title: Late Middle Ages

text: Though many of the events were outside the traditional time period of the Middle Ages, the end of the unity of the Western Church (the Protestant Reformation), was one of the distinguishing characteristics of the medieval period. The Catholic Church had long fought against heretic movements, but during the Late Middle Ages, it started to experience demands for reform from within. The first of these came from Oxford professor John Wycliffe in England. Wycliffe held that the Bible should be the only authority in religious questions, and he spoke out against transubstantiation, celibacy and indulgences. In spite of influential supporters among the English aristocracy, such as John of Gaunt, the movement was not allowed to survive. Though Wycliffe himself was left unmolested, his supporters, the Lollards, were eventually suppressed in England.


title: Late Middle Ages

text: The marriage of Richard II of England to Anne of Bohemia established contacts between the two nations and brought Lollard ideas to her homeland. The teachings of the Czech priest Jan Hus were based on those of John Wycliffe, yet his followers, the Hussites, were to have a much greater political impact than the Lollards. Hus gained a great following in Bohemia, and in 1414, he was requested to appear at the Council of Constance to defend his cause. When he was burned as a heretic in 1415, it caused a popular uprising in the Czech lands. The subsequent Hussite Wars fell apart due to internal quarrels and did not result in religious or national independence for the Czechs, but both the Catholic Church and the German element within the country were weakened.


title: Late Middle Ages

text: Martin Luther, a German monk, started the German Reformation by posting 95 theses on the castle church of Wittenberg on October 31, 1517. The immediate provocation spurring this act was Pope Leo X’s renewal of the indulgence for the building of the new St. Peter's Basilica in 1514. Luther was challenged to recant his heresy at the Diet of Worms in 1521. When he refused, he was placed under the ban of the Empire by Charles V. Receiving the protection of Frederick the Wise, he was then able to translate the Bible into German.


title: Late Middle Ages

text: To many secular rulers the Protestant reformation was a welcome opportunity to expand their wealth and influence. The Catholic Church met the challenges of the reforming movements with what has been called the Catholic Reformation, or Counter-Reformation. Europe became split into northern Protestant and southern Catholic parts, resulting in the Religious Wars of the 16th and 17th centuries.


title: Late Middle Ages

text: The increasingly dominant position of the Ottoman Empire in the eastern Mediterranean presented an impediment to trade for the Christian nations of the west, who in turn started looking for alternatives. Portuguese and Spanish explorers found new trade routes – south of Africa to India, and across the Atlantic Ocean to America. As Genoese and Venetian merchants opened up direct sea routes with Flanders, the Champagne fairs lost much of their importance.


title: Late Middle Ages

text: At the same time, English wool export shifted from raw wool to processed cloth, resulting in losses for the cloth manufacturers of the Low Countries. In the Baltic and North Sea, the Hanseatic League reached the peak of their power in the 14th century, but started going into decline in the fifteenth.


title: Late Middle Ages

text: In the late 13th and early 14th centuries, a process took place – primarily in Italy but partly also in the Empire – that historians have termed a "commercial revolution". Among the innovations of the period were new forms of partnership and the issuing of insurance, both of which contributed to reducing the risk of commercial ventures; the bill of exchange and other forms of credit that circumvented the canonical laws for gentiles against usury and eliminated the dangers of carrying bullion; and new forms of accounting, in particular double-entry bookkeeping, which allowed for better oversight and accuracy.


title: Late Middle Ages

text: With the financial expansion, trading rights became more jealously guarded by the commercial elite. Towns saw the growing power of guilds, while on a national level special companies would be granted monopolies on particular trades, like the English wool Staple. The beneficiaries of these developments would accumulate immense wealth. Families like the Fuggers in Germany, the Medicis in Italy, the de la Poles in England, and individuals like Jacques Coeur in France would help finance the wars of kings, and achieve great political influence in the process.


title: Late Middle Ages

text: Though there is no doubt that the demographic crisis of the 14th century caused a dramatic fall in production and commerce in "absolute" terms, there has been a vigorous historical debate over whether the decline was greater than the fall in population. While the older orthodoxy held that the artistic output of the Renaissance was a result of greater opulence, more recent studies have suggested that there might have been a so-called 'depression of the Renaissance'. In spite of convincing arguments for the case, the statistical evidence is simply too incomplete for a definite conclusion to be made.


title: Late Middle Ages

text: In the 14th century, the predominant academic trend of scholasticism was challenged by the humanist movement. Though primarily an attempt to revitalise the classical languages, the movement also led to innovations within the fields of science, art and literature, helped on by impulses from Byzantine scholars who had to seek refuge in the west after the Fall of Constantinople in 1453.


title: Late Middle Ages

text: In science, classical authorities like Aristotle were challenged for the first time since antiquity. Within the arts, humanism took the form of the Renaissance. Though the 15th-century Renaissance was a highly localised phenomenon – limited mostly to the city states of northern Italy – artistic developments were taking place also further north, particularly in the Netherlands.


title: Late Middle Ages

text: The predominant school of thought in the 13th century was the Thomistic reconciliation of the teachings of Aristotle with Christian theology. The Condemnation of 1277, enacted at the University of Paris, placed restrictions on ideas that could be interpreted as heretical; restrictions that had implication for Aristotelian thought. An alternative was presented by William of Ockham, following the manner of the earlier Franciscan John Duns Scotus, who insisted that the world of reason and the world of faith had to be kept apart. Ockham introduced the principle of parsimony – or Occam's razor – whereby a simple theory is preferred to a more complex one, and speculation on unobservable phenomena is avoided. This maxim is, however, often misquoted. Occam was referring to his nominalism in this quotation. Essentially saying the theory of absolutes, or metaphysical realism, was unnecessary to make sense of the world.


title: Late Middle Ages

text: This new approach liberated scientific speculation from the dogmatic restraints of Aristotelian science, and paved the way for new approaches. Particularly within the field of theories of motion great advances were made, when such scholars as Jean Buridan, Nicole Oresme and the Oxford Calculators challenged the work of Aristotle. Buridan developed the theory of "impetus" as the cause of the motion of projectiles, which was an important step towards the modern concept of inertia. The works of these scholars anticipated the heliocentric worldview of Nicolaus Copernicus.


title: Late Middle Ages

text: Certain technological inventions of the period – whether of Arab or Chinese origin, or unique European innovations – were to have great influence on political and social developments, in particular gunpowder, the printing press and the compass. The introduction of gunpowder to the field of battle affected not only military organisation, but helped advance the nation state. Gutenberg's movable type printing press made possible not only the Reformation, but also a dissemination of knowledge that would lead to a gradually more egalitarian society. The compass, along with other innovations such as the cross-staff, the mariner's astrolabe, and advances in shipbuilding, enabled the navigation of the World Oceans, and the early phases of colonialism. Other inventions had a greater impact on everyday life, such as eyeglasses and the weight-driven clock.


title: Late Middle Ages

text: A precursor to Renaissance art can be seen already in the early 14th-century works of Giotto. Giotto was the first painter since antiquity to attempt the representation of a three-dimensional reality, and to endow his characters with true human emotions. The most important developments, however, came in 15th-century Florence. The affluence of the merchant class allowed extensive patronage of the arts, and foremost among the patrons were the Medici.


title: Late Middle Ages

text: The period saw several important technical innovations, like the principle of linear perspective found in the work of Masaccio, and later described by Brunelleschi. Greater realism was also achieved through the scientific study of anatomy, championed by artists like Donatello. This can be seen particularly well in his sculptures, inspired by the study of classical models. As the centre of the movement shifted to Rome, the period culminated in the High Renaissance masters da Vinci, Michelangelo and Raphael.


title: Late Middle Ages

text: The ideas of the Italian Renaissance were slow to cross the Alps into northern Europe, but important artistic innovations were made also in the Low Countries. Though not – as previously believed – the inventor of oil painting, Jan van Eyck was a champion of the new medium, and used it to create works of great realism and minute detail. The two cultures influenced each other and learned from each other, but painting in the Netherlands remained more focused on textures and surfaces than the idealized compositions of Italy.


title: Late Middle Ages

text: In northern European countries Gothic architecture remained the norm, and the gothic cathedral was further elaborated. In Italy, on the other hand, architecture took a different direction, also here inspired by classical ideals. The crowning work of the period was the Santa Maria del Fiore in Florence, with Giotto's clock tower, Ghiberti's baptistery gates, and Brunelleschi's cathedral dome of unprecedented proportions.


title: Late Middle Ages

text: The most important development of late medieval literature was the ascendancy of the vernacular languages. The vernacular had been in use in England since the 8th century and France since the 11th century, where the most popular genres had been the chanson de geste, troubadour lyrics and romantic epics, or the romance. Though Italy was later in evolving a native literature in the vernacular language, it was here that the most important developments of the period were to come.


title: Late Middle Ages

text: Dante Alighieri's "Divine Comedy", written in the early 14th century, merged a medieval world view with classical ideals. Another promoter of the Italian language was Boccaccio with his "Decameron". The application of the vernacular did not entail a rejection of Latin, and both Dante and Boccaccio wrote prolifically in Latin as well as Italian, as would Petrarch later (whose "Canzoniere" also promoted the vernacular and whose contents are considered the first modern lyric poems). Together the three poets established the Tuscan dialect as the norm for the modern Italian language.


title: Late Middle Ages

text: The new literary style spread rapidly, and in France influenced such writers as Eustache Deschamps and Guillaume de Machaut. In England Geoffrey Chaucer helped establish Middle English as a literary language with his "Canterbury Tales", which contained a wide variety of narrators and stories (including some translated from Boccaccio). The spread of vernacular literature eventually reached as far as Bohemia, and the Baltic, Slavic and Byzantine worlds.


title: Late Middle Ages

text: Music was an important part of both secular and spiritual culture, and in the universities it made up part of the "quadrivium" of the liberal arts. From the early 13th century, the dominant sacred musical form had been the motet; a composition with text in several parts. From the 1330s and onwards, emerged the polyphonic style, which was a more complex fusion of independent voices. Polyphony had been common in the secular music of the Provençal troubadours. Many of these had fallen victim to the 13th-century Albigensian Crusade, but their influence reached the papal court at Avignon.


