In the history of Europe, the Middle Ages or medieval period lasted approximately from the 5th to late 15th centuries, comparable with the post-classical period of global history. The medieval period is the middle epoch of the three traditional divisions of Western history: classical antiquity, the medieval period, and the modern period. The medieval period is itself subdivided into the Early, High, and Late Middle Ages.
The Middle Ages began with the fall of the Western Roman Empire and transitioned into the Modern age during the Renaissance, the Reformation, the European wars of religion, and the Age of Discovery. Early Modernity is a single term adopted to describe this end-stage of the period, during which medieval Europe shades into the modern period.
Population decline, counterurbanisation, the collapse of centralised authority, invasions, and mass migrations of tribes had begun in late antiquity (c. ~3rd–8th centuries) and lasted into the Early Middle Ages (c. 5th–10th centuries). The large-scale movements of the Migration Period, including various Germanic peoples, formed new kingdoms in what remained of the Western Roman Empire. In the 7th century, North Africa and the Middle East—once part of the Byzantine Empire—came under the rule of the Umayyad Caliphate, an Islamic empire, after conquest by Muhammad's successors. Although there were substantial changes in society and political structures, the break with classical antiquity was incomplete. The still-sizeable Byzantine Empire, Rome's direct continuation, survived in the Eastern Mediterranean and remained a major power. The empire's law code, the Corpus Juris Civilis or "Code of Justinian", was rediscovered in Northern Italy in the 11th century. In the West, most kingdoms incorporated the few extant Roman institutions. Monasteries were founded as campaigns to Christianise the remaining pagans across Europe continued. The Franks, under the Carolingian dynasty, briefly established the Carolingian Empire during the later 8th and early 9th centuries. It covered much of Western Europe but later succumbed to the pressures of internal civil wars combined with external invasions: Vikings from the north, Magyars from the east, and Saracens from the south.
During the High Middle Ages, which began after 1000, the population of Europe increased significantly as technological and agricultural innovations allowed trade to flourish and the Medieval Warm Period climate change allowed crop yields to increase. Manorialism, the organisation of peasants into villages that owed rent and labour services to the nobles, and feudalism, the political structure whereby knights and lower-status nobles owed military service to their overlords in return for the right to rent from lands and manors, were two of the ways society was organised in the High Middle Ages. This period also saw the collapse of the unified Christian church with the East–West Schism of 1054. The Crusades, first preached in 1095, were military attempts by Western European Christians to regain control of the Holy Land from Muslims. Kings became the heads of centralised nation-states, reducing crime and violence but making the ideal of a unified Christendom more distant. Intellectual life was marked by scholasticism, a philosophy that emphasised joining faith to reason, and by the founding of universities. The theology of Thomas Aquinas, the paintings of Giotto, the poetry of Dante and Chaucer, the travels of Marco Polo, and the Gothic architecture of cathedrals such as Chartres are among the outstanding achievements toward the end of this period and into the Late Middle Ages.
The Late Middle Ages was marked by difficulties and calamities, including famine, plague, and war, which significantly diminished the population of Europe; between 1347 and 1350, the Black Death killed about a third of Europeans. Controversy, heresy, and the Western Schism within the Catholic Church paralleled the interstate conflict, civil strife, and peasant revolts that occurred in the kingdoms. Cultural and technological developments transformed European society, concluding the Late Middle Ages and beginning the early modern period.

== Terminology and periodisation ==
The Middle Ages is one of the three major periods in the most enduring scheme for analysing European history: classical civilisation or antiquity, the Middle Ages and the modern period. The "Middle Ages" first appears in Latin in 1469 as media tempestas or "middle season". In early usage, there were many variants, including medium aevum, or "middle age", first recorded in 1604, and media saecula, or "middle centuries", first recorded in 1625. The adjective "medieval" (or sometimes "mediaeval" or "mediæval"), meaning pertaining to the Middle Ages, derives from medium aevum.
Medieval writers divided history into periods such as the "Six Ages" or the "Four Empires" and considered their time to be the last before the end of the world. When referring to their own times, they spoke of them as being "modern". In the 1330s, the Italian humanist and poet Petrarch referred to pre-Christian times as antiqua ('ancient') and to the Christian period as nova ('new'). Petrarch regarded the post-Roman centuries as "dark" compared to the "light" of classical antiquity. Leonardo Bruni was the first historian to use tripartite periodisation in his History of the Florentine People (1442), with a middle period "between the fall of the Roman Empire and the revival of city life sometime in late eleventh and twelfth centuries". Tripartite periodisation became standard after the 17th-century German historian Christoph Cellarius divided history into three periods: ancient, medieval, and modern.
The most commonly given starting point for the Middle Ages is around 500, with the date of 476 first used by Bruni--mapping to the removal of the last (native) Roman emperor in the West from power and his replacement by a German chieftain. Later starting dates are sometimes used in the outer parts of Europe. For Europe as a whole, 1500 is often considered to be the end of the Middle Ages, but there is no universally agreed upon end date. Depending on the context, events such as the conquest of Constantinople by the Turks in 1453, Christopher Columbus's first voyage to the Americas in 1492, or the Reformation in 1517 are sometimes used. English historians often use the Battle of Bosworth Field in 1485 to mark the end of the period. For Spain, dates commonly used are the death of King Ferdinand II in 1516, the death of Queen Isabella I of Castile in 1504, or the conquest of Granada in 1492. 1648, marking the end of the European wars of religion, might be considered an upper-bound that preserves the tripartite schema of the terminology (classical antiquity, the medieval, and the modern). The European Renaissance, the Reformation, and Early Modernity would, in that case, all refer to a transition between the Middle Ages and modernity in Western Europe instead of being counted as their own periods, similar to the way that the fall of the Western Roman Empire (occurring over a period of centuries) marks the beginning of the medieval period. By the end of the Thirty Years War, this transition has been accomplished in a geopolitical sense and the territory previously known as Christendom begins to be called Europe.
Historians from Romance-speaking countries tend to divide the Middle Ages into two parts: an earlier "High" and later "Low" period. English-speaking historians, following their German counterparts, generally subdivide the Middle Ages into three intervals: "Early", "High", and "Late". In the 19th century, the entire Middle Ages were often referred to as the "Dark Ages", but with the adoption of these subdivisions, use of this term was restricted to the Early Middle Ages, at least among historians.

== Later Roman Empire ==

The Roman Empire reached its greatest territorial extent during the 2nd century AD; the following two centuries wit


The Renaissance (UK:  rin-AY-sənss, US:   REN-ə-sahnss) was a European period of history and cultural movement taking place at the end of the Late Middle Ages and the beginning of the early modern era. It is variously defined as covering the 15th and 16th centuries or, more broadly, as lasting from the 14th century to the 17th. It was characterized by the European rediscovery and revival of the literary, philosophical, and artistic achievements of classical antiquity. Associated with great change in art, architecture, politics, literature, exploration and technology, the Renaissance was first centered in the Republic of Florence, then spread to the rest of Italy and later throughout Europe.
The Renaissance's intellectual basis was founded in its version of humanism, derived from the concept of Roman humanitas and the rediscovery of classical Greek philosophy, such as that of Protagoras, who said that "man is the measure of all things". Although the invention of metal movable type sped the dissemination of ideas from the later 15th century, the changes of the Renaissance were not uniform across Europe: the first traces appear in Italy as early as the late 13th century, in particular with the writings of Dante and the paintings of Giotto.
As a cultural movement, the Renaissance encompassed innovative flowering of literary Latin and an explosion of vernacular literatures, beginning with the 14th-century resurgence of learning based on classical sources, which contemporaries credited to Petrarch; the development of linear perspective and other techniques of rendering a more natural reality in painting; and gradual but widespread educational reform. It saw myriad artistic developments and contributions from such polymaths as Leonardo da Vinci and Michelangelo, who inspired the term "Renaissance man". In politics, the Renaissance contributed to the development of the customs and conventions of diplomacy. The period also saw revolutions in printing and navigation, as well as the introduction of modern banking and the field of accounting.

== Period ==
The Renaissance began in Italy during the crisis of the Late Middle Ages. It had a different period and characteristics north of the Alps and in Spain. In Italy, the period conventionally ends with the waning of humanism, and the advent of the Reformation (1517), the Sack of Rome (1527) or the Counter-Reformation (1545), and in art, the Baroque period. Proponents of a "long Renaissance," however, may propose that (outside of Italy) the period extended into the 17th century.
The traditional view focuses more on the Renaissance's early modern aspects and argues that it was a break from the past, but many historians today focus more on its medieval aspects and argue that it was an extension of the Middle Ages.

