Early life and education.

Family background.

Chirac was born in the 5th arrondissement of Paris. He was the son of Abel François Marie Chirac (1898–1968), a successful executive for an aircraft company, and Marie-Louise Valette (1902–1973), a housewife. His great-grandparents on both sides were peasants in the rural south-western region of the Corrèze. His grandparents were teachers from Sainte-Féréole in Corrèze. According to Chirac, his name "originates

Education and early career.

Inspired by Charles de Gaulle, Chirac started to pursue a civil service career in the 1950s. During this period, he joined the French Communist Party, sold copies of "L'Humanité", and took part in meetings of a communist cell. In 1950, he signed the Soviet-inspired Stockholm Appeal for the abolition of nuclear weapons – which led him to be questioned when he applied for his first visa to the United States.

Early political career.

The "Bulldozer": 1962–1971.

In April 1962, Chirac was appointed head of the personal staff of Prime Minister Georges Pompidou. This appointment launched Chirac's political career. Pompidou considered Chirac his protégé, and referred to him as "my bulldozer" for his skill at getting things done. The nickname "Le Bulldozer" caught on in French political circles, where it also referred to his abrasive manner. As late as the 1988 presidential election, Chirac maintained this reputation.  At Pompidou's suggestion, Chirac ran as a Gaullist for

Cabinet minister: 1971–1974.

After some months in the ministry for Relations with Parliament, Chirac's first high-level post came in 1972 when he became Minister of Agriculture and Rural Development under Pompidou, who had been elected president in 1969, after de Gaulle retired. Chirac quickly earned a reputation as a champion of French farmers' interests, and first attracted international attention when he assailed U.S., West German, and European Commission agricultural policies which conflicted with French interests.  On 27 February 1974, after the resignation of Raymond Marcellin, Chirac was appointed Minister of

Prime Minister of Giscard: 1974–1976.

When Valéry Giscard d'Estaing became president, he nominated Chirac as prime minister on 27 May 1974, to reconcile the "Giscardian" and "non-Giscardian" factions of the parliamentary majority. At the age of 41, Chirac stood out as the very model of the "jeunes loups" ("young wolves") of French politics, but he was faced with the hostility of the "Barons of Gaullism" who considered him a traitor for his role during the previous presidential campaign. In December 1974, he took the lead of the Union of Democrats for the Republic (UDR) against the will of its more senior personalities.  As

Mayor of Paris: 1977–1995.

After his departure from the cabinet, Chirac wanted to gain the leadership of the political right, to gain the French presidency in the future. The RPR was conceived as an electoral machine against President Giscard d'Estaing. Paradoxically, Chirac benefited from Giscard's decision to create the office of mayor in Paris, which had been in abeyance since the 1871 Commune, because the leaders of

Governmental opposition.

Struggle for the right-wing leadership: 1976–1986.

In 1978, Chirac attacked the pro-European policy of Valéry Giscard d'Estaing (VGE), and made a nationalist turn with the December 1978 Call of Cochin, initiated by his counsellors Marie-France Garaud and Pierre Juillet, which had first been called by Pompidou. Hospitalised in Hôpital Cochin after a car crash, he declared that "as always about the drooping of France, the pro-foreign party acts with its peaceable and reassuring voice". He appointed Yvan Blot, an intellectual who would later join the National Front, as director of his campaigns for the 1979 European election. After the poor results of the election, Chirac broke with Garaud and Juillet. Vexed Marie-France Garaud stated: "We thought Chirac was made of the same marble of which statues are carved in, we perceive he's of the same faience bidets are made of." His rivalry with Giscard d'Estaing intensified. Although it has been often interpreted by historians as the struggle between two rival French right-wing families (the Bonapartists, represented by Chirac, and the Orleanists, represented by VGE), both figures in fact were members of the liberal, Orleanist tradition, according to historian Alain-Gérard Slama. But the eviction of the Gaullist barons and of President Giscard d'Estaing convinced Chirac to assume

Prime Minister of Mitterrand: 1986–1988.

When the RPR/UDF right-wing coalition won a slight majority in the National Assembly in the 1986 election, Mitterrand (PS) appointed Chirac prime minister (though many in Mitterrand's inner circle lobbied him to choose Jacques Chaban-Delmas instead). This unprecedented power-sharing arrangement, known as cohabitation, gave Chirac the lead in domestic affairs. However, it is generally conceded that Mitterrand used the areas granted to the President of the Republic, or "reserved domains" of the Presidency, Defence and Foreign Affairs, to belittle his Prime Minister.  Chirac's cabinet sold many public companies, renewing the liberalisation initiated under Laurent Fabius's Socialist government of 1984–1986, and abolished the solidarity tax on wealth (ISF), a symbolic tax on those with high value assets introduced by Mitterrand's government. Elsewhere, the plan for university reform (plan Devaquet) caused a crisis in 1986

Crossing the desert: 1988–1995.

