Melanin and genes.

Melanin is produced by cells called melanocytes in a process called melanogenesis. Melanin is made within small membrane–bound packages called melanosomes. As they become full of melanin, they move into the slender arms of melanocytes, from where they are transferred to the keratinocytes. Under normal conditions, melanosomes cover the upper part of the keratinocytes and protect them from genetic damage. One melanocyte supplies melanin to thirty-six keratinocytes according to signals from the keratinocytes. They also regulate melanin production and replication of melanocytes. People have different skin colors mainly because their melanocytes produce different amount and kinds of melanin.  The genetic mechanism behind human skin color is mainly regulated by the enzyme tyrosinase, which creates the color of the skin, eyes, and hair shades. Differences in skin color are also attributed to differences in size and distribution of melanosomes in the skin. Melanocytes produce two types of melanin. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms. Most are derived from the amino acid tyrosine. Eumelanin is found in hair, areola, and skin, and the hair colors gray, black, blond, and brown. In humans, it is more abundant in people with dark skin. Pheomelanin, a pink to red hue is found in particularly large quantities in red hair, the lips, nipples, glans of the penis, and vagina.  Both the amount and type of melanin produced is controlled by a number of genes that operate under incomplete dominance. One copy of each of the various genes is inherited from each parent. Each gene can come in several alleles, resulting in the great variety of human skin tones. Melanin controls the amount of ultraviolet (UV) radiation from the sun that penetrates the skin by absorption. While UV radiation can assist in the production of vitamin D, excessive exposure to UV can damage health.

Evolution of skin color.

Loss of body hair in Hominini species is assumed to be related to the emergence of bipedalism some 5 to 7 million years ago. Bipedal hominin body hair may have disappeared gradually to allow better heat dissipation through sweating. The emergence of skin pigmentation dates to at about 1.2 million years ago, under conditions of a megadrought that drove early humans into arid, open landscapes. Such conditions likely caused excess UV-B radiation. This favored the emergence of skin pigmentation in order to protect from folate depletion due to the increased exposure to sunlight. A theory that the pigmentation helped counter xeric stress by increasing the epidermal permeability barrier has been disproved.  With the evolution of hairless skin, abundant sweat glands, and skin rich in melanin, early humans could walk, run, and forage for food for long periods of time under the hot sun without brain damage due to overheating, giving them an evolutionary advantage over other species. By 1.2 million years ago, around the time of "Homo ergaster", archaic humans (including the ancestors of "Homo sapiens") had exactly the same receptor protein as modern sub-Saharan Africans.  This was the genotype inherited by anatomically modern humans, but retained only by part of the extant populations, thus forming an aspect of human genetic variation. About 100,000–70,000 years ago, some anatomically modern humans ("Homo sapiens") began to migrate away from the tropics to the north where they were exposed to less intense sunlight. This was possibly in part due to the need for greater use of clothing to protect against the colder climate. Under these conditions there was less photodestruction of folate and so the evolutionary pressure working against the survival of lighter-skinned gene variants was reduced. In addition, lighter skin is able to generate more vitamin D (cholecalciferol) than darker skin, so it would have represented a health benefit in reduced sunlight if there were limited sources of vitamin D. Hence the leading hypothesis for the evolution of human skin color proposes that: The genetic mutations leading to light skin, though partially different among East Asians and Western Europeans, suggest the two groups experienced a similar selective pressure after settlement in northern latitudes.  The theory is partially supported by a study into the SLC24A5 gene which found that the allele associated with light skin in Europe "determined [...] that 18,000 years had passed since the light-skin allele was fixed in Europeans" but may have originated as recently as 12,000–6,000 years ago "given the imprecision of method", which is in line with the earliest evidence of farming.  Research by Nina Jablonski suggests that an estimated time of about 10,000 to 20,000 years is enough for human populations to achieve optimal skin pigmentation in a particular geographic area but that development of ideal skin coloration may happen faster if the evolutionary pressure is stronger, even in as little as 100 generations. The length of time is also affected by cultural practices such as food intake, clothing, body coverings, and shelter usage which can alter the ways in which the environment affects populations. One of the most recently proposed drivers of the evolution of skin pigmentation in humans is based on research that shows a superior barrier function in darkly pigmented skin. Most protective functions of the skin, including the permeability barrier and the antimicrobial barrier, reside in the stratum corneum (SC) and the researchers surmise that the SC has undergone the most genetic change since the loss of human body hair. Natural selection would have favored mutations that protect this essential barrier; one such protective adaptation is the pigmentation of interfollicular epidermis, because it improves barrier function as compared to non-pigmented skin. In lush rainforests, however, where UV-B radiation and xeric stress were not in excess, light pigmentation would not have been nearly as detrimental. This explains the side-by-side residence of lightly pigmented and darkly pigmented peoples.  Population and admixture studies suggest a three-way model for the evolution of human skin color, with dark skin evolving in early hominids in Africa and light skin evolving partly separately at least two times after modern humans had expanded out of Africa.  For the most part, the evolution of light skin has followed different genetic paths in Western and Eastern Eurasian populations. Two genes however, KITLG and ASIP, have mutations associated with lighter skin that have high frequencies in Eurasian populations and have estimated origin dates after humans spread out of Africa but before the divergence of the two lineages.

Genetics.

The understanding of the genetic mechanisms underlying human skin color variation is still incomplete, however genetic studies have discovered a number of genes that affect human skin color in specific populations, and have shown that this happens independently of other physical features such as eye and hair color. Different populations have different allele frequencies of these genes, and it is the combination of these allele variations that bring about the complex, continuous variation in skin coloration we can observe today in modern humans. Population and admixture studies suggest a 3-way model for the evolution of human skin color, with dark skin evolving in early hominids in sub-Saharan Africa and light skin evolving independently in Europe and East Asia after modern humans had expanded out of Africa.

Dark skin.

All modern humans share a common ancestor who lived around 200,000 years ago in Africa. Comparisons between known skin pigmentation genes in chimpanzees and modern Africans show that dark skin evolved along with the loss of body hair about 1.2 million years ago and that this common ancestor had dark skin. Investigations into dark skinned populations in South Asia and Melanesia indicate that skin pigmentation in these populations is due to the preservation of this ancestral state and not due to new variations on a previously lightened population.

Light skin.

For the most part, the evolution of light skin has followed different genetic paths in European and East Asian populations. Two genes however, KITLG and ASIP, have mutations associated with lighter skin that have high frequencies in both European and East Asian populations. They are thought to have originated after humans spread out of Africa but before the divergence of the European and Asian lineages around 30,000 years ago. Two subsequent genome-wide association studies found no significant correlation between these genes and skin color, and suggest that the earlier findings may have been the result of incorrect correction methods and small panel sizes, or that the genes have an effect too small to be detected by the larger studies.

Europe.

A number of genes have been positively associated with the skin pigmentation difference between European and non-European populations. Mutations in SLC24A5 and SLC45A2 are believed to account for the bulk of this variation and show very strong signs of selection. A variation in TYR has also been identified as a contributor.  Research indicates the selection for the light-skin alleles of these genes in Europeans is comparatively recent, having occurred later than 20,000 years ago and perhaps as recently as 12,000 to 6,000 years ago. In the 1970s, Luca Cavalli-Sforza suggested that the selective sweep that rendered light skin ubiquitous in Europe might be correlated with the advent of farming and thus have taken place only around 6,000 years ago; This scenario found support in a 2014 analysis of mesolithic (7,000 years old) hunter-gatherer DNA from La Braña, Spain, which showed a version of these genes not corresponding with light skin color. In 2015 researchers analysed for light skin genes in the DNA of 94 ancient skeletons ranging from 8,000 to 3,000 years old from Europe and Russia. They found c. 8,000-year-old hunter-gatherers in Spain, Luxembourg, and Hungary were dark skinned while similarly aged hunter gatherers in Sweden were light skinned (having predominately derived alleles of SLC24A5, SLC45A2 and also HERC2/OCA2). Neolithic farmers entering Europe at around the same time were intermediate, being nearly fixed for the derived SLC24A5 variant but only having the derived SLC45A2 allele in low frequencies. The SLC24A5 variant spread very rapidly throughout central and southern Europe from about 8,000 years ago, whereas the light skin variant of SLC45A2 spread throughout Europe after 5,800 years ago.

East Asia.

A number of genes known to affect skin color have alleles that show signs of positive selection in East Asian populations. Of these only OCA2 has been directly related to skin color measurements, while DCT, MC1R and ATTRN are marked as candidate genes for future study.

Tanning response.