=== Italian Renaissance ===

The beginnings of the period—the early Renaissance of the 15th century and the Italian Proto-Renaissance from around 1250 or 1300—overlap considerably with the Late Middle Ages, conventionally dated to c. 1350–1500, and the Middle Ages themselves were a long period filled with gradual changes, like the modern age; as a transitional period between both, the Renaissance has close similarities to both, especially the late and early sub-periods of either.
The Renaissance began in Florence, one of the many states of Italy. The Italian Renaissance concluded in 1527 when Holy Roman Emperor Charles V launched an assault on Rome during the war of the League of Cognac. Nevertheless, its impact endured in the art of renowned Italian painters like Tintoretto, Sofonisba Anguissola, and Paolo Veronese, who continued their work during the mid-to-late 16th century.
Various theories have been proposed to account for its origins and characteristics, focusing on a variety of factors, including Florence's social and civic peculiarities at the time: its political structure, the patronage of its dominant family, the Medici, and the migration of Greek scholars and their texts to Italy following the fall of Constantinople to the Ottoman Empire. Other major centers were Venice, Genoa, Milan, Rome during the Renaissance Papacy, and Naples. From Italy, the Renaissance spread throughout Europe and also to American, African and Asian territories ruled by the European colonial powers of the time or where Christian missionaries were active.
The Renaissance has a long and complex historiography, and in line with general skepticism of discrete periodizations, there has been much debate among historians reacting to the 19th-century glorification of the "Renaissance" and individual cultural heroes as "Renaissance men", questioning the usefulness of Renaissance as a term and as a historical delineation.
Some observers have questioned whether the Renaissance was a cultural "advance" from the Middle Ages, instead seeing it as a period of pessimism and nostalgia for classical antiquity, while social and economic historians, especially of the longue durée, have instead focused on the continuity between the two eras, which are linked, as Panofsky observed, "by a thousand ties".

== Overview ==
The Renaissance was a cultural movement that profoundly affected European intellectual life in the early modern period. Beginning in Italy, and spreading to the rest of Europe by the 16th century, its influence was felt in art, architecture, philosophy, literature, music, science, technology, politics, religion, and other aspects of intellectual inquiry. Renaissance scholars employed the humanist method in study, and searched for realism and human emotion in art.
Renaissance humanists such as Poggio Bracciolini sought out in Europe's monastic libraries the Latin literary, historical, and oratorical texts of antiquity, while the fall of Constantinople (1453) generated a wave of émigré Greek scholars bringing precious manuscripts in ancient Greek, many of which had fallen into obscurity in the West. It was in their new focus on literary and historical texts that Renaissance scholars differed so markedly from the medieval scholars of the Renaissance of the 12th century, who had focused on studying Greek and Arabic works of natural sciences, philosophy, and mathematics, rather than on such cultural texts.

In the revival of neoplatonism, Renaissance humanists did not reject Christianity; on the contrary, many of the Renaissance's greatest works were devoted to it, and the Church patronized many works of Renaissance art. But a subtle shift took place in the way that intellectuals approached religion that was reflected in many other areas of cultural life. In addition, many Greek Christian works, including the Greek New Testament, were brought back from Byzantium to Western Europe and engaged Western scholars for the first time since late antiquity. This new engagement with Greek Christian works, and particularly the return to the original Greek of the New Testament promoted by humanists Lorenzo Valla and Erasmus, helped pave the way for the Reformation.
Well after the first artistic return to classicism had been exemplified in the sculpture of Nicola Pisano, Florentine painters led by Masaccio strove to portray the human form realistically, developing techniques to render perspective and light more naturally. Political philosophers, most famously Niccolò Machiavelli, sought to describe political life as it really was, that is, to understand it rationally. A critical contribution to Italian Renaissance humanism, Giovanni Pico della Mirandola wrote De hominis dignitate (Oration on the Dignity of Man, 1486), a series of theses on philosophy, natural thought, faith, and magic defended against any opponent on the grounds of reason. In addition to studying classical Latin and Greek, Renaissance authors also began increasingly to use vernacular languages; combined with the introduction of the printing press, this allowed many more people access to books, especially the Bible.
In all, the Renaissance can be viewed as an attempt by intel


The Age of Enlightenment, also known as the Age of Reason or simply the Enlightenment, was a period of intellectual and cultural flourishing in Europe and Western civilization, emerging in the late 17th century in Western Europe. It reached its peak in the 18th century as its ideas spread more widely across Europe and into the European colonies in the Americas and Oceania. Characterized by an emphasis on reason, empirical evidence, and the scientific method, the Enlightenment promoted ideals of individual liberty, religious tolerance, progress, and natural rights. Its thinkers advocated for constitutional government, the separation of church and state, and the application of rational principles to social and political reform.
The Enlightenment emerged from and built upon the Scientific Revolution of the 16th and 17th centuries, which had established new methods of empirical inquiry through the work of figures such as Galileo Galilei, Johannes Kepler, Francis Bacon, Pierre Gassendi, Christiaan Huygens, and Isaac Newton. Philosophical foundations were laid by thinkers including René Descartes, Thomas Hobbes, Baruch Spinoza, and John Locke, whose ideas about reason, natural rights, and empirical knowledge became central to Enlightenment thought. The dating of the period of the beginning of the Enlightenment can be attributed to the publication of Descartes' Discourse on the Method in 1637, with his method of systematically disbelieving everything unless there was a well-founded reason for accepting it, and featuring his dictum, Cogito, ergo sum ('I think, therefore I am'). Others cite the publication of Newton's Principia Mathematica (1687) as the culmination of the Scientific Revolution and the beginning of the Enlightenment. European historians traditionally dated its beginning with the death of Louis XIV of France in 1715 and its end with the outbreak of the French Revolution in 1789. Many historians now date the end of the Enlightenment as the start of the 19th century, with the latest proposed year being the death of Immanuel Kant in 1804.
The movement was characterized by the widespread circulation of ideas through new institutions: scientific academies, literary salons, coffeehouses, Masonic lodges, and an expanding print culture of books, journals, and pamphlets. The ideas of the Enlightenment undermined the authority of the monarchy and religious officials and paved the way for the political revolutions of the 18th and 19th centuries. A variety of 19th-century movements, including liberalism, socialism, and neoclassicism, trace their intellectual heritage to the Enlightenment. The Enlightenment was marked by an increasing awareness of the relationship between the mind and the everyday media of the world, and by an emphasis on the scientific method and reductionism, along with increased questioning of religious dogma—an attitude captured by Kant's essay Answering the Question: What Is Enlightenment?, where the phrase sapere aude ('dare to know') can be found.
The central doctrines of the Enlightenment were individual liberty, representative government, the rule of law, and religious freedom, in contrast to an absolute monarchy or single party state and the religious persecution of faiths other than those formally established and often controlled outright by the State. By contrast, other intellectual currents included arguments in favour of anti-Christianity, Deism and Atheism, accompanied by demands for secular states, bans on religious education, suppression of monasteries, the suppression of the Jesuits, and the expulsion of religious orders. The Enlightenment also faced contemporary criticism, later termed the "Counter-Enlightenment" by Sir Isaiah Berlin, which defended traditional religious and political authorities against rationalist critique.

== Influential intellectuals ==

The Enlightenment was preceded by and closely associated with the Scientific Revolution. Earlier philosophers whose work influenced the Enlightenment included Francis Bacon, Pierre Gassendi, René Descartes, Thomas Hobbes, Baruch Spinoza, John Locke, Pierre Bayle, and Gottfried Wilhelm Leibniz. Some of the figures of the Enlightenment included Cesare Beccaria, George Berkeley, Denis Diderot, David Hume, Immanuel Kant, Lord Monboddo, Montesquieu, Jean-Jacques Rousseau, Adam Smith, Roger Williams, Hugo Grotius, and Voltaire.
One of the most influential Enlightenment publications was the Encyclopédie (Encyclopedia). Published between 1751 and 1772 in 35 volumes, it was compiled by Diderot, Jean le Rond d'Alembert, and a team of 150 others. The Encyclopédie helped spread the ideas of the Enlightenment across Europe and beyond.
Other publications of the Enlightenment included Locke's A Letter Concerning Toleration (1689) and Two Treatises of Government (1689); Berkeley's A Treatise Concerning the Principles of Human Knowledge (1710), Voltaire's Letters on the English (1733) and Philosophical Dictionary (1764); Hume's A Treatise of Human Nature (1740); Montesquieu's The Spirit of the Laws (1748); Rousseau's Discourse on Inequality (1754) and The Social Contract (1762); Cesare Beccaria's On Crimes and Punishments (1764); Adam Smith's The Theory of Moral Sentiments (1759) and The Wealth of Nations (1776), Kant's Critique of Pure Reason (1781), and at the close of the age, the pioneering proto-feminist text, Wollstoncraft's A Vindication Of The Rights Of Woman (1792).