Chirac ran against Mitterrand for a second time in the 1988 election. He obtained 20 percent of the vote in the first round, but lost the second with only 46 percent. He resigned from the cabinet and the right lost the next legislative election.  For the first time, his leadership over the RPR was challenged. Charles Pasqua and Philippe Séguin criticised his abandonment of Gaullist doctrines. On the right, a new generation of politicians, the "renovation men", accused Chirac and Giscard of being responsible for the electoral defeats. In 1992, convinced a candidate could not become President whilst advocating anti-European policies, he called for a "yes" vote in the referendum on the Maastricht Treaty, against the opinion of

Presidency (1995–2007).

First term: 1995–2002.

Juppé ministry.

During the 1995 presidential campaign, Chirac criticised the "sole thought" ("pensée unique") of neoliberalism represented by his challenger on the right and promised to reduce the "social fracture", placing himself more to the centre and thus forcing Balladur to radicalise himself. Ultimately, he obtained more votes than Balladur in the first round (20.8 percent), and then defeated the Socialist candidate Lionel Jospin in the second round (52.6 percent).  Chirac was elected on a platform of tax cuts and job programmes, but his policies did little to ease the labour strikes during his first months in office. On the domestic front, neo-liberal economic austerity measures introduced by Chirac and his conservative prime minister Alain Juppé, including budgetary cutbacks, proved highly unpopular. At about the same time, it became apparent

State responsibility for the roundup of Jews.

Prior to 1995, the French government had maintained that the French Republic had been dismantled when Philippe Pétain instituted a new French State during World War II and that the Republic had been re-established when the war was over. It was not for France, therefore, to apologise for the roundup of Jews for deportation that happened while the Republic had not existed and was carried out by a state, Vichy France, which it did not recognise. President François Mitterrand had reiterated

"Cohabitation" with Jospin.

In 1997, Chirac dissolved parliament for early legislative elections in a gamble designed to bolster support for his conservative economic program. But instead, it created an uproar, and his power was weakened by the subsequent backlash. The Socialist Party (PS), joined by other parties on the left, soundly defeated Chirac's conservative allies, forcing Chirac into a new period of cohabitation with Jospin as prime minister (1997–2002), which lasted five years.  Cohabitation significantly weakened the power of Chirac's presidency. The French president, by a constitutional convention, only controls foreign and military policy— and even then, allocation of funding is under the control of Parliament and under the significant influence of the prime minister. Short of dissolving parliament and calling for new elections, the president was left with little power to influence public policy regarding crime, the economy, and public services. Chirac seized the occasion to periodically criticise Jospin's government.  Nevertheless, his position was weakened by scandals about the financing of RPR by Paris municipality. In 2001, the left, represented

Defence policy.

As the Supreme Commander of the French armed forces, he reduced the military budget, as did his predecessor. At the end of his first term it accounted for three percent of GDP. In 1997 the aircraft carrier "Clemenceau" was decommissioned after 37 years of service, with her sister ship "Foch" decommissioned in 2000 after 37 years of service, leaving the French Navy with no aircraft carrier until 2001, when "Charles de Gaulle" was commissioned. He also reduced expenditure on nuclear

Close call.

On 25 July 2000, as Chirac and the first lady were returning from the G7 Summit in Okinawa, Japan, they were placed in a dangerous situation by Air France Flight 4590 after they landed at Charles de Gaulle International Airport. The first couple were in an Air France Boeing 747 taxiing toward the terminal when the jet had to stop and wait for Flight 4590 to take off. The departing plane, an Aérospatiale-BAC Concorde, ran over a strip of metal on takeoff puncturing its left fuel tank and sliced electrical wires near the left landing gear. The sequence of events ignited a large fire and caused the Concorde to veer left on its takeoff roll. As it reached takeoff speed and lifted off the ground, it came within 30 feet of hitting Chirac's 747. The photograph of Flight 4590 ablaze, the only picture taken of the Concorde on fire, was taken by passenger Toshihiko Sato on Chirac's jetliner.

Second term: 2002–2007.