Tanning response in humans is controlled by a variety of genes. "MC1R" variants "Arg151Sys" (rs1805007), "Arg160Trp" (rs1805008), "Asp294Sys" (rs1805009), "Val60Leu" (rs1805005) and "Val92Met" (rs2228479) have been associated with reduced tanning response in European and/or East Asian populations. These alleles show no signs of positive selection and only occur in relatively small numbers, reaching a peak in Europe with around 28% of the population having at least one allele of one of the variations. A study of self-reported tanning ability and skin type in American non-Hispanic Caucasians found that "SLC24A5 Phe374Leu" is significantly associated with reduced tanning ability and also associated "TYR Arg402Gln" (rs1126809), "OCA2 Arg305Trp" (rs1800401) and a 2-SNP haplotype in "ASIP" (rs4911414 and rs1015362) to skin type variation within a "fair/medium/olive" context.

Albinism.

Oculocutaneous albinism (OCA) is a lack of pigment in the eyes, skin and sometimes hair that occurs in a very small fraction of the population. The four known types of "OCA" are caused by mutations in the "TYR", "OCA2", "TYRP1", and "SLC45A2" genes.

Age.

In hominids, the parts of the body not covered with hair, like the face and the back of the hands, start out pale in infants and turn darker as the skin is exposed to more sun. All human babies are born pale, regardless of what their adult color will be. In humans, melanin production does not peak until after puberty.  The skin of children becomes darker as they go through puberty and experience the effects of sex hormones. This darkening is especially noticeable in the skin of the nipples, the areola of the nipples, the labia majora in females, and the scrotum in males. In some people, the armpits become slightly darker during puberty. The interaction of genetic, hormonal, and environmental factors on skin coloration with age is still not adequately understood, but it is known that men are at their darkest baseline skin color around the age of 30, without considering the effects of tanning. Around the same age, women experience darkening of some areas of their skin.  Human skin color fades with age. Humans over the age of thirty experience a decrease in melanin-producing cells by about 10% to 20% per decade as melanocyte stem cells gradually die. The skin of face and hands has about twice the amount of pigment cells as unexposed areas of the body, as chronic exposure to the sun continues to stimulate melanocytes. The blotchy appearance of skin color in the face and hands of older people is due to the uneven distribution of pigment cells and to changes in the interaction between melanocytes and keratinocytes.

Sexual dimorphism.

It has been observed that females are found to have lighter skin pigmentation than males in some studied populations. This may be a form of sexual dimorphism due to the requirement in women for high amounts of calcium during pregnancy and lactation. Breastfeeding newborns, whose skeletons are growing, require high amounts of calcium intake from the mother's milk (about 4 times more than during prenatal development), part of which comes from reserves in the mother's skeleton. Adequate vitamin D resources are needed to absorb calcium from the diet, and it has been shown that deficiencies of vitamin D and calcium increase the likelihood of various birth defects such as spina bifida and rickets. Natural selection may have led to females with lighter skin than males in some indigenous populations because women must get enough vitamin D and calcium to support the development of fetus and nursing infants and to maintain their own health. However in some populations such as in Italy, Poland, Ireland, Spain and Portugal men are found to have fairer complexions, and this has been ascribed as a cause to increased melanoma risk in men.  The sexes also differ in how they change their skin color with age. Men and women are not born with different skin color, they begin to diverge during puberty with the influence of sex hormones. Women can also change pigmentation in certain parts of their body, such as the areola, during the menstrual cycle and pregnancy and between 50 and 70% of pregnant women will develop the "mask of pregnancy" (melasma or chloasma) in the cheeks, upper lips, forehead, and chin. This is caused by increases in the female hormones estrogen and progesterone and it can develop in women who take birth control pills or participate in hormone replacement therapy.

Disorders of pigmentation.

Uneven pigmentation of some sort affects most people, regardless of bioethnic background or skin color. Skin may either appear lighter, or darker than normal, or lack pigmentation at all; there may be blotchy, uneven areas, patches of brown to gray discoloration or freckling. Apart from blood-related conditions such as jaundice, carotenosis, or argyria, skin pigmentation disorders generally occur because the body produces either too much or too little melanin.

Depigmentation.

Albinism.

Some types of albinism affect only the skin and hair, while other types affect the skin, hair and eyes, and in rare cases only the eyes. All of them are caused by different genetic mutations. Albinism is a recessively inherited trait in humans where both pigmented parents may be carriers of the gene and pass it down to their children. Each child has a 25% chance of being albino and a 75% chance of having normally pigmented skin. One common type of albinism is oculocutaneous albinism or OCA, which has many subtypes caused by different genetic mutations. Albinism is a serious problem in areas of high sunlight intensity, leading to extreme sun sensitivity, skin cancer, and eye damage.  Albinism is more common in some parts of the world than in others, but it is estimated that 1 in 70 humans carry the gene for OCA. The most severe type of albinism is OCA1A, which is characterized by complete, lifelong loss of melanin production, other forms of OCA1B, OCA2, OCA3, OCA4, show some form of melanin accumulation and are less severe. The four known types of "OCA" are caused by mutations in the "TYR", "OCA2", "TYRP1", and "SLC45A2" genes.  Albinos often face social and cultural challenges (even threats), as the condition is often a source of ridicule, racism, fear, and violence. Many cultures around the world have developed beliefs regarding people with albinism. Albinos are persecuted in Tanzania by witchdoctors, who use the body parts of albinos as ingredients in rituals and potions, as they are thought to possess magical power.

Vitiligo.

Vitiligo is a condition that causes depigmentation of sections of skin. It occurs when melanocytes die or are unable to function. The cause of vitiligo is unknown, but research suggests that it may arise from autoimmune, genetic, oxidative stress, neural, or viral causes. The incidence worldwide is less than 1%. Individuals affected by vitiligo sometimes suffer psychological discomfort because of their appearance.

Hyperpigmentation.

Increased melanin production, also known as hyperpigmentation, can be a few different phenomena:  Aside from sun exposure and hormones, hyperpigmentation can be caused by skin damage, such as remnants of blemishes, wounds or rashes. This is especially true for those with darker skin tones.  The most typical cause of darkened areas of skin, brown spots or areas of discoloration is unprotected sun exposure. Once incorrectly referred to as liver spots, these pigment problems are not connected with the liver.  On lighter to medium skin tones, solar lentigenes emerge as small- to medium-sized brown patches of freckling that can grow and accumulate over time on areas of the body that receive the most unprotected sun exposure, such as the back of the hands, forearms, chest, and face. For those with darker skin colors, these discolorations can appear as patches or areas of ashen-gray skin.

Exposure to the Sun.

Melanin in the skin protects the body by absorbing solar radiation. In general, the more melanin there is in the skin the more solar radiation can be absorbed. Excessive solar radiation causes direct and indirect DNA damage to the skin and the body naturally combats and seeks to repair the damage and protect the skin by creating and releasing further melanin into the skin's cells. With the production of the melanin, the skin color darkens, but can also cause sunburn. The tanning process can also be created by artificial UV radiation.  There are two different mechanisms involved. Firstly, the UVA-radiation creates oxidative stress, which in turn oxidizes existing melanin and leads to rapid darkening of the melanin, also known as IPD (immediate pigment darkening). Secondly, there is an increase in production of melanin known as melanogenesis. Melanogenesis leads to delayed tanning and first becomes visible about 72 hours after exposure. The tan that is created by an increased melanogenesis lasts much longer than the one that is caused by oxidation of existing melanin. Tanning involves not just the increased melanin production in response to UV radiation but the thickening of the top layer of the epidermis, the stratum corneum.  A person's natural skin color affects their reaction to exposure to the sun. Generally, those who start out with darker skin color and more melanin have better abilities to tan. Individuals with very light skin and albinos have no ability to tan. The biggest differences resulting from sun exposure are visible in individuals who start out with moderately pigmented brown skin: the change is dramatically visible as tan lines, where parts of the skin which tanned are delineated from unexposed skin.  Modern lifestyles and mobility have created mismatch between skin color and environment for many individuals. Vitamin D deficiencies and UVR overexposure are concerns for many. It is important for these people individually to adjust their diet and lifestyle according to their skin color, the environment they live in, and the time of year. For practical purposes, such as exposure time for sun tanning, six skin types are distinguished following Fitzpatrick (1975), listed in order of decreasing lightness:

Fitzpatrick scale.

The following list shows the six categories of the Fitzpatrick scale in relation to the 36 categories of the older von Luschan scale: Dark skin with large concentrations of melanin protects against ultraviolet light and skin cancers; light-skinned people have about a tenfold greater risk of dying from skin cancer, compared with dark-skinned persons, under equal sunlight exposure. Furthermore, UV-A rays from sunlight are believed to interact with folic acid in ways that may damage health. In a number of traditional societies the sun was avoided as much as possible, especially around noon when the ultraviolet radiation in sunlight is at its most intense. Midday was a time when people stayed in the shade and had the main meal followed by a nap, a practice similar to the modern siesta.

Geographic variation.