title: Late Middle Ages

text: The main representatives of the new style, often referred to as "ars nova" as opposed to the "ars antiqua", were the composers Philippe de Vitry and Guillaume de Machaut. In Italy, where the Provençal troubadours had also found refuge, the corresponding period goes under the name of trecento, and the leading composers were Giovanni da Cascia, Jacopo da Bologna and Francesco Landini. Prominent reformer of Orthodox Church music from the first half of 14th century was John Kukuzelis; he also introduced a system of notation widely used in the Balkans in the following centuries.


title: Late Middle Ages

text: In the British Isles, plays were produced in some 127 different towns during the Middle Ages. These vernacular Mystery plays were written in cycles of a large number of plays: York (48 plays), Chester (24), Wakefield (32) and Unknown (42). A larger number of plays survive from France and Germany in this period and some type of religious dramas were performed in nearly every European country in the Late Middle Ages. Many of these plays contained comedy, devils, villains and clowns.


title: Late Middle Ages

text: Morality plays emerged as a distinct dramatic form around 1400 and flourished until 1550, an example being "The Castle of Perseverance", which depicts mankind's progress from birth to death. Another famous morality play is "Everyman". Everyman receives Death's summons, struggles to escape and finally resigns himself to necessity. Along the way, he is deserted by Kindred, Goods, and Fellowship – only Good Deeds goes with him to the grave.


title: Late Middle Ages

text: At the end of the Late Middle Ages, professional actors began to appear in England and Europe. Richard III and Henry VII both maintained small companies of professional actors. Their plays were performed in the Great Hall of a nobleman's residence, often with a raised platform at one end for the audience and a "screen" at the other for the actors. Also important were Mummers' plays, performed during the Christmas season, and court masques. These masques were especially popular during the reign of Henry VIII who had a House of Revels built and an Office of Revels established in 1545.


title: Late Middle Ages

text: The end of medieval drama came about due to a number of factors, including the weakening power of the Catholic Church, the Protestant Reformation and the banning of religious plays in many countries. Elizabeth I forbid all religious plays in 1558 and the great cycle plays had been silenced by the 1580s. Similarly, religious plays were banned in the Netherlands in 1539, the Papal States in 1547 and in Paris in 1548. The abandonment of these plays destroyed the international theatre that had thereto existed and forced each country to develop its own form of drama. It also allowed dramatists to turn to secular subjects and the reviving interest in Greek and Roman theatre provided them with the perfect opportunity.


title: Late Middle Ages

text: After the end of the late Middle Ages period, the Renaissance spread unevenly over continental Europe from the southern European region. The intellectual transformation of the Renaissance is viewed as a bridge between the Middle Ages and the Modern era. Europeans would later begin an era of world discovery. Combined with the influx of classical ideas was the invention of printing which facilitated dissemination of the printed word and democratized learning. These two things would lead to the Protestant Reformation. Europeans also discovered new trading routes, as was the case with Columbus’ travel to the Americas in 1492, and Vasco da Gama’s circumnavigation of Africa and India in 1498. Their discoveries strengthened the economy and power of European nations.


title: Late Middle Ages

text: By the end of the 15th century the Ottoman Empire had advanced all over Southeastern Europe, eventually conquering the Byzantine Empire and extending control over the Balkan states. Hungary was the last bastion of the Latin Christian world in the East, and fought to keep its rule over a period of two centuries. After the death of the young king Vladislaus I of Hungary during the Battle of Varna in 1444 against the Ottomans, the Kingdom was placed in the hands of count John Hunyadi, who became Hungary's regent-governor (1446–1453). Hunyadi was considered one of the most relevant military figures of the 15th century: Pope Pius II awarded him the title of "Athleta Christi" or Champion of Christ for being the only hope of resisting the Ottomans from advancing to Central and Western Europe.


title: Late Middle Ages

text: Hunyadi succeeded during the Siege of Belgrade in 1456 against the Ottomans, the biggest victory against that empire in decades. This battle became a real Crusade against the Muslims, as the peasants were motivated by the Franciscan friar Saint John of Capistrano, who came from Italy predicating Holy War. The effect that it created in that time was one of the main factors that helped in achieving the victory. However the premature death of the Hungarian Lord left Pannonia defenseless and in chaos. In an extremely unusual event for the Middle Ages, Hunyadi's son, Matthias, was elected as King of Hungary by the Hungarian nobility. For the first time, a member of an aristocratic family (and not from a royal family) was crowned.


title: Late Middle Ages

text: King Matthias Corvinus of Hungary (1458–1490) was one of the most prominent figures of the period, directing campaigns to the West, conquering Bohemia in answer to the Pope's call for help against the Hussite Protestants. Also, in resolving political hostilities with the German emperor Frederick III of Habsburg, he invaded his western domains. Matthew organized the Black Army of mercenary soldiers; it was considered as the biggest army of its time. Using this powerful tool, the Hungarian king led wars against the Turkish armies and stopped the Ottomans during his reign. After the death of Matthew, and with end of the Black Army, the Ottoman Empire grew in strength and Central Europe was defenseless. At the Battle of Mohács, the forces of the Ottoman Empire annihilated the Hungarian army and Louis II of Hungary drowned in the Csele Creek while trying to escape. The leader of the Hungarian army, Pál Tomori, also died in the battle. This is considered to be one of the final battles of Medieval times.


title: Teasing Master Takagi-san

text: An anime television series by Shin-Ei Animation aired from January to March 2018. An original video animation (OVA) was released in July 2018. A second season aired from July to September 2019. A third season aired from January to March 2022, and a premiered on June 10.


title: Teasing Master Takagi-san

text: Middle school students Nishikata and Takagi sit next to each other in class. Takagi enjoys teasing Nishikata with embarrassing pranks and jokes. In response, Nishikata creates plans to get his revenge, but he fails when she identifies his weaknesses and capitalizes on them. In some rare instances where Takagi loses the challenge, Nishikata does not feel like he really won. The setting is based on the town of Tonoshō in the Kagawa Prefecture.


title: Teasing Master Takagi-san

text: "Teasing Master Takagi-san" is written by Sōichirō Yamamoto. The series began serialization in Shogakukan's "shōnen" manga magazine supplement "Monthly Shōnen Sunday Mini" on June 12, 2013, and it moved to the main "Monthly Shōnen Sunday" magazine on July 12, 2016. As of June 2022, it has been collected in eighteen "tankōbon" volumes. In November 2017, Yen Press announced the acquisition of the manga for an English release in North America.


title: Teasing Master Takagi-san

text: A spin-off manga series, titled , was serialized in the newspaper "Yomiuri Chūkōsei Shimbun" from November 7, 2014 to November 2015, and was collected into two "tankōbon" volumes. It was also adapted within the "Karakai Jōzu no Takagi-san" adaptation in 2018.


title: Teasing Master Takagi-san

text: A second spin-off manga series, titled , was serialized in "Monthly Shōnen Sunday" from July 12, 2017 to April 11, 2020, and was collected into five tankōbon volumes.


title: Teasing Master Takagi-san

text: A third spin-off, titled , featuring an adult Takagi, now married to Nishikata, and their daughter, Chi, started in "MangaONE" app on July 15, 2017. It has been collected into sixteen "tankōbon" volumes.


title: Teasing Master Takagi-san

text: An anime television series adaptation was announced in the August 2017 issue of Shogakukan's "Monthly Shōnen Sunday" magazine. The series was directed by Hiroaki Akagi at Shin-Ei Animation, with scripts written by Michiko Yokote and character designs by Aya Takano. It aired from January 8 to March 26, 2018 on Tokyo MX and other channels.


title: Teasing Master Takagi-san

text: Crunchyroll simulcasted the series, while Funimation streamed the series with an English dub. The series ran 12 episodes. The opening theme is performed by Yuiko Ōhara. For the ending themes, Rie Takahashi performed covers of previously-existing songs: by Ikimonogakari (episodes 1–2), "AM11:00" by HY (ep. 3–4), by Judy and Mary (ep. 5–6), by Chatmonchy (ep. 7–8), by Mongol800 (ep. 9–10), by Greeeen (ep. 11), and by Every Little Thing (ep. 12). An OVA episode was bundled with the manga's ninth volume, which was released on July 12, 2018.


title: Teasing Master Takagi-san

text: On January 10, 2019, it was announced that the series would receive a second season; the staff and cast reprised their respective roles. It aired from July 7 to September 22, 2019 on Tokyo MX and other channels, with episodes being exclusively streamed on Netflix in Japan; a worldwide release on Netflix took place on December 6. The opening theme for the second season is performed by Yuiko Ōhara. Like the first season, the ending themes consist of covers by Rie Takahashi: by Sukima Switch (ep. 1), by Remioromen (ep. 2), by Greeeen (ep. 3–4), by Ikimonogakari (ep. 5–6), "STARS" by Mika Nakashima (ep. 7), by Mongol800 (ep. 8–9), "Iwanai Kedo ne." by Ōhara (ep. 10–11), and by Chara (ep. 12). Ōhara also performed the insert song for episode 12, which is .


title: Teasing Master Takagi-san

text: A third season and a film were officially announced in September 2021 after they were first teased with the release of the sixteenth volume of the manga. The third season aired on the Super Animeism block on MBS and TBS, and other networks from January 8 to March 26, 2022. The opening theme is performed by Yuiko Ōhara. Like the first two seasons, the ending themes consist of covers by Rie Takahashi: by Eiichi Ohtaki (ep. 1), "Over Drive" by Judy and Mary (ep. 2–3), by Motohiro Hata (ep. 4–5), by Finger 5 (ep. 6), by Ikimonogakari (ep. 7–8), (ep. 9), by Sekai no Owari (ep. 10–11), and by Orange Range (ep. 12). Muse Communication secured the distribution rights for the third season in Southeast Asia. On December 28, 2021, Sentai Filmworks announced it had acquired the rights to the third season and the film for worldwide distribution excluding Asia, and is streaming it on HIDIVE.


title: Teasing Master Takagi-san

text: The features returning staff members from the third season of the anime series. It was released in Japan on June 10, 2022.


title: Teasing Master Takagi-san

text: By December 2016, the manga had over 1 million copies in print. By February 2018, that number had increased to 4 million copies. As of August 2021, the manga has 10 million copies in print.


title: Teasing Master Takagi-san

text: The manga was nominated for the 10th Manga Taishō awards in 2017. In 2021, along with "Chainsaw Man", "Teasing Master Takagi-san" won the 66th Shogakukan Manga Award in the "shōnen" category.


title: Hickey

text: A hickey, hickie or love bite in British English, is a bruise or bruise-like mark caused by kissing or sucking skin, usually on the neck, arm, or earlobe. While biting may be part of giving a hickey, sucking is sufficient to burst small superficial blood vessels under the skin.


