial, as they no longer allow the organism to see, and are remnants of their ancestors' functional eyes. Animals that reproduce without sex (via asexual reproduction) generally lose their sexual traits, such as the ability to locate/recognize the opposite sex and copulation behavior.

Boas and pythons have vestigial pelvis remnants, which are externally visible as two small pelvic spurs on each side of the cloaca. These spurs are sometimes used in copulation, but are not essential, as no colubrid snake (the vast majority of species) possesses these remnants. Furthermore, in most snakes, the left lung is greatly reduced or absent. Amphisbaenians, which independently evolved limblessness, also retain vestiges of the pelvis as well as the pectoral girdle, and have lost their right lung.

Vestigial attachment clamps in various genera of protomicrocotylids. Accessory sclerites (black) are present in normal clamps but absent in simplified clamps. Lethacotyle (right) has no clamp at all.

A case of vestigial organs was described in polyopisthocotylean Monogeneans (parasitic flatworms). These parasites usually have a posterior attachment organ with several clamps, which are sclerotised organs attaching the worm to the gill of the host fish. These clamps are extremely important for the survival of the parasite. In the family Protomicrocotylidae, species have either normal clamps, simplified clamps, or no clamps at all (in the genus Lethacotyle). After a comparative study of the relative surface of clamps in more than 100 Monogeneans, this has been interpreted as an evolutionary sequence leading to the loss of clamps. Coincidentally, other attachment structures (lateral flaps, transverse striations) have evolved in protomicrocotylids. Therefore, clamps in protomicrocotylids were considered vestigial organs.

In the foregoing examples the vestigiality is generally the (sometimes incidental) result of adaptive evolution. However, there are many examples of vestigiality as the product of drastic mutation, and such vestigiality is usually harmful or counter-adaptive. One of the earliest documented examples was that of vestigial wings in Drosophila. Many examples in many other contexts have emerged since.

Humans

Main article: Human vestigiality

The muscles connected to the ears of a human do not develop enough to have the same mobility allowed to many animals.

Human vestigiality is related to human evolution, and includes a variety of characters occurring in the human species. Many examples of these are vestigial in other primates and related animals, whereas other examples are still highly developed. The human caecum is vestigial, as often is the case in omnivores, being reduced to a single chamber receiving the content of the ileum into the colon. The ancestral caecum would have been a large, blind diverticulum in which resistant plant material such as cellulose would have been fermented in preparation for absorption in the colon. Analogous organs in other animals similar to humans continue to perform similar functions. The coccyx, or tailbone, though a vestige of the tail of some primate ancestors, is functional as an anchor for certain pelvic muscles including: the levator ani muscle and the largest gluteal muscle, the gluteus maximus.

Other structures that are vestigial include the plica semilunaris on the inside corner of the eye (a remnant of the nictitating membrane); and (as seen at right) muscles in the ear. Other organic structures (such as the occipitofrontalis muscle) have lost their original functions (to keep the head from falling) but are still useful for other purposes (facial expression).

Humans also bear some vestigial behaviors and reflexes. The formation of goose bumps in humans under stress is a vestigial reflex; its function in human ancestors was to raise the body's hair, making the ancestor appear larger and scaring off predators. The arrector pili (muscle that connects the hair follicle to connective tissue) contracts and creates goosebumps on skin.

There are also vestigial molecular structures in humans, which are no longer in use but may indicate common ancestry with other species. One example of this is a gene that is functional in most other mammals and which produces L-gulonolactone oxidase, an enzyme that can make vitamin C. A documented mutation deactivated the gene in an ancestor of the modern infraorder of monkeys, and apes, and it now remains in their genomes, including the human genome, as a vestigial sequence called a pseudogene.

The shift in human diet towards soft and processed food over time caused a reduction in the number of powerful grinding teeth, especially the third molars (also known as wisdom teeth), which were highly prone to impaction.

