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Edward Jenner

Edward Jenner (17 May 1749 – 26 January 1823) was an English physician and scientist who pioneered the concept of vaccines and created the smallpox vaccine, the world's first vaccine. The terms vaccine and vaccination are derived from Variolae vaccinae ('pustules of the cow'), the term devised by Jenner to denote cowpox. He used it in 1798 in the title of his Inquiry into the Variolae vaccinae known as the Cow Pox, in which he described the protective effect of cowpox against smallpox.

In the West, Jenner is often called "the father of immunology", and his work is said to have saved "more lives than any other man". In Jenner's time, smallpox killed around 10% of the global population, with the number as high as 20% in towns and cities where infection spread more easily. In 1821, he was appointed physician to King George IV, and was also made mayor of Berkeley and justice of the peace. He was a member of the Royal Society. In the field of zoology, he was among the first modern scholars to describe the brood parasitism of the cuckoo (Aristotle also noted this behaviour in his History of Animals). In 2002, Jenner was named in the BBC's list of the 100 Greatest Britons.

Early life
Edward Jenner was born on 17 May 1749 in Berkeley, Gloucestershire, England as the eighth of nine children. His father, the Reverend Stephen Jenner, was the vicar of Berkeley, so Jenner received a strong basic education.

Education and training
When he was young, he went to school in Wotton-under-Edge at Katherine Lady Berkeley's School and in Cirencester. During this time, he was inoculated (by variolation) for smallpox, which had a lifelong effect upon his general health. At the age of 14, he was apprenticed for seven years to Daniel Ludlow, a surgeon of Chipping Sodbury, South Gloucestershire, where he gained most of the experience needed to become a surgeon himself.

In 1770, aged 21, Jenner became apprenticed in surgery and anatomy under surgeon John Hunter and others at St George's Hospital, London. William Osler records that Hunter gave Jenner William Harvey's advice, well known in medical circles (and characteristic of the Age of Enlightenment), "Don't think; try." Hunter remained in correspondence with Jenner over natural history and proposed him for the Royal Society. Returning to his native countryside by 1773, Jenner became a successful family doctor and surgeon, practising on dedicated premises at Berkeley. In 1792, "with twenty years' experience of general practice and surgery, Jenner obtained the degree of MD from the University of St Andrews".

Later life
Jenner and others formed the Fleece Medical Society or Gloucestershire Medical Society, so called because it met in the parlour of the Fleece Inn, Rodborough, Gloucestershire. Members dined together and read papers on medical subjects. Jenner contributed papers on angina pectoris, ophthalmia, and cardiac valvular disease and commented on cowpox. He also belonged to a similar society which met in Alveston, near Bristol.

He became a master mason on 30 December 1802, in Lodge of Faith and Friendship #449. From 1812 to 1813, he served as worshipful master of Royal Berkeley Lodge of Faith and Friendship.

Zoology
Jenner was elected fellow of the Royal Society in 1788, following his publication of a careful study of the previously misunderstood life of the nested cuckoo, a study that combined observation, experiment, and dissection.

Jenner described how the newly hatched cuckoo pushed its host's eggs and fledgling chicks out of the nest (contrary to existing belief that the adult cuckoo did it). Having observed this behaviour, Jenner demonstrated an anatomical adaptation for it – the baby cuckoo has a depression in its back, not present after 12 days of life, that enables it to cup eggs and other chicks. The adult does not remain long enough in the area to perform this task. Jenner's findings were published in Philosophical Transactions of the Royal Society in 1788.

"The singularity of its shape is well adapted to these purposes; for, different from other newly hatched birds, its back from the scapula downwards is very broad, with a considerable depression in the middle. This depression seems formed by nature for the design of giving a more secure lodgement to the egg of the Hedge-sparrow, or its young one, when the young Cuckoo is employed in removing either of them from the nest. When it is about twelve days old, this cavity is quite filled up, and then the back assumes the shape of nestling birds in general." Jenner's nephew assisted in the study. He was born on 30 June 1737.

Jenner's understanding of the cuckoo's behaviour was not entirely believed until the artist Jemima Blackburn, a keen observer of birdlife, saw a blind nestling pushing out a host's egg. Blackburn's description and illustration were enough to convince Charles Darwin to revise a later edition of On the Origin of Species.

Jenner's interest in zoology played a large role in his first experiment with inoculation. Not only did he have a profound understanding of human anatomy due to his medical training, but he also understood animal biology and its role in human-animal trans-species boundaries in disease transmission. At the time, there was no way of knowing how important this connection would be to the history and discovery of vaccinations. We see this connection now; many present-day vaccinations include animal parts from cows, rabbits, and chicken eggs, which can be attributed to the work of Jenner and his cowpox/smallpox vaccination.

Marriage and human medicine
Jenner married Catherine Kingscote (who died in 1815 from tuberculosis) in March 1788. He might have met her while he and other fellows were experimenting with balloons. Jenner's trial balloon descended into Kingscote Park, Gloucestershire, owned by Catherine's father Anthony Kingscote. They had three children: Edward Robert (1789–1810), Robert Fitzharding (1792–1854) and Catherine (1794–1833).

He earned his MD from the University of St Andrews in 1792. He is credited with advancing the understanding of angina pectoris. In his correspondence with Heberden, he wrote: "How much the heart must suffer from the coronary arteries not being able to perform their functions".

Invention of the vaccine
Inoculation was already a standard practice in Asian and African medicine but involved serious risks, including the possibility that those inoculated would become contagious and spread the disease to others. In 1721, Lady Mary Wortley Montagu had imported variolation to Britain after having observed it in Istanbul. While Johnnie Notions had great success with his self-devised inoculation (and was reputed not to have lost a single patient), his method's practice was limited to the Shetland Isles. Voltaire wrote that at this time 60% of the population caught smallpox and 20% of the population died from it. Voltaire also states that the Circassians used the inoculation from times immemorial, and the custom may have been borrowed by the Turks from the Circassians. In 1766, Daniel Bernoulli analysed smallpox morbidity and mortality data to demonstrate the efficacy of inoculation.