Approximately 10% of the variance in skin color occurs within regions, and approximately 90% occurs between regions. Because skin color has been under strong selective pressure, similar skin colors can result from convergent adaptation rather than from genetic relatedness; populations with similar pigmentation may be genetically no more similar than other widely separated groups. Furthermore, in some parts of the world where people from different regions have mixed extensively, the connection between skin color and ancestry has substantially weakened. In Brazil, for example, skin color is not closely associated with the percentage of recent African ancestors a person has, as estimated from an analysis of genetic variants differing in frequency among continent groups.  In general, people living close to the equator are highly darkly pigmented, and those living near the poles are generally very lightly pigmented. The rest of humanity shows a high degree of skin color variation between these two extremes, generally correlating with UV exposure. The main exception to this rule is in the New World, where people have only lived for about 10,000 to 15,000 years and show a less pronounced degree of skin pigmentation.  In recent times, humans have become increasingly mobile as a consequence of improved technology, domestication, environmental change, strong curiosity, and risk-taking. Migrations over the last 4000 years, and especially the last 400 years, have been the fastest in human history and have led to many people settling in places far away from their ancestral homelands. This means that skin colors today are not as confined to geographical location as they were previously.

Social status, colorism and racism.

According to classical scholar Frank Snowden, skin color did not determine social status in ancient Egypt, Greece or Rome. These ancient civilizations viewed relations between the major power and the subordinate state as more significant in a person's status than their skin colors.  Nevertheless, some social groups favor specific skin coloring. The preferred skin tone varies by culture and has varied over time. A number of indigenous African groups, such as the Maasai, associated pale skin with being cursed or caused by evil spirits associated with witchcraft. They would abandon their children born with conditions such as albinism and showed a sexual preference for darker skin.  Many cultures have historically favored lighter skin for women. Before the Industrial Revolution, inhabitants of the continent of Europe preferred pale skin, which they interpreted as a sign of high social status. The poorer classes worked outdoors and got darker skin from exposure to the sun, while the upper class stayed indoors and had light skin. Hence light skin became associated with wealth and high position. Women would put lead-based cosmetics on their skin to whiten their skin tone artificially. However, when not strictly monitored, these cosmetics caused lead poisoning. Other methods also aimed at achieving a light-skinned appearance, including the use of arsenic to whiten skin, and powders. Women would wear full-length clothes when outdoors, and would use gloves and parasols to provide shade from the sun.  Colonization and enslavement as carried out by European countries became involved with colorism and racism, associated with the belief that people with dark skin were uncivilized, inferior, and should be subordinate to lighter-skinned invaders. This belief exists to an extent in modern times as well. Institutionalized slavery in North America led people to perceive lighter-skinned African-Americans as more intelligent, cooperative, and beautiful. Such lighter-skinned individuals had a greater likelihood of working as house slaves and of receiving preferential treatment from plantation owners and from overseers. For example, they had a chance to get an education. The preference for fair skin remained prominent until the end of the Victorian era, but racial stereotypes about worth and beauty persisted in the last half of the 20th century and continue in the present day. African-American journalist Jill Nelson wrote that, "To be both prettiest and black was impossible," and elaborated: We learn as girls that in ways both subtle and obvious, personal and political, our value as females is largely determined by how we look.... For black women, the domination of physical aspects of beauty in women's definition and value render us invisible, partially erased, or obsessed, sometimes for a lifetime, since most of us lack the major talismans of Western beauty. Black women find themselves involved in a lifelong effort to self-define in a culture that provides them no positive reflection. A preference for fair or lighter skin continues in some countries, including Latin American countries where whites form a minority. In Brazil, a dark-skinned person is more likely to experience discrimination. Many actors and actresses in Latin America have European features—blond hair, blue eyes, and pale skin. A light-skinned person is more privileged and has a higher social status; a person with light skin is considered more beautiful and lighter skin suggests that the person has more wealth. Skin color is such an obsession in some countries that specific words describe distinct skin tones - from (for example) ""jincha"", Puerto Rican slang for "glass of milk" to ""morena"", literally "brown".  In North India, society regards pale skin as more attractive and associates dark skin with lower class status; this results in a massive market for skin-whitening creams. Fairer skin-tones also correlate to higher caste-status in the Hindu social order—although the system is not based on skin tone. Actors and actresses in Indian cinema tend to have light skin tones, and Indian cinematographers have used graphics and intense lighting to achieve more "desirable" skin tones. Fair skin tones are advertised as an asset in Indian marketing.  Skin-whitening products have remained popular over time, often due to historical beliefs and perceptions about fair skin. Sales of skin-whitening products across the world grew from $40 billion to $43 billion in 2008. In South and East Asian countries, people have traditionally seen light skin as more attractive, and a preference for lighter skin remains prevalent. In ancient China and Japan, for example, pale skin can be traced back to ancient drawings depicting women and goddesses with fair skin tones. In ancient China, Japan, and Southeast Asia, pale skin was seen as a sign of wealth. Thus skin-whitening cosmetic products are popular in East Asia. Four out of ten women surveyed in Hong Kong, Malaysia, the Philippines and South Korea used a skin-whitening cream, and more than 60 companies globally compete for Asia's estimated $18 billion market. Changes in regulations in the cosmetic industry led to skin-care companies introducing harm-free skin lighteners. In Japan, the geisha have a reputation for their white-painted faces, and the appeal of the, or "beautiful white", ideal leads many Japanese women to avoid any form of tanning. There are exceptions to this, with Japanese fashion trends such as ganguro emphasizing tanned skin. Skin whitening is also not uncommon in Africa, and several research projects have suggested a general preference for lighter skin in the African-American community. In contrast, one study on men of the Bikosso tribe in Cameroon found no preference for attractiveness of females based on lighter skin color, bringing into question the universality of earlier studies that had exclusively focused on skin-color preferences among non-African populations.  Significant exceptions to a preference for lighter skin started to appear in Western culture in the mid-20th century. However a 2010 study found a preference for lighter-skinned women in New Zealand and California. Though sun-tanned skin was once associated with the sun-exposed manual labor of the lower class, the associations became dramatically reversed during this time—a change usually credited to the trendsetting Frenchwoman Coco Chanel (1883-1971) presenting tanned skin as fashionable, healthy, and luxurious., though an overall preference for lighter skin remains prevalent in the United States, many within the country regard tanned skin as both more attractive and healthier than pale or very dark skin. Western mass media and popular culture continued to reinforce negative stereotypes about dark skin, but in some circles pale skin has become associated with indoor office-work while tanned skin has become associated with increased leisure time, sportiness and good health that comes with wealth and higher social status. Studies have also emerged indicating that the degree of tanning is directly related to how attractive a young woman is.

References.

Notes Bibliography  Further reading

Human skin color ranges in variety from the darkest brown to the lightest hues. An individual's skin pigmentation is the result of genetics, being the product of both of the individual's biological parents' genetic makeup, and exposure to sun. In evolution, skin pigmentation in human beings evolved by a process of natural selection primarily to regulate the amount of ultraviolet radiation penetrating the skin, controlling its biochemical effects.

Die Hautfarbe (auch Teint) ist ein körperliches Merkmal, das vor allem durch die Pigmentierung der Haut und die Struktur der Blutgefäße bestimmt wird. Bei sehr vielen Lebewesen, insbesondere bei unbehaarten und unbefiederten, dient die Hautfarbe der Tarnung oder für Signale, etwa als Warnsignal giftiger Tiere oder beim Balzverhalten.


Name.

Old High German "Strödu" means 'boggy thicket' and "un-" is a prefix to intensify the meaning, and so the Unstrut region was a very swampy area. In 575, the river was attested as the "Onestrudis", in the 7th century it was referred to as the "Unestrude", and in 994 as the "Vnstruod".

History.

In 531, according to the "Decem Libri" of Gregory of Tours, the decisive battle between the Franconians and Thuringians took place along the Unstrut, which resulted in the destruction and annexation of the early medieval Thuringian kingdom by the Frankish empire. In 933 the German king Henry I fought, after a ten-year truce, against a Hungarian army in the Battle of Riade, a place near the Unstrut, but which is now unknown. His victory led to a period of peace, until the Hungarians returned in 955 and were defeated again. One of his favourite places was Memleben on the Unstrut, where a royal residence, a so-called "Pfalz", "palatium" or "villa regia", was built. He died there in 936, as did his son, Otto I, in 973. A monastery was built there in the next years, becoming one of the most important in the German realm for a short time. Its ruins may still be seen; the exact location of the "palatium" is not known any more.  Due to its marshy character, the Unstrut was not navigable for ships for a long time. Finally, in the years 1790–94, the river was made navigable on the orders of the Elector of Saxony. It became an important shipping lane for a century; in particular, sandstone and limestone were shipped. From 1889, when the Unstrut Railway ("Unstrutbahn"), was built alongside the river, the significance of the waterway as a transport route was much reduced. Although the Unstrut wine-growing region, with an area of, is one of the smallest, it is quite well known.