title: Hickey

text: The origin of the word is from its earlier meaning of "pimple, skin lesion" (c. 1915); perhaps a sense extension and spelling variation from the earlier word meaning "small gadget, device; any unspecified object" which has an unknown origin (1909).


title: Hickey

text: Hickeys typically last from 5 to 12 days and may be treated in the same way as other bruises. Ways to reduce the appearance of hickeys include icing recent hickeys to reduce swelling, rubbing them with a chilled spoon to remove the bruise, and applying a warm compress to older hickeys to dilate vessels and promote blood flow. They can be covered with a concealer or powder corresponding to the sufferer's skin tone, or a fake tan. Alternatively, articles of clothing such as scarves, snoods, turtle necks, or sleeves may be used to conceal hickeys.


title: Brendan Coyle

text: David "Brendan" Coyle (born 2 December 1962) is an English-Irish actor. He won the Olivier Award for Best Performance in a Supporting Role for "The Weir" in 1999. He also played Nicholas Higgins in the miniseries "North & South", Robert Timmins in the first three series of "Lark Rise to Candleford", and more recently Mr Bates, the valet, in "Downton Abbey", which earned him a nomination for a Primetime Emmy Award for Outstanding Supporting Actor in a Drama Series and a BAFTA nomination for Best Supporting Actor


title: Brendan Coyle

text: Brendan Coyle was born David Coyle in Corby on 2 December 1962, the son of a Scottish mother and Irish father. He has an older brother named Shaun, who works as a butcher. Due to his British birth and Irish heritage, he holds both British and Irish citizenship. He is the great-nephew of football manager Sir Matt Busby. He studied drama in Dublin in 1981 and received a scholarship to Mountview Academy of Theatre Arts in London in 1983.


title: Brendan Coyle

text: Coyle received a Laurence Olivier Award in 1999 for his performance in Conor McPherson's "The Weir" and won a New York Critics Theater World Award for Outstanding Broadway Debut for the same play in its New York production. In 2001, Coyle appeared in the film "Conspiracy" as Gestapo Chief Heinrich Müller. He played Kaz Sweeney in the British drama, "True Dare Kiss", and Nicholas Higgins in "North & South" for the BBC.


title: Brendan Coyle

text: From 2008 he played Robert Timmins in three BBC series based on the "Lark Rise to Candleford" novels, written by Flora Thompson. In 2010, he began playing John Bates, valet and former British Army batman to the Earl of Grantham in Julian Fellowes's period drama series, "Downton Abbey". Fellowes wrote the part for Coyle, and it won him nominations for a BAFTA and IFTA, as well as a nomination for the Primetime Emmy Awards as Outstanding Supporting Actor in a Drama Series in 2012. He also won three Screen Actors Guild Awards 2013–16. Coyle also played the character of Terry Starling in the short-lived Sky comedy series "Starlings".


title: Brendan Coyle

text: Coyle divides his time between London and Norfolk. He is a fan of the football team Manchester United FC, which was famously managed by his great-uncle Matt Busby.


title: Brendan Coyle

text: In July 2014, Brendan Coyle and Joy Harrison formed Anderson Shelter Productions Limited with the mission to "find talented young filmmakers" and assist in funding their short film projects. On 14 September 2014, Coyle announced via Twitter his involvement with Council Child Production's short film, "Starcross".


title: Lil Loaded

text: Dashawn Maurice Robertson (August 1, 2000 – May 31, 2021), known professionally as Lil Loaded, was an American rapper from Dallas, Texas. He rose to fame in mid-2019 after his song "6locc 6a6y" went viral.


title: Lil Loaded

text: Robertson was born in San Bernardino, California, and raised in Dallas, Texas. When asked what it was like growing up in Dallas, he said: "It's like everywhere in the city, you see different stuff, I guess you kind of grow up a little bit faster I would say in Dallas". He grew up with five siblings, an older brother,


title: Lil Loaded

text: two older sisters, a younger sister, and a younger brother and was raised by a single mom while his dad was in prison. In 2015, when Robertson was 15, his older brother who was 23 at the time was murdered. He was affiliated with the Rollin' 60s Neighborhood Crips.


title: Lil Loaded

text: Robertson started rapping in late 2018. His first song was "B.O.S.", a take on YNW Melly's song "Butter Pecan". He rose to prominence in 2019 when YouTuber Tommy Craze included his song "6locc 6a6y" in a reaction video in which he watched YouTube music videos that had 0 views. "6locc 6a6y" was certified gold in May 2021, by which point it had received over 28million views on YouTube. Robertson later released "Gang Unit", which had garnered more than 59million YouTube views by May 2022.


title: Lil Loaded

text: Robertson later signed with Epic Records. He released his "6locc 6a6y" mixtape in 2019, and returned in 2020 with "A Demon in 6lue" and "Criptape".


title: Lil Loaded

text: On May 31, 2022, Robertson's team posthumously released "Cell Tales" on the first anniversary of his death.


title: Lil Loaded

text: On October 25, 2020, Robertson allegedly shot and killed a friend, 18-year-old Khalil Walker, while recording a music video. Robertson turned himself in to police on November 9, 2020, after a warrant was issued for his arrest. He was indicted on a lesser charge of manslaughter in connection with the incident in February 2021. Robertson maintained that the incident was an accident.


title: Lil Loaded

text: Robertson died, apparently by suicide via gunshot wound to the head, on May 31, 2021, at the age of 20. He was found dead by his mother who then called the police. When police arrived, they saw his mother outside of the home crying and she told them Robertson was inside the house with a gunshot wound to the head. She claimed he had been upset over a breakup with his girlfriend the night before.


title: Pemmican

text: Pemmican (also pemican in older sources) is a mixture of tallow, dried meat, and sometimes dried berries. A calorie-rich food, it can be used as a key component in prepared meals or eaten raw. Historically, it was an important part of indigenous cuisine in certain parts of North America and it is still prepared today. The word comes from the Cree word (), which is derived from the word (), "fat, grease". The Lakota (or Sioux) word is , originally meaning "grease derived from marrow bones", with the creating a noun, and referring to small pieces that adhere to something. It was invented by the Indigenous peoples of North America.


title: Pemmican

text: Pemmican was widely adopted as a high-energy food by Europeans involved in the fur trade and later by Arctic and Antarctic explorers, such as Captain Robert Bartlett, Ernest Shackleton, Richard E. Byrd, Fridtjof Nansen, Robert Falcon Scott, George W. DeLong, and Roald Amundsen.


title: Pemmican

text: Traditionally, the specific ingredients used for pemmican were usually whatever was available. The dried meat is often in the form of large game meat such as bison, deer, elk, or moose, but the use of fish such as salmon, and smaller game such as duck, is not uncommon. The meats used in contemporary pemmican also include beef. Dried fruit, such as cranberries and saskatoon berries (Cree ) sometimes are added. Blueberries, cherries, chokeberries, and currants are also used, but in some regions, these fruits are used almost exclusively in ceremonial and wedding pemmican. The additional use of sugar was noted in the journals of European fur traders. These ingredients are mixed together with rendered animal fat (tallow).


title: Pemmican

text: Among the Lakota and Dakota nations, there is also a corn (or pemmican) that does not contain dried meat. This is made from toasted cornmeal, animal fat, fruit, and sugar.


title: Pemmican

text: Traditionally, pemmican was prepared from the lean meat of large game such as bison, elk, deer, or moose. The meat was cut in thin slices and dried, either over a slow fire or in the hot sun until it was hard and brittle. Approximately of meat are required to make of dried meat suitable for pemmican. This thin brittle meat is known in Cree as pânsâwân and colloquially in North American English, as "dry meat". The pânsâwân was then spread across a tanned animal hide pinned to the ground, where it was beaten with flails or ground between two large stones till it turned into very small pieces, almost powder-like in its consistency. The pounded meat was mixed with melted fat in an approximate 1:1 ratio by weight. Typically, the melted fat would be suet that has been rendered into tallow. In some cases, dried fruits, such as blueberries, chokecherries, cranberries, or Saskatoon berries, were pounded into powder and then added to the meat-fat mixture. The resulting mixture was then packed into rawhide bags for storage where it would cool, and then harden into pemmican.


title: Pemmican

text: Today, some people store their pemmican in glass jars or tin boxes. Since there is no "official" recipe for pemmican, the shelf life may vary depending on ingredients and storage conditions. At room temperature, pemmican can generally last from one to five years, but there are anecdotal stories of pemmican stored in cool cellars being safely consumed after a decade or more.


title: Pemmican

text: A bag of bison pemmican weighing approximately was called a (French for "bull") by the Métis of Red River. These bags of ( "bulls"), when mixed with fat from the udder, were known as , when mixed with bone marrow, as , and when mixed with berries, as . It generally took the meat of one bison to fill a .


title: Pemmican

text: In his notes of 1874, North-West Mounted Police Sergeant-Major Sam Steele recorded three ways of serving pemmican: raw, boiled in a stew called "rubaboo", or fried, known in the West as a "rechaud":


title: Pemmican

text: As bone grease is an essential ingredient in pemmican, archaeologists consider evidence of its manufacture a strong indicator of pemmican making. There is widespread archaeological evidence (bone fragments and boiling pits) for bone grease production on Great Plains by AD 1, but it likely developed much earlier. However, calcified bone fragments from Paleo-Indian times do not offer that clear evidence, due to lack of boiling pits and other possible usages.


title: Pemmican

text: It has also been suggested that pemmican may have come through the Bering Strait crossing 40–60 centuries ago. The first written account of pemmican is considered to be Francisco Vázquez de Coronado records from 1541, of the Querecho people and Teya people, traversing Texas Panhandle, who sundried and minced bison meat and then would make a stew of it and bison fat. The first written English usage is attributed to James Isham who in 1743 wrote that ‘pimmegan’ was a mixture of finely pounded dried meat, fat and cranberries.


title: Pemmican

text: The voyageurs of the Canadian fur trade had no time to live off the land during the short season when the lakes and rivers were free of ice. They had to carry all of their food with them if the distance traveled was too great to be resupplied along the way. A north canoe ("canot du nord") with six men and 25 standard packs required about four packs of food per . Montreal-based canoemen could be supplied by sea or with locally grown food. Their main food was dried peas or beans, sea biscuit, and salt pork. (Western canoemen called their Montreal-based fellows "mangeurs de lard" or "pork-eaters".) In the Great Lakes, some maize and wild rice could be obtained locally. By the time trade reached the Winnipeg area, the pemmican trade was developed.