== Topics ==

=== Philosophy ===

Bacon's empiricism and Descartes' rationalist philosophy laid the foundation for enlightenment thinking. Descartes' attempt to construct the sciences on a secure metaphysical foundation was not as successful as his method of doubt applied to philosophy, which led to a dualistic doctrine of mind and matter. His skepticism was refined by Locke's Essay Concerning Human Understanding (1690) and Hume's writings in the 1740s. Descartes' dualism was challenged by Spinoza's uncompromising assertion of the unity of matter in his Tractatus (1670) and Ethics (1677).
According to Jonathan Israel, these laid down two distinct lines of Enlightenment thought: first, the moderate variety, following Descartes, Locke, and Christian Wolff, which sought accommodation between reform and the traditional systems of power and faith, and, second, the Radical Enlightenment, inspired by the philosophy of Spinoza, advocating democracy, individual liberty, freedom of expression, and eradication of religious authority. The moderate variety tended to be deistic whereas the radical tendency separated the basis of morality entirely from theology. Both lines of thought were eventually opposed by a conservative Counter-Enlightenment which sought a return to faith.
In the mid-18th century, Paris became the center of philosophic and scientific activity challenging traditional doctrines and dogmas. After the Edict of Fontainebleau in 1685, the relationship between church and the absolutist government was very strong. The early enlightenment emerged in protest to these circumstances, gaining ground under the support of Madame de Pompadour, the mistress of Louis XV. Called the Siècle des Lumières, the philosophical movement of the Enlightenment had already started by the early 18th century, when Pierre Bayle launched the popular and scholarly Enlightenment critique of religion. As a skeptic Bayle only partially accepted the philosophy and principles of rationality. He did draw a strict boundary between morality and religion. The rigor of his Dictionnaire Historique et Critique influenced many of the Enlightenment Encyclopédistes. By the mid-18th century the French Enlightenment had found a focus in the project of the Encyclopédie. The philosophical movement was led by Voltaire and Rousseau, who argued for a society based upon reason rather than faith and Catholic doctrine, for a new civil order based on natural law, and for science based on experiments and observation. The political philosopher Montesquieu introd


Natural selection is the differential survival and reproduction of individuals due to differences in the relative fitness endowed on them by their own particular complement of observable characteristics. It is a key law or mechanism of evolution which changes the heritable traits characteristic of a population or species over generations. Charles Darwin popularised the term "natural selection", contrasting it with artificial selection, which is intentional, whereas natural selection is not.
For Darwin, natural selection was a law or principle which resulted from three different kinds of process: inheritance, including the transmission of heritable material from parent to offspring and its development (ontogeny) in the offspring; variation, which partly resulted from an organism's own agency (see phenotype; Baldwin effect); and the struggle for existence, which included both competition between organisms and cooperation or 'mutual aid' (particularly in 'social' plants and social animals).
Variation of traits, both genotypic and phenotypic, exists within all populations of organisms. However, some traits are more likely to facilitate survival and reproductive success. Thus, these traits are more likely to be passed on to the next generation. These traits can also become more common within a population if the environment that favours these traits remains fixed. If new traits become more favoured due to changes in a specific niche, microevolution occurs. If new traits become more favoured due to changes in the broader environment, macroevolution occurs. Sometimes, new species can arise especially if these new traits are radically different from the traits possessed by their predecessors.
The likelihood of these traits being 'selected' and passed down is determined by many factors. Some are likely to be passed down because they adapt well to their environments. Others are passed down because these traits are actively preferred by mating partners, which is known as sexual selection. Female bodies also prefer traits that confer the lowest cost to their reproductive health, which is known as fecundity selection.
Natural selection is a cornerstone of modern biology. The concept, published by Darwin and Alfred Russel Wallace in a joint presentation of papers in 1858, was elaborated in Darwin's influential 1859 book On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. He described natural selection as analogous to artificial selection, a process by which animals and plants with traits considered desirable by human breeders are systematically favoured for reproduction. The concept of natural selection originally developed in the absence of a valid theory of heredity; at the time of Darwin's writing, science had yet to develop modern theories of genetics. The union of traditional Darwinian evolution with subsequent discoveries in classical genetics formed the modern synthesis of the mid-20th century.
New evidence has prompted 21st century  evolutionary biologists to challenge the 20th century's gene-centred view of evolution, producing several  extended evolutionary syntheses which bring organisms back to the heart of the theory of natural selection. Convergently, the growth of molecular genetics has led to evolutionary developmental biology, which compares the developmental processes of different organisms to infer how developmental processes evolved. While it is now recognised that genotypes can slowly change by random genetic drift, natural selection remains the primary explanation for adaptive evolution.

== Historical development ==

=== Pre-Darwinian theories ===

Several philosophers of the classical era, including Empedocles and his intellectual successor, the Roman poet Lucretius, expressed the idea that nature produces a huge variety of creatures, randomly, and that only those creatures that manage to provide for themselves and reproduce successfully persist. Empedocles' idea that organisms arose entirely by the incidental workings of causes such as heat and cold was criticised by Aristotle in Book II of Physics. He posited natural teleology in its place, and believed that form was achieved for a purpose, citing the regularity of heredity in species as proof. Nevertheless, he accepted in his biology that new types of animals, monstrosities (τερας), can occur in very rare instances (Generation of Animals, Book IV). As quoted in Darwin's 1872 edition of The Origin of Species, Aristotle considered whether different forms (e.g., of teeth) might have appeared accidentally, but only the useful forms survived:

So what hinders the different parts [of the body] from having this merely accidental relation in nature? as the teeth, for example, grow by necessity, the front ones sharp, adapted for dividing, and the grinders flat, and serviceable for masticating the food; since they were not made for the sake of this, but it was the result of accident. And in like manner as to the other parts in which there appears to exist an adaptation to an end. Wheresoever, therefore, all things together (that is all the parts of one whole) happened like as if they were made for the sake of something, these were preserved, having been appropriately constituted by an internal spontaneity, and whatsoever things were not thus constituted, perished, and still perish.
But Aristotle rejected this possibility in the next paragraph, making clear that he is talking about  the development of animals as embryos with the phrase "either invariably or normally come about", not the origin of species:

... Yet it is impossible that this should be the true view. For teeth and all other natural things either invariably or normally come about in a given way; but of not one of the results of chance or spontaneity is this true. We do not ascribe to chance or mere coincidence the frequency of rain in winter, but frequent rain in summer we do; nor heat in the dog-days, but only if we have it in winter. If then, it is agreed that things are either the result of coincidence or for an end, and these cannot be the result of coincidence or spontaneity, it follows that they must be for an end; and that such things are all due to nature even the champions of the theory which is before us would agree. Therefore action for an end is present in things which come to be and are by nature.
The struggle for existence was later described by the Islamic writer Al-Jahiz in the 9th century, particularly in the context of top-down population regulation, but not in reference to individual variation or natural selection.
At the turn of the 16th century Leonardo da Vinci collected a set of fossils of ammonites as well as other biological material. He extensively reasoned in his writings that the shapes of animals are not given once and forever by the "upper power" but instead are generated in different forms naturally and then selected for reproduction by their compatibility with the environment.
The more recent classical arguments were reintroduced in the 18th century by Pierre Louis Maupertuis and others, including Darwin's grandfather, Erasmus Darwin.
Until the early 19th century, the prevailing view in Western societies was that differences between individuals of a species were uninteresting departures from their Platonic ideals (or typus) of created kinds. However, the theory of uniformitarianism in geology promoted the idea that simple, weak forces could act continuously over long periods of time to produce radical changes in the Earth's landscape. The success of this theory raised awareness of the vast scale of geological time and made plausible the idea that tiny, virtually imperceptible changes in successive generations could produce consequences on the scale of differences between species.
The early 19th-century zoologist Jean-Baptiste Lamarck suggested the inheritance of acquired characteristics as a mechanism for evolutionary change; adapt


Charles Robert Darwin ( DAR-win; 12 February 1809 – 19 April 1882) was an English naturalist, geologist, and biologist, widely known for his contributions to evolutionary biology. His proposition that all species of life have descended from a common ancestor is now generally accepted and considered a fundamental scientific concept. In a joint presentation with Alfred Russel Wallace, he introduced his scientific theory that this branching pattern of evolution resulted from a process he called natural selection, in which the struggle for existence has a similar effect to the artificial selection involved in selective breeding. Darwin has been described as one of the most influential figures in human history and was honoured by burial in Westminster Abbey.
Darwin's early interest in nature led him to neglect his medical education at the University of Edinburgh; instead, he helped Robert Edmond Grant to investigate marine invertebrates. His studies at the University of Cambridge's Christ's College from 1828 to 1831 encouraged his passion for natural science. However, it was his five-year voyage on HMS Beagle from 1831 to 1836 that truly established Darwin as an eminent geologist. The observations and theories he developed during his voyage supported Charles Lyell's concept of gradual geological change. Publication of his journal of the voyage made Darwin famous as a popular author. His first scientific work was The Structure and Distribution of Coral Reefs (1842). Along with his work on barnacles, it won him the Royal Medal in 1853.
Puzzled by the geographical distribution of wildlife and fossils he collected on the voyage, Darwin began detailed investigations and, in 1838, devised his theory of natural selection. Although he discussed his ideas with several naturalists, he needed time for extensive research, and his geological work had priority. He was writing up his theory in 1858 when Wallace sent him an essay that described the same idea, prompting the immediate joint submission of both their theories to the Linnean Society of London. Darwin's work established evolutionary descent with modification as the dominant scientific explanation of natural diversification. Darwin published his theory of evolution with compelling evidence in On the Origin of Species (1859). He explored coevolution in Fertilisation of Orchids (1862) and human evolution and sexual selection in The Descent of Man, and Selection in Relation to Sex (1871). The Expression of the Emotions in Man and Animals (1872) was an early work of psychology, and one of the first books to feature photographs. His final book was The Formation of Vegetable Mould, through the Actions of Worms (1881).
By the 1870s, the scientific community and a majority of the educated public had accepted evolution as a fact. However, many initially favoured  competing explanations that gave only a minor role to natural selection. It was not until the emergence of the modern evolutionary synthesis from the 1930s to the 1950s that a broad consensus developed in which natural selection was the basic mechanism of evolution. Darwin's discovery is the unifying theory of the life sciences, explaining the unity and diversity of life.