The Unstrut is a river in eastern Germany and a left tributary of the Saale. The Unstrut originates in northern Thuringia near Dingelstädt (west of Kefferhausen in the Eichsfeld area) and its catchment area is the whole of the Thuringian Basin. It breaks out of the basin through the Thuringian Gate west of Heldrungen and, in its lower reaches, flows through Saxony-Anhalt before emptying into the Saale near Naumburg. The total length of the Unstrut is. Towns along the Unstrut include Mühlhausen, Sömmerda, Bad Frankenhausen, Artern, Roßleben, and Freyburg. The main tributaries of the Unstrut are the Gera, Wipper, Helme, and Lossa.

Die Unstrut ([], mitunter auch []) ist ein etwa 192 km langer, linker Nebenfluss der Saale und deren wasserreichster Zufluss. Einzugsgebiet ist fast das gesamte Thüringer Becken nebst einem Teil der westlichen und nördlichen Randplatten, Teile des Südharzes und kleinere Teile des nördlichen Thüringer Waldes. Dabei entspringen die wasserreicheren Zuflüsse wie auch die Unstrut selbst in den im Vergleich zum Becken niederschlagsreicheren Randgebirgen.


Geography.

The main headwaters of the Snowy River, which include the Eucumbene, Gungarlin and Thredbo Rivers and many smaller alpine watercourses, are predominantly located in Kosciuszko National Park and meet near Jindabyne. From this point the river winds southwards through inaccessible country, comprising private lands and the Snowy River National Park, eventually reaching the sea in the Snowy Inlet, at Marlo, near Orbost, Victoria.  In New South Wales, the river runs through the Snowy Monaro Regional Council. The tributaries of the Snowy River below Jindabyne include: the Mowamba, Wullwye Creek, Maclaughlin, Delegate, Jacobs, Pinch, Suggan Buggan, Deddick, Buchan, Rodger and Brodribb rivers.  In 1986, Jennings and Mabbutt mapped four geomorphic classes in the Snowy River Basin; (i) Australian Alps; (ii) the Monaro Tablelands; (iii) the East Victorian Uplands and (iv) the Gippsland Plains. Each class is physically distinct from one another.

Rainfall.

The general distribution of rainfall over the Snowy River drainage basin (catchment) is controlled by orographic effects. There is a strong rainfall gradient across the basin.  The highest average annual rainfall is recorded in the higher alpine reaches of the Snowy Catchment, with recorded in areas above. The lowest average rainfall is recorded in the rain shadow affected north eastern catchment on the Monaro Plains around Dalgety, with average rain below. The lower eastern sub-catchments are more strongly influenced by coastal rainfall patterns. For example, peak rainfall in the Delegate catchment is strongly influenced by east coast lows, rather than the alpine dominated precipitation patterns in the upper Snowy River catchment. These local variations in rainfall result in distinctly different hydrology in the rivers across the Snowy River catchment.

Hydrology.

The snow melt derived rivers in the Snowy Mountains typically have the lowest average stream flow in the months from November to June, with October having the largest monthly flows of the year, "e.g.", mean monthly flow for October at Dalgety was prior to the Snowy Scheme. The large flows in September and October are derived from snowmelt and hydrologically it is one of the key aspects that defines these mountain waterways. Typically, Australian rivers can be defined as having highly variable river flows, with frequent zero flows even in humid areas due to the extreme age of soils and consequent extremely high water absorption to absorb minimal phosphorus via proteoid and similar root types. The mixed snow melt-rainfall rivers of the Snowy Mountains can be defined by strong seasonal patterns and remain permanent throughout the year, with no record of zero flow ever observed in the Lower Snowy. Prolonged base flows over the summer months are another feature of these types of rivers, driven by snowmelt derived groundwater.  In the lower reaches of the Snowy River catchment, the larger tributaries have a distinctly different flow regime to the snow melt rivers of the Alps. These tributaries are typically dominated by the winter rainfall and often have peak monthly flows a few months earlier than the snow melt tributaries. The peak monthly flows for these lower Snowy River tributaries occur in June through July. Additionally, the flow regime in the lower tributaries is far more variable and unpredictable.

Waterfalls.

The Snowy River below Jindabyne Dam contains four major waterfalls; Stone Bridge Falls, Corrowong Falls, Snowy Falls and Pinch Falls. Potentially, many of these waterfalls act as barriers for the large scale movement of aquatic species in the main stem of the Snowy River. The flows required to drown out the largest barrier, Snowy Falls, is potentially larger than the environmental water releases to the river via Jindabyne Dam.

Parklands and protected areas.

Around 70–80% of the Snowy River's length is protected by national parks, these include, from upstream to downstream:

River ecology.

The aquatic flora and fauna of the snowy mountain snow melt rivers have evolved with the predictable seasonal hydrological snow melt peaks and constant summer base flow conditions. Many of these flora and fauna are coldwater specialists.

River habitat.

The instream habitat of the Snowy River below Jindabyne can be best described as highly disturbed. Many of the in-stream features of a large upland river are not evident today. The substrate was previously typified by a clean cobble stone substrate. Today, the river channel has contracted and the substrate has a heavy cover of sediment, overlaying much of the cobble stone riverbed.  The bushfires of 2002–03, added to this problem as large amounts of sediment and organic matter were deposited in the river via tributary inflows. This input of sediment lead to the substrate becoming finer. This pattern of increased silt in the pools of rivers and streams has been observed across the Snowy Mountains following the bushfires. These bushfires are likely to have a long lasting influence on these waterways.  Larger events are required to start to improve the condition of the river bed. Events of per day will start to move the unconsolidated fine particles of the riverbed. Events between per day are important for conditioning the riffle habitats ("i.e.", a type of flowing water habitat).  The current poor condition of the river bed is one of the key factors inhibiting the aquatic fauna typical in a snow melt river.

Water quality.

The mountain streams and rivers are typically low in nutrients and electrical conductivity. Conductivity is generally below 50 μS/cm.  Large dams can essentially influence downstream water quality via two key mechanisms, either by poor water quality released from the waters of the dam itself and reduced mixing of the river water column attributable to lower water velocities leading to anoxic conditions at the bottom of deep river pools.

Influence of Jindabyne Dam on water quality.

Possibly the main influence on downstream water quality from Jindabyne Dam, is the influence on water temperature. Unlike many other dams were coldwater pollution is a concern, where water is released from the below the thermocline in the reservoir (i.e. the bottom water of the lake), the water is released from the surface waters of lake Jindabyne. The water temperature of the Snowy River downstream can reach temperatures of in summer.  The Snowy River is on average warmer than the surrounding unregulated snow melt rivers, with a peak difference of up to. The water temperature in spring appears to be the greatly warmer than the surrounding snow melt rivers.

Thermal stratification.

Thermal stratification in the river reaches below Jindabyne is typically restricted to a few of the larger or deeper pools. In general thermal stratification is spatially restricted to the pools that are typically greater than deep. Pools shallower than have not displayed any thermal stratification.  Stratification can occur between October and March, but typically does not persist for very long in the Snowy River in the Jindabyne Gorge. Breakdown of thermal stratification is frequently driven by the cooling overnight air temperature. This region experiences a very large temperature range between day and night (i.e. diurnal temperature range).

Algae.

Algae is present in the water column and on the bed of the Snowy River. The water column algae is called phytoplankton, whereas the riverbed algae is defined as periphyton (attached algae).

Riverbed algae.

Much of the bed of the Snowy River below Jindabyne contains high levels of attached algae. These taxa are typically filamentous algae. In the snowy mountains rivers unaffected by water diversions, large stands of filamentous algae are uncommon.

Water column algae.

During 2008–09, the river pools of Jindabyne Gorge and the Dalgety uplands were typically dominated by blue green algae. Two blue green algae "Aphanotheca" spp. and "Aphanocaspa" spp. comprise about 25% of the total abundance. However, these abundances are still under the guidelines and its unclear if this is solely related to river regulation, but also reflects other catchment inputs.  The composition of algae in the free flowing snow melt rivers are typically defined by diatoms. Over 58% of taxa are diatoms, with "Fragilaria" spp. being the most numerically abundant taxa.

Water bugs.

The water bugs in the Snowy River differ from the bugs of the snowmelt rivers. Dams have been shown to have an adverse impact on the water bugs of rivers.  Caenid mayflies (riffles) and oligochaete worms (pool edges) are generally typical of the upland regulated Snowy River. Other studies have also found greater densities of Caenidae mayflies in regulated rivers compared to unregulated rivers. Reduced high flows and constant low flows in the upper Snowy River are likely to have favoured high densities of worms through the buildup of silt and organic matter in the pools. Nichols et al. (2006) and Petts et al. (1993) also found greater densities of segmented worms associated with soft sediments and coarse organic debris in response to river regulation. Chironomids were also numerically dominant in riffles sampled in the regulated Snowy River. This response has been found in many other studies of regulated rivers and has been attributed to an increase of periphytic growth in riffles that increased overall habitat area and food availability. Conoesucidae caddisflies (riffles), larval and adult elimids (riffles) and Oniscigastridae (pool edges) distinguished the snow melt rivers from regulated Snowy River. Marchant and Hehir (2002) reported that AUSRIVAS models (>50% probability) predicted Conoesucidae and elmids to be present in the upper Snowy River, but these taxa were not found in their study. The greater density of these taxa in snowmelt rivers compared the Snowy River is consistent with river regulation.  Marchant and Hehir attribute the absence of these taxa to dams acting as a barrier to drift and limiting recolonisation of these taxa and not to flow regulation. The upper Snowy River sites are all below the confluence of the Mowamba River which provides a pathway for recolonisation of the Snowy River. Therefore, the reduced flow and altered flow regime is likely to be the primary cause of reduced densities of these taxa in the upper Snowy River rather than the barrier effects of Jindabyne Dam. There is little information on the responses of Oniscigastridae to reduced flows and altered flow regimes, but it is probable that an elevated temperature regime combined with lack of suitable sandy edge habitat has reduced their densities in the Snowy River.