title: Pemmican

text: Trading people of mixed heritage and becoming known as the Métis would go southwest onto the prairie in Red River carts, slaughter bison, convert it into pemmican, and carry it north to trade from settlements they would make adjacent to North West Company posts. For these people on the edge of the prairie, the pemmican trade was as important a source of trade goods as was the beaver trade for the Indigenous peoples farther north. This trade was a major factor in the emergence of the new and distinct Métis society. Packs of pemmican would be shipped north and stored at the major fur posts: Fort Alexander, Cumberland House, Île-à-la-Crosse, Fort Garry, Norway House, and Edmonton House.


title: Pemmican

text: So important was pemmican that, in 1814, governor Miles Macdonell started the Pemmican War with the Métis when he passed the short-lived Pemmican Proclamation, which forbade the export of pemmican from the Red River Colony.


title: Pemmican

text: North Pole explorer Robert Peary used pemmican on all three of his expeditions, from 1886 to 1909, for both his men and his dogs. In his 1917 book, "Secrets of Polar Travel", he devoted several pages to the food, stating, "Too much cannot be said of the importance of pemmican to a polar expedition. It is an absolute "sine qua non". Without it a sledge-party cannot compact its supplies within a limit of weight to make a serious polar journey successful."


title: Pemmican

text: British polar expeditions fed a type of pemmican to their dogs as "sledging rations". Called "Bovril pemmican" or simply "dog pemmican", it was a beef product consisting, by volume, of protein and fat (i.e., a 2:1 ratio of protein to fat), without carbohydrate. It was later ascertained that although the dogs survived on it, this was not a nutritious and healthy diet for them, being too high in protein. Members of Ernest Shackleton's 1914–1916 expedition to the Antarctic resorted to eating dog pemmican when they were stranded on ice during the antarctic summer.


title: Pemmican

text: During the Second Boer War (1899–1902), British troops were given an iron ration made of four ounces of pemmican and four ounces of chocolate and sugar. The pemmican would keep in perfect condition for decades. It was considered much superior to biltong, a form of cured game meats commonly used in Africa. This iron ration was prepared in two small tins (soldered together) that were fastened inside the belts of the soldiers. It was the last ration used and it was used only as a last resort—when ordered by the commanding officer. A man could march on this for 36 hours before he began to drop from hunger.


title: Pemmican

text: While serving as chief of scouts for the British Army in South Africa, American adventurer Frederick Russell Burnham required pemmican to be carried by every scout.


title: Pemmican

text: Pemmican, likely condensed meat bars, was used as a ration for French troops fighting in Morocco in the 1920s.


title: Pemmican

text: A 1945 scientific study of pemmican criticized using it exclusively as a survival food because of the low levels of certain vitamins.


title: Pemmican

text: A study was later done by the U.S. military in January 1969, entitled "Arctic Survival Rations, III. The Evaluation of Pemmican Under Winter Field Conditions." The study found that during a cycle of two starvation periods the subjects could stave off starvation for the first cycle of testing with only 1000 calories worth of pemmican.


title: Pemmican

text: Today, people in many indigenous communities across North America continue to make pemmican for personal, community, and ceremonial consumption. Some contemporary pemmican recipes incorporate ingredients that have been introduced to the Americas in the past 500 years, including beef. There are also indigenous-owned companies, such as Tanka Bar, based on Pine Ridge Indian Reservation in South Dakota, that produce pemmican or foods based on traditional pemmican recipes, for commercial distribution.


title: Port (computer networking)

text: In computer networking, a port is a number assigned to uniquely identify a connection endpoint and to direct data to a specific service. At the software level, within an operating system, a port is a logical construct that identifies a specific process or a type of network service. A port is identified for each transport protocol and address combination by a 16-bit unsigned number, known as the port number. The most common transport protocols that use port numbers are the Transmission Control Protocol (TCP) and the User Datagram Protocol (UDP).


title: Port (computer networking)

text: A port number is always associated with an IP address of a host and the type of transport protocol used for communication. It completes the destination or origination network address of a message. Specific port numbers are reserved to identify specific services so that an arriving packet can be easily forwarded to a running application. For this purpose, port numbers lower than 1024 identify the historically most commonly used services and are called the well-known port numbers. Higher-numbered ports are available for general use by applications and are known as ephemeral ports.


title: Port (computer networking)

text: Ports provide a multiplexing service for multiple services or multiple communication sessions at one network address. In the client–server model of application architecture, multiple simultaneous communication sessions may be initiated for the same service.


title: Port (computer networking)

text: A port number is a 16-bit unsigned integer, thus ranging from 0 to 65535. For TCP, port number 0 is reserved and cannot be used, while for UDP, the source port is optional and a value of zero means no port. A process associates its input or output channels via an internet socket, which is a type of file descriptor, associated with a transport protocol, an IP address, and a port number. This is known as "binding". A socket is used by a process to send and receive data via the network. The operating system's networking software has the task of transmitting outgoing data from all application ports onto the network, and forwarding arriving network packets to processes by matching the packet's IP address and port number to a socket. For TCP, only one process may bind to a specific IP address and port combination. Common application failures, sometimes called "port conflicts", occur when multiple programs attempt to use the same port number on the same IP address with the same protocol.


title: Port (computer networking)

text: Applications implementing common services often use specifically reserved well-known port numbers for receiving service requests from clients. This process is known as "listening", and involves the receipt of a request on the well-known port potentially establishing a one-to-one server-client dialog, using this listening port. Other clients may simultaneously connect to the same listening port; this works because a TCP connection is identified by a tuple consisting of the local address, the local port, the remote address, and the remote port. The well-known ports are defined by convention overseen by the Internet Assigned Numbers Authority (IANA). In many operating systems special privileges are required for applications to bind to these ports because these are often deemed critical to the operation of IP networks. Conversely, the client end of a connection typically uses a high port number allocated for short term use, therefore called an ephemeral port.


title: Port (computer networking)

text: IANA is responsible for the global coordination of the DNS root, IP addressing, and other protocol resources. This includes the registration of commonly used port numbers for well-known internet services.


title: Port (computer networking)

text: The port numbers are divided into three ranges: the "well-known ports", the "registered ports", and the "dynamic" or "private ports".


title: Port (computer networking)

text: The well-known ports (also known as "system ports") are those numbered from 0 through 1023. The requirements for new assignments in this range are stricter than for other registrations.


title: Port (computer networking)

text: The registered ports are those from 1024 through 49151. IANA maintains the official list of well-known and registered ranges.


title: Port (computer networking)

text: The dynamic or private ports are those from 49152 through 65535. One common use for this range is for ephemeral ports.


title: Port (computer networking)

text: Transport-layer protocols, such as the Transmission Control Protocol (TCP) and the User Datagram Protocol (UDP), transfer data using protocol data units (PDUs). For TCP, the PDU is a segment, and for UDP it is a datagram. Both protocols use a header field for indicating the source and destination port numbers. The port numbers are encoded in the transport protocol packet header, and they can be readily interpreted not only by the sending and receiving hosts but also by other components of the networking infrastructure. In particular, firewalls are commonly configured to differentiate between packets based on their source or destination port numbers. Port forwarding is an example application of this.


title: Port (computer networking)

text: The practice of attempting to connect to a range of ports in sequence on a single host is commonly known as port scanning. This is usually associated either with malicious cracking attempts or with network administrators looking for possible vulnerabilities to help prevent such attacks. Port connection attempts are frequently monitored and logged by hosts. The technique of port knocking uses a series of port connections (knocks) from a client computer to enable a server connection.


title: Port (computer networking)

text: An example of the use of ports is the delivery of email. A server used for sending and receiving email generally needs two services. The first service is used to transport email to and from other servers. This is accomplished with the Simple Mail Transfer Protocol (SMTP). A standard SMTP service application listens on TCP port 25 for incoming requests. The second service is usually either the Post Office Protocol (POP) or the Internet Message Access Protocol (IMAP) which is used by email client applications on users' personal computers to fetch email messages from the server. The POP service listens on TCP port number 110. Both services may be running on the same host computer, in which case the port number distinguishes the service that was requested by a remote computer, be it a user's computer or another mail server.


title: Port (computer networking)

text: While the listening port number of a server is well defined (IANA calls these the well-known ports), the client's port number is often chosen from the dynamic port range (see below). In some applications, the clients and the server each use specific port numbers assigned by the IANA. A good example of this is DHCP in which the client always uses UDP port 68 and the server always uses UDP port 67.


title: Port (computer networking)

text: Port numbers are sometimes seen in web or other uniform resource locators (URLs). By default, HTTP uses port 80 and HTTPS uses port 443, but a URL like codice_1 specifies that the web browser connects instead to port 8080 of the HTTP server.


title: Port (computer networking)

text: The concept of port numbers was established by the early developers of the ARPANET in informal cooperation of software authors and system administrators. The term "port number" was not yet in use. It was preceded by the use of the term "socket number" in the early development stages of the network. A socket number for a remote host was a 40-bit quantity. The first 32 bits were similar to today's IPv4 address, but at the time the most-significant 8 bits were the host number. The least-significant portion of the socket number (bits 33 through 40) was an entity called "Another Eightbit Number", abbreviated AEN. Today, "network socket" refers to a related but distinct concept, namely the internal address of an endpoint used only within the node.


title: Port (computer networking)

text: On March 26, 1972, Vint Cerf and Jon Postel called for documenting the then-current usages and establishing a socket number catalog in RFC 322. Network administrators were asked to submit a note or place a phone call, ""describing the function and socket numbers of network service programs at each HOST"". This catalog was subsequently published as RFC 433 in December 1972 and included a list of hosts and their port numbers and the corresponding function used at each host in the network. This first registry function served primarily as documentation of usage and indicated that port number usage was conflicting between some hosts for ""useful public services"". The document promised a resolution of the conflicts based on a standard that Postel had published in May 1972 in RFC 349, in which he first proposed official assignments of port numbers to network services and suggested a dedicated administrative function, which he called a "czar", to maintain a registry.


title: Port (computer networking)

text: In the early ARPANET, the AEN was also called a "socket name", and was used with the Initial Connection Protocol (ICP), a component of the Network Control Protocol (NCP). NCP was the forerunner of the modern Internet protocols. Today the terminology "service name" is still closely connected with port numbers, the former being text strings used in some network functions to represent a numerical port number.