== Biography ==

=== Early life and education ===

Charles Robert Darwin was born on 12 February 1809 at his family's home, The Mount, in Shrewsbury, Shropshire. He was the fifth of six children of wealthy society doctor and financier Robert Darwin and Susannah Darwin (née Wedgwood). His grandfathers Erasmus Darwin and Josiah Wedgwood were both prominent abolitionists. Erasmus Darwin had praised general concepts of evolution and common descent in his Zoonomia (1794), a poetic fantasy of gradual creation including undeveloped ideas anticipating concepts his grandson expanded.

Both families were largely Unitarian, though the Wedgwoods were adopting Anglicanism. Robert Darwin, a freethinker, had baby Charles baptised in November 1809 in the Anglican St Chad's Church, Shrewsbury, but Charles and his siblings attended the local Unitarian Church with their mother. The eight-year-old Charles already had a taste for natural history and collecting when he joined the day school run by its preacher in 1817. That July, his mother died. From September 1818, he joined his older brother Erasmus in attending the nearby Anglican Shrewsbury School as a boarder.
Darwin spent the summer of 1825 as an apprentice doctor, helping his father treat impoverished people in Shropshire, before going to the well-regarded University of Edinburgh Medical School with his brother Erasmus in October 1825. Darwin found lectures dull and surgery distressing, so he neglected his studies. He learned taxidermy in around 40 daily hour-long sessions from John Edmonstone, a Black Briton from Demerara in the South American rainforest, who had been taught there by Charles Waterton, and when brought to Scotland was freed from slavery.
In Darwin's second year at the university, he joined the Plinian Society, a student natural-history group featuring lively debates in which radical democratic students with materialistic views challenged orthodox religious concepts of science. He assisted Robert Edmond Grant's investigations of the anatomy and life cycle of marine invertebrates in the Firth of Forth, and on 27 March 1827 presented at the Plinian his own discovery that black spores found in oyster shells were the eggs of a skate leech.
One day, Grant praised Lamarck's evolutionary ideas. Darwin was astonished by Grant's audacity, but had recently read similar ideas in his grandfather Erasmus' journals. Darwin was rather bored by Robert Jameson's natural-history course, which covered geology – including the debate between neptunism and plutonism. He learned the classification of plants. He assisted with work on the collections of the University Museum, one of the largest museums in Europe at the time.
Darwin's neglect of medical studies annoyed his father, who sent him to Christ's College, Cambridge in January 1828 to study for a Bachelor of Arts degree as the first step towards becoming an Anglican country parson. Darwin was unqualified for Cambridge's Tripos exams and was required instead to join the ordinary degree course. He preferred riding and shooting to studying. At Cambridge, Darwin joined a society known as the "Glutton Club," which consumed "birds and beasts which were before unknown to human palate." Darwin would continue to eat the meat of exotic animals for the rest of his life; on the voyage of the Beagle, he ate puma, iguanas, giant tortoises, armadillos, and mistakenly ate a rhea which he intended to study.

During the first few months of Darwin's enrolment at Christ's College, his second cousin William Darwin Fox was still studying there. Fox impressed him with his butterfly collection, introducing Darwin to entomology and influencing him to pursue beetle collecting. He did this zealously and had some of his finds published in James Francis Stephens' Illustrations of British entomology (1829–1932).
Through Fox, Darwin became a close friend and follower of botany professor John Stevens Henslow. He met other leading parson-naturalists who saw scientific work as religious natural theology, becoming known to these dons as "the man who walks with Henslow". When his own exams drew near, Darwin applied himself to his studies and was delighted by the language and logic of William Paley's Evidences of Christianity (1795). In his final examination in January 1831, Darwin did well, coming tenth out of 178 candidates for the ordinary degree.
Darwin had to stay at Cambridge until June 1831. He studied Paley's Natural Theology or Evidences of the Existence and Attributes of the Deity (first published in 1802), which made an argument for divine design in nature, explaining adaptation as God acting through laws of nature. He read John Herschel's new book, Preliminary Discourse on the Study of Natural Philosophy (1831), which described


Genetics is the study of genes, genetic variation, and heredity in organisms. It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working in the 19th century in Brno, was the first to study genetics scientifically. Mendel studied "trait inheritance", patterns in the way traits are handed down from parents to offspring over time. He observed that organisms (pea plants) inherit traits by way of discrete "units of inheritance". This term, still used today, is a somewhat ambiguous definition of what is referred to as a gene.
Trait inheritance and molecular inheritance mechanisms of genes are still primary principles of genetics in the 21st century, but modern genetics has expanded to study the function and behavior of genes. Gene structure and function, variation, and distribution are studied within the context of the cell, the organism (e.g. dominance), and within the context of a population. Genetics has given rise to a number of subfields, including molecular genetics, epigenetics, population genetics, and paleogenetics. Organisms studied within the broad field span the domains of life (archaea, bacteria, and eukarya).
Genetic processes work in combination with an organism's environment and experiences to influence development and behavior, often referred to as nature versus nurture. The intracellular or extracellular environment of a living cell or organism may increase or decrease gene transcription. A classic example is two seeds of genetically identical corn, one placed in a temperate climate and one in an arid climate (lacking sufficient waterfall or rain). While the average height the two corn stalks could grow to is genetically determined, the one in the arid climate only grows to half the height of the one in the temperate climate due to lack of water and nutrients in its environment.

== Etymology ==
William Bateson coined genetics from the ancient Greek γενετικός genetikos meaning "genitive"/"generative", which in turn derives from γένεσις genesis meaning "origin".

== History ==

The observation that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding. The modern science of genetics, seeking to understand this process, began with the work of the Augustinian friar Gregor Mendel in the mid-19th century.

Prior to Mendel, Imre Festetics, a Hungarian noble, who lived in Kőszeg before Mendel, was the first who used the word "genetic" in hereditarian context, and is considered the first geneticist. He described several rules of biological inheritance in his work The genetic laws of nature (Die genetischen Gesetze der Natur, 1819). His second law is the same as that which Mendel published. In his third law, he developed the basic principles of mutation (he can be considered a forerunner of Hugo de Vries). Festetics argued that changes observed in the generation of farm animals, plants, and humans are the result of scientific laws. Festetics empirically deduced that organisms inherit their characteristics, not acquire them. He recognized recessive traits and inherent variation by postulating that traits of past generations could reappear later, and organisms could produce progeny with different attributes. These observations represent an important prelude to Mendel's theory of particulate inheritance insofar as it features a transition of heredity from its status as myth to that of a scientific discipline, by providing a fundamental theoretical basis for genetics in the twentieth century.

Other theories of inheritance preceded Mendel's work. A popular theory during the 19th century, and implied by Charles Darwin's 1859 On the Origin of Species, was blending inheritance: the idea that individuals inherit a smooth blend of traits from their parents. Mendel's work provided examples where traits were definitely not blended after hybridization, showing that traits are produced by combinations of distinct genes rather than a continuous blend. Blending of traits in the progeny is now explained by the action of multiple genes with quantitative effects. Another theory that had some support at that time was the inheritance of acquired characteristics: the belief that individuals inherit traits strengthened by their parents. This theory (commonly associated with Jean-Baptiste Lamarck) is now known to be wrong—the experiences of individuals do not affect the genes they pass to their children. Other theories included Darwin's pangenesis (which had both acquired and inherited aspects) and Francis Galton's reformulation of pangenesis as both particulate and inherited.