At the age of 69, Chirac faced his fourth presidential campaign in 2002. He received 20% of the vote in the first ballot of the presidential elections in April 2002. It had been expected that he would face incumbent prime minister Lionel Jospin (PS) in the second round of elections; instead, Chirac faced far-right politician Jean-Marie Le Pen of the National Front (FN), who came in 200,000 votes ahead of Jospin. All parties other than the National Front (except for Lutte ouvrière) called for opposing Le Pen, even if it meant voting for Chirac. The 14-day period between the two rounds of voting was marked by demonstrations against Le Pen and slogans such as "Vote for the crook, not for the fascist" or "Vote with a clothespin on your nose". Chirac won re-election by a landslide, with 82 percent of the vote on the second ballot. However, Chirac became increasingly unpopular during his second term. According to a July 2005 poll, 32 percent judged Chirac favourably and 63 percent unfavorably. In 2006, "The Economist" wrote that Chirac "is the most unpopular occupant of the Elysée Palace in the fifth republic's history."

Early term.

As the left-wing Socialist Party was in thorough disarray following Jospin's defeat, Chirac reorganised politics on the right, establishing a new party – initially called the Union of the Presidential Majority, then the Union for a Popular Movement (UMP). The RPR had broken down; a number of members had formed Eurosceptic breakaways. While the Giscardian liberals of the Union for French Democracy (UDF) had

Assassination attempt.

On 14 July 2002, during Bastille Day celebrations, Chirac survived an assassination attempt by a lone gunman with a rifle hidden in a guitar case.

Foreign policy.

Along with Vladimir Putin (who he called "a personal friend"), Hu Jintao, and Gerhard Schröder, Chirac emerged as a leading voice against George W. Bush and Tony Blair in 2003 during the organisation and deployment of American and British forces participating in a military coalition to forcibly remove the government of Iraq controlled by the Ba'ath Party under the leadership of Saddam Hussein that resulted in the 2003–2011 Iraq War. Despite British and American pressure, Chirac threatened to veto, at that given point, a resolution in the UN Security Council that would authorise the use of military force to rid Iraq of alleged weapons of mass destruction, and rallied other governments to his position. "Iraq today does not represent an immediate threat that justifies an immediate war", Chirac said on 18 March 2003. Future Prime Minister Dominique de Villepin acquired much of his popularity for his speech against the war at the United Nations (UN).  After Togo's leader Gnassingbé Eyadéma's death on 5 February 2005, Chirac gave him tribute and supported his son, Faure Gnassingbé, who has

Flight tax.

Chirac requested the "Landau-report" (published in September 2004) and combined with the "Report of the Technical Group on Innovative Financing Mechanisms" formulated upon request by the Heads of State of

2005 referendum on TCE.

On 29 May 2005, a referendum was held in France to decide whether the country should ratify the proposed treaty for a Constitution of the European Union (TCE). The result was a victory for the No campaign, with 55 percent of voters rejecting the treaty on a turnout of 69

2005 civil unrest and CPE protests.

Following major student protests in spring 2006, which followed civil unrest in autumn 2005 after the death of two young boys in Clichy-sous-Bois, one of the poorest communes in Paris' suburbs, Chirac retracted the

Retirement.

In early September 2005, Chirac suffered an event that his doctors described as a "vascular incident". It was officially reported as a "minor stroke" or a mild stroke (also known as a transient ischemic attack). He recovered and returned to his duties soon afterward.  In a pre-recorded television broadcast aired on 11 March 2007, he announced, in a widely predicted move, that he would not choose to seek a third term as president. (In 2000 the constitution had been amended

Post-presidency and death.

Shortly after leaving office, he launched the Fondation Chirac in June 2008. Since then it has been striving for peace through five advocacy programmes: conflict prevention, access to water and sanitation, access to quality medicines and healthcare, access to land resources, and preservation of cultural diversity. It supports field projects that involve local people and provide concrete and innovative solutions. Chirac chaired the jury for the Prize for Conflict Prevention awarded every year by his foundation.  As a former President of France, he was entitled to a lifetime pension and personal security protection, and was an "ex officio" member for life of the Constitutional Council. He sat for the first time on the Council on 15 November 2007, six months after leaving the presidency. Immediately after Sarkozy's victory, Chirac moved into a duplex on the Quai Voltaire in Paris lent to him by the family of former Lebanese Prime Minister Rafik Hariri. During the Didier Schuller affair, the latter accused Hariri of having participated in illegal funding of the RPR's political campaigns, but the judge closed the case without further investigations.  In Volume 2 of his memoirs published in June 2011, Chirac mocked his successor Nicolas Sarkozy as "irritable, rash, impetuous, disloyal, ungrateful, and un-French". Chirac wrote that he considered firing Sarkozy previously, and conceded responsibility in allowing Jean-Marie Le Pen to advance in 2002. A poll conducted in 2010 suggested he was the most admired political figure in France, while Sarkozy was 32nd.  On 11 April 2008, Chirac's office announced that he had undergone successful surgery to fit a pacemaker.  Chirac suffered from frail health and memory loss in later life. In February 2014 he was admitted to hospital because of pains related to gout. On 10 December 2015, Chirac was hospitalised in Paris for undisclosed reasons, although his state of health did not "give any cause for concern", he remained for about a week in ICU. According to his son-in-law Frederic Salat-Baroux, Chirac was again hospitalised in Paris with a lung infection on 18 September 2016.