By 1768, English physician John Fewster had realised that prior infection with cowpox rendered a person immune to smallpox. In the years following 1770, at least five investigators in England and Germany (Sevel, Jensen, Jesty 1774, Rendell, Plett 1791) successfully tested in humans a cowpox vaccine against smallpox. For example, Dorset farmer Benjamin Jesty successfully vaccinated and presumably induced immunity with cowpox in his wife and two children during a smallpox epidemic in 1774, but it was not until Jenner's work that the procedure became widely understood. Jenner may have been aware of Jesty's procedures and success. A similar observation was later made in France by Jacques Antoine Rabaut-Pommier in 1780.

Jenner postulated that the pus in the blisters that affected individuals affected by cowpox (a disease similar to smallpox, but much less virulent) protected them from smallpox. On 14 May 1796, Jenner tested his hypothesis by inoculating James Phipps, an eight-year-old boy who was the son of Jenner's gardener. He scraped pus from cowpox blisters on the hands of Sarah Nelmes, a milkmaid who had caught cowpox from a cow called Blossom, whose hide now hangs on the wall of the St. George's Medical School library (now in Tooting). Phipps was the 17th case described in Jenner's first paper on vaccination.

Jenner inoculated Phipps in both arms that day, subsequently producing in Phipps a fever and some uneasiness, but no full-blown infection. Later, he injected Phipps with variolous material, the routine method of immunization at that time. No disease followed. The boy was later challenged with variolous material and again showed no sign of infection. No unexpected side effects occurred, and neither Phipps nor any other recipients underwent any future 'breakthrough' cases.

Jenner's biographer John Baron would later speculate that Jenner understood one could be inoculated against smallpox by being exposed to cowpox by observing the unblemished complexion of milkmaids, rather than building on the work of his predecessors. The milkmaids story is still widely repeated even though it appears to be a myth.

Donald Hopkins has written, "Jenner's unique contribution was not that he inoculated a few persons with cowpox, but that he then proved [by subsequent challenges] that they were immune to smallpox. Moreover, he demonstrated that the protective cowpox pus could be effectively inoculated from person to person, not just directly from cattle." Jenner successfully tested his hypothesis on 23 additional subjects.

Jenner continued his research and reported it to the Royal Society, which did not publish the initial paper. After revisions and further investigations, he published his findings on the 23 cases, including his 11-month-old son Robert. Some of his conclusions were correct, some erroneous; modern microbiological and microscopic methods would make his studies easier to reproduce. The medical establishment deliberated at length over his findings before accepting them. Eventually, vaccination was accepted, and in 1840, the British government banned variolation – the use of smallpox to induce immunity – and provided vaccination using cowpox free of charge (see Vaccination Act).

The success of his discovery soon spread around Europe and was used en masse in the Spanish Balmis Expedition (1803–1806), a three-year-long mission to the Americas, the Philippines, Macao, China, led by Francisco Javier de Balmis with the aim of giving thousands the smallpox vaccine. The expedition was successful, and Jenner wrote: "I don't imagine the annals of history furnish an example of philanthropy so noble, so extensive as this". Napoleon, who at the time was at war with Britain, had all his French troops vaccinated, awarded Jenner a medal, and at the request of Jenner, he released two English prisoners of war and permitted their return home. Napoleon remarked he could not "refuse anything to one of the greatest benefactors of mankind".

Jenner's continuing work on vaccination prevented him from continuing his ordinary medical practice. He was supported by his colleagues and the King in petitioning Parliament, and was granted £10,000 in 1802 for his work on vaccination. In 1807, he was granted another £20,000 after the Royal College of Physicians confirmed the widespread efficacy of vaccination.

Later life
Jenner was later elected a foreign honorary member of the American Academy of Arts and Sciences in 1802, a member of the American Philosophical Society in 1804, and a foreign member of the Royal Swedish Academy of Sciences in 1806. In 1803 in London, he became president of the Jennerian Society, concerned with promoting vaccination to eradicate smallpox. The Jennerian ceased operations in 1809. Jenner became a member of the Medical and Chirurgical Society on its founding in 1805 (now the Royal Society of Medicine) and presented several papers there. In 1808, with government aid, the National Vaccine Establishment was founded, but Jenner felt dishonoured by the men selected to run it and resigned his directorship.

Returning to London in 1811, Jenner observed a significant number of cases of smallpox after vaccination. He found that in these cases the severity of the illness was notably diminished by previous vaccination. In 1821, he was appointed physician extraordinary to King George IV, and was also made mayor of Berkeley and magistrate (justice of the peace). He continued to investigate natural history, and in 1823, the last year of his life, he presented his "Observations on the Migration of Birds" to the Royal Society.

Jenner was a Freemason.

Death
Jenner was found in a state of apoplexy on 25 January 1823, with his right side paralysed. He did not recover and died the next day of an apparent stroke, his second, on 26 January 1823, aged 73. He was buried in the family vault at the Church of St Mary, Berkeley.

Religious views
Neither fanatic nor lax, Jenner was a Christian who in his personal correspondence showed himself quite spiritual. Some days before his death, he stated to a friend: "I am not surprised that men are not grateful to me; but I wonder that they are not grateful to God for the good which He has made me the instrument of conveying to my fellow creatures".

Legacy
In 1980, the World Health Organization declared smallpox an eradicated disease. This was the result of coordinated public health efforts, but vaccination was an essential component. Although the disease was declared eradicated, some pus samples still remain in laboratories in Centers for Disease Control and Prevention in Atlanta in the US, and in State Research Center of Virology and Biotechnology VECTOR in Koltsovo, Novosibirsk Oblast, Russia.

Jenner's vaccine laid the foundation for contemporary discoveries in immunology. In 2002, Jenner was named in the BBC's list of the 100 Greatest Britons following a UK-wide vote. Commemorated on postage stamps issued by the Royal Mail, in 1999 he featured in their World Changers issue along with Charles Darwin, Michael Faraday and Alan Turing. The lunar crater Jenner is named in his honour.