title: Eli Lilly and Company

text: Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel Eli Lilly, a pharmaceutical chemist and veteran of the American Civil War.


title: Eli Lilly and Company

text: As of 2022, Lilly is known for its clinical depression drugs Prozac (fluoxetine) (1986) and Cymbalta (duloxetine) (2004) and its antipsychotic medication Zyprexa (olanzapine) (1996), although its primary revenue drivers are the diabetes drugs Humalog (insulin lispro) (1996) and Trulicity (dulaglutide) (2014). Lilly's achievements include being the first company to mass-produce the polio vaccine developed by Jonas Salk, and insulin. It was one of the first pharmaceutical companies to produce human insulin using recombinant DNA including Humulin (insulin medication), Humalog (insulin lispro), and the first approved biosimilar insulin product in the US, Basaglar (insulin glargine).


title: Eli Lilly and Company

text: In 2009 Lilly pleaded guilty for illegally marketing Zyprexa and agreed to pay a $1.415 billion penalty that included criminal fine of $515 million, the largest ever in a healthcare case and the largest criminal fine for an individual corporation ever imposed in a US criminal prosecution of any kind at the time.


title: Eli Lilly and Company

text: As of 1997, it was the largest corporation and the largest charitable benefactor in Indiana. In 2019, the company was ranked 123rd on the Fortune 500. It is ranked 221st on the Forbes Global 2000 list of the largest public companies in the world and 252nd on the Forbes list of America's Best Employers. Lilly is a full member of the Pharmaceutical Research and Manufacturers of America and the European Federation of Pharmaceutical Industries and Associations (EFPIA).


title: Eli Lilly and Company

text: The company's founder was Colonel Eli Lilly, a pharmaceutical chemist and Union army veteran of the American Civil War. Lilly served as the company president until his death in 1898.


title: Eli Lilly and Company

text: In 1869, after working for drugstores in Indiana, Lilly became a partner in a Paris, Illinois, drugstore with James W. Binford. In 1873, Lilly left the partnership with Binford and returned to Indianapolis. In 1874, Lilly partnered with John F. Johnston and opened a drug manufacturing operation called Johnston and Lilly, but dissolved the partnership in 1876. Lilly used his share of the assets to open his own pharmaceutical manufacturing business in Indianapolis in May 1876. His new business venture became Eli Lilly and Company.


title: Eli Lilly and Company

text: On 10 May 1876, Lilly opened his own laboratory in Indianapolis, where he began to manufacture medicinal drugs. The sign outside, above the shop's door, read: "Eli Lilly, Chemist." Lilly began his manufacturing venture with three employees including Lilly's son, Josiah (J. K.).


title: Eli Lilly and Company

text: One of the first medicines that Lilly produced was quinine, a drug used to treat malaria. By the end of 1876, sales reached $4,470. By 1879, the company had grown to $48,000. In 1878, Lilly hired his brother, James, as his first full-time salesman and the subsequent sales team marketed the company's drugs nationally.


title: Eli Lilly and Company

text: The company moved from Pearl Street to larger quarters at 36 South Meridian Street. In 1881, the company moved to its headquarters in Indianapolis's south-side industrial area. Lilly later purchased additional facilities for research and production.


title: Eli Lilly and Company

text: Lilly's first innovation was gelatin-coating for pills and capsules. The company's other early innovations included fruit flavorings and sugarcoated pills, which made the medicines easier to swallow.


title: Eli Lilly and Company

text: In 1881, Lilly formally incorporated the business as Eli Lilly and Company, elected a board of directors, and issued stock to family members and close associates. Colonel Lilly's only son, Josiah (J. K.), a pharmaceutical chemist, graduated from the Philadelphia College of Pharmacy in 1882, and joined the family business as a superintendent of its laboratory after college. J. K. became company president in 1898.


title: Eli Lilly and Company

text: In 1883 the company contracted to mix and sell Succus Alteran, its first widely successful product and one its best sellers. The product was marketed as a "blood purifier" and as a treatment for syphilis, some types of rheumatism, and skin diseases such as eczema and psoriasis. Sales from this product provided funds for Lilly to expand its manufacturing and research facilities. By the late 1880s, Colonel Lilly was one of the Indianapolis area's leading businessmen, whose company had more than one-hundred employees and had $200,000 ($ in 2015 chained dollars) in annual sales.


title: Eli Lilly and Company

text: As the Lilly company grew, other businesses set up operations near the plant on Indianapolis's near south side. The area developed into one of the city's major business and industrial hubs. Lilly's production, manufacturing, research, and administrative operations in Indianapolis eventually occupied a complex of more than two dozen buildings covering a fifteen-block area, as well as production plants along Kentucky Avenue.


title: Eli Lilly and Company

text: Around 1890, Colonel Lilly turned over the day-to-day management of the business to his son, J. K., who ran the company for thirty-four years. Although the 1890s were a tumultuous decade economically, the company flourished and came out stronger than ever. In 1894 Lilly purchased a manufacturing plant to be used solely for creating capsules. The company also made several technological advances in the manufacturing process, including automating its capsule production. Over the next few years the company annually created tens of millions of capsules and pills.


title: Eli Lilly and Company

text: Until the turn of the century, Lilly operated in Indianapolis and the surrounding area as many other pharmaceutical businesses did—manufacturing and selling "sugar-coated pills, fluid extracts, elixirs, and syrups". The company used plants for its raw materials and produced its products by hand. One historian noted, "Although the Indianapolis firm was more careful in making and promoting drugs than the patent medicine men of the era, the company remained ambivalent about scientific research."


title: Eli Lilly and Company

text: In addition to Colonel Lilly, his brother, James, and son, Josiah (J. K.), the growing company employed other Lilly family. Colonel Lilly's cousin, Evan Lilly, was hired as a bookkeeper. As young boys, Lilly's grandsons, Eli and Josiah Jr. (Joe), ran errands and performed other odd jobs. Eli and Joe joined the family business after college. Eventually, each grandson served as company president and chairman of the board.


title: Eli Lilly and Company

text: Josiah (J. K.), Colonel Lilly's son and Eli and Joe's father, inherited the company after Colonel Lilly died and became its president in 1898. At the time of Colonel Lilly's death the company had a product line of 2,005 items and annual sales of more than $300,000 ($ in 2015 chained dollars). Colonel Lilly was a pioneer in the modern pharmaceutical industry, with many of his early innovations later becoming standard practice. His ethical reforms in a trade that was marked by outlandish claims of miracle medicines began a period of rapid advancement in the development of medicinal drugs. J. K. Lilly continued to advocate for federal regulation on medicines. Under J. K.'s leadership, the company introduced scientific management concepts, organized the company's research department, increased its sales force, and began international distribution of its products. In addition J. K. oversaw a large expansion of the company. By 1905 the company reached sales of $1 million ($ in 2015 chained dollars).


title: Eli Lilly and Company

text: Just before and after World War I, the Eli Lilly and Company experienced rapid change. Expansion of Lilly's manufacturing facilities at the McCarty Street plant improved production capacity with a new Science Building (Building 14), opened in 1911, and a new capsule plant (Building 15) in 1913. The company also began constructions of the Lilly Biological Laboratories, a research and manufacturing plant on 150 acres near Greenfield, Indiana, in 1913.


title: Eli Lilly and Company

text: In addition to development of new medicines, the company achieved several technological advances, including automation of its production facilities. Lilly was also an innovator in pill capsule manufacturing. It was among the first manufacturers to insert medications into empty gelatin capsules, which provided a more exact dosage. Lilly manufactured capsules for its own needs and sold its excess capacity to others. A 1917 "Scientific American" article claimed the Lilly operation in Indianapolis was "the largest capsule factory in the world" and was "capable of producing 2.5 million capsules a day". One of Lilly's innovations was fruit flavoring for medicines and sugar-coated pills to make their medicines easier to swallow. Over the next few years the company began to create tens of millions of capsules and pills annually.


title: Eli Lilly and Company

text: Other advances improved plant efficiency and eliminated production errors. Eli Lilly, grandson of the company founder, introduced a method for blueprinting manufacturing tickets in 1909. This process, which created multiples copies of a drug formula, helped eliminate manufacturing and transcription errors. In the 1920s Eli introduced the new concept of straight-line production, where raw materials entered at one end of the facility and the finished product came out the other end, in the company's manufacturing process. Under Eli's supervision, the design for Building 22, a new 5-floor plant that opened in Indianapolis in 1926, implemented the straight-line concept to improve production efficiency and lower production costs. One historian noted, "It was probably the most sophisticated production system in the American pharmaceutical industry." This more efficient manufacturing process also allowed the company to hire a regular workforce. Instead of recalling workers at peak times and laying them off when production demand fell, Lilly's regular workforce produced less-costly medicines in off-peak times using the same manufacturing facilities.


title: Eli Lilly and Company

text: During the 1920s the introduction of new products also brought the company financial success. In 1919 Josiah hired biochemist George Henry Alexander Clowes as director of biochemical research.


title: Eli Lilly and Company

text: In 1921 three University of Toronto scientists, J. J. R. Macleod, Frederick G. Banting, and Charles H. Best, were working on the development of insulin for treatment of diabetes. Clowes proposed a collaboration with the researchers in December 1921, then again March and May 1922. The researchers were hesitant to work with a commercial drug firm, particularly since they had the Connaught Laboratories' non-commercial facilities at hand. Nonetheless, as limits were reached at the scale to which Connaught could produce insulin, Clowes and Eli Lilly met with the researchers in 1922 to negotiate an agreement with the University of Toronto scientists to mass-produce insulin. The collaboration greatly accelerated the large-scale production of the extract.


title: Eli Lilly and Company

text: In 1923, Lilly began selling Iletin (Insulin, Lilly), their tradename for the first commercially available insulin product in the U.S for the treatment of diabetes. Numerous objections were registered by the Insulin Committee of the University of Toronto in regard to Lilly's use of the term "Iletin", although production continued under this name and the objection was later dropped "as a concession".


title: Eli Lilly and Company

text: Banting and Macleod won a Nobel Prize in 1923 for their research, which they subsequently shared with co-discoverers Charles Best and James Collip. Insulin, "the most important drug" in the company's history, did "more than any other" to make Lilly "one of the major pharmaceutical manufacturers in the world." Eli Lilly and Company enjoyed effective monopoly on the sale of insulin in the U.S. for almost two years, until the first of the new American licensees, Frederick Stearns & Co., entered the market in June 1924.