Plants and fungi

Plants also have vestigial parts, including functionless stipules and carpels, leaf reduction of Equisetum, paraphyses of Fungi. Well known examples are the reductions in floral display, leading to smaller and/or paler flowers, in plants that reproduce without outcrossing, for example via selfing or obligate clonal reproduction.

Objects

The uniform of the German Feldgendarmerie during WW2, complete with gorget.

Many objects in daily use contain vestigial structures. While not the result of natural selection through random mutation, much of the process is the same. Product design, like evolution, is iterative; it builds on features and processes that already exist, with limited resources available to make tweaks. To spend resources on completely weeding out a form that serves no purpose (if at the same time it is not an obstruction either) is not economically astute. These vestigial structures differ from the concept of skeuomorphism in that a skeuomorph is a design feature that has been specifically implemented as a reference to the past, enabling users to acclimatise quicker. A vestigial feature does not exist intentionally, or even usefully.

For example, men's business suits often contain a row of buttons at the bottom of the sleeve. These used to serve a purpose, allowing the sleeve to be split and rolled up. The feature has been lost entirely, though most suits still give the impression that it is possible, complete with fake button holes. There is also an example of exaptation to be found in the business suit: it was previously possible to button a jacket up all the way to the top. As it became the fashion to fold the lapel over, the top half of buttons and their accompanying buttonholes disappeared, save for a single hole at the top; it has since found a new use as a place to fasten pins, badges, or boutonnières.

As a final example, soldiers in ceremonial or parade uniform can sometimes be seen wearing a gorget: a small decorative piece of metal suspended around the neck with a chain. The gorget serves no protection to the wearer, yet there exists an unbroken lineage from the gorget to the full suits of armour of the middle ages. With the introduction of gunpowder weapons, armour increasingly lost its usefulness on the battlefield. At the same time, military men were keen to retain the status it provided them. The result: a breastplate that "shrank" away over time, but never disappeared completely.

The Shock Doctrine

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/The_Shock_Doctrine

 

The Shock Doctrine: The Rise of Disaster Capitalism

Front cover of The Shock Doctrine
Author	Naomi Klein
Language	English
Subject	Economics
Publisher	Knopf Canada (first edition)
Publication date	2007
Publication place	Canada
Media type	Print e-book
Pages	662 (first edition)
ISBN	978-0-676-97800-1 (hardcover)
Dewey Decimal	330.12/2
Preceded by	Fences and Windows
Followed by	This Changes Everything

The Shock Doctrine: The Rise of Disaster Capitalism is a 2007 book by Canadian author and social activist Naomi Klein. In the book, Klein argues that neoliberal economic policies promoted by Milton Friedman and the Chicago School of Economics have risen to global prominence because of a deliberate strategy she calls "disaster capitalism". In this strategy, political actors exploit the chaos of natural disasters, wars, and other crises to push through unpopular policies such as deregulation and privatization. This economic "shock therapy" favors corporate interests while disadvantaging and disenfranchising citizens when they are too distracted and overwhelmed to respond or resist effectively. The book challenges the narrative that free market capitalist policies have been welcomed by the inhabitants of regions where they have been implemented, and it argues that several man-made events, including the Iraq War, were intentionally undertaken with the goal of pushing through these unpopular policies in their wake.

Some reviewers claimed the book oversimplifies political phenomena, while others lauded it as a compelling and important work. The book served as the main source of a 2009 documentary feature film with the same title directed by Michael Winterbottom.

Synopsis

The book is divided into seven parts with a total of 21 chapters.

Part 1 begins with a chapter on psychiatric shock therapy and the covert experiments conducted by the psychiatrist Ewen Cameron in collusion with the Central Intelligence Agency. The second chapter introduces Milton Friedman and his Chicago school of economics, whom Klein describes as leading a laissez-faire capitalist movement committed to creating free markets that are even less regulated than those that existed before the Great Depression.