Fish.

The fish assemblage of the Snowy River below Jindabyne are clearly divided into two components. This division is based on that which occurred in the upper catchment (above Snowy Falls) and that in the lower catchment (below Snowy Falls). The major differences between the two zones were the low abundance or absence of diadromous migratory fish (except eels) and the greater abundance of short-finned eel and trout in the upper catchment, and the greater abundance of Australian smelt, congoli and long-finned eel below Snowy Falls. These upper and lower Snowy River zone differences were greater than the differences between un-regulated tributary streams and the highly regulated main channel of the Snowy River within either zone. In the upper catchment, river blackfish, brown trout and short-finned eel were more abundant in un-regulated tributaries, whilst long-finned eel and goldfish were more abundant in the regulated upper part of the Snowy River. In the lower zone, eastern gambusia, long-finned eel, Australian smelt, short-finned eel and congoli were all more abundant in Snowy River while common galaxias and short-headed lamprey were more abundant at tributaries.

Flow thresholds below Jindabyne.

River scientists are currently undertaking studies to determine the flow thresholds for a range of riverine processes. Some preliminary flow thresholds that have been developed include:  Further defining of ecological flow thresholds is currently in progress via modelling, field based studies, and flow trials. See Snowy Flow Response Monitoring and Modelling.

History of water management.

Early history.

The Snowy River was initially utilised sustainably as a food and water resource by Indigenous Australians for around 30,000–40,000 years prior to European settlement. Evidence of human occupation at Cloggs Cave, near the Snowy River, near Buchan, was dated at up to 17,000 years. Despite the cold climate in the river's higher reaches, the Ngarigo nation held territory around the Australian Alps and the Snowy Mountains in modern-day New South Wales. As the river flowed southwards into modern day Victoria, it flowed in the Gunai nation's territory, particularly, the Krauatungalung clan's territory.

1950–1990s reduced water flow.

The Snowy River originally had a huge, often destructive flow during the spring snow-melt which flowed directly into the sea. In the 1950s and 1960s, as part of the Snowy Mountains Scheme, a network of four dams (i.e. Guthega, Island Bend, Eucumebene and Jindabyne) and many smaller water diversion structures were built to collect and divert 99% (as measured at Jindabyne) of the Snowy River's flow through the mountains, to provide more water to the Murray and Murrumbidgee River agricultural basins for irrigation. Several hydro-electric power stations were also constructed to generate electricity. While there was initial public opposition to the diversion of the river's water during the 1950s and '60s, it was largely ignored as the scheme provided agriculture with more water. It generated a large number of jobs in construction initially, then in agriculture and logistics, and added permanent and reliable, on-demand electricity generation to two states.

1990s–2000: Increased awareness.

By the 1990s, the reduced flows in the Snowy River became a major environmental concern in Victoria, New South Wales and across Australia. After the scheme was built downstream flows were insufficient to keep the channel clear of vegetation or move sediment in the stream bed. Salt water intrusion extended seven to ten kilometres up the estuary and outdoor recreational activities were curtailed along the lower reaches of the river.  This period of increased awareness of the impacts of water diversions lead to the Snowy Water Inquiry, which looked at options to improve the health of the Snowy River. The key outcomes of the Snowy Water Inquiry was an initial agreement to increase environmental water releases to the Snowy River below Jindabyne by 15% and the Snowy Montane Rivers.  These series of staged flow targets (up to 28% of mean annual natural discharge) were set for the Snowy River below Jindabyne, with these dependent on water savings in the Murray and Murrumbidgee River catchments. The targets included 15% by 2009 and 21% by 2012.

2002–2006: Environmental water releases from the Mowamba River in a low allocation period.

From 28 August 2002 until January 2006, the first stage of environmental water was released to the Snowy River via the Mowamba River. The Mowamba River aqueduct was "turned out", preventing water being diverted to Jindabyne Dam. The releases from the Mowamba River essentially doubled the daily discharge at Dalgety from about per day. Additionally, it provided a small snow melt signal, peaking in September. Only a small percentage of the Mowamba River catchment is covered by snow in winter, compared to some of the upper catchments in the Snowy River catchment. Additionally, the release increased daily river flow variability, between per day, and the timing of flows was in keeping with natural events across the catchment. These small discharges saw a 20% increase in wetted habitat and a doubling of running water habitat (i.e. riffles) in the upper reaches of the Snowy River in the Dalgety Uplands, whereas the rest of the river saw a decline in discharge due to the prevailing drought.  This stage increased flows from 1% to approximately 4% of mean annual river discharge. Typically an annual release of per year.

2006–2010: Environmental water releases from Jindabyne Dam in a low allocation period.

After the completion of capital works (i.e. multi-level offtake and the cone values) at Jindabyne Dam the environmental water releases were essentially released from Jindabyne Dam, rather than the Mowamba River. The second stage of environmental flow releases saw a very small increase in the median flow rate, but also a decline in daily flow variability compared to base flow compared to stage one.  Overall the annual volume released remained around 38GL year given the historical record drought.

2010–2011: Environmental water releases in a higher allocation period.

During this stage the "Water for Rivers" were able to secure more water entitlements (i.e. up ) in the Western Rivers and the allocations increased as the drought broke in South Eastern Australia. Actual allocations are weather dependent, so in dry periods the allocation will be smaller than during wet periods. During this period the annual water availability jumped from about per annum. Although water is released all year, this period has seen two significant spring snow melt environmental water releases to the Snowy River.  In November 2010 the first spring snow melt release occurred. This small but important release had a peak discharge of per day, and was sufficient to start to scour the fines sediment from some sections of the bed of the Snowy.  In October 2011, with substantially greater water available a much larger spring snow melt release has occurred i.e. over 19 days. This second and substaitially larger release with a peak discharge rate of per day over three days is expected to scour the bed of the river. This releases targeted much larger particles, up to the size of, as the bed of the river is heavily "armoured" and larger flows are required to move these particles to improve the instream habitat of the river. Once the armouring had been removed it is expected the fine sediment would be scoured within the river bed profile.

Politics.

A political campaign began, which aimed to increase the water flow from 1% to 28% of its original flow from the dam at Jindabyne. An independent candidate from the East Gippsland district, Craig Ingram, was elected to the Victorian Legislative Assembly in 1999 and re-elected in 2002 and 2006, on a platform to increase the flow of water in the Snowy River.  After Ingram was elected to office, he became instrumental in the three shareholding governments reaching agreement to return of up to 28% ANF of an environmental flow to the Snowy River which was an outcome of the corporatisation of the Snowy Scheme, swinging the Victorian Government to sign the legislation. Although the Victorian, NSW and Federal governments promised that corporatisation would not lead to privatisation, in November 2005 they announced their intention to sell Snowy Hydro through a public float. Community groups rallied to stop the sale of Snowy Hydro and by June 2006 the Australian Prime Minister withdrew the Commonwealth's intention to sell Snowy Hydro.

Cultural references.

The poem "The Man from Snowy River" was written by 'Banjo' Paterson in 1890, which formed the basis of many subsequent works in film, TV and music theatre.  The natural environment surrounding the Snowy River formed part of the subject matter and setting for the 'Banjo' Paterson poem "The Man from Snowy River", first published in 1890. The Snowy River has also been immortalised in a 1920 "The Man from Snowy River" silent film, as well as in the better-known 1982 Fox film "The Man from Snowy River" and its 1988 Disney sequel film "The Man from Snowy River II" (U.S. title: ""Return to Snowy River"" — UK title: ""The Untamed""), as well as in "The Man from Snowy River (TV series)" and "", all of which were based on the Banjo Paterson's poem.

Settlements.

There are very few towns located on the Snowy River, the following is a list of towns that sit on the Snowy River, ordered from upstream to downstream;

The Snowy River is a major river in south-eastern Australia. It originates on the slopes of Mount Kosciuszko, Australia's highest mainland peak, draining the eastern slopes of the Snowy Mountains in New South Wales, before flowing through the Alpine National Park and the Snowy River National Park in Victoria and emptying into Bass Strait.