Monuments and buildings

 * Jenner's house in the village of Berkeley, Gloucestershire, is now a small museum, housing, among other things, the horns of the cow, Blossom.
 * A statue of Jenner by Robert William Sievier was erected in the nave of Gloucester Cathedral.
 * Another statue was erected in Trafalgar Square and later moved to Kensington Gardens.
 * Near the Gloucestershire village of Uley, Downham Hill is locally known as "Smallpox Hill" for its possible role in Jenner's studies of the disease.
 * London's St. George's Hospital Medical School has a Jenner Pavilion, where his bust may be found.
 * A group of villages in Somerset County, Pennsylvania, United States, was named in Jenner's honour by early 19th-century English settlers, including Jenners, Jenner Township, Jenner Crossroads, and Jennerstown, Pennsylvania
 * Jennersville, Pennsylvania, is located in Chester County.
 * The Edward Jenner Institute for Vaccine Research is an infectious disease vaccine research centre, also the Jenner Institute part of the University of Oxford.
 * A section at Gloucestershire Royal Hospital is known as the Edward Jenner Unit; it is where blood is drawn.
 * A ward at Northwick Park Hospital is called Jenner Ward.
 * Jenner Gardens at Cheltenham, Gloucestershire, opposite one of the scientist's former offices, is a small garden and cemetery.
 * A statue of Jenner was erected at the Tokyo National Museum in 1896 to commemorate the centenary of Jenner's discovery of vaccination.
 * A monument outside the walls of the upper town of Boulogne sur Mer, France.
 * A street in Stoke Newington, north London: Jenner Road, N16 51.55867°N, -0.06761°W
 * Built around 1970, The Jenner Health Centre, 201 Stanstead Road, Forest Hill, London, SE23 1HU
 * Jenner's name is featured on the Frieze of the London School of Hygiene & Tropical Medicine. Twenty-three names of public health and tropical medicine pioneers were chosen to feature on the Keppel Street building when it was constructed in 1926.
 * Minor planet 5168 Jenner is named in his honour.

Publications

 * 1798 An Inquiry Into the Causes and Effects of the Variolæ Vaccinæ
 * 1799 Further Observations on the Variolæ Vaccinæ, or Cow-Pox.
 * 1800 A Continuation of Facts and Observations relative to the Variolæ Vaccinæ 40pgs
 * 1801 The Origin of the Vaccine Inoculation

title: Edward Jenner


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Encyclopædia Britannica

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Krishnan, an educator at New York University's Stern School of Business, believes in the "transformative power of education" and set steering the company toward solidifying its place among leaders in educational technology and supplemental curriculum. Krishnan aimed at providing more useful and relevant solutions to customer needs, extending and renewing Britannica's historical emphasis on "utility", which had been the watchword of its first edition in 1768.

Competition
As the Britannica is a general encyclopaedia, it does not seek to compete with specialized encyclopaedias such as the Encyclopaedia of Mathematics or the Dictionary of the Middle Ages, which can devote much more space to their chosen topics. In its first years, the Britannica main competitor was the general encyclopaedia of Ephraim Chambers and, soon thereafter, Rees's Cyclopædia and Coleridge's Encyclopædia Metropolitana. In the 20th century, successful competitors included Collier's Encyclopedia, the Encyclopedia Americana, and the World Book Encyclopedia. Nevertheless, from the 9th edition onwards, the Britannica was widely considered to have the greatest authority of any general English-language encyclopaedia, especially because of its broad coverage and eminent authors. The print version of the Britannica was significantly more expensive than its competitors.

Since the early 1990s, the Britannica has faced new challenges from digital information sources. The Internet, facilitated by the development of Web search engines, has grown into a common source of information for many people, and provides easy access to reliable original sources and expert opinions, thanks in part to initiatives such as Google Books, MIT's release of its educational materials and the open PubMed Central library of the National Library of Medicine.

The Internet tends to provide more current coverage than print media, due to the ease with which material on the Internet can be updated. In rapidly changing fields such as science, technology, politics, culture and modern history, the Britannica has struggled to stay up to date, a problem first analysed systematically by its former editor Walter Yust. Eventually, the Britannica turned to focus more on its online edition.

Print encyclopaedias
The Encyclopædia Britannica has been compared with other print encyclopaedias, both qualitatively and quantitatively. A well-known comparison is that of Kenneth Kister, who gave a qualitative and quantitative comparison of the 1993 Britannica with two comparable encyclopaedias, Collier's Encyclopedia and the Encyclopedia Americana. For the quantitative analysis, ten articles were selected at random—circumcision, Charles Drew, Galileo, Philip Glass, heart disease, IQ, panda bear, sexual harassment, Shroud of Turin and Uzbekistan—and letter grades of A–D or F were awarded in four categories: coverage, accuracy, clarity, and recency. In all four categories and for all three encyclopaedias, the four average grades fell between B− and B+, chiefly because none of the encyclopaedias had an article on sexual harassment in 1994. In the accuracy category, the Britannica received one "D" and seven "A"s, Encyclopedia Americana received eight "A"s, and Collier's received one "D" and seven "A"s; thus, Britannica received an average score of 92% for accuracy to Americana 95% and Collier's 92%. In the timeliness category, Britannica averaged an 86% to Americana's 90% and Collier's 85%.

In 2013, the President of Encyclopædia Britannica announced that after 244 years, the encyclopaedia would cease print production and all future editions would be entirely digital.

Digital encyclopaedias on optical media
The most notable competitor of the Britannica among CD/DVD-ROM digital encyclopaedias was Encarta, now discontinued, a modern multimedia encyclopaedia that incorporated three print encyclopaedias: Funk & Wagnalls, Collier's and the New Merit Scholar's Encyclopedia. Encarta was the top-selling multimedia encyclopaedia, based on total US retail sales from January 2000 to February 2006. Both occupied the same price range, with the 2007 Encyclopædia Britannica Ultimate CD or DVD costing US$40–50 and the Microsoft Encarta Premium 2007 DVD costing US$45.