=== Mendelian genetics ===

Modern genetics started with Mendel's studies of the nature of inheritance in plants. In his paper "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to the Naturforschender Verein (Society for Research in Nature) in Brno, Mendel traced the inheritance patterns of certain traits in pea plants and described them mathematically. Although this pattern of inheritance could only be observed for a few traits, Mendel's work suggested that heredity was particulate, not acquired, and that the inheritance patterns of many traits could be explained through simple rules and ratios.
The importance of Mendel's work did not gain wide understanding until 1900, after his death, when Hugo de Vries and other scientists rediscovered his research. William Bateson, a proponent of Mendel's work, coined the word genetics in 1905. The adjective genetic, derived from the Greek word genesis—γένεσις, "origin", predates the noun and was first used in a biological sense in 1860. Bateson both acted as a mentor and was aided significantly by the work of other scientists from Newnham College at Cambridge, specifically the work of Becky Saunders, Nora Darwin Barlow, and Muriel Wheldale Onslow. Bateson popularized the usage of the word genetics to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in London in 1906.
After the rediscovery of Mendel's work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1900, Nettie Stevens began studying the mealworm. Over the next 11 years, she discovered that females only had the X chromosome and males had both X and Y chromosomes. She was able to conclude that sex is a chromosomal factor and is determined by the male. In 1911, Thomas Hunt Morgan argued that genes are on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies. In 1913, his student Alfred Sturtevant used the phenomenon of genetic linkage to show that genes are arranged linearly on the chromosome.

=== Molecular genetics ===

Although genes were known to exist on chromosomes, chromosomes are composed of both protein and DNA, and scientists did not know which of the two was responsible for inheritance. In 1928, Frederick Griffith discovered the phenomenon of transformation: dead bacteria could transfer genetic material to "transform" other still-living bacteria. Sixteen years later, in 1944, the Avery–MacLeod–McCarty experiment identified DNA as the molecule responsible for transformation. The role of the nucleus as the repository of genetic information in eukaryotes had been established by Hämmerling in 1943 in his work on the single celled alga Acetabularia. The Hershey–Chase experiment in 1952 confirmed that DNA (rather than protein) is the genetic material of the viruses that infect bacteria, providing further evidence that DNA is the molecule responsible for inheritance.
James Watson and Francis Crick determined the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin and Maurice Wilkins that indicated DNA has a helical structure (i.e., shaped like a corkscrew). Their double-helix model had two strands of DNA


Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses. DNA and ribonucleic acid (RNA) are nucleic acids. Alongside proteins, lipids and complex carbohydrates (polysaccharides), nucleic acids are one of the four major types of macromolecules that are essential for all known forms of life.
The two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases (cytosine [C], guanine [G], adenine [A] or thymine [T]), a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds (known as the phosphodiester linkage) between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules (A with T and C with G), with hydrogen bonds to make double-stranded DNA. The complementary nitrogenous bases are divided into two groups, the single-ringed pyrimidines and the double-ringed purines. In DNA, the pyrimidines are thymine and cytosine; the purines are adenine and guanine.
Both strands of double-stranded DNA store the same biological information. This information is replicated when the two strands separate. The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (or bases). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription, where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes uracil (U). Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation.
Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms (animals, plants, fungi and protists) store most of their DNA inside the cell nucleus as nuclear DNA, and some in the mitochondria as mitochondrial DNA or in chloroplasts as chloroplast DNA. In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm, in circular chromosomes. Within eukaryotic chromosomes, chromatin proteins, such as histones, compact and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

== Properties ==

DNA is a long polymer made from repeating units called nucleotides.
DNA does not usually exist as a single strand, but instead as a pair of strands that are held tightly together. These two long strands coil around each other, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside, and a base linked to a sugar and to one or more phosphate groups is called a nucleotide. A biopolymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.
The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. The two chains are coiled around the same axis (but not directly opposite one to the other), and have the same pitch of 34 ångströms (3.4 nm). Ignoring the identities of the bases, the line group is D1(q), where q stands for the turn per base pair, which is around a tenth of a full turn. In the usual form (B-DNA), the twist is right-handed, like a normal screw that advances when turned clockwise. The pair of chains have a radius of 10 Å (1.0 nm). According to another study, when measured in a different solution, the DNA chain measured 22–26 Å (2.2–2.6 nm) wide, and one nucleotide unit measured 3.3 Å (0.33 nm) long. The buoyant density of most DNA is 1.7g/cm3.
The backbone of the DNA strand is made from alternating phosphate and sugar groups. The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These are known as the 3′-end (three prime end), and 5′-end (five prime end) carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond.
Therefore, any DNA strand normally has one end at which there is a phosphate group attached to the 5′ carbon of a ribose (the 5′ phosphoryl) and another end at which there is a free hydroxyl group attached to the 3′ carbon of a ribose (the 3′ hydroxyl). The orientation of the 3′ and 5′ carbons along the sugar-phosphate backbone confers directionality (sometimes called polarity) to each DNA strand. In a nucleic acid double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime end (5′ ), and three prime end (3′), with the 5′ end having a terminal phosphate group and the 3′ end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the related pentose sugar ribose in RNA.

The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine, forming A-T and G-C base pairs.

=== Nucleobase classification ===
The nucleobases are classified into two types: the purines, A and G, which are fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T. A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.

=== Non-canonical bases ===
Modified bases occur in DNA. The first of these recognized was 5-methylcytosine, which was found in the genome of Mycobacterium tuberculosis in 1925. The reason for the presence of these noncanonical bases in bacterial viruses (bacteriophages) is to avoid the restriction enzymes present in bacteria. This enzyme system acts at least in part as a molecular immune system protecting bacteria from infection by viruses. Modifications of the bases cytosine and adenine, the more common and modified DNA bases, play vital roles in the epigenetic control of gene expression in plants and animals.
A number of noncanonical bases are known to occur in DNA. Most of these are modifications of the canonical bases plus uracil.

Modified Adenine
N6-carbamoyl-methyladenine
N6-methyadenine
Modified Guanine
7-Deazaguanine
7-Methylguanine
Modified Cytosine
N4-Methylcytosine
5-Carboxylcytosine
5-Formylcytosine
5-Glycosylhydroxymethylcytosine
5-Hydroxycytosine
5-Methylcytosine
Modified Thymidine
α-Gluta


Molecular biology is a branch of biology that seeks to understand the molecular structures and chemical processes that are the basis of biological activity within and between cells. It is centered largely on the study of nucleic acids (such as DNA and RNA) and proteins. It examines the structure, function, and interactions of these macromolecules as they orchestrate processes such as replication, transcription, translation, protein synthesis, and complex biomolecular interactions. The field of molecular biology is multi-disciplinary, relying on principles from genetics, biochemistry, physics, mathematics, and more recently computer science (bioinformatics).
Though cells and other microscopic structures had been observed in organisms as early as the 18th century, a detailed understanding of the mechanisms and interactions governing their behavior did not emerge until the 20th century, when technologies used in physics and chemistry had advanced sufficiently to permit their application in the biological sciences. The term 'molecular biology' was first used in 1945 by the English physicist William Astbury, who described it as an approach focused on discerning the underpinnings of biological phenomena—i.e. uncovering the physical and chemical structures and properties of biological molecules, as well as their interactions with other molecules and how these interactions explain observations of so-called classical biology, which instead studies biological processes at larger scales and higher levels of organization. In 1953, Francis Crick, James Watson, Rosalind Franklin, and their colleagues at the Medical Research Council Unit, Cavendish Laboratory, were the first to describe the double helix model for the chemical structure of deoxyribonucleic acid (DNA), which is often considered a landmark event for the nascent field because it provided a physico-chemical basis by which to understand the previously nebulous idea of nucleic acids as the primary substance of biological inheritance. They proposed this structure based on previous research done by Franklin, which was conveyed to them by Maurice Wilkins and Max Perutz. Their work led to the discovery of DNA in other microorganisms, plants, and animals.
The field of molecular biology includes techniques which enable scientists to learn about molecular processes. These techniques are used to efficiently target new drugs, diagnose disease, and better understand cell physiology. Some clinical research and medical therapies arising from molecular biology are covered under gene therapy, whereas the use of molecular biology or molecular cell biology in medicine is now referred to as molecular medicine.