Death and state funeral.

Chirac died at his home in Paris on 26 September 2019, surrounded by his family. His requiem mass was held at the Saint-Sulpice Church on 30 September 2019, celebrated by Michel Aupetit, Archbishop of Paris, and attended by representatives from about 175 countries, included 69 past and present heads of state, government and international organizations

Popular culture.

Impact on French popular culture.

Because of Jacques Chirac's long career in visible government positions, he was often parodied or caricatured: Young Jacques Chirac is the basis of a young, dashing bureaucrat character in the 1976 Asterix comic strip album "Obelix and Co.", proposing methods to quell Gallic unrest to elderly, old-style Roman politicians. Chirac was also featured in "Le Bêbête Show" as an overexcited, jumpy character.  Jacques Chirac was a favorite character of "Les Guignols de l'Info", a satiric

Portrayals in film.

Charles Fathy appears as Chirac in the Oliver Stone film "W." Marc Rioufol plays him in

Controversies.

Osirak controversy.

At the invitation of Saddam Hussein (then vice-president of Iraq, but "de facto" dictator), Chirac made an official visit to Baghdad in 1975. Saddam approved a deal granting French oil companies a number of privileges plus a 23-percent share of Iraqi oil. As part of this deal, France sold Iraq the Osirak MTR nuclear reactor, designed to test nuclear materials.  The Israeli Air Force alleged that the

Conviction for corruption.

Chirac has been named in several cases of alleged corruption that occurred during his term as mayor, some of which have led to felony convictions of some politicians and aides. However, a controversial judicial decision in 1999 granted Chirac immunity while he was president of France. He refused to testify on these matters, arguing that it would be incompatible with his presidential functions. Investigations concerning the running of Paris's city hall, the number of whose municipal employees increased by 25% from 1977 to 1995 (with 2,000 out of approximately 35,000 coming from the Corrèze region where Chirac had held his seat as deputy), as well as a lack of financial transparency ("marchés publics") and the communal debt, were thwarted by the legal impossibility of questioning him as president. The conditions of the privatisation of the Parisian water system acquired very cheaply by the Compagnie Générale des Eaux and the Lyonnaise des Eaux, then directed by Jérôme Monod, a close friend of Chirac, were also criticised. Furthermore, the satirical newspaper "Le Canard enchaîné" revealed the astronomical "food expenses" paid by the Parisian municipality (€15 million a year according to the "Canard"), expenses managed by Roger Romani (who allegedly

The Clearstream Affair.

During April and May 2006, Chirac's administration was beset by a crisis as his chosen Prime Minister, Dominique de Villepin, was accused of asking Philippe Rondot, a top level French spy, for a secret investigation into Villepin's chief political rival, Nicolas Sarkozy, in 2004. This matter

Personal life.

In 1956, Chirac married Bernadette Chodron de Courcel, with whom he had two daughters: (4 March 195814 April 2016) and Claude (born 6 December 1962). Claude was a long-term public relations assistant and personal adviser to her father, while

Academic works.

In 1954, Chirac presented "The Development of the Port of New-Orleans", a short geography/economic thesis to the "Institut d'Etudes

Political career.