The Britannica disc contains 100,000 articles and Merriam-Webster's Dictionary and Thesaurus (US only), and offers Primary and Secondary School editions. Encarta contained 66,000 articles, a user-friendly Visual Browser, interactive maps, math, language and homework tools, a US and UK dictionary, and a youth edition. Like Encarta, the digital Britannica has been criticized for being biased towards United States audiences; the United Kingdom-related articles are updated less often, maps of the United States are more detailed than those of other countries, and it lacks a UK dictionary. Like the Britannica, Encarta was available online by subscription, although some content could be accessed free.

Wikipedia
The main online alternative to Britannica is Wikipedia. The key differences between the two lie in accessibility; the model of participation they bring to an encyclopedic project; their respective style sheets and editorial policies; relative ages; the number of subjects treated; the number of languages in which articles are written and made available; and their underlying economic models: unlike Britannica, Wikipedia is a not-for-profit, does not carry advertising on its site, and is not connected with traditional profit- and contract-based publishing distribution networks.

Britannica's articles either have known authorship or a set of possible authors (the editorial staff). With the exception of the editorial staff, most of Britannica contributors are experts in their field—some are Nobel laureates. By contrast, the articles of Wikipedia are written by people of unknown degrees of expertise: most do not claim any particular expertise, and of those who do, many are anonymous and have no verifiable credentials. It is for this lack of institutional vetting, or certification, that former Britannica editor-in-chief Robert McHenry noted his belief in 2004 that Wikipedia could not hope to rival the Britannica in accuracy.

In 2005, the journal Nature chose articles from both websites in a wide range of science topics and sent them to what it called "relevant" field experts for peer review. The experts then compared the competing articles—one from each site on a given topic—side by side, but were not told which article came from which site. Nature got back 42 usable reviews.

The journal found just eight serious errors, such as general misunderstandings of vital concepts: four from each site. It also discovered many factual errors, omissions or misleading statements: 162 in Wikipedia and 123 in Britannica, an average of 3.86 mistakes per article for Wikipedia and 2.92 for Britannica.

Although Britannica was revealed as the more accurate encyclopaedia, with fewer errors, in its rebuttal called Nature's study flawed and misleading and called for a "prompt" retraction. It noted that two of the articles in the study were taken from a Britannica yearbook and not the encyclopaedia, and another two were from Compton's Encyclopedia (called the Britannica Student Encyclopedia on the company's website).

Nature defended its story and declined to retract, stating that, as it was comparing Wikipedia with the web version of Britannica, it used whatever relevant material was available on Britannica website. Interviewed in February 2009, the managing director of Britannica UK said: "Wikipedia is a fun site to use and has a lot of interesting entries on there, but their approach wouldn't work for Encyclopædia Britannica. My job is to create more awareness of our very different approaches to publishing in the public mind. They're a chisel, we're a drill, and you need to have the correct tool for the job."

For the 15th anniversary of Wikipedia, the Telegraph published two opinion pieces which compared Wikipedia to Britannica and falsely claimed that Britannica had gone bankrupt in 1996. In a January 2016 press release, Britannica responded by calling Wikipedia "an impressive achievement" but argued that critics should avoid "false comparisons" to Britannica in terms of differing models and purposes.

Reputation
Since the 3rd edition, the Britannica has enjoyed a popular and critical reputation for general excellence. The 3rd and 9th editions were pirated for sale in the United States, beginning with Dobson's Encyclopædia. On the release of the 14th edition, Time magazine dubbed the Britannica the "Patriarch of the Library". In a related advertisement, naturalist William Beebe was quoted as saying that the Britannica was "beyond comparison because there is no competitor". References to the Britannica can be found throughout English literature, most notably in one of Sir Arthur Conan Doyle favourite Sherlock Holmes stories, "The Red-Headed League". The tale was highlighted by the Lord Mayor of London, Gilbert Inglefield, at the bicentennial of the Britannica.

The Britannica has a reputation for summarizing knowledge. To further their education, some people have devoted themselves to reading the entire Britannica, taking anywhere from three to 22 years to do so. When Fat'h Ali became the Shah of Persia in 1797, he was given a set of the Britannica 3rd edition; after reading the complete set, he extended his royal title to include "Most Formidable Lord and Master of the Encyclopædia Britannica".

Writer George Bernard Shaw claimed to have read the complete 9th edition, except for the science articles; Richard Evelyn Byrd took the Britannica as reading material for his five-month stay at the South Pole in 1934; and Philip Beaver read it during a sailing expedition. More recently, A. J. Jacobs, an editor at Esquire magazine, read the entire 2002 version of the 15th edition, describing his experiences in the well-received 2004 book The Know-It-All: One Man's Humble Quest to Become the Smartest Person in the World. Only two people are known to have read two independent editions: the author C. S. Forester and Amos Urban Shirk, an American businessman who read the 11th and 14th editions, devoting roughly three hours per night for four and a half years to read the 11th.

Awards
The CD/DVD-ROM version of the Britannica, Encyclopædia Britannica Ultimate Reference Suite, received the 2004 Distinguished Achievement Award from the Association of Educational Publishers. On 15 July 2009, Encyclopædia Britannica was awarded a spot as one of "Top Ten Superbrands in the UK" by a panel of more than 2,000 independent reviewers, as reported by the BBC.

Coverage of topics
Topics are chosen in part by reference to the Propædia "Outline of Knowledge". The bulk of the Britannica is devoted to geography (26% of the Macropædia), biography (14%), biology and medicine (11%), literature (7%), physics and astronomy (6%), religion (5%), art (4%), Western philosophy (4%), and law (3%). A complementary study of the Micropædia found that geography accounted for 25% of articles, science 18%, social sciences 17%, biography 17%, and all other humanities 25%. Writing in 1992, one reviewer judged that the "range, depth, and catholicity of coverage [of the Britannica] are unsurpassed by any other general Encyclopaedia."