Der Snowy River ist ein rund 400 Kilometer langer Fluss im Südosten Australiens. Er entspringt an den Osthängen des Mount Kosciuszko in den Snowy Mountains in New South Wales und mündet bei Marlo, in der Nähe von Orbost, in die Bass-Straße. Bis Mitte des 20. Jahrhunderts war der Fluss für seine große Wassermenge, sein breites Flussbett und seine großen Stromschnellen bekannt.


Uses.

Medical.

The primary therapeutic use of nicotine is treating nicotine dependence to eliminate smoking and the damage it does to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, inhalers, or nasal sprays to wean them off their dependence. A 2018 Cochrane Collaboration review found high quality evidence that all current forms of nicotine replacement therapy (gum, patch, lozenges, inhaler, and nasal spray) therapies increase the chances of successfully quitting smoking by, regardless of setting.  Combining nicotine patch use with a faster acting nicotine replacement, like gum or spray, improves the odds of treatment success. 4 mg versus 2 mg nicotine gum also increase the chances of success.  In contrast to recreational nicotine products, which have been designed to maximize the likelihood of addiction, nicotine replacement products (NRTs) are designed to minimize addictiveness. The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk.

Pesticide.

Nicotine has been used as an insecticide since at least the 1690s, in the form of tobacco extracts (although other components of tobacco also seem to have pesticide effects). Nicotine pesticides have not been commercially available in the US since 2014, and homemade pesticides are banned on organic crops and not recommended for small gardeners. Nicotine pesticides have been banned in the EU since 2009. Foods are imported from countries in which nicotine pesticides are allowed, such as China, but foods may not exceed maximum nicotine levels. Neonicotinoids, which are derived from and structurally similar to nicotine, are widely used as agricultural and veterinary pesticides as of 2016.  In nicotine-producing plants, nicotine functions as an antiherbivory chemical; consequently, nicotine has been widely used as an insecticide, and neonicotinoids, such as imidacloprid, are widely used.

Performance.

Nicotine-containing products are sometimes used for the performance-enhancing effects of nicotine on cognition. A meta-analysis of 41 double-blind, placebo-controlled studies concluded that nicotine or smoking had significant positive effects on aspects of fine motor abilities, alerting and orienting attention, and episodic and working memory. A 2015 review noted that stimulation of the α4β2 nicotinic receptor is responsible for certain improvements in attentional performance; among the nicotinic receptor subtypes, nicotine has the highest binding affinity at the α4β2 receptor (k=1 ), which is also the biological target that mediates nicotine's addictive properties. Nicotine has potential beneficial effects, but it also has paradoxical effects, which may be due to the inverted U-shape of the dose-response curve or pharmacokinetic features.

Recreational.

Nicotine is used as a recreational drug. It is widely used, highly addictive and hard to discontinue. Nicotine is often used compulsively, and dependence can develop within days. Recreational drug users commonly use nicotine for its mood-altering effects. Other recreational nicotine products include chewing tobacco, cigars, cigarettes, e-cigarettes, snuff, pipe tobacco, and snus.

Contraindications.

Nicotine use for tobacco cessation has few contraindications.  It is not known whether nicotine replacement therapy is effective for smoking cessation in adolescents, as of 2014. It is therefore not recommended to adolescents. It is not safe to use nicotine during pregnancy or breastfeeding, although it is safer than smoking; the desirability of NRT use in pregnancy is therefore debated.  Precautions are needed when using NRT in people who have had a myocardial infarction within two weeks, a serious or worsening angina pectoris, and/or a serious underlying arrhythmia. Using nicotine products during cancer treatment is counterrecommended, as nicotine promotes tumour growth, but temporary use of NRTs to quit smoking may be advised for harm reduction.  Nicotine gum is contraindicated in individuals with temporomandibular joint disease. People with chronic nasal disorders and severe reactive airway disease require additional precautions when using nicotine nasal sprays. Nicotine in any form is contraindicated in individuals with a known hypersensitivity to nicotine.

Adverse effects.

Nicotine is classified as a poison. Exposure to nicotine causes many adverse health effects. The common side effects from nicotine exposure are listed in the table below. Serious adverse events due to the use of nicotine replacement therapy are extremely rare. At low amounts, it has a mild analgesic effect. At sufficiently high doses, nicotine may result in nausea, vomiting, diarrhea, salivation, bradyarrhythmia, and possibly seizures, hypoventilation, and death.

Sleep.

Nicotine reduces the amount of rapid eye movement (REM) sleep, slow-wave sleep (SWS), and total sleep time in healthy nonsmokers given nicotine via a transdermal patch, and the reduction is dose-dependent. Acute nicotine intoxication has been found to significantly reduce total sleep time and increase REM latency, sleep onset latency, and non-rapid eye movement (NREM) stage 2 sleep time. Depressive non-smokers experience mood improvements under nicotine administration, but then the withdrawal effect has a negative effect on both mood and sleep.

Cardiovascular system.

A 2018 Cochrane review found that, in rare cases, nicotine replacement therapy can cause non-ischemic chest pain (i.e., chest pain that is unrelated to a myocardial infarction) and heart palpitations. The same review indicated that nicotine replacement therapy does not increase the incidence of serious cardiac adverse events (i.e., myocardial infarction, stroke, and cardiac death) relative to controls.

Reinforcement disorders.

Nicotine is highly addictive. Its addictiveness depends on how it is administered. Nicotine dependence involves aspects of both psychological dependence and physical dependence, since discontinuation of extended use has been shown to produce both affective (e.g., anxiety, irritability, craving, anhedonia) and somatic (mild motor dysfunctions such as tremor) withdrawal symptoms. Withdrawal symptoms peak in one to three days and can persist for several weeks. Some people experience symptoms for 6 months or longer.  Normal between-cigarettes discontinuation, in unrestricted smokers, causes mild but measurable nicotine withdrawal symptoms. These include mildly worse mood, stress, anxiety, cognition, and sleep, all of which briefly return to normal with the next cigarette. Smokers have worse mood than they would have if they were not nicotine-dependent; they experience normal moods only immediately after smoking. Nicotine dependence is associated with poor sleep quality and shorter sleep duration among smokers.  In dependent smokers, withdrawal causes impairments in memory and attention, and smoking during withdrawal returns these cognitive abilities to pre-withdrawal levels. The temporarily increased cognitive levels of smokers after inhaling smoke are offset by periods of cognitive decline during nicotine withdrawal. Therefore, the overall daily cognitive levels of smokers and non-smokers are roughly similar.  Nicotine activates the mesolimbic pathway and induces long-term ΔFosB expression (i.e., produces phosphorylated ΔFosB isoforms) in the nucleus accumbens when inhaled or injected frequently or at high doses, but not necessarily when ingested. Consequently, high daily exposure (possibly excluding oral route) to nicotine can cause ΔFosB overexpression in the nucleus accumbens, resulting in nicotine addiction.

Cancer.

Although nicotine does not cause cancer in humans, it is unclear whether it functions as a tumor promoter. A 2018 report by the National Academies of Sciences, Engineering, and Medicine concludes, “[w]hile it is biologically plausible that nicotine can act as a tumor promoter, the existing body of evidence indicates this is unlikely to translate into increased risk of human cancer.”  Low levels of nicotine stimulate cell proliferation, while high levels are cytotoxic. Nicotine increases cholinergic signaling and adrenergic signaling in colon cancer cells, thereby impeding apoptosis (programmed cell death), promoting tumor growth, and activating growth factors and cellular mitogenic factors such as 5-lipoxygenase (5-LOX), and epidermal growth factor (EGF). Nicotine also promotes cancer growth by stimulating angiogenesis and neovascularization. Nicotine promotes lung cancer development and accelerates its proliferation, angiogenesis, migration, invasion and epithelial–mesenchymal transition (EMT), via its influence on nAChRs receptors, whose presence has been confirmed in lung cancer cells. In cancer cells, nicotine promotes the epithelial–mesenchymal transition which makes the cancer cells more resistant to drugs that treat cancer.

Pregnancy and breastfeeding.

Nicotine has been shown to produce birth defects in some animal species, but not others; consequently, it is considered to be a possible teratogen in humans. In animal studies that resulted in birth defects, researchers found that nicotine negatively affects fetal brain development and pregnancy outcomes; the negative effects on early brain development are associated with abnormalities in brain metabolism and neurotransmitter system function. Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke.  Nicotine exposure "in utero" is responsible for several complications of pregnancy and birth: pregnant women who smoke are at greater risk for both miscarriage and stillbirth and infants exposed to nicotine "in utero" tend to have lower birth weights. Some evidence suggests that "in utero" nicotine exposure influences the occurrence of certain conditions later in life, including type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.

Overdose.