President of the French Republic: 1995–2007. Reelected in 2002.  Member of the Constitutional Council of France: Since 2007.  Governmental functions  Prime minister: 1974–76 (Resignation) / 1986–88.  Minister of Interior: March–May 1974.  Minister of Agriculture and Rural Development: 1972–74.  Minister of Relation with Parliament: 1971–72.  Secretary of State for Economy and Finance: 1968–71.  Secretary of State for Social Affairs: 1967–68.  Electoral mandates  European Parliament  Member of European Parliament: 1979–80 (Resignation). Elected in 1979.  National Assembly of France  Elected in 1967, reelected in 1968, 1973, 1976, 1981, 1986, 1988, 1993: Member for Corrèze: March–April 1967 (became Secretary of State in April 1967), reelected in 1968, 1973, but he remained a minister in 1976–1986 (became Prime Minister in 1986), 1988–95 (resigned to become President of the French Republic in 1995).  General Council  President of the General Council of Corrèze: 1970–1979. Reelected in 1973, 1976.  General councillor of Corrèze: 1968–88. Reelected in 1970, 1976, 1982.  Municipal Council  Mayor of Paris: 1977–95 (Resignation, became President of the French Republic in 1995). Reelected in 1983, 1989.  Councillor of Paris: 1977–1995 (Resignation). Reelected in 1983, 1989.  Municipal councillor of Sainte-Féréole: 1965–77. Reelected in 1971.  Political function  President of the Rally for the Republic: 1976–94 (Resignation).

Jacques René Chirac (,, ; 29 November 1932 – 26 September 2019) was a French politician who served as President of France from 1995 to 2007. Chirac was previously the Prime Minister of France from 1974 to 1976 and from 1986 to 1988, as well as the Mayor of Paris from 1977 to 1995.

Jacques René Chirac (29. listopadu 1932 Paříž – 26. září 2019, Paříž) byl francouzský politik. Byl zvolen do funkce francouzského prezidenta v letech 1995 a 2002. Svůj poslední mandát 22. prezidenta Francouzské republiky ukončil 16. května 2007.


Medical uses.

Thalidomide is used as a first-line treatment in multiple myeloma in combination with dexamethasone or with melphalan and prednisone, to treat acute episodes of erythema nodosum leprosum, and for maintenance therapy.  The bacterium that causes tuberculosis (TB) is related to leprosy. Thalidomide may be helpful in some cases where standard TB drugs and corticosteroids are not sufficient to resolve severe inflammation in the brain.  It is used as a second-line treatment to manage graft versus host disease and aphthous stomatitis in children and has been prescribed for other conditions in children including actinic prurigo and epidermolysis bullosa; the evidence for these uses is weak. It is recommended only as a third line treatment in graft-versus-host-disease in adults, based on lack of efficacy and side effects observed in clinical trials.

Contraindications.

Thalidomide should not be used by people who are breastfeeding or pregnant, trying or able to conceive a child, or cannot or will not follow the risk management program to prevent pregnancies. The prescribing doctor is required to ensure that contraception is being used, and regular pregnancy tests are taken. Those allergic to thalidomide should not take it. It should be used with caution in people with chronic infections like HIV or hepatitis B.

Adverse effects.

Thalidomide causes birth defects. The U.S. Food and Drug Administration (FDA) and other regulatory agencies have approved marketing of the drug only with an auditable risk evaluation and mitigation strategy that ensures that people using the drug are aware of the risks and avoid pregnancy; this applies to both men and women, as the drug can be transmitted in semen.  There is a high risk that thalidomide can cause excessive blood clots. There is also a high risk that thalidomide can interfere with formation of various kinds of new blood cells, creating a risk of infection via neutropenia, leukopenia, and lymphopenia, and risks that blood will not clot via thrombocytopenia. There is also a risk of anemia via lack of red blood cells. The drug can also damage nerves, causing peripheral neuropathy that may be irreversible.  Thalidomide has several cardiovascular adverse effects, including risk of heart attacks, pulmonary hypertension, and changes in heart rhythm including syncope, bradycardia, and atrioventricular block.  It can cause liver damage and severe skin reactions like Stevens–Johnson syndrome. It tends to make people sleepy, which creates risk when driving and operating other machinery. As it kills cancer cells, it can cause tumor lysis syndrome. Thalidomide can prevent menstruation.  Other than the above, very common (reported in more than 10% of people) adverse effects include tremor, dizziness, tingling, numbness, constipation, and peripheral edema.  Common adverse effects (reported by 1–10% of people) include confusion, depressed mood, reduced coordination, heart failure, difficulty breathing, interstitial lung disease, lung inflammation, vomiting, dry mouth, rashes, dry skin, fever, weakness, and a sense of unwellness.

Interactions.

There are no expected pharmacokinetic interactions between thalidomide and other medicines due to its neutral effects on P-glycoprotein and the cytochrome P450 family. It may interact with sedatives due to its sedative action and bradycardic agents, like beta-blockers, due to its bradycardia-inducing effects. The risk of peripheral neuropathy may be increased by concomitant treatment with other agents known to cause peripheral neuropathy. The risk of venous thromboembolisms with thalidomide seems to be increased when patients are treated with oral contraceptives or other cytotoxic agents (including doxorubicin and melphalan) concurrently. Thalidomide may interfere with various contraceptives, and hence it is advised that women of reproductive age use at least two different means of contraception to ensure that no child will be conceived while they are taking thalidomide.