== History of molecular biology ==

Molecular biology sits at the intersection of biochemistry and genetics; as these scientific disciplines emerged and evolved in the 20th century, it became clear that they both sought to determine the molecular mechanisms that underlie vital cellular functions. Advances in molecular biology have been closely related to the development of new technologies and their optimization.
The field of genetics arose from attempts to understand the set of rules underlying reproduction and heredity, and the nature of the hypothetical units of heredity known as genes. Gregor Mendel pioneered this work in 1866, when he first described the laws of inheritance he observed in his studies of mating crosses in pea plants. One such law of genetic inheritance is the law of segregation, which states that diploid individuals with two alleles for a particular gene will pass one of these alleles to their offspring. Because of his critical work, the study of genetic inheritance is commonly referred to as Mendelian genetics.
A major milestone in molecular biology was the discovery of the structure of DNA. This work began in 1869 by Friedrich Miescher, a Swiss biochemist who first proposed a structure called nuclein, which we now know to be (deoxyribonucleic acid), or DNA. He discovered this unique substance by studying the components of pus-filled bandages, and noting the unique properties of the "phosphorus-containing substances". Another notable contributor to the DNA model was Phoebus Levene, who proposed the "polynucleotide model" of DNA in 1919 as a result of his biochemical experiments on yeast. In 1950, Erwin Chargaff expanded on the work of Levene and elucidated a few critical properties of nucleic acids: first, the sequence of nucleic acids varies across species. Second, the total concentration of purines (adenine and guanine) is always equal to the total concentration of pyrimidines (cytosine and thymine). This is now known as Chargaff's rule. In 1953, James Watson and Francis Crick published the double helical structure of DNA, based on the X-ray crystallography work done by Rosalind Franklin which was conveyed to them by Maurice Wilkins and Max Perutz. Watson and Crick described the structure of DNA and conjectured about the implications of this unique structure for possible mechanisms of DNA replication. Watson and Crick were awarded the Nobel Prize in Physiology or Medicine in 1962, along with Wilkins, for proposing a model of the structure of DNA.
In 1961, it was demonstrated that when a gene encodes a protein, three sequential bases of a gene's DNA specify each successive amino acid of the protein. Thus the genetic code is a triplet code, where each triplet (called a codon) specifies a particular amino acid. Furthermore, it was shown that the codons do not overlap with each other in the DNA sequence encoding a protein, and that each sequence is read from a fixed starting point.
During 1962–1964, through the use of conditional lethal mutants of a bacterial virus, fundamental advances were made in our understanding of the functions and interactions of the proteins employed in the machinery of DNA replication, DNA repair, DNA recombination, and in the assembly of molecular structures.

== Griffith's experiment ==

In 1928, Frederick Griffith, encountered a virulence property in pneumococcus bacteria, which was killing lab rats. According to Mendel, prevalent at that time, gene transfer could occur only from parent to daughter cells. Griffith advanced another theory, stating that gene transfer occurring in members of the same generation is known as horizontal gene transfer (HGT). This phenomenon is now referred to as genetic transformation.
Griffith's experiment addressed the pneumococcus bacteria, which had two different strains, one virulent and smooth and one avirulent and rough. The smooth strain had a glistering appearance owing to the presence of a type of specific polysaccharide – a polymer of glucose and glucuronic acid capsule. Due to this polysaccharide layer of bacteria, a host's immune system cannot recognize the bacteria and it kills the host. The rough strain lacks this polysaccharide capsule, resulting in a dull, rough colony appearance and making it avirulent because it is more readily recognized and destroyed by the host immune system.
The presence or absence of a capsule in the strain, is known to be genetically determined. Smooth and rough strains occur in several different type such as S-I, S-II, S-III, etc. and R-I, R-II, R-III, etc., respectively. All these subtypes of S and R bacteria differ with each other in antigen type they produce.

== Avery–MacLeod–McCarty experiment ==

The Avery–MacLeod–McCarty experiment was an experimental demonstration by Oswald Avery, Colin MacLeod, and Maclyn McCarty that, in 1944, reported that DNA is the substance that causes bacterial transformation, in an era when it had been widely believed that it was proteins that served the function of carrying genetic information (with the very word protein itself coined to indicate a belief that its function was primary). It was the culmination of research in the 1930s and early 20th century at the Rockefeller Institute for Medical Research to purify and characterize the "transforming principle"


Cell biology, cellular biology, or cytology, is the branch of biology that studies the structure, function, and behavior of the cells. All organisms are made of cells. A cell is the basic unit of life that is responsible for the living and functioning of an organism. Cell biology encompasses both prokaryotic and eukaryotic cells, with subtopics including the study of cell metabolism, cell communication, cell cycle, biochemistry, and cell composition.
The study of cells is performed using microscopy techniques, cell culture, and cell fractionation. These are used for research into how cells function, which ultimately gives insight into larger organisms. Knowing the components of cells and how cells work is fundamental to all biological sciences and is essential for research in biomedical fields such as cancer, and other diseases. Research in cell biology is interconnected to other fields such as genetics, molecular genetics, molecular biology, medical microbiology, immunology, and cytochemistry.

== History ==
Cells were first seen in 17th-century Europe with the invention of the compound microscope. In 1665, Robert Hooke referred to the building blocks of all living organisms as "cells" (published in Micrographia) after looking at a piece of cork and observing a structure reminiscent of monastic cells; however, the cells were dead. They gave no indication to the actual overall components of a cell. A few years later, in 1674, Anton Van Leeuwenhoek was the first to analyze live cells in his examination of algae. Many years later, in 1831, Robert Brown discovered the nucleus. All of this preceded the cell theory which states that all living things are made up of cells and that cells are organisms' functional and structural units. This was ultimately concluded by plant scientist Matthias Schleiden and animal scientist Theodor Schwann in 1838, who viewed live cells in plant and animal tissue, respectively. 19 years later, Rudolf Virchow further contributed to the cell theory, adding that all cells come from the division of pre-existing cells. Viruses are not considered in cell biology – they lack the characteristics of a living cell and instead are studied in the microbiology subclass of virology.

== Techniques ==

Cell biology research looks at different ways to culture and manipulate cells outside of a living body to further research in human anatomy and physiology, and to derive medications. The techniques by which cells are studied have evolved. Due to advancements in microscopy, techniques and technology have allowed scientists to hold a better understanding of the structure and function of cells. Many techniques commonly used to study cell biology are listed below:

Cell culture: Utilizes rapidly growing cells on media which allows for a large amount of a specific cell type and an efficient way to study cells. Cell culture is one of the major tools used in cellular and molecular biology, providing excellent model systems for studying the normal physiology and biochemistry of cells (e.g., metabolic studies, aging), the effects of drugs and toxic compounds on the cells, and mutagenesis and carcinogenesis. It is also used in drug screening and development, and large scale manufacturing of biological compounds (e.g., vaccines, therapeutic proteins).
Fluorescence microscopy: Fluorescent markers such as GFP, are used to label a specific component of the cell. Afterwards, a certain light wavelength is used to excite the fluorescent marker which can then be visualized.
Phase-contrast microscopy: Uses the optical aspect of light to represent the solid, liquid, and gas-phase changes as brightness differences.
Confocal microscopy: Combines fluorescence microscopy with imaging by focusing light and snap shooting instances to form a 3-D image.
Transmission electron microscopy: Involves metal staining and the passing of electrons through the cells, which will be deflected upon interaction with metal. This ultimately forms an image of the components being studied.
Cytometry: The cells are placed in the machine which uses a beam to scatter the cells based on different aspects and can therefore separate them based on size and content. Cells may also be tagged with GFP-fluorescence and can be separated that way as well.
Cell fractionation: This process requires breaking up the cell using high temperature or sonification followed by centrifugation to separate the parts of the cell allowing for them to be studied separately.

== Pathology ==

The scientific branch that studies and diagnoses diseases on the cellular level is called cytopathology. Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to the pathology branch of histopathology, which studies whole tissues. Cytopathology is commonly used to investigate diseases involving a wide range of body sites, often to aid in the diagnosis of cancer but also in the diagnosis of some infectious diseases and other inflammatory conditions. For example, a common application of cytopathology is the Pap smear, a screening test used to detect cervical cancer, and precancerous cervical lesions that may lead to cervical cancer.

== Cell biologists ==

=== 17th century ===

Robert Hooke
Anton van Leeuwenhoek

=== 19th century ===
Jean Baptiste Carnoy
Robert Brown
Henri Dutrochet
Jan Evangelista Purkyně
Matthias Jakob Schleiden
Theodor Schwann
Rudolf Virchow

=== Modern ===

Peter Agre
Günter Blobel
Geoffrey M. Cooper
Christian de Duve
H. Robert Horvitz
Marc Kirschner
Ira Mellman
Marta Miączyńska
Kenneth R. Miller
Peter D. Mitchell
Paul Nurse
Yoshinori Ohsumi
George Emil Palade
Keith R. Porter
Ray Rappaport
Michael Swann
Roger Tsien
Edmund Beecher Wilson

== See also ==
The American Society for Cell Biology
Cell ablation
Cell biophysics
Cell physiology
Cellular microbiology
Clonogenic assay
Outline of cell biology

== References ==

== Notes ==
 This article incorporates public domain material from Science Primer. NCBI. Archived from the original on 8 December 2009.

== External links ==

 Media related to Cell biology at Wikimedia Commons
Aging Cell
"Francis Harry Compton Crick (1916–2004)" by A. Andrei at the Embryo Project Encyclopedia
Fundamentals of Cell Biology by Lauren Dalton and Robin Young


Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions, and its disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, developmental biology, cytology, psychology, physics, computer science, chemistry, medicine, statistics, and mathematical modeling to understand the fundamental and emergent properties of neurons, glia, and neural circuits. The understanding of the biological basis of learning, memory, behavior, perception, and consciousness has been described by Eric Kandel as the "epic challenge" of the biological sciences.
The scope of neuroscience has broadened over time to include different approaches used to study the nervous system at different scales. The techniques used by neuroscientists have expanded enormously, from molecular and cellular studies of individual neurons to imaging of sensory, motor, and cognitive tasks in the brain.