It is unlikely that a person would overdose on nicotine through smoking alone. The US Food and Drug Administration (FDA) stated in 2013 that there are no significant safety concerns associated with the use of more than one form of over-the-counter (OTC) nicotine replacement therapy at the same time, or using OTC NRT at the same time as another nicotine-containing product, like cigarettes. The median lethal dose of nicotine in humans is unknown. Nevertheless, nicotine has a relatively high toxicity in comparison to many other alkaloids such as caffeine, which has an LD of 127 mg/kg when administered to mice. At sufficiently high doses, it is associated with nicotine poisoning, which, while common in children (in whom poisonous and lethal levels occur at lower doses per kilogram of body weight) rarely results in significant morbidity or death.  The initial symptoms of a nicotine overdose typically include nausea, vomiting, diarrhea, hypersalivation, abdominal pain, tachycardia (rapid heart rate), hypertension (high blood pressure), tachypnea (rapid breathing), headache, dizziness, pallor (pale skin), auditory or visual disturbances, and perspiration, followed shortly after by marked bradycardia (slow heart rate), bradypnea (slow breathing), and hypotension (low blood pressure). Respiratory stimulation (i.e., tachypnea) is one of the primary signs of nicotine poisoning. At sufficiently high doses, somnolence (sleepiness or drowsiness), confusion, syncope (loss of consciousness from fainting), shortness of breath, marked weakness, seizures, and coma may occur. Lethal nicotine poisoning rapidly produces seizures, and death – which may occur within minutes – is believed to be due to respiratory paralysis.

Toxicity.

Today nicotine is less commonly used in agricultural insecticides, which was a main source of poisoning. More recent cases of poisoning typically appear to be in the form of Green Tobacco Sickness, accidental ingestion of tobacco or tobacco products, or ingestion of nicotine-containing plants. People who harvest or cultivate tobacco may experience Green Tobacco Sickness (GTS), a type of nicotine poisoning caused by dermal exposure to wet tobacco leaves. This occurs most commonly in young, inexperienced tobacco harvesters who do not consume tobacco. People can be exposed to nicotine in the workplace by breathing it in, skin absorption, swallowing it, or eye contact. The Occupational Safety and Health Administration (OSHA) has set the legal limit (permissible exposure limit) for nicotine exposure in the workplace as 0.5 mg/m skin exposure over an 8-hour workday. The US National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) of 0.5 mg/m skin exposure over an 8-hour workday. At environmental levels of 5 mg/m, nicotine is immediately dangerous to life and health.

Drug interactions.

Pharmacokinetic.

Nicotine and cigarette smoke both induce the expression of liver enzymes (e.g., certain cytochrome P450 proteins) which metabolize drugs, leading to the potential for alterations in drug metabolism.

Pharmacology.

Pharmacodynamics.

Central nervous system.

By binding to nicotinic acetylcholine receptors in the brain, nicotine elicits its psychoactive effects and increases the levels of several neurotransmitters in various brain structures – acting as a sort of "volume control". Nicotine has a higher affinity for nicotinic receptors in the brain than those in skeletal muscle, though at toxic doses it can induce contractions and respiratory paralysis. Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes. Nicotine is unusual in comparison to most drugs, as its profile changes from stimulant to sedative with increasing dosages, a phenomenon known as "Nesbitt's paradox" after the doctor who first described it in 1969. At very high doses it dampens neuronal activity. Nicotine induces both behavioral stimulation and anxiety in animals. Research into nicotine's most predominant metabolite, cotinine, suggests that some of nicotine's psychoactive effects are mediated by cotinine.  Nicotine activates nicotinic receptors (particularly α4β2 nicotinic receptors) on neurons that innervate the ventral tegmental area and within the mesolimbic pathway where it appears to cause the release of dopamine. This nicotine-induced dopamine release occurs at least partially through activation of the cholinergic–dopaminergic reward link in the ventral tegmental area. Nicotine can modulate the firing rate of the ventral tegmental area neurons. Nicotine also appears to induce the release of endogenous opioids that activate opioid pathways in the reward system, since naltrexone – an opioid receptor antagonist – blocks nicotine self-administration. These actions are largely responsible for the strongly reinforcing effects of nicotine, which often occur in the absence of euphoria; however, mild euphoria from nicotine use can occur in some individuals. Chronic nicotine use inhibits class I and II histone deacetylases in the striatum, where this effect plays a role in nicotine addiction.

Sympathetic nervous system.

Nicotine also activates the sympathetic nervous system, acting via splanchnic nerves to the adrenal medulla, stimulating the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the bloodstream.

Adrenal medulla.

By binding to ganglion type nicotinic receptors in the adrenal medulla, nicotine increases flow of adrenaline (epinephrine), a stimulating hormone and neurotransmitter. By binding to the receptors, it causes cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream. The release of epinephrine (adrenaline) causes an increase in heart rate, blood pressure and respiration, as well as higher blood glucose levels.

Pharmacokinetics.

As nicotine enters the body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within 10–20 seconds after inhalation. The elimination half-life of nicotine in the body is around two hours. Nicotine is primarily excreted in urine and urinary concentrations vary depending upon urine flow rate and urine pH.  The amount of nicotine absorbed by the body from smoking can depend on many factors, including the types of tobacco, whether the smoke is inhaled, and whether a filter is used. However, it has been found that the nicotine yield of individual products has only a small effect (4.4%) on the blood concentration of nicotine, suggesting "the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation".  Nicotine has a half-life of 1–2 hours. Cotinine is an active metabolite of nicotine that remains in the blood with a half-life of 18–20 hours, making it easier to analyze.  Nicotine is metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6, and also by CYP2B6) and FMO3, which selectively metabolizes ("S")-nicotine. A major metabolite is cotinine. Other primary metabolites include nicotine "N"'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide. Under some conditions, other substances may be formed such as myosmine.  Glucuronidation and oxidative metabolism of nicotine to cotinine are both inhibited by menthol, an additive to mentholated cigarettes, thus increasing the half-life of nicotine "in vivo".

Metabolism.

Nicotine decreases hunger and food consumption. The majority of research shows that nicotine reduces body weight, but some researchers have found that nicotine may result in weight gain under specific types of eating habits in animal models. Nicotine effect on weight appears to result from nicotine's stimulation of α3β4 nAChR receptors located in the POMC neurons in the arcuate nucleus and subsequently the melanocortin system, especially the melatocortin-4 receptors on second-order neurons in the paraventricular nucleus of the hypothalamus, thus modulating feeding inhibition. POMC neurons are a precursor of the melanocortin system, a critical regulator of body weight and peripheral tissue such as skin and hair.

Chemistry.

Nicotine is a hygroscopic, colorless to yellow-brown, oily liquid, that is readily soluble in alcohol, ether or light petroleum. It is miscible with water in its neutral amine base form between 60 °C and 210 °C. It is a dibasic nitrogenous base, having K=1×10−6, K=1×10−11. It readily forms ammonium salts with acids that are usually solid and water-soluble. Its flash point is 95 °C and its auto-ignition temperature is 244 °C. Nicotine is readily volatile (vapor pressure 5.5 Pa at 25 °C) On exposure to ultraviolet light or various oxidizing agents, nicotine is converted to nicotine oxide, nicotinic acid (niacin, vitamin B3), and methylamine.  Nicotine is optically active, having two enantiomeric forms. The naturally occurring form of nicotine is levorotatory with a specific rotation of [α]=–166.4° ((−)-nicotine). The dextrorotatory form, (+)-nicotine is physiologically less active than (−)-nicotine. (−)-nicotine is more toxic than (+)-nicotine. The salts of (+)-nicotine are usually dextrorotatory; this conversion between levorotatory and dextrorotatory upon protonation is common among alkaloids. The hydrochloride and sulfate salts become optically inactive if heated in a closed vessel above 180 °C. Anabasine is a structural isomer of nicotine, as both compounds have the molecular formula. Pod mod electronic cigarettes use nicotine in the form of a protonated nicotine, rather than free-base nicotine found in earlier generations.

Occurrence.

Nicotine is a natural product of tobacco, occurring in the leaves of "Nicotiana tabacum" in a range of 0.5 to 7.5% depending on variety. Nicotine is also found in the leaves of "Nicotiana rustica", in amounts of 2–14%; in "Duboisia hopwoodii"; and in "Asclepias syriaca".  Nicotine also naturally occurs in smaller amounts (varying from 2–7 μg/kg, or 20–70 millionths of a percent wet weight) in Solanaceaein plants from the family Solanaceae (such as potatoes, tomatoes, eggplant, and peppers).  The amounts of nicotine of in tomatoes lowers substantially as the fruit ripens. Nicotine content in tea leaves is greatly inconsistent and in some cases considerably greater than in the Solanaceae fruits. A 1999 report found "In some papers it is suggested that the contribution of dietary nicotine intake is significant when compared with exposure to ETS [environmental tobacco smoke] or by active smoking of small numbers of cigarettes. Others consider the dietary intake to be negligible unless inordinately large amounts of specific vegetables are consumed." The amount of nicotine eaten per day is roughly around 1.4 and 2.25 μg/day at the 95th percentile. These numbers may be low due to insufficient food intake data. Since the amounts of nicotine from the Solanum family including potato, tomato, eggplant, and from the Capsicum family vary in the parts per billion, they are tough to measure.