Overdose.

As of 2013, eighteen cases of overdoses had been reported with doses of up to 14.4 grams, none of them fatal. No specific antidote for overdose exists and treatment is purely supportive.

Pharmacology.

The precise mechanism of action for thalidomide is not known, although efforts to identify thalidomide's teratogenic action generated 2,000 research papers and the proposal of 15 or 16 plausible mechanisms by the year 2000. As of 2015, the main theories were inhibition of the process of angiogenesis, its inhibition of cereblon, a ubiquitin ligase, and its ability to generate reactive oxygen species which in turn kills cells. In 2018, results were first published which suggested that thalidomide's teratogenic effects are mediated through degradation of the transcription factor, SALL4, an as yet unverified finding.  Thalidomide also binds to and acts as an antagonist of the androgen receptor (AR) and hence is a nonsteroidal antiandrogen (NSAA) of some capacity. In accordance, it can produce gynecomastia and sexual dysfunction as side effects in men.  Thalidomide is provided as a racemic mixture of two enantiomers; while there are reports that only one of the enantiomers may cause birth defects, the body converts each enantiomer into the other through mechanisms that are not well understood.

Chemistry.

Thalidomide is racemic; while R-thalidomide is the bioactive form of the molecule, the individual enantiomers can racemize to each other due to the acidic hydrogen at the chiral centre, which is the carbon of the glutarimide ring bonded to the phthalimide substituent. The racemization process can occur "in vivo".  Celgene Corporation originally synthesized thalidomide using a three-step sequence starting with L-glutamic acid treatment, but this has since been reformed by the use of L-glutamine. As shown in the image below, N-carbethoxyphtalimide (1) can react with L-glutamine to yield N-phthaloyl-L-glutamine (2). Cyclization of N-phthaloyl-L-glutamine occurs using carbonyldiimidazole, which then yields thalidomide (3). Celgene Corporation's original method resulted in a 31% yield of S-thalidomide, whereas the two-step synthesis yields 85–93% product that is 99% pure.

History.