The Britannica does not cover topics in equal detail; for example, the whole of Buddhism and most other religions is covered in a single Macropædia article, whereas 14 articles are devoted to Christianity, comprising nearly half of all religion articles. The Britannica covers 50,479 biographies, 5,999 of them about women, with 11.87% being British citizens and 25.51% US citizens. However, the Britannica has been lauded as the least biased of general Encyclopaedias marketed to Western readers and praised for its biographies of important women of all eras.

"It can be stated without fear of contradiction that the 15th edition of the Britannica accords non-Western cultural, social, and scientific developments more notice than any general English-language encyclopedia currently on the market."

Criticism of editorial decisions
On rare occasions, the Britannica has been criticized for its editorial choices. Given its roughly constant size, the encyclopaedia has needed to reduce or eliminate some topics to accommodate others, resulting in controversial decisions. The initial 15th edition (1974–1985) was faulted for having reduced or eliminated coverage of children's literature, military decorations, and the French poet Joachim du Bellay; editorial mistakes were also alleged, such as inconsistent sorting of Japanese biographies. Its elimination of the index was condemned, as was the apparently arbitrary division of articles into the Micropædia and Macropædia. Summing up, one critic called the initial 15th edition a "qualified failure...[that] cares more for juggling its format than for preserving." More recently, reviewers from the American Library Association were surprised to find that most educational articles had been eliminated from the 1992 Macropædia, along with the article on psychology.

Some very few Britannica-appointed contributors are mistaken. A notorious instance from the Britannica early years is the rejection of Newtonian gravity by George Gleig, the chief editor of the 3rd edition (1788–1797), who wrote that gravity was caused by the classical element of fire. The Britannica has also staunchly defended a scientific approach to cultural topics, as it did with William Robertson Smith's articles on religion in the 9th edition, particularly his article stating that the Bible was not historically accurate (1875).

Other criticisms
The Britannica has received criticism, particularly as editions become outdated. It is expensive to produce a completely new edition of the Britannica, and its editors delay for as long as fiscally sensible (usually about 25 years). For example, despite continuous revision, the 14th edition became outdated after 35 years (1929–1964). When American physicist Harvey Einbinder detailed its failings in his 1964 book, The Myth of the Britannica, the encyclopaedia was provoked to produce the 15th edition, which required 10 years of work. Editors have struggled at times to keep the Britannica current: one 1994 critic writes, "it is not difficult to find articles that are out-of-date or in need of revision", noting that the longer Macropædia articles are more likely to be outdated than the shorter Micropædia articles. Information in the Micropædia is sometimes inconsistent with the corresponding Macropædia article(s), mainly because of the failure to update one or the other. The bibliographies of the Macropædia articles have been criticized for being more out-of-date than the articles themselves.

In 2005, a 12-year-old schoolboy in Britain found several inaccuracies in the Britannica entries on Poland and wildlife in Eastern Europe. In 2010, an entry about the Irish Civil War, which incorrectly described it as having been fought between the north and south of Ireland, was discussed in the Irish press following a decision by the Department of Education and Science to pay for online access.

Writing about the 3rd edition (1788–1797), Britannica chief editor George Gleig observed that "perfection seems to be incompatible with the nature of works constructed on such a plan, and embracing such a variety of subjects." In March 2006, the Britannica wrote, "we in no way mean to imply that Britannica is error-free; we have never made such a claim". However, the Britannica sales department had previously made a well-known claim in 1962 regarding the 14th edition that "[i]t is truth. It is unquestionable fact." The sentiment of the 2006 statement was also reflected in the introduction to the first edition of the Britannica, written by its original editor William Smellie:

"With regard to errors in general, whether falling under the denomination of mental, typographical or accidental, we are conscious of being able to point out a greater number than any critic whatever. Men who are acquainted with the innumerable difficulties attending the execution of a work of such an extensive nature will make proper allowances. To these we appeal, and shall rest satisfied with the judgment they pronounce."

History
Past owners have included, in chronological order, the Edinburgh, Scotland-based printers Colin Macfarquhar and Andrew Bell, Scottish bookseller Archibald Constable, Scottish publisher A & C Black, Horace Everett Hooper, Sears Roebuck and William Benton.

The present owner of Encyclopædia Britannica Inc. is Jacqui Safra, a Brazilian billionaire and actor. Recent advances in information technology and the rise of electronic encyclopaedias such as Encyclopædia Britannica Ultimate Reference Suite, Encarta and Wikipedia have reduced the demand for print encyclopaedias. To remain competitive, Encyclopædia Britannica, Inc. has stressed the reputation of the Britannica, reduced its price and production costs, and developed electronic versions on CD-ROM, DVD, and the World Wide Web. Since the early 1930s, the company has promoted spin-off reference works.

Editions
The Britannica has been issued in 15 editions, with multi-volume supplements to the 3rd and 4th editions (see the Table below). The 5th and 6th editions were reprints of the 4th, and the 10th edition was only a supplement to the 9th, just as the 12th and 13th editions were supplements to the 11th. The 15th underwent massive reorganization in 1985, but the updated, current version is still known as the 15th. The 14th and 15th editions were edited every year throughout their runs, so that later printings of each were entirely different from early ones.

Throughout history, the Britannica has had two aims: to be an excellent reference book, and to provide educational material. In 1974, the 15th edition adopted a third goal: to systematize all human knowledge. The history of the Britannica can be divided into five eras, punctuated by changes in management, or reorganization of the dictionary.

1768–1826
In the first era (1st–6th editions, 1768–1826), the Britannica was managed and published by its founders, Colin Macfarquhar and Andrew Bell, by Archibald Constable, and by others. The Britannica was first published between December 1768 and 1771 in Edinburgh as the Encyclopædia Britannica, or, A Dictionary of Arts and Sciences, compiled upon a New Plan. In part, it was conceived in reaction to the French Encyclopédie of Denis Diderot and Jean le Rond d'Alembert (published 1751–1772), which had been inspired by Chambers's Cyclopaedia (first edition 1728). It went on sale 10 December.