== History ==

The earliest study of the nervous system dates to ancient Egypt. Trepanation, the surgical practice of either drilling or scraping a hole into the skull for the purpose of curing head injuries or mental disorders, or relieving cranial pressure, was first recorded during the Neolithic period. Manuscripts dating to 1700 BC indicate that the Egyptians had some knowledge about symptoms of brain damage.
Early views on the function of the brain regarded it to be a "cranial stuffing" of sorts. In Egypt, from the late Middle Kingdom onwards, the brain was regularly removed in preparation for mummification. It was believed at the time that the heart was the seat of intelligence. According to Herodotus, the first step of mummification was to "take a crooked piece of iron, and with it draw out the brain through the nostrils, thus getting rid of a portion, while the skull is cleared of the rest by rinsing with drugs."
Greek thinkers, beginning with Alcmaeon of Croton, advanced the cephalocentric hypothesis that the brain is the seat of sensation and thought. The view that the heart was the source of consciousness was not challenged until the time of the Greek physician Hippocrates. He believed that the brain was not only involved with sensation—since most specialized organs (e.g., eyes, ears, tongue) are located in the head near the brain—but was also the seat of intelligence. Plato also speculated that the brain was the seat of the rational part of the soul. Aristotle, however, believed the heart was the center of intelligence and that the brain regulated the amount of heat from the heart. This view was generally accepted until the Roman physician Galen, a follower of Hippocrates and physician to Roman gladiators, observed that his patients lost their mental faculties when they had sustained damage to their brains.
Abulcasis, Averroes, Avicenna, Avenzoar, and Maimonides, active in the Medieval Muslim world, described a number of medical problems related to the brain. In Renaissance Europe, Vesalius (1514–1564), René Descartes (1596–1650), Thomas Willis (1621–1675) and Jan Swammerdam (1637–1680) also made several contributions to neuroscience.

Luigi Galvani's pioneering work in the late 1700s set the stage for studying the electrical excitability of muscles and neurons. In 1843 Emil du Bois-Reymond demonstrated the electrical nature of the nerve signal, whose speed Hermann von Helmholtz proceeded to measure, and in 1875 Richard Caton found electrical phenomena in the cerebral hemispheres of rabbits and monkeys. Adolf Beck published in 1890 similar observations of spontaneous electrical activity of the brain of rabbits and dogs. Studies of the brain became more sophisticated after the invention of the microscope and the development of a staining procedure by Camillo Golgi during the late 1890s. The procedure used a silver chromate salt to reveal the intricate structures of individual neurons. His technique was used by Santiago Ramón y Cajal and led to the formation of the neuron doctrine, the hypothesis that the functional unit of the brain is the neuron. Golgi and Ramón y Cajal shared the Nobel Prize in Physiology or Medicine in 1906 for their extensive observations, descriptions, and categorizations of neurons throughout the brain.
In parallel with this research, in 1815 Jean Pierre Flourens induced localized lesions of the brain in living animals to observe their effects on motricity, sensibility and behavior. Work with brain-damaged patients by Marc Dax in 1836 and Paul Broca in 1865 suggested that certain regions of the brain were responsible for certain functions. At the time, these findings were seen as a confirmation of Franz Joseph Gall's theory that language was localized and that certain psychological functions were localized in specific areas of the cerebral cortex. The localization of function hypothesis was supported by observations of epileptic patients conducted by John Hughlings Jackson, who correctly inferred the organization of the motor cortex by watching the progression of seizures through the body. Carl Wernicke further developed the theory of the specialization of specific brain structures in language comprehension and production. In 1894, neurologist and psychiatrist Edward Flatau published a human brain atlas “Atlas of the Human Brain and the Course of the Nerve-Fibres” which consisted of long-exposure photographs of fresh brain sections. In 1897, Charles Scott Sherrington introduced the name "synapse" for the connection between neurons.

In 1909, German anatomist Korbinian Brodmann published his original research on brain mapping, defining 52 distinct regions of the cerebral cortex, known as Brodmann areas. Modern research through neuroimaging techniques, still uses the Brodmann cerebral cytoarchitectonic map (referring to the study of cell structure) anatomical definitions from this era in continuing to show that distinct areas of the cortex are activated in the execution of specific tasks.
During the 20th century, neuroscience began to be recognized as a distinct academic discipline in its own right, rather than as studies of the nervous system within other disciplines. Eric Kandel and collaborators have cited David Rioch, Francis O. Schmitt, and Stephen Kuffler as having played critical roles in establishing the field. Rioch originated the integration of basic anatomical and physiological research with clinical psychiatry at the Walter Reed Army Institute of Research, starting in the 1950s. During the same period, Schmitt established a neuroscience research program within the Biology Department at the Massachusetts Institute of Technology, bringing together biology, chemistry, physics, and mathematics. The first freestanding neuroscience department (then called Psychobiology) was founded in 1964 at the University of California, Irvine by James L. McGaugh. This was followed by the Department of Neurobiology at Harvard Medical School, which was founded in 1966 by Stephen Kuffler.

In the process of treating epilepsy, Wilder Penfield produced maps of the location of various functions (motor, sensory, memory, vision) in the brain. He summarized his findings in a 1950 book called The Cerebral Cortex of Man. Wilder Penfield and his co-investigators Edwin Boldrey and Theodore Rasmussen are considered to be the originators of the cortical homunculus.
The understanding of neurons and of nervous system function became increasingly precise and molecular during the 20th century. For example, in 1952, Alan Lloyd Hodgkin and Andrew Huxley presented a mathematical model for the transmission of electrical signals in neurons of the giant axon of a squid, which they called "action potentials", and how they are initiated and propagated, known as the Hodgkin–Huxley model. In 1961–1962, Richard FitzHugh and J. Nagumo simplified Hodgkin–Huxley, in what is called the FitzHugh–Nagumo model. In 1962, Bernard Katz modeled neurotransmission across the space between neurons known as syna


Consciousness is being aware of something internal to one's self, or of states or objects in one's external environment. It has been the topic of extensive explanations, analyses, and debate among philosophers, scientists, and theologians for millennia. There is no consensus on what exactly needs to be studied, or whether consciousness can be considered a scientific concept. In some explanations it is synonymous with mind, while in others it is considered an aspect of it.
In the past, consciousness meant one's "inner life": the world of introspection, private thought, imagination, and volition. Today, it often includes various forms of cognition, experience, feeling, or perception. It may be awareness, awareness of awareness, metacognition, or self-awareness, either continuously changing or not. There is also a medical definition that helps, for example, to discern "coma" from other states. The disparate range of research, notions, and speculations raises some curiosity about whether the right questions are being asked.
Examples of the range of descriptions, definitions and explanations are: ordered distinction between self and environment, simple wakefulness, one's sense of selfhood or soul explored by "looking within", being a metaphorical "stream" of contents, or being a mental state, mental event, or mental process of the brain.

== Etymology ==
The words "conscious" and "consciousness" in the English language date to the 17th century, and the first recorded use of "conscious" as a simple adjective was applied figuratively to inanimate objects ("the conscious Groves", 1643). It derived from the Latin conscius (con- "together" and scio "to know") which meant "knowing with" or "having joint or common knowledge with another", especially as in sharing a secret. Thomas Hobbes in Leviathan (1651) wrote: "Where two, or more men, know of one and the same fact, they are said to be Conscious of it one to another". There were also many occurrences in Latin writings of the phrase conscius sibi, which translates literally as "knowing with oneself", or in other words "sharing knowledge with oneself about something". This phrase has the figurative sense of "knowing that one knows", which is something like the modern English word "conscious", but it was rendered into English as "conscious to oneself" or "conscious unto oneself". For example, Archbishop Ussher wrote in 1613 of "being so conscious unto myself of my great weakness".
The Latin conscientia, literally "knowledge-with", first appears in Roman juridical texts by writers such as Cicero. It means a kind of shared knowledge with moral value, specifically what a witness knows of someone else's deeds. Although René Descartes (1596–1650), writing in Latin, is generally taken to be the first philosopher to use conscientia in a way less like the traditional meaning and more like the way modern English speakers would use "conscience", his meaning is nowhere defined. In Search after Truth (Regulæ ad directionem ingenii ut et inquisitio veritatis per lumen naturale, Amsterdam 1701) he wrote the word with a gloss: conscientiâ, vel interno testimonio (translatable as "conscience, or internal testimony"). It might mean the knowledge of the value of one's own thoughts. One way that this shift during the seventeenth century from "conscience" to "consciousness" took place was through the poetry of John Milton, as the scholar Timothy M. Harrison has shown.

The origin of the modern concept of consciousness is often attributed to John Locke who defined the word in his Essay Concerning Human Understanding, published in 1690, as "the perception of what passes in a man's own mind". The essay strongly influenced 18th-century British philosophy, and Locke's definition appeared in Samuel Johnson's celebrated Dictionary (1755).
The French term conscience is defined roughly like English "consciousness" in the 1753 volume of Diderot and d'Alembert's Encyclopédie as "the opinion or internal feeling that we ourselves have from what we do".