title: Eli Lilly and Company

text: The success of insulin enabled the company to attract well-respected scientists and, with them, make more medical advances. By its fiftieth anniversary in 1926 sales reached $9 million and the company produced more than 2,800 different items.


title: Eli Lilly and Company

text: In 1928, Lilly introduced Liver Extract 343 for the treatment of pernicious anemia, a blood disorder, in a joint venture with two Harvard University scientists, George R. Minot and William P. Murphy. In 1930, Lilly introduced Liver Extract No. 55 in collaboration with George Whipple, a University of Rochester scientist. Minot, Murphy, and Whipple won the 1934 Nobel Prize in medicine for their research.


title: Eli Lilly and Company

text: Despite the economic challenges of the Great Depression, Lilly's sales rose to $13 million in 1932. That same year Eli Lilly, the eldest grandson of Col. Lilly, was named as the company's president to succeed his father, who remained as chairman of the board until 1948. Eli joined the family business in 1909. In his early years at the company Eli was especially interested in improving production efficiency and introduced a number of labor-saving devices. He also introduced scientific management principles and implemented cost-savings measures that modernized the company. In addition Eli was involved in expanding the company's research efforts and collaborations with university researchers.


title: Eli Lilly and Company

text: In 1934, the firm opened two new facilities on the McCarty Street complex: a replica of Lilly's 1876 laboratory and the new Lilly Research Laboratories, "one of the most fully equipped facilities in the world." In the 1930s the company also continued expansion overseas. In 1934, Eli Lilly and Company Limited, the company's first overseas subsidiary was established in England, with headquarters in London and a manufacturing plant in Basingstoke.


title: Eli Lilly and Company

text: World War II brought production at Lilly to a new high with the manufacturing of Merthiolate and penicillin. During the war Lilly also cooperated with the American Red Cross to process blood plasma and by war's end the company had dried over two million pints of blood, "about 20 percent of the United States' total". Merthiolate, first introduced in 1930, was an "anticeptic and germicide" that became a U.S. army "standard issue" during World War II. In the early 1940s Lilly became one of the companies mass-producing penicillin.


title: Eli Lilly and Company

text: International operations expanded even further during World War II. Eli Lilly International Corp. was formed in 1943 as a subsidiary to encourage business trade abroad. By 1948 Lilly employees worked in thirty-five countries, most of them as sales representatives in Latin America, Asia, and Africa.


title: Eli Lilly and Company

text: At the end of World War II the company continued to grow. In 1945, Lilly began a major expansion effort that would include two manufacturing operations in Indianapolis. The company purchased the massive Curtiss-Wright propeller plant on South Kentucky Avenue, west of the company's McCarty Street operation. When renovation was completed in mid-1947, the Kentucky Avenue location manufactured antibiotics and capsules and housed the company's shipping department. By 1948 Lilly employed nearly 7,000 people.


title: Eli Lilly and Company

text: Eli Lilly, who had served as the company's president since 1932, retired from active management of the company in 1948, became chairman of the board, and relinquished the presidency to his brother, Josiah K. Lilly, Jr. (Joe). During Eli's sixteen-year presidency sales rose from $13 million in 1932 to $117 million in 1948. Joe joined the company in 1914 and concentrated on the company's personnel and marketing efforts. He served as company president from 1948 to 1953, then became chairman of the board and remained in that capacity until his death in 1966.


title: Eli Lilly and Company

text: In 1952 the company offered its first public shares of stock. In 1953, Eugene N. Beesley was named the company's new president, the first non-family member to run the company.


title: Eli Lilly and Company

text: Over the next several decades Lilly continued to develop and introduce new drugs to the marketplace. In the 1950s, Lilly introduced two new antibiotics: vancomycin and erythromycin. In addition Lilly was heavily involved in production and distribution of Jonas Salk's poliomyelitis (polio) vaccine.


title: Eli Lilly and Company

text: In 1954, the National Foundation for Infantile Paralysis (NFIP) contracted with five pharmaceutical companies to produce Salk's polio vaccine for clinical trials. These included Lilly as well as Parke, Davis and Company, Cutter Laboratories, Wyeth Laboratories, and Pitman-Moore Company. Lilly's selection to produce the vaccine was, in part, due to its previous experience in collaborations with university researchers. Lilly manufactured 60 percent of the Salk vaccine in 1955.


title: Eli Lilly and Company

text: During the mid-twentieth century Lilly continued to expand its production facilities outside of Indianapolis. In 1950, Lilly began Tippecanoe Laboratories in Lafayette, Indiana, and increased antibiotic production with its patent on erythromycin. In 1954, Lilly formed Elanco Products Company, named after its parent company, for the production of veterinary pharmaceuticals.


title: Eli Lilly and Company

text: After a company reorganization and transition to non-family management in 1953, Lilly continued to expand its global presence. In the 1960s Lilly operated thirteen affiliate companies outside the United States. In 1962, with an acquisition from Distillers Company, the company established a major factory in Liverpool, England. In 1968, Lilly built its first research facility, the Lilly Research Centre Limited, outside the United States near London, England in Surrey.


title: Eli Lilly and Company

text: During the 1970s and 1980s, Eli Lilly and Company saw a flurry of drug production: an antibiotic, Keflex, in 1971; a heart drug, Dobutrex, in 1977; Ceclor, which would become the world's top selling oral antibiotic, in 1979; a leukemia drug, Eldisine; an antiarthritic, Oraflex; and an analgesic, Darvon. When generic drugs flooded the marketplace after the expiration of patents for drugs discovered in the 1950s and 1960s, Lilly diversified into other areas, most notably agricultural chemicals, animal-health products, cosmetics, and medical instruments.


title: Eli Lilly and Company

text: To further diversify its product line, Lilly made an uncharacteristic, but ultimately profitable move in 1971, when it bought cosmetic manufacturer Elizabeth Arden, Inc. for $38 million. Although the subsidiary continued to lose money for five years after Lilly acquired it, executive management changes at Arden helped turn it into a financial success. By 1982 the subsidiary's "sales were up 90 percent from 1978, with profits doubling to nearly $30 million." Sixteen years after its acquisition, Lilly sold Arden to Fabergé in 1987 for $657 million.


title: Eli Lilly and Company

text: In 1977, Lilly ventured into medical instruments with the acquisition of IVAC Corporation, which manufactures vital signs and intravenous fluid infusion monitoring systems. Lilly also purchased Cardiac Pacemakers Incorporated, a manufacturer of heart pacemakers in 1977. In 1980, Lilly acquired Physio-Control Corporation. Other acquisitions included Advance Cardiovasular Systems Incorporated in 1984, Hybritech in 1986, and Devices for Vascular Intervention, Incorporated in 1989. Lilly acquired Pacific Biotech in 1990 and Origin Medsystems and Heart Rhythm Technologies, Incorporated in 1992. In the early 1990s, Lilly combined these medical equipment companies into a Medical Devices and Diagnostics Division that "contributed about 20 percent" of Lilly's annual revenues.


title: Eli Lilly and Company

text: In 1989, a joint agri-chemical venture between Elanco Products Company and Dow Chemical created DowElanco. In 1997, Lilly sold its 40% share in the company to Dow Chemical for $1.2 billion and the name was changed to Dow AgroSciences.


title: Eli Lilly and Company

text: In 1994, Lilly acquired PCS Systems, a drug delivery business for Health Maintenance Organizations, and later added two similar organizations to its holdings. Lilly purchased PCS, which was the largest U.S. prescription drug benefits manager at the time, for $4 billion.


title: Eli Lilly and Company

text: In 1991, Vaughn Bryson was named CEO of Eli Lilly and Company. During his 20-month tenure, the company reported its first quarterly loss as a publicly traded company. In 1993, Randall L. Tobias, a vice-chairman of AT&T Corporation and Lilly board member, was named Lilly's chairman, president, and CEO after "product and competitive pressures" had "steadily eroded Lilly's stock price since early 1992." Tobias was the first president and CEO recruited from outside of the company. Under Tobias's leadership the company "cut costs and narrowed its mission". Lilly sold companies in its Medical Device and Diagnostics Division, expanded international sales, made new acquisitions, and funded additional research and product development. Sidney Taurel, former chief operating officer of Lilly, was named CEO in 1998, replacing Tobias. Taurel was named chairman in January 1999. In 2000, Lilly reported $10.86 billion in net sales.


title: Eli Lilly and Company

text: In 1998, Lilly formed a joint venture with Icos Corporation (ICOS), a Bothell, Washington-based biotechnology company, to develop and commercialize Cialis, a product for the treatment of erectile dysfunction. In October 2006, Lilly announced its intention to acquire Icos for $2.1 billion, or $32 per share. After its initial attempt to acquire Icos failed under pressure from large institutional shareholders, Lilly revised its offer to $34 per share. Institutional Shareholder Services (ISS), a proxy advisory firm, advised Icos shareholders to reject the proposal as undervalued, but the buyout was approved by Icos shareholders and Lilly completed its acquisition of the company on 29 January 2007. Lilly closed Icos manufacturing operations, terminated nearly 500 Icos employees, and left 127 employees working at the biologics facility. In December 2007, CMC Biopharmaceuticals A/S (CMC), a Copenhagen, Denmark-based provider of contract biomanufacturing services, bought the Bothell-based biologics facility from Lilly and retained the existing 127 employees.


title: Eli Lilly and Company

text: In January 2009, the largest criminal fine in U.S. history, totaling $1.415 billion was imposed on Lilly for illegal marketing of its best-selling product, the atypical antipsychotic medication, Zyprexa.


title: Eli Lilly and Company

text: In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced their global agreement for the joint development and marketing of new APIs for diabetes therapy. Lilly could receive more than $1 billion for their work on the project, while Boehringer Ingelheim could receive more than $800 million from development of the new drugs. Oral anti-diabetic of Boehringer Ingelheim–Linagliptin and BI 10773–and two insulin analogs of Lilly–LY2605541 and LY2963016–were in phase II and III of clinical developmentat that time.


title: Eli Lilly and Company

text: In April 2014, Lilly announced plans to buy Swiss drugmaker Novartis AG's animal health business for $5.4 billion in cash to strengthen and diversify its Elanco unit. Lilly said it planned to fund the deal with about $3.4 billion of cash on hand and $2 billion of loans. As a condition of the acquisition, the Sentinel heartworm treatment would be divested to Virbac in order to avoid a monopoly in a subsector of the heartworm (Dirofilaria immitis) treatment market.