The Britannica of this period was primarily a Scottish enterprise, and it is one of the most enduring legacies of the Scottish Enlightenment. In this era, the Britannica moved from being a three-volume set (1st edition) compiled by one young editor—William Smellie —to a 20-volume set written by numerous authorities. Several other encyclopaedias competed throughout this period, among them editions of Abraham Rees's Cyclopædia and Coleridge's Encyclopædia Metropolitana and David Brewster's Edinburgh Encyclopædia.

1827–1901
During the second era (7th–9th editions, 1827–1901), the Britannica was managed by the Edinburgh publishing firm A & C Black. Although some contributors were again recruited through friendships of the chief editors, notably Macvey Napier, others were attracted by the Britannica reputation. The contributors often came from other countries and included the world's most respected authorities in their fields. A general index of all articles was included for the first time in the 7th edition, a practice maintained until 1974.

Production of the 9th edition was overseen by Thomas Spencer Baynes, the first English-born editor-in-chief. Dubbed the "Scholar's Edition", the 9th edition is the most scholarly of all Britannicas. After 1880, Baynes was assisted by William Robertson Smith. No biographies of living persons were included. James Clerk Maxwell and Thomas Huxley were special advisors on science. However, by the close of the 19th century, the 9th edition was outdated, and the Britannica faced financial difficulties.

1901–1973
In the third era (10th–14th editions, 1901–1973), the Britannica was managed by American businessmen who introduced direct marketing and door-to-door sales. The American owners gradually simplified articles, making them less scholarly for a mass market. The 10th edition was an eleven-volume supplement (including one each of maps and an index) to the 9th, numbered as volumes 25–35, but the 11th edition was a completely new work, and is still praised for excellence; its owner, Horace Hooper, lavished enormous effort on its perfection.

When Hooper fell into financial difficulties, the Britannica was managed by Sears Roebuck for 18 years (1920–1923, 1928–1943). In 1932, the vice-president of Sears, Elkan Harrison Powell, assumed presidency of the Britannica; in 1936, he began the policy of continuous revision. This was a departure from earlier practice, in which the articles were not changed until a new edition was produced, at roughly 25-year intervals, some articles unchanged from earlier editions. Powell developed new educational products that built upon the Britannica reputation.

In 1943, Sears donated the Encyclopædia Britannica to the University of Chicago. William Benton, then a vice president of the university, provided the working capital for its operation. The stock was divided between Benton and the university, with the university holding an option on the stock. Benton became chairman of the board and managed the Britannica until his death in 1973. Benton set up the Benton Foundation, which managed the Britannica until 1996, and whose sole beneficiary was the University of Chicago. In 1968, the Britannica celebrated its bicentennial.

1974–1994
In the fourth era (1974–1994), the Britannica introduced its 15th edition, which was reorganized into three parts: the Micropædia, the Macropædia, and the Propædia. Under Mortimer J. Adler (member of the Board of Editors of Encyclopædia Britannica since its inception in 1949, and its chair from 1974; director of editorial planning for the 15th edition of Britannica from 1965), the Britannica sought not only to be a good reference work and educational tool, but to systematize all human knowledge. The absence of a separate index and the grouping of articles into parallel encyclopaedias (the Micro- and Macropædia) provoked a "firestorm of criticism" of the initial 15th edition.
 * In response, the 15th edition was completely reorganized and indexed for a re-release in 1985. This second version of the 15th edition continued to be published and revised through the release of the 2010 print version. The official title of the 15th edition is the New Encyclopædia Britannica, although it has also been promoted as Britannica 3.
 * In response, the 15th edition was completely reorganized and indexed for a re-release in 1985. This second version of the 15th edition continued to be published and revised through the release of the 2010 print version. The official title of the 15th edition is the New Encyclopædia Britannica, although it has also been promoted as Britannica 3.
 * In response, the 15th edition was completely reorganized and indexed for a re-release in 1985. This second version of the 15th edition continued to be published and revised through the release of the 2010 print version. The official title of the 15th edition is the New Encyclopædia Britannica, although it has also been promoted as Britannica 3.
 * In response, the 15th edition was completely reorganized and indexed for a re-release in 1985. This second version of the 15th edition continued to be published and revised through the release of the 2010 print version. The official title of the 15th edition is the New Encyclopædia Britannica, although it has also been promoted as Britannica 3.
 * In response, the 15th edition was completely reorganized and indexed for a re-release in 1985. This second version of the 15th edition continued to be published and revised through the release of the 2010 print version. The official title of the 15th edition is the New Encyclopædia Britannica, although it has also been promoted as Britannica 3.
 * In response, the 15th edition was completely reorganized and indexed for a re-release in 1985. This second version of the 15th edition continued to be published and revised through the release of the 2010 print version. The official title of the 15th edition is the New Encyclopædia Britannica, although it has also been promoted as Britannica 3.
 * In response, the 15th edition was completely reorganized and indexed for a re-release in 1985. This second version of the 15th edition continued to be published and revised through the release of the 2010 print version. The official title of the 15th edition is the New Encyclopædia Britannica, although it has also been promoted as Britannica 3.
 * In response, the 15th edition was completely reorganized and indexed for a re-release in 1985. This second version of the 15th edition continued to be published and revised through the release of the 2010 print version. The official title of the 15th edition is the New Encyclopædia Britannica, although it has also been promoted as Britannica 3.

On 9 March 1976 the US Federal Trade Commission entered an opinion and order enjoining Encyclopædia Britannica, Inc. from using: a) deceptive advertising practices in recruiting sales agents and obtaining sales leads, and b) deceptive sales practices in the door-to-door presentations of its sales agents.

1994–present
In the fifth era (1994–present), digital versions have been developed and released on optical media and online.