Part 2 discusses the use of the "shock doctrine" to transform South American economies in the 1970s, focusing on the 1973 coup in Chile led by General Augusto Pinochet and influenced by the Chicago Boys, a group of Chilean economists who had studied under Friedman at the Chicago School and were funded by the CIA. Klein connects torture with economic shock therapy.

Part 3 covers attempts to apply the shock doctrine without the need for extreme violence against sections of the population. Klein says that Margaret Thatcher applied mild shock "therapy" facilitated by the Falklands War, while free market reform in Bolivia was possible due to a combination of pre-existing economic crises and the charisma of Jeffrey Sachs.

Part 4 reports on how Klein thinks the shock doctrine was applied in Poland, China, South Africa, Russia, and the Four Asian Tigers. In Poland she discusses how the left-leaning trade union Solidarity won the country's 1989 legislative elections, but subsequently employed the shock doctrine due to IMF pressure. The section on China discusses the 1989 Tiananmen Square Protests, and the liberalization of China's economy. In South Africa she explains that the negotiations to end apartheid resulted in economic policy that went against the core of the Freedom Charter. In Russia she describes how Boris Yeltsin took power after the collapse of the Soviet Union and crafted an economic policy that turned Russia into an oligarchy. Finally, she says that during the 1997 Asian financial crisis the Tiger Nations were forced to sell off numerous state enterprises to private, foreign companies.

Part 5 introduces the "Disaster Capitalism Complex", a complex series of networks and influence employed by private companies that allows them to profit from disasters. She mirrors this new Disaster Capitalism Complex with the Military Industrial Complex and explains that both employ the blurring of the line between private and public, through tactics like the revolving door.

Part 6 discusses the use of "shock and awe" in the 2003 invasion of Iraq and the subsequent occupation of Iraq, which Klein describes as the most comprehensive and full-scale implementation of the shock doctrine ever attempted, with mass privatization of Iraqi state-owned enterprises (including thousands of men being laid off) which is argued as contributing to the insurgency, since many of the unemployed became embittered toward the US as a result and joined insurgent groups afterward.

Part 7 is about winners and losers of economic shock therapy – how small groups will often do very well by moving into luxurious gated communities while large sections of the population are left with decaying public infrastructure, declining incomes and increased unemployment. Klein describes economic policy after Hurricane Katrina, the 2004 Sri Lanka Tsunami, and the apartheid-style policy of the Israeli government toward Palestinians.

The Conclusion details the backlash against the "shock doctrine" and economic institutions which, in Klein's view, encourage it – like the World Bank and IMF. South America and Lebanon post-2006 are shown in a positive light, where politicians are already rolling back free-market policies, with some mention of the increased campaigning by community-minded activists in South Africa and China.

Reactions

Favourable

Paul B. Farrell from the Dow Jones Business News argued that The Shock Doctrine "may be the most important book on economics in the 21st century." In The Guardian, John Gray hailed it as one of the "very few books that really help us understand the present", describing the work as "both timely and devastating". William S. Kowinski of the San Francisco Chronicle praised Klein's prose and wrote that the author "may well have revealed the master narrative of our time." In The Irish Times, Tom Clonan reported that she "systematically and calmly demonstrates to the reader" the way in which neoconservative figures were intimately linked to seismic events that "resulted in the loss of millions of lives."

In the Los Angeles Times, Richard Rayner opined, "Not everybody's going to agree with her, but this is reporting and history-writing in the tradition of Izzy Stone and Upton Sinclair. Klein upends assumptions and demands that we think – her book is thrilling, troubling and very dark." Stephen Amidon of the New York Observer affirmed the applicability of Klein's thesis to the Iraq War and argued, "Seen through the lens of Naomi Klein's analysis, [it] makes horrifying sense, right down to Mr. Rumsfeld's decision to allow the looting of the nation's cultural identity." Shashi Tharoor noted the work's "meticulous endnotes" and stated, referring to globalization, that Klein "has established herself as its principal naysayer." Katy Guest of The Independent praised the book as "a compelling account of the way big business and politics use global disasters for their own ends." Juan Santos, winner of the 2016 Nobel Peace Prize, called the book "as gripping as the best murder mystery, as well researched as the best investigative journalism – on a par with the work of a Seymour Hersh."