Thalidomide was discovered by the German pharmaceutical company Chemie Grünenthal (now Grünenthal GmbH) circa 1953. The company had been established as a soap maker after World War II ended, to address the urgent market need for antibiotics. Heinrich Mueckter was appointed to head the discovery program based on his experience working with the German army's antiviral research. While preparing reagents for the work, Mueckter's assistant Wilhelm Kunz isolated a by-product that was recognized by pharmacologist Herbert Keller as an analog of glutethimide, a sedative. The medicinal chemistry work turned to improving the lead compound into a suitable drug: the result was thalidomide. The toxicity was examined in several animals, and the drug was introduced in 1956 as a sedative; it was never tested on pregnant women.  Researchers at Chemie Grünenthal found that thalidomide was a particularly effective antiemetic that had an inhibitory effect on morning sickness. On October 1, 1957, the company launched thalidomide and began marketing it under the trade name Contergan. It was proclaimed a "wonder drug" for insomnia, coughs, colds and headaches.  During this period, the use of medications during pregnancy was not strictly controlled, and drugs were not thoroughly tested for potential harm to the fetus. Thousands of pregnant women took the drug to relieve their symptoms. At the time of the drug's development, scientists did not believe any drug taken by a pregnant woman could pass across the placental barrier and harm the developing fetus, even though the effect of alcohol on fetal development had been documented by case studies on alcoholic mothers since at least 1957. There soon appeared reports of abnormalities in children being born to mothers using thalidomide. In late 1959, it was noticed that peripheral neuritis developed in patients who took the drug over a period of time, and it was only after this point that thalidomide ceased to be provided over the counter.  While initially considered safe, the drug was responsible for teratogenic deformities in children born after their mothers used it during pregnancies, prior to the third trimester. In November 1961, thalidomide was taken off the market due to massive pressure from the press and public. Experts estimate that the drug thalidomide led to the death of approximately 2,000 children and serious birth defects in more than 10,000 children, about 5,000 of them in West Germany. The regulatory authorities in East Germany did not approve thalidomide. One reason for the initially unobserved side effects of the drug and the subsequent approval in West Germany was that at that time drugs did not have to be tested for teratogenic effects. They had been tested on rodents only, as was usual at the time.  In the UK, the British pharmaceutical company The Distillers Company (Biochemicals) Ltd, a subsidiary of Distillers Co. Ltd (now part of Diageo plc), marketed thalidomide under the brand name Distaval as a remedy for morning sickness throughout the UK, Australia and New Zealand. Their advertisement claimed that "Distaval can be given with complete safety to pregnant women and nursing mothers without adverse effect on mother or child...Outstandingly safe Distaval has been prescribed for nearly three years in this country." Globally, more pharmaceutical companies started to produce and market the drug under license from Chemie Grünenthal. By the mid-1950s, 14 pharmaceutical companies were marketing thalidomide in 46 countries under at least 37 different trade names.  In the US, representatives from Chemie Grünenthal approached Smith, Kline & French (SKF), now GlaxoSmithKline (GSK), with a request to market and distribute the drug in North America. A memorandum rediscovered in 2010 in the archives of the FDA shows that, as part of its in-licensing approach, Smith, Kline and French conducted animal tests and ran a clinical trial of the drug in the US involving 875 people, including pregnant women, in 1956–57. In 1956, researchers at SKF involved in clinical trials noted that even when used in very high doses, thalidomide could not induce sleep in mice. And when administered at doses 50 to 650 times larger than that claimed by Chemie Grünenthal to be "sleep inducing", the researchers could still not achieve the hypnotic effect in animals that it had on humans. After completion of the trial, and based on reasons kept hidden for decades, SKF declined to commercialize the drug. Later, Chemie Grünenthal, in 1958, reached an agreement with William S Merrell Company in Cincinnati, Ohio, (later Richardson-Merrell, now part of Sanofi), to market and distribute thalidomide throughout the US  The US FDA refused to approve thalidomide for marketing and distribution. However, the drug was distributed in large quantities for testing purposes, after the American distributor and manufacturer Richardson-Merrell had applied for its approval in September 1960. The official in charge of the FDA review, Frances Oldham Kelsey, did not rely on information from the company, which did not include any test results. Richardson-Merrell was called on to perform tests and report the results. The company demanded approval six times, and was refused each time. Nevertheless, a total of 17 children with thalidomide-induced malformations were born in the US. Oldham Kelsey was given a Presidential award for distinguished service from the federal government for not allowing thalidomide to be approved for sale in the US.  In Canada, the history of the drug thalidomide dates back to April 1, 1961. There were many different forms sold, with the most common variant being Talimol. Two months after Talimol went on sale, pharmaceutical companies sent physicians letters warning about the risk of birth defects. It was not until March 2, 1962, that both drugs were banned from the Canadian market by the FDD, and soon afterward physicians were warned to destroy their supplies.

Leprosy treatment.

In 1964, Israeli physician Jacob Sheskin administered thalidomide to a patient critically ill with leprosy. The patient exhibited erythema nodosum leprosum (ENL), a painful skin condition, one of the complications of leprosy. This was attempted despite the ban on thalidomide's use, but results were favourable: the patient slept for hours and was able to get out of bed without aid upon awakening. A clinical trial studying the use of thalidomide in leprosy soon followed.  Thalidomide has been used by Brazilian physicians as the drug of choice for the treatment of severe ENL since 1965, and by 1996, at least 33 cases of thalidomide embryopathy were recorded in people born in Brazil after 1965. Since 1994, the production, dispensing, and prescription of thalidomide have been strictly controlled, requiring women to use two forms of birth control and submit to regular pregnancy tests. Despite this, cases of thalidomide embryopathy continue, with at least 100 cases identified in Brazil between 2005 and 2010. 5.8 million thalidomide pills were distributed throughout Brazil in this time period, largely to poor Brazilians in areas with poor access to healthcare, and these cases have occurred despite the controls.  In 1998, the FDA approved the drug's use in the treatment of ENL. Because of thalidomide's potential for causing birth defects, the drug may be distributed only under tightly controlled conditions. The FDA required that Celgene Corporation, which planned to market thalidomide under the brand name "Thalomid", establish a system for thalidomide education and prescribing safety (STEPS) oversight program. The conditions required under the program include limiting prescription and dispensing rights to authorized prescribers and pharmacies only, keeping a registry of all patients prescribed thalidomide, providing extensive patient education about the risks associated with the drug, and providing periodic pregnancy tests for women who take the drug.  In 2010, the World Health Organization (WHO) stated that it did not recommend thalidomide for leprosy due to the difficulty of adequately controlling its use, and due to the availability of clofazimine.