title: Eli Lilly and Company

text: In March 2015, the company announced it would join Hanmi Pharmaceutical in developing and commercialising Hanmi's phase I Bruton's tyrosine kinase inhibitor HM71224 in a deal which could yield $690 million. A day later the company announced another deal with China's Innovent Biologics to co-develop and commercialize at least three of Innovent's treatments over the next decade, in a deal which could generate up to $456 million; the collaboration was subsequently expanded in 2022, according to Innovent. As part of the deal the company will contribute its c-Met monoclonal antibody whilst Innovent will contribute a monoclonal antibody which targets CD-20. The second compound from Innovent is a preclinical immuno-oncology molecule. The following week the company announced it would restart its collaboration with Pfizer surrounding the Phase III trial of Tanezumab. Pfizer is expected to receive an upfront sum of $200 million from the company. In April 2015, the company engaged CBRE Group to sell its biomanufacturing facility in Vacaville, California. The facility resides on a campus and is one of the largest biopharmaceutical manufacturing centers in the United States.


title: Eli Lilly and Company

text: In January 2017, Elanco Animal Health, a subsidiary of the company completed the acquisition of Boehringer Ingelheim Vetmedica, Inc's (a subsidiary of Boehringer Ingelheim) US feline, canine and rabies vaccines portfolio.


title: Eli Lilly and Company

text: In March 2017, the company acquired CoLucid Pharmaceuticals for $960 million, specifically gaining the late clinical-stage migraine therapy candidate, lasmiditan.


title: Eli Lilly and Company

text: In August 2017, Lilly and Shionogi jointly licensed their product varespladib to Ophirex for the latter's novel snakebite treatment program.


title: Eli Lilly and Company

text: In May 2018, the company acquired Armo Biosciences for $1.6 billion. Days later the company announced it would acquire Aurora kinase A inhibitor developer - AurKa Pharma - and control over the lead compound, AK-01, for up to $575 million.


title: Eli Lilly and Company

text: In January 2019, Lilly announced it would acquire Loxo Oncology for $235 per share - valuing the business at around $8 billion - significantly expanding the business' oncology offerings. The deal would give Lilly Loxo's oral TRK inhibitor, Vitrakvi (larotrectinib), LOXO-292, an oral proto-oncogene receptor tyrosine kinase rearranged during transfection (RET) inhibitor, LOXO-305, an oral Bruton's tyrosine kinase (BTK) inhibitor and LOXO-195, a follow-on TRK inhibitor. In August 2019, Elanco acquired the Bayer animal health business for $7.6 billion.


title: Eli Lilly and Company

text: In January 2020, the company announced its acquisition of Dermira for $1.1 billion, gaining control of two key assets, among others; lebrikizumab and glycopyrronium cloth used to treat hyperhidrosis. In June 2020, the company announced it had begun the world's first study of a potential monoclonal antibody treatment for COVID-19, with a Phase 1 trial of LY-CoV555, in collaboration with Vancouver-based company AbCellera. By August 2020, the challenging aspects of running a clinical trial in a long-term care facility during a pandemic prompted Lilly to create the first of many customized recreational vehicles into mobile research units (MRU) to meet people were they were and support mobile labs and clinical trial material preparation. A trailer truck could escort the MRU with supplies to create an on-site infusion clinic. Lilly deployed the mobile research unit fleet in response to outbreaks of the virus at long-term care facilities across the U.S. In September 2020, Amgen announced that they had partnered with Eli Lilly to manufacture their COVID-19 antibody therapies.


title: Eli Lilly and Company

text: On 7 October 2020, Lilly announced that its cocktail was effective and that it had filed with the Food and Drug Administration for an emergency use authorization (EUA). This was the same day that rival company Regeneron also filed for an EUA for its own monoclonal antibody treatment. In October 2020, Lilly announced it would acquire Disarm Therapeutics at its experimental treatments for axonal degeneration, via SARM1 inhibitors, for $135 million (plus a further $1.225 billion based on regulatory and commercial milestones). In October 2020, Lilly announced that the National Institutes of Health (NIH) ACTIV-3 clinical trial evaluating its monoclonal antibody, bamlanivimab (LYCoV555), found that bamlanivimab was not effective in treating people hospitalized with COVID-19, however data showed bamlanivimab might have been effective in treating COVID-19 by reducing viral load, symptoms and the risk of hospitalization in outpatients. Other studies, including the NIH ACTIV-2 trial and its own BLAZE-1 trial, continued to evaluate bamlanivimab. In November 2020, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the investigational monoclonal antibody therapy bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients. In December 2020, Lilly announced it would acquire Prevail Therapeutics Inc for $1 billion, boosting its pipeline in neurodegenerative disease gene therapies.


title: Eli Lilly and Company

text: On 16 April 2021, the FDA revoked the emergency use authorization (EUA) that allowed and signaled FDA agreement for the investigational monoclonal antibody therapy bamlanivimab, when administered alone, to be used for the treatment of mild-to-moderate COVID-19 in adults and certain pediatric patients. 18 May 2021, the FDA had accepted Lilly's application for Tyvyt (sintilimab), in combination with Lilly's own Alimta (pemetrexed) and platinum chemotherapy for newly diagnosed nonsquamous non-small cell lung cancer. In July 2021, the company announced it would acquire Protomer Technologies for more than $1 billion.


title: Eli Lilly and Company

text: In 2022, distribution of Lilly's COVID-19 antibody drug was paused due to lack of efficacy against the emerging omicron variant. A second COVID-19 monoclonal antibody therapy (bebtelovimab) developed with AbCellera was given Emergency Use Authorization in February 2022, with the U.S. Government committing to a $720 million purchase of up to 600,000 doses. In October, the business announced it would acquire Akouos Inc. for $487 million upfront (a further $123 million deferred). On November 10, after a verified Twitter account posing as Eli Lilly and Co. posted a tweet saying that insulin would now be free, the company lost $15 billion in valuation, after which the company rejected the veracity of the claims.


title: Eli Lilly and Company

text: The company's 2023 research and development focus has been reported to be on drugs in the obesity, diabetes, Alzheimer's and autoimmune areas.


title: Eli Lilly and Company

text: Eli Lilly and Company has a long history of collaboration with research scientists. In 1886 Ernest G. Eberhardt, a chemist, joined the company as its first full-time research scientist. Lilly also hired two botanists, Walter H. Evans and John S. Wright, to join its early research efforts. After World War I the company's expanded production facilities and introduction of new management methods set the stage for Lilly's next crucial phase—its "aggressive entry into scientific research and development." The first big step came in 1919 when Josiah Lilly hired biochemist George Henry Alexander Clowes as director of biochemical research. Clowes had extensive medical research expertise and links to the scientific research community, which led to the company's collaborations with researchers in the U.S. and elsewhere. Clowes's first major collaboration with researchers who developed insulin at the University of Toronto significantly impacted the company's future. Lilly's success with insulin production secured the company's position as a leading research-based pharmaceutical manufacturer, allowing it to attract and hire more research scientists and to collaborate with other universities in additional medical research. In 1934 the company built a new research laboratory in Indianapolis. As part of its research and product development process Lilly also conducted clinical studies at Indianapolis City Hospital (Wishard Memorial Hospital). Lilly continues to conduct clinical studies to test medications before their introduction to the market. In 1949 Eli Lilly actually went into partnership with the United States Army Reserve setting up a local Strategic Intelligence Research and Analysis (SIRA)Unit to allow employees to research company data for the Scientific Logistics and Eurasian fields of study (source: declassified Defense Intelligence Agency document MDR -0191-2008 dated 17 September 2012). In 1998 the company dedicated new laboratories for clinical research at the Indiana University Medical Center in Indianapolis.


title: Eli Lilly and Company

text: In addition to internal research and development activities, Lilly is also involved in publicly funded research projects with other industrial and academic partners. One example in the area of non-clinical safety assessment is the InnoMed PredTox, a collaboration with pharmaceutical companies, research organizations, and the European Commission to improve the safety of drugs. In 2008 this consortium, which included Lilly S.A. (Switzerland), secured an €8 million budget for a 40-month project that was coordinated by the European Federation of Pharmaceutical Industries and Associations (EFPIA), an organization who represents the research-based pharmaceutical industry and biotech companies operating in Europe. In 2008 Lilly's activities included research projects within the framework of the Innovative Medicines Initiative, a public-private research initiative in Europe that is a joint effort of the EFPIA and the European Commission.


title: Eli Lilly and Company

text: The company's most important products introduced prior to World War II included insulin, which Lilly marketed as Iletin (Insulin, Lilly), Amytal, Merthiolate, ephedrine, and liver extracts. Introduced in 1923, Iletin (Insulin, Lilly) was Lilly's first commercial insulin product.


title: Eli Lilly and Company

text: During World War II Lilly produced penicillins and other antibiotics. In addition to penicillin, other wartime production included "antimalarials," blood plasma, encephalitis vaccine, typhus and influenza vaccine, gas gangrene antitoxin, Merthiolate, and Iletin (Insulin, Lilly).


title: Eli Lilly and Company

text: Among the company's more recent pharmaceutical developments are cephalosporin, erythromycin, and Prozac (fluoxetine), a selective serotonin reuptake inhibitor (SSRI) for the treatment of clinical depression. Ceclor, introduced in the 1970s, was an oral cephalosporin antibiotic. Prozac, introduced in the 1980s, quickly became the company's best-selling product for treatment of depression, but Lilly lost its U.S. patent protection for this product in 2001. Among other distinctions, Lilly is the world's largest manufacturer and distributor of medications used in a broad range of psychiatric and mental health-related conditions, including clinical depression, generalized anxiety disorder, narcotic addiction, insomnia, bipolar disorder, schizophrenia, and others.


title: Eli Lilly and Company

text: Eli Lilly has focused on patent-protected medicines, with generic manufacturers taking over production of earlier drugs whose patents have expired.


title: Eli Lilly and Company

text: In 2003, Eli Lilly introduced Cialis (tadalafil), a competitor to Pfizer's blockbuster Viagra for erectile dysfunction. Cialis maintains an active period of 36 hours, causing it sometimes to be dubbed the "weekend pill". Cialis was developed in a partnership with biotechnology company Icos Corporation. On 18 December 2006, Lilly bought Icos in order to gain full control of the product.