The Shock Doctrine was named one of the best books of 2007 by the Village Voice, Publishers Weekly, The Observer, and the Seattle Times. In 2019, The Guardian ranked it the 18th greatest book since 2000.

Mixed

The Nobel Laureate and former Chief Economist of the World Bank Joseph Stiglitz wrote a review of The Shock Doctrine for The New York Times calling the parallel between economic shock therapy and the psychological experiments conducted by Ewen Cameron "overdramatic and unconvincing" and claiming that "Klein is not an academic and cannot be judged as one. There are many places in her book where she oversimplifies." He also said, "the case against these policies is even stronger than the one Klein makes" and that the book contains "a rich description of the political machinations required to force unsavory economic policies on resisting countries." Shashi Tharoor in The Washington Post says that The Shock Doctrine takes Klein's criticism of capitalism an important step further. He also said Klein "is too ready to see conspiracies where others might discern little more than the all-too-human pattern of chaos and confusion, good intentions and greed."

Sociologists as Ulrich Beck envisioned the society of risk as a new cultural value which posed risk as a commodity to be exchanged in globalized economies. As Klein observed, this suggested that disasters and capitalist economy was inevitably entwined. Some voices have praised the contributions of Klein to the study of the "spectacle of disasters".

Unfavourable

In the London Review of Books, Stephen Holmes criticizes The Shock Doctrine as naïve, and opines that it conflates "'free market orthodoxy' with predatory corporate behaviour." John Willman of the Financial Times describes it as "a deeply flawed work that blends together disparate phenomena to create a beguiling – but ultimately dishonest – argument." Tom Redburn in The New York Times states that "what she is most blind to is the necessary role of entrepreneurial capitalism in overcoming the inherent tendency of any established social system to lapse into stagnation."

Jonathan Chait wrote in The New Republic that Klein "pays shockingly (but, given her premises, unsurprisingly) little attention to right-wing ideas. She recognizes that neoconservatism sits at the heart of the Iraq war project, but she does not seem to know what neoconservatism is; and she makes no effort to find out." Robert Cole from The Times said, "Klein derides the 'disaster capitalism complex' and the profits and privatisations that go with it but she does not supply a cogently argued critique of free market principles, and without this The Shock Doctrine descends into a muddle of stories that are often worrying, sometimes interesting, and occasionally bizarre."

Economist Tyler Cowen, who called Klein's arguments "ridiculous" and the book a "true economics disaster", wrote on The New York Sun that the book contains "a series of fabricated claims, such as the suggestion that Margaret Thatcher created the Falkland Islands crisis to crush the unions and foist unfettered capitalism upon an unwilling British public." Johan Norberg of the libertarian Cato Institute criticizes the book, saying that "Klein's analysis is hopelessly flawed at virtually every level." Norberg finds fault with specifics of the analysis, such as with the Chinese government crackdown on the Tiananmen Square protests of 1989. He argues that, rather than crushing opposition to pro-market reforms (as Klein would have it), the crackdown itself caused liberalization to stall for years. Klein responded on her website to both Norberg and Chait, stating that both had misrepresented her positions. Klein wrote that Norberg had erected a straw man by claiming that her book is about one man, Friedman, but that it is in fact about a "multifaceted ideological trend". Norberg again responded that Klein "actually defends only one of her central claims that I criticized. Instead, she gives the impression that I have just tried to find small mistakes here and there in her book." He went on to say that the numbers Klein supplied in her reply reveal the statistics in her central argument to be "rubbish".

Later comments

In a piece related to the COVID-19 pandemic, Klein wrote in 2020 that a "Pandemic Shock Doctrine" was beginning to emerge and called it the "Screen New Deal".

Awards

• Winner of the Warwick Prize for Writing (2008/2009)