== Problem of definition ==
Scholars are divided  as to whether Aristotle had a concept of consciousness. He does not use any single word or terminology that is clearly similar to the phenomenon or concept defined by John Locke. Victor Caston contends that Aristotle did have a concept more clearly similar to perception.
Modern dictionary definitions of the word consciousness evolved over several centuries and reflect a range of seemingly related meanings, with some differences that have been controversial, such as the distinction between inward awareness and perception of the physical world, or the distinction between conscious and unconscious, or the notion of a mental entity or mental activity that is not physical.
The common-usage definitions of consciousness in Webster's Third New International Dictionary (1966) are as follows:

awareness or perception of an inward psychological or spiritual fact; intuitively perceived knowledge of something in one's inner self
inward awareness of an external object, state, or fact
concerned awareness; INTEREST, CONCERN—often used with an attributive noun [e.g. class consciousness]
the state or activity that is characterized by sensation, emotion, volition, or thought; mind in the broadest possible sense; something in nature that is distinguished from the physical
the totality in psychology of sensations, perceptions, ideas, attitudes, and feelings of which an individual or a group is aware at any given time or within a particular time span—
waking life (as that to which one returns after sleep, trance, fever) wherein all one's mental powers have returned . . .
the part of mental life or psychic content in psychoanalysis that is immediately available to the ego—
The Cambridge English Dictionary defines consciousness as "the state of being awake, thinking, and knowing what is happening around you", as well as "the state of understanding and realizing something". The Oxford Living Dictionary defines consciousness as "[t]he state of being aware of and responsive to one's surroundings", "[a] person's awareness or perception of something", and "[t]he fact of awareness by the mind of itself and the world".
Philosophers have attempted to clarify technical distinctions by using a jargon of their own. The corresponding entry in the Routledge Encyclopedia of Philosophy (1998) reads:

Consciousness
Philosophers have used the term consciousness for four main topics: knowledge in general, intentionality, introspection (and the knowledge it specifically generates) and phenomenal experience... Something within one's mind is 'introspectively conscious' just in case one introspects it (or is poised to do so). Introspection is often thought to deliver one's primary knowledge of one's mental life. An experience or other mental entity is 'phenomenally conscious' just in case there is 'something it is like' for one to have it. The clearest examples are: perceptual experience, such as tastings and seeings; bodily-sensational experiences, such as those of pains, tickles and itches; imaginative experiences, such as those of one's own actions or perceptions; and streams of thought, as in the experience of thinking 'in words' or 'in images'. Introspection and phenomenality seem independent, or dissociable, although this is controversial.

=== Traditional metaphors for mind ===
During the early 19th century, the emerging field of geology inspired a popular metaphor that the mind likewise had hidden layers "which recorded the past of the individual". By 1875, most psychologists believed that "consciousness was but a small part of mental life", and this idea underlies the goal of Freudian therapy, to expose the unconscious layer of the mind.
Other metaphors from various sciences inspired other analyses of the mind, for example: Johann Friedrich Herbart described ideas as being attracted and repulsed like magnets; John Stuart Mill developed the idea of "mental chemistry" and "mental


Artificial intelligence (AI) is the capability of computational systems to perform tasks typically associated with human intelligence, such as learning, reasoning, problem-solving, perception, and decision-making. It is a field of research in engineering, mathematics, and computer science that develops and studies methods and software that enable machines to perceive their environment and use learning and intelligence to take actions that maximize their chances of achieving defined goals.
High-profile applications of AI include advanced web search engines, chatbots, virtual assistants, autonomous vehicles, and play and analysis in strategy games (e.g., chess and Go). Since the 2020s, generative AI has become widely available to generate images, audio, and videos from text prompts.
The traditional goals of AI research include learning, reasoning, knowledge representation, planning, natural language processing, and perception, as well as support for robotics. To reach these goals, AI researchers use techniques including state space search and mathematical optimization, formal logic, artificial neural networks, and methods based on statistics, operations research, and economics. AI also draws upon psychology, linguistics, philosophy, neuroscience, and other fields. Some companies, such as OpenAI, Google DeepMind, and Meta, aim to create artificial general intelligence (AGI)—AI that can complete nearly any cognitive task at least as well as a human.
Artificial intelligence was founded as an academic discipline in 1956. The field went through multiple cycles of optimism throughout its history, followed by periods of disappointment and loss of funding, known as AI winters. Funding and interest increased substantially after 2012, when graphics processing units (GPUs) started being used to accelerate neural networks, and deep learning outperformed previous AI techniques. This growth accelerated further after 2017 with the transformer architecture. In the 2020s, an AI boom coincided with advances in generative AI, which allowed for the creation and modification of media. In addition to AI safety and unintended consequences and harms from the use of AI, ethical concerns, AI's long-term effects, environmental effects, and potential existential risks have prompted discussions of AI regulation.

== Goals ==
The general problem of simulating (or creating) intelligence has been broken down into subproblems. These consist of specific traits or capabilities that researchers expect an intelligent system to display. The traits described below have received the most attention and cover the scope of AI research.

=== Reasoning and problem-solving ===
Early researchers developed algorithms that imitated step-by-step reasoning that humans use when solving puzzles or making logical deductions. By the late 1980s and 1990s, methods were developed for dealing with uncertain or incomplete information, employing concepts from probability and economics.
Many of these algorithms were insufficient for solving large reasoning problems because they experienced a "combinatorial explosion", meaning they become exponentially slower as the problems grow. Even humans rarely use the step-by-step deduction that early AI research could model. Humans solve most of their problems using fast, intuitive judgments.
Reasoning models, a type of large language model (LLM) trained to generate intermediate chains-of-thought, emerged in 2024 and allowed improved performance on complex problems in mathematics and coding. These models can produce incorrect outputs or "hallucinations," unlike symbolic reasoning systems.

=== Knowledge representation ===

Knowledge representation and knowledge engineering allow AI programs to answer questions intelligently and make deductions about real-world facts. Formal knowledge representations are used in content-based indexing and retrieval, scene interpretation, clinical decision support, knowledge discovery (mining "interesting" and actionable inferences from large databases), and other areas.
A knowledge base is a body of knowledge represented in a form that can be used by a program. An ontology is the set of objects, relations, concepts, and properties used by a particular domain of knowledge. Knowledge bases need to represent things such as objects, properties, categories, and relations between objects; situations, events, states, and time; causes and effects; knowledge about knowledge (what we know about what other people know); default reasoning (things humans assume are true until they are told differently and will remain true even when other facts are changing); and many other aspects and domains of knowledge.
Among the most difficult problems in knowledge representation are the breadth of commonsense knowledge (the set of atomic facts the average person knows is enormous) and the sub-symbolic form of most commonsense knowledge (much of what people know is not represented as "facts" or "statements" they can express verbally). There is also the difficulty of knowledge acquisition, the problem of obtaining knowledge for AI applications.

=== Planning and decision-making ===
An "agent" is any entity (artificial or not) that perceives and takes actions in the world. A rational agent has goals or preferences and takes actions to make them happen. In automated planning, the agent has a specific goal. In automated decision-making, the agent has preferences—there are some situations it would prefer to be in, and some situations it is trying to avoid. The decision-making agent assigns a number to each situation (called its "utility") that measures how much the agent prefers it. For each possible action, it can calculate the "expected utility": the utility of all possible outcomes of the action, weighted by the probability that the outcome will occur. It can then choose the action with the maximum expected utility.
In classical planning, the agent knows exactly what the effect of any action will be. In most real-world problems, however, the agent may not be certain about the situation it is in (it is "unknown" or "unobservable") and it may not know for certain what will happen after each possible action (it is not "deterministic"). It must choose an action by making a probabilistic guess and then reassess the situation to see if the action worked.
Alongside thorough testing and improvement based on previous decisions, having an explanation for why the agent took certain decisions is a way to build trust, especially when the decisions have to be relied upon.
In some problems, the agent's preferences may be uncertain, especially if there are other agents or humans involved. These preferences may be learned (e.g., with inverse reinforcement learning), or the agent can seek information to improve them. Information value theory can be used to weigh the value of exploratory or experimental actions. The space of possible future actions and situations is typically intractably large, so the agents must take actions and evaluate situations while being uncertain of the outcome.
A Markov decision process has a transition model that describes the probability that a particular action will change the state in a particular way and a reward function that supplies the utility of each state and the cost of each action. A policy associates a decision with each possible state. The policy could be calculated (e.g., by policy iteration), determined by a heuristic, or learned.
Game theory describes the rational behavior of multiple interacting agents and is used in AI programs that make decisions involving other agents.

=== Learning ===
Machine learning is the study of programs that can improve their performance on a given task automatically. It has been a part of AI from the beginning.

There are several kinds of machine learning:

Unsupervised learning analyzes a stream of data, finds patterns, and makes predictions without any other guidance.
Supervised learning requires labelin