In 1996, the Britannica was bought by Jacqui Safra at well below its estimated value, owing to the company's financial difficulties. Encyclopædia Britannica, Incorporated split in 1999. One part retained the company name and developed the print version, and the other, Britannica.com Incorporated, developed digital versions. Since 2001, the two companies have shared a CEO, Ilan Yeshua, who has continued Powell's strategy of introducing new products with the Britannica name. In March 2012, Britannica's president, Jorge Cauz, announced that it would not produce any new print editions of the encyclopaedia, with the 2010 15th edition being the last. The company will focus only on the online edition and other educational tools.

Britannica final print edition was in 2010, a 32-volume set. Britannica Global Edition was also printed in 2010, containing 30 volumes and 18,251 pages, with 8,500 photographs, maps, flags, and illustrations in smaller "compact" volumes, as well as over 40,000 articles written by scholars from across the world, including Nobel Prize winners. Unlike the 15th edition, it did not contain Macro- and Micropædia sections, but ran A through Z as all editions up through the 14th had. The following is Britannica description of the work:

"The editors of Encyclopædia Britannica, the world standard in reference since 1768, present the Britannica Global Edition. Developed specifically to provide comprehensive and global coverage of the world around us, this unique product contains thousands of timely, relevant, and essential articles drawn from the Encyclopædia Britannica itself, as well as from the Britannica Concise Encyclopedia, the Britannica Encyclopedia of World Religions, and Compton's by Britannica. Written by international experts and scholars, the articles in this collection reflect the standards that have been the hallmark of the leading English-language encyclopedia for over 240 years."

In 2020, Encyclopædia Britannica, Inc. released the Britannica All New Children's Encyclopedia: What We Know and What We Don't, an encyclopaedia aimed primarily at younger readers, covering major topics. The encyclopedia was widely praised for bringing back the print format. It was Britannica 's first encyclopaedia for children since 1984.

Dedications
The Britannica was dedicated to the reigning British monarch from 1788 to 1901 and then, upon its sale to an American partnership, to the British monarch and the President of the United States. Thus, the 11th edition is "dedicated by Permission to His Majesty George the Fifth, King of Great Britain and Ireland and of the British Dominions beyond the Seas, Emperor of India, and to William Howard Taft, President of the United States of America." The order of the dedications has changed with the relative power of the United States and Britain, and with relative sales; the 1954 version of the 14th edition is "Dedicated by Permission to the Heads of the Two English-Speaking Peoples, Dwight David Eisenhower, President of the United States of America, and Her Majesty, Queen Elizabeth the Second."

Consistent with this tradition, the 2007 version of the current 15th edition was "dedicated by permission to the current President of the United States of America, George W. Bush, and Her Majesty, Queen Elizabeth II", while the 2010 version of the current 15th edition is "dedicated by permission to Barack Obama, President of the United States of America, and Her Majesty Queen Elizabeth II."

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Encyclopædia Britannica


text:
Endometrium

The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer thickens and then is shed during menstruation in humans and some other mammals, including other apes, Old World monkeys, some species of bat, the elephant shrew and the Cairo spiny mouse. In most other mammals, the endometrium is reabsorbed in the estrous cycle. During pregnancy, the glands and blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus. The speculated presence of an endometrial microbiota has been argued against.

Structure

The endometrium consists of a single layer of columnar epithelium plus the stroma on which it rests. The stroma is a layer of connective tissue that varies in thickness according to hormonal influences. In the uterus, simple tubular glands reach from the endometrial surface through to the base of the stroma, which also carries a rich blood supply provided by the spiral arteries. In women of reproductive age, two layers of endometrium can be distinguished. These two layers occur only in the endometrium lining the cavity of the uterus, and not in the lining of the fallopian tubes where a potentially life-threatening ectopic pregnancy may occur nearby.

In the absence of progesterone, the arteries supplying blood to the functional layer constrict, so that cells in that layer become ischaemic and die, leading to menstruation.
 * The functional layer is adjacent to the uterine cavity. This layer is built up after the end of menstruation during the first part of the previous menstrual cycle. Proliferation is induced by estrogen (follicular phase of menstrual cycle), and later changes in this layer are engendered by progesterone from the corpus luteum (luteal phase). It is adapted to provide an optimum environment for the implantation and growth of the embryo. This layer is completely shed during menstruation.
 * The basal layer, adjacent to the myometrium and below the functional layer, is not shed at any time during the menstrual cycle. It contains stem cells that regenerate the functional layer, which develops on top of it.

It is possible to identify the phase of the menstrual cycle by reference to either the ovarian cycle or the uterine cycle by observing microscopic differences at each phase—for example in the ovarian cycle:

Gene and protein expression
About 20,000 protein coding genes are expressed in human cells and some 70% of these genes are expressed in the normal endometrium. Just over 100 of these genes are more specifically expressed in the endometrium with only a handful genes being highly endometrium specific. The corresponding specific proteins are expressed in the glandular and stromal cells of the endometrial mucosa. The expression of many of these proteins vary depending on the menstrual cycle, for example the progesterone receptor and thyrotropin-releasing hormone both expressed in the proliferative phase, and PAEP expressed in the secretory phase. Other proteins such as the HOX11 protein that is required for female fertility, is expressed in endometrial stroma cells throughout the menstrual cycle. Certain specific proteins such as the estrogen receptor are also expressed in other types of female tissue types, such as the cervix, fallopian tubes, ovaries and breast.

Microbiome speculation
The uterus and endometrium was for a long time thought to be sterile. The cervical plug of mucosa was seen to prevent the entry of any microorganisms ascending from the vagina. In the 1980s this view was challenged when it was shown that uterine infections could arise from weaknesses in the barrier of the cervical plug. Organisms from the vaginal microbiota could enter the uterus during uterine contractions in the menstrual cycle. Further studies sought to identify microbiota specific to the uterus which would be of help in identifying cases of unsuccessful IVF and miscarriages. Their findings were seen to be unreliable due to the possibility of cross-contamination in the sampling procedures used. The well-documented presence of Lactobacillus species, for example, was easily explained by an increase in the vaginal population being able to seep into the cervical mucous. Another study highlighted the flaws of the earlier studies including cross-contamination. It was also argued that the evidence from studies using germ-free offspring of axenic animals (germ-free) clearly showed the sterility of the uterus. The authors concluded that in light of these findings there was no existence of a microbiome.