title: Eli Lilly and Company

text: Another Lilly manufactured anti-depressant, Cymbalta, a serotonin-norepinephrine reuptake inhibitor used predominantly in the treatment of major depressive disorders and generalized anxiety disorder, ranks with Prozac as one of the most financially successful pharmaceuticals in industry history. It is also used in the treatment of fibromyalgia, neuropathy, chronic pain and osteoarthritis.


title: Eli Lilly and Company

text: In 1996, the U.S. Food and Drug Administration approved Gemzar for the treatment of pancreatic cancer. Gemzar is commonly used in the treatment of pancreatic cancer, usually in coordination with 5-FU chemotherapy and radiation therapy. Gemzar also is routinely used in the treatment of non-small cell lung cancer.


title: Eli Lilly and Company

text: Eli Lilly was the first distributor of methadone in the United States, an analgesic used frequently in the treatment of heroin, opium and other opioid and narcotic drug addictions. Eli Lilly was able to acquire the right to produce the drug commercially for just $1 because the patent rights of the original patent holders, IG Farben and Farbwerke Hoechst, were not protected after the Allies of World War II seized all German patents, research records and trade names. Eli Lilly introduced the drug to the United States in 1947, marketed under the trade name "Dolophine".


title: Eli Lilly and Company

text: Prozac was one of the first therapies in its class to treat clinical depression by blocking the uptake of serotonin within the human brain. Prozac was approved by the U.S. FDA in 1987 for use in treating depression, with generic versions appearing after 2002.


title: Eli Lilly and Company

text: Eli Lilly has manufactured Secobarbital, a barbiturate derivative with anaesthetic, anticonvulsant, sedative and hypnotic properties. Lilly marketed Secobarbital under the brand name Seconal. Secobarbital is indicated for the treatment of epilepsy, temporary insomnia and as a pre-operative medication to produce anaesthesia and anxiolysis in short surgical, diagnostic, or therapeutic procedures which are minimally painful. With the onset of new therapies for the treatment of these conditions, Secobarbital has been less utilized, and Lilly ceased manufacturing it in 1999.


title: Eli Lilly and Company

text: Secobarbital gained considerable attention during the 1970s, when it gained wide popularity as a recreational drug. On 18 September 1970, rock guitarist legend Jimi Hendrix died from a secobarbital overdose. On 22 June 1969, secobarbital overdose was the cause of death of actress Judy Garland. The drug was a central part of the plot of the hugely popular novel "Valley of the Dolls" (1966) by Jacqueline Susann in which three highly successful Hollywood women each fall victim, in various ways, to the drug. The novel was later released as a film by the same name.


title: Eli Lilly and Company

text: Eli Lilly has developed the vaccine preservative thiomersal (also called merthiolate and thimerosal). Thiomersal is effective by causing susceptible bacteria to autolyze. Launched in 1930, merthiolate was a mercury-based antiseptic and germicide that "had been formulated at the University of Maryland with support of a Lilly research fellowship." In November 2002, congressional Republicans inserted a provision into a domestic security bill that President George W. Bush signed into a law, protecting Eli Lilly from all suits in the federal courts, alleging that the drug, Thiomersal caused autism and other neurological disorders in children, such that all such matters be heard by a special master appointed for the purpose, rather than regular federal courts. Its toxicology was that it metabolized into ethylmercury (C2H5Hg+) and thiosalicylate, in the body, which was immensely hazardous to developing countries like India.


title: Eli Lilly and Company

text: Zyprexa (Olanzapine) (for schizophrenia and bipolar disorder, as well as off-label uses) Released in 1996, (see Illegal marketing of Zyprexa) it was the company's best selling drug through 2010, when the patent expired.


title: Eli Lilly and Company

text: After three generations of Lilly family leadership under company founder, Col. Eli Lilly, his son, Josiah K. Lilly Sr., and two grandsons, Eli Lilly Jr. and Josiah K. Lilly Jr., the company announced a reorganization in 1944 that prepared the way for future expansion and the eventual separation of company management from its ownership. The large, complex corporation was divided into smaller groups headed by vice presidents and in 1953 Eugene N. Beesley was named the first non-family member to become the company's president.


title: Eli Lilly and Company

text: Although Lilly family members continued to serve as chairman of the board until 1969, Beesley's appointment began the transition to non-family management. In 1972 Richard Donald Wood became Lilly's president and CEO after the retirement of Burton E. Beck. In 1991 Vaughn Bryson became president and CEO and Wood became board chairman. During Bryson's 20-month tenure as Lilly's president and CEO, the company reported its first quarterly loss as a publicly traded company.


title: Eli Lilly and Company

text: Randall L. Tobias, a vice chairman of AT&T Corporation, was named chairman, president, and CEO in June 1993. Tobias, a Lilly board member since 1986, was recruited from outside the company's executive ranks first to replace Lilly's president and CEO, Vaughn Bryson, at Bryson's predecessor and then board chairman Richard Wood's urging and then, in short order, also Wood. Tobias later became the U.S. director of Foreign Assistance and administrator of the U.S. Agency for International Development (USAID), with the rank of ambassador.


title: Eli Lilly and Company

text: Sidney Taurel, former chief operating officer of Lilly, was named CEO in July 1998 to replace Tobias, who retired. Taurel became chairman of the board in January 1999. Taurel retired as CEO on 31 March 2008, but remained as chairman of the board until 31 December 2008. John C. Lechleiter was elected as Lilly's CEO and president, effective 1 April 2008. Lechleiter had served as Lilly's president and chief operating officer since October 2005.


title: Eli Lilly and Company

text: The Lilly family as well as Eli Lilly and Company has a long history of community service. Around 1890 Col. Lilly turned over operation of the family business to his son, Josiah, who ran the company for the next several decades. Col. Lilly remained active in civic affairs and assisted a number of local organizations, including the Commercial Club of Indianapolis, which later became the Indianapolis Chamber of Commerce, and the Charity Organization Society, a forerunner to the Family Services Association of Central Indiana, an organization supported by United Way. Josiah's sons, Eli and Joe, were also philanthropists who supported numerous cultural and educational organizations.


title: Eli Lilly and Company

text: Josiah Sr. continued his father's civic mindedness and began the company tradition of sending aid to disaster victims. Following the 1906 San Francisco earthquake, the company sent much needed medicine to support recovery efforts and provided relief after the 1936 Johnstown Flood.


title: Eli Lilly and Company

text: In 1917, Lilly Field Hospital 32, named in Josiah's honor, was equipped in Indianapolis and moved overseas to Contrexville, France, during World War I, where it remained in operation until 1919. Throughout World War II, Lilly manufactured more than two hundred products for military use, including aviator survival kits and seasickness medications for the D-Day invasion. In addition Lilly dried more than two million pints of blood plasma by the war's end.


title: Eli Lilly and Company

text: In 1937, Josiah K. Lilly Sr. and his two sons, Eli and Joe, founded the Lilly Endowment, a private charitable foundation, with gifts of Lilly stock. The endowment still owns 11.3% of the company.


title: Eli Lilly and Company

text: The Eli Lilly and Company Foundation, which is separate from the Lilly Endowment, operates as a tax-exempt private charitable foundation that the company established in 1968. The Foundation is funded through Lilly's corporate profits.


title: Eli Lilly and Company

text: In August 2008, Eli Lilly purchased the right to manufacture bovine growth hormone, used to increase milk production in dairy cattle, from Monsanto. Use of the supplement has become controversial due to the animal ethics and human health concerns.


title: Eli Lilly and Company

text: In 2021 Eli Lilly filed a court motion against in response to an advisory opinion of the Department of Health and Human Services indicating that Eli Lilly and other drug manufacturers must continue to offer reduced pricing to covered outpatient drugs through pharmacies contracted to hospitals rather than only to the hospitals themselves.


title: Eli Lilly and Company

text: On 14 September 1989, Joseph T. Wesbecker killed eight people and injured twelve before committing suicide. His relatives and victims blamed his actions on the Prozac medication he had begun taking a month prior. The incident set off a chain of lawsuits and public outcries. Lawyers began using Prozac to justify the abnormal behaviors of their clients. Eli Lilly was accused of not doing enough to warn patients and doctors about the adverse effects, which it had described as "activation", years prior to the incident. The link between suicide and antidepressants remains a subject of public and academic dispute.


title: Eli Lilly and Company

text: In October 2004, the FDA added a black box warning to all antidepressant drugs regarding use in children. In 2006, the FDA included adults aged 25 or younger. In February 2018, the FDA ordered an update to the warnings based on statistical evidence from twenty-four trials in which the risk of such events increased from two percent to four percent relative to the placebo trials.


title: Eli Lilly and Company

text: Eli Lilly has faced many lawsuits from people who claimed they developed diabetes or other diseases after taking olanzapine (branded Zyprexa), an antipsychotic medication, as well as by various governmental entities, insurance companies, and others. Internal documents provided to The New York Times revealed that Lilly had downplayed the risks of Zyprexa. According to the documents, 16 percent of people taking Zyprexa gained more than 66 pounds in their first year, a much larger figure than Eli Lilly had shared with doctors. In 2006, Lilly paid $700 million to settle around 8,000 of these lawsuits, and in early 2007, Lilly settled around 18,000 suits for $500 million, which brought the total Lilly had paid to settle suits related to the drug to $1.2 billion.


title: Eli Lilly and Company

text: In March 2008, Lilly settled a suit with the state of Alaska, and in October 2008, Lilly agreed to pay $62 million to 32 states and the District of Columbia to settle suits brought under state consumer protection laws. In 2009, four sales representatives for Eli Lilly filed separate qui tam lawsuits against the company for illegally marketing Zyprexa for uses not approved by the Food and Drug Administration.


title: Eli Lilly and Company

text: Eli Lilly pleaded guilty to a US federal criminal misdemeanor charge of illegally marketing Zyprexa, actively promoting the drug for off-label uses, particularly for the treatment of dementia in the elderly. The $1.415 billion penalty included an $800 million civil settlement, a $515 million criminal fine, and forfeit assets of $100 million. The US Justice Department said the criminal fine of $515 million was the largest ever in a healthcare case and the largest criminal fine for an individual corporation ever imposed in a US criminal prosecution of any kind. "That was a blemish for us," John C. Lechleiter, CEO of Lilly, said. "We don't ever want that to happen again. We put measures in place to assure that not only do we have the right intentions in integrity and compliance, but we have systems in place to support that." In an internal email, Lechleiter had stated "we must seize the opportunity to expand our work with Zyprexa in this same child-adolescent population" for off-label use.