Biosynthesis.

The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that comprise nicotine. Metabolic studies show that the pyridine ring of nicotine is derived from niacin (nicotinic acid) while the pyrrolidine is derived from "N"-methyl-Δ-pyrrollidium cation. Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for niacin and the tropane pathway for "N"-methyl-Δ-pyrrollidium cation.  The NAD pathway in the genus "Nicotiana" begins with the oxidation of aspartic acid into α-imino succinate by aspartate oxidase (AO). This is followed by a condensation with glyceraldehyde-3-phosphate and a cyclization catalyzed by quinolinate synthase (QS) to give quinolinic acid. Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form niacin mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce niacin via the conversion of nicotinamide by the enzyme nicotinamidase.  The "N"-methyl-Δ-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with decarboxylation of ornithine by ornithine decarboxylase (ODC) to produce putrescine. Putrescine is then converted into "N"-methyl putrescine via methylation by SAM catalyzed by putrescine "N"-methyltransferase (PMT). "N"-methylputrescine then undergoes deamination into 4-methylaminobutanal by the "N"-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize into "N"-methyl-Δ-pyrrollidium cation.  The final step in the synthesis of nicotine is the coupling between "N"-methyl-Δ-pyrrollidium cation and niacin. Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of niacin into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with "N"-methyl-Δ-pyrrollidium cation to form enantiomerically pure (−)-nicotine.

Detection in body fluids.

Nicotine can be quantified in blood, plasma, or urine to confirm a diagnosis of poisoning or to facilitate a medicolegal death investigation. Urinary or salivary cotinine concentrations are frequently measured for the purposes of pre-employment and health insurance medical screening programs. Careful interpretation of results is important, since passive exposure to cigarette smoke can result in significant accumulation of nicotine, followed by the appearance of its metabolites in various body fluids. Nicotine use is not regulated in competitive sports programs.

History, society, and culture.

Nicotine was originally isolated from the tobacco plant in 1828 by chemists Wilhelm Heinrich Posselt and Karl Ludwig Reimann from Germany, who believed it was a poison. Its chemical empirical formula was described by Melsens in 1843, its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893, and it was first synthesized by Amé Pictet and A. Rotschy in 1904.  Nicotine is named after the tobacco plant "Nicotiana tabacum," which in turn is named after the French ambassador in Portugal, Jean Nicot de Villemain, who sent tobacco and seeds to Paris in 1560, presented to the French King, and who promoted their medicinal use. Smoking was believed to protect against illness, particularly the plague.  Tobacco was introduced to Europe in 1559, and by the late 17th century, it was used not only for smoking but also as an insecticide. After World War II, over 2,500 tons of nicotine insecticide were used worldwide, but by the 1980s the use of nicotine insecticide had declined below 200 tons. This was due to the availability of other insecticides that are cheaper and less harmful to mammals.  The nicotine content of popular American-brand cigarettes has increased over time, and one study found that there was an average increase of 1.78% per year between the years of 1998 and 2005.

Legal status.

In the United States, nicotine products and Nicotine Replacement Therapy products like Nicotrol are only available to persons 21 and above; proof of age is required; not for sale in vending machine or from any source where proof of age cannot be verified. In some states, these products are only available to persons over the age of 21. Many states in the US have implemented a Tobacco 21 law for tobacco products, raising the minimum age from 18 to 21. As of 2019, the minimum age to use tobacco is 21 at the federal level.  In the European Union, the minimum age to purchase nicotine products is 18. However, there is no minimum age requirement to use tobacco or nicotine products.

In media.

In some anti-smoking literature, the harm that tobacco smoking and nicotine addiction does is personified as Nick O'Teen, represented as a humanoid with some aspect of a cigarette or cigarette butt about him or his clothes and hat. Nick O'Teen was a villain that was created for the Health Education Council.  Nicotine was often compared to caffeine in advertisements in the 1980s by the tobacco industry, and later in the 2010s by the electronic cigarettes industry, in an effort to reduce the stigmatization and the public perception of the risks associated with nicotine use.

Research.

Central nervous system.

While acute/initial nicotine intake causes activation of neuronal nicotine receptors, chronic low doses of nicotine use leads to desensitization of those receptors (due to the development of tolerance) and results in an antidepressant effect, with early research showing low dose nicotine patches could be an effective treatment of major depressive disorder in non-smokers.  Though tobacco smoking is associated with an increased risk of Alzheimer's disease, there is evidence that nicotine itself has the potential to prevent and treat Alzheimer's disease.  Smoking is associated with a decreased risk of Parkinson's Disease; however, it is unknown whether this is due to people with healthier brain dopaminergic reward centers (the area of the brain affected by Parkinson's) being more likely to enjoy smoking and thus pick up the habit, nicotine directly acting as a neuroprotective agent, or other compounds in cigarette smoke acting as neuroprotective agents.

Immune system.

Immune cells of both the Innate immune system and adaptive immune systems frequently express the α2, α5, α6, α7, α9, and α10 subunits of nicotinic acetylcholine receptors. Evidence suggests that nicotinic receptors which contain these subunits are involved in the regulation of immune function.

Optopharmacology.

A photoactivatable form of nicotine, which releases nicotine when exposed to ultraviolet light with certain conditions, has been developed for studying nicotinic acetylcholine receptors in brain tissue.

Oral health.

Several "in vitro" studies have investigated the potential effects of nicotine on a range of oral cells. A recent systematic review concluded that nicotine was unlikely to be cytotoxic to oral cells "in vitro" in most physiological conditions but further research is needed. Understanding the potential role of nicotine in oral health has become increasingly important given the recent introduction of novel nicotine products and their potential role in helping smokers quit.

Nicotine is a widely-used stimulant and potent parasympathomimetic alkaloid that is naturally produced in the nightshade family of plants. It is used for smoking cessation to relieve withdrawal symptoms. Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor subunits (nAChRα9 and nAChRα10) where it acts as a receptor antagonist.

Nicotin, auch Nikotin, ist ein natürlich in den Blättern der Tabakpflanze sowie in geringerer Konzentration auch in anderen Nachtschattengewächsen vorkommendes Alkaloid, das erregende oder lähmende Wirkungen auf Ganglien des vegetativen Nervensystem hat. Selten werden Nicotinderivate als "Nicotinoide" bezeichnet; meist sind damit die synthetischen, als Insektizide eingesetzten Neonicotinoide gemeint.


Starting out.

Paul Cassirer started out as a student of art history, and then became a writer in 1890s Munich, where he worked for the weekly magazine "Simplicissimus" and published two novels.  Cassirer moved to Berlin, and he and his cousin Bruno, while still in their mid 20s, opened their gallery on the ground floor of Paul's house in the up-market Viktoriastrasse. The cousins came from a prominent family, whose members included the neurologist Richard Cassirer and the philosopher Ernst Cassirer. Paul was born into a Jewish family. His father, Louis, was an engineer and businessman, whose company — Kabelwerke Dr. Cassirer & Co. — manufactured telegraphic cables, and was eventually taken over by Siemens.  In 1895 he married Lucie Oberwarth.  In 1901 Cassirer visited Julien Leclercq's retrospective of Van Gogh's work, and later that year he organized the inclusion of five Van Gogh canvases in the May show of the Berlin Secession.  On 21 May 1904, Cassirer and Lucie divorced.

Second marriage.

In 1910 he married Ottilie Godefroy (18 August 1880, Vienna – 21 February 1971, Berlin), the actress well-known under her pseudonym Tilla Durieux. Tilla had very briefly been married to the painter Eugen Spiro six years earlier. She and Cassirer were married for sixteen years, but the union was to end tragically.  In 1910 Cassirer also resurrected the periodical "Pan".

Death.

On 7 January 1926, Cassirer met his wife in a lawyer's office to finalize the divorce proceedings. He excused himself and walked into another room, where he shot himself. Like that of Van Gogh, the artist he had done so much to promote, Cassirer's suicide was not immediately successful. He died from the injury a few hours later.

Paul Cassirer (21 February 1871, in Görlitz – 7 January 1926, in Berlin) was a German art dealer and editor who played a significant role in the promotion of the work of artists of the Berlin Secession and of French Impressionists and Post-Impressionists, in particular that of Vincent van Gogh and Paul Cézanne.

Paul Cassirer (* 21. Februar 1871 in Görlitz; † 7. Januar 1926 in Berlin) war ein deutscher Verleger, Kunsthändler und Galerist jüdischer Herkunft in Berlin. Der Kunsthandel mit Kunstsalon und Auktionen existierte in Berlin von 1898 bis 1935, in Amsterdam bis in die 2000er Jahre. Der "Paul Cassirer Verlag" existierte von 1908 bis zur Machtergreifung der Nationalsozialisten im Jahr 1933.