The normal dominance of Lactobacilli in the vagina is seen as a marker for vaginal health. However, in the uterus this much lower population is seen as invasive in a closed environment that is highly regulated by female sex hormones, and that could have unwanted consequences. In studies of endometriosis Lactobacillus is not the dominant type and there are higher levels of Streptococcus and Staphylococcus species. Half of the cases of bacterial vaginitis showed a polymicrobial biofilm attached to the endometrium.

Function
The endometrium is the innermost lining layer of the uterus, and functions to prevent adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a thick, blood vessel-rich, glandular tissue layer. This represents an optimal environment for the implantation of a blastocyst upon its arrival in the uterus. The endometrium is central, echogenic (detectable using ultrasound scanners), and has an average thickness of 6.7 mm.

During pregnancy, the glands and blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus.

Cycle
The functional layer of the endometrial lining undergoes cyclic regeneration from stem cells in the basal layer. Humans, apes, and some other species display the menstrual cycle, whereas most other mammals are subject to an estrous cycle. In both cases, the endometrium initially proliferates under the influence of estrogen. However, once ovulation occurs, the ovary (specifically the corpus luteum) will produce much larger amounts of progesterone. This changes the proliferative pattern of the endometrium to a secretory lining. Eventually, the secretory lining provides a hospitable environment for one or more blastocysts.

Upon fertilization, the egg may implant into the uterine wall and provide feedback to the body with human chorionic gonadotropin (hCG). hCG provides continued feedback throughout pregnancy by maintaining the corpus luteum, which will continue its role of releasing progesterone and estrogen. In case of implantation, the endometrial lining remains as decidua. The decidua becomes part of the placenta; it provides support and protection for the gestation.

Without implantation of a fertilized egg, the endometrial lining is either reabsorbed (estrous cycle) or shed (menstrual cycle). In the latter case, the process of shedding involves the breaking down of the lining, the tearing of small connective blood vessels, and the loss of the tissue and blood that had constituted it through the vagina. The entire process occurs over a period of several days. Menstruation may be accompanied by a series of uterine contractions; these help expel the menstrual endometrium.

If there is inadequate stimulation of the lining, due to lack of hormones, the endometrium remains thin and inactive. In humans, this will result in amenorrhea, or the absence of a menstrual period. After menopause, the lining is often described as being atrophic. In contrast, endometrium that is chronically exposed to estrogens, but not to progesterone, may become hyperplastic. Long-term use of oral contraceptives with highly potent progestins can also induce endometrial atrophy.

In humans, the cycle of building and shedding the endometrial lining lasts an average of 28 days. The endometrium develops at different rates in different mammals. Various factors including the seasons, climate, and stress can affect its development. The endometrium itself produces certain hormones at different stages of the cycle and this affects other parts of the reproductive system.

Diseases related with endometrium

Chorionic tissue can result in marked endometrial changes, known as an Arias-Stella reaction, that have an appearance similar to cancer. Historically, this change was diagnosed as endometrial cancer and it is important only in so far as it should not be misdiagnosed as cancer.

 * Adenomyosis is the growth of the endometrium into the muscle layer of the uterus (the myometrium).
 * Endometriosis is the growth of tissue similar to the endometrium, outside the uterus.
 * Endometrial hyperplasia
 * Endometrial cancer is the most common cancer of the human female genital tract.
 * Asherman's syndrome, also known as intrauterine adhesions, occurs when the basal layer of the endometrium is damaged by instrumentation (e.g., D&C) or infection (e.g., endometrial tuberculosis) resulting in endometrial sclerosis and adhesion formation partially or completely obliterating the uterine cavity.

Thin endometrium may be defined as an endometrial thickness of less than 8 mm. It usually occurs after menopause. Treatments that can improve endometrial thickness include Vitamin E, L-arginine and sildenafil citrate.

Gene expression profiling using cDNA microarray can be used for the diagnosis of endometrial disorders. The European Menopause and Andropause Society (EMAS) released Guidelines with detailed information to assess the endometrium.

Embryo transfer
An endometrial thickness (EMT) of less than 7 mm decreases the pregnancy rate in in vitro fertilization by an odds ratio of approximately 0.4 compared to an EMT of over 7 mm. However, such low thickness rarely occurs, and any routine use of this parameter is regarded as not justified. The optimal endometrial thickness is 10mm. Nevertheless, in human a perfect synchrony it is not necessary, if the emdometrium is not ready to receive the embryo a ectopic pregnancy may occur. This consist of the implantation of the blast outside the uterus, which can be extremely dangerous. Observation of the endometrium by transvaginal ultrasonography is used when administering fertility medication, such as in in vitro fertilization. At the time of embryo transfer, it is favorable to have an endometrium of a thickness of between 7 and 14 mm with a triple-line configuration, which means that the endometrium contains a hyperechoic (usually displayed as light) line in the middle surrounded by two more hypoechoic (darker) lines. A triple-line endometrium reflects the separation of the basal layer and the functional layer, and is also observed in the periovulatory period secondary to rising estradiol levels, and disappears after ovulation.

Endometrial thickness is also associated with live births in IVF. The live birth rate in a normal endometrium is halved when the thickness is <5mm.

Endometrial protection
Estrogens stimulate endometrial proliferation and carcinogenesis. Conversely, progestogens inhibit endometrial proliferation and carcinogenesis caused by estrogens and stimulate differentiation of the endometrium into decidua, which is termed endometrial transformation or decidualization. This is mediated by the progestogenic and functional antiestrogenic effects of progestogens in this tissue. These effects of progestogens and their protection against endometrial hyperplasia and endometrial cancer caused by estrogens is referred to as endometrial protection.

title: Endometrium