Cancer treatment.

Shortly after the teratogenic properties of thalidomide were recognized in the mid-1960s, its anti-cancer potential was explored and two clinical trials were conducted in people with advanced cancer, including some people with multiple myeloma; the trials were inconclusive.  Little further work was done with thalidomide in cancer until the 1990s.  Judah Folkman pioneered studies into the role of angiogenesis (the proliferation and growth of blood vessels) in the development of cancer, and in the early 1970s had shown that solid tumors could not expand without it. In 1993 he surprised the scientific world by hypothesizing the same was true of blood cancers, and the next year he published work showing that a biomarker of angiogenesis was higher in all people with cancer, but especially high in people with blood cancers, and other evidence emerged as well. Meanwhile, a member of his lab, Robert D'Amato, who was looking for angiogenesis inhibitors, discovered in 1994 that thalidomide inhibited angiogenesis and was effective in suppressing tumor growth in rabbits. Around that time, the wife of a man who was dying of multiple myeloma and whom standard treatments had failed, called Folkman asking him about his anti-angiogenesis ideas. Folkman persuaded the patient's doctor to try thalidomide, and that doctor conducted a clinical trial of thalidomide for people with multiple myeloma in which about a third of the subjects responded to the treatment. The results of that trial were published in the New England Journal of Medicine in 1999.  After further work was done by Celgene and others, in 2006 the U.S. Food and Drug Administration granted accelerated approval for thalidomide in combination with dexamethasone for the treatment of newly diagnosed multiple myeloma patients.

Society and culture.

Birth defect crisis.

In the late 1950s and early 1960s, more than 10,000 children in 46 countries were born with deformities, such as phocomelia, as a consequence of thalidomide use. The severity and location of the deformities depended on how many days into the pregnancy the mother was before beginning treatment; thalidomide taken on the 20th day of pregnancy caused central brain damage, day 21 would damage the eyes, day 22 the ears and face, day 24 the arms, and leg damage would occur if taken up to day 28. Thalidomide did not damage the fetus if taken after 42 days gestation.  It is not known exactly how many worldwide victims of the drug there have been, although estimates range from 10,000 to 20,000. Despite the side effects, thalidomide was sold in pharmacies in Canada until 1962.

Change in drug regulations.

The disaster prompted many countries to introduce tougher rules for the testing and licensing of drugs, such as the Kefauver Harris Amendment (U.S.), Directive 65/65/EEC1 (E.U.), and the Medicines Act 1968 (UK). In the United States, the new regulations strengthened the FDA, among other ways, by requiring applicants to prove efficacy and to disclose all side effects encountered in testing. The FDA subsequently initiated the Drug Efficacy Study Implementation to reclassify drugs already on the market.

Quality of life.

In the 1960s, thalidomide was successfully marketed as a safer alternative to barbiturates. Due to a successful marketing campaign, thalidomide was widely used by pregnant women during the first trimester of pregnancy. However, thalidomide is a teratogenic substance, and a proportion of children born during the 1960s were afflicted with a syndrome known as thalidomide embryopathy (TE). Of these babies born with TE, "about 40% of them died before their first birthday". The surviving individuals are now middle-aged and they report experiencing challenges (physical, psychological, and socioeconomic) related to TE.  Individuals born with TE frequently experience a wide variety of health problems secondary to their TE. These health conditions include both physical and psychological conditions. When compared to individuals of similar demographic profiles, those born with TE report less satisfaction with their quality of life and their overall health. Access to health care services can also be a challenge for these people, and women in particular have experienced difficulty in locating healthcare professionals who can understand and embrace their needs.

Brand names.

Brand names include Contergan, Thalomid, Talidex, Talizer, Neurosedyn, Distaval and many others.

Cost.

In the United Kingdom, it costs the NHS about £1,194 per month as of 2018. This amount in the United States costs about US$9,236 as of 2019.

Research.

Research efforts have been focused on determining how thalidomide causes birth defects and its other activities in the human body, efforts to develop safer analogs, and efforts to find further uses for thalidomide.

Thalidomide analogs.

The exploration of the antiangiogenic and immunomodulatory activities of thalidomide has led to the study and creation of thalidomide analogs. Celgene has sponsored numerous clinical trials with analogues to thalidomide, such as lenalidomide, that are substantially more powerful and have fewer side effects — except for greater myelosuppression. In 2005, Celgene received FDA approval for lenalidomide (Revlimid) as the first commercially useful derivative. Revlimid is available only in a restricted distribution setting to avoid its use during pregnancy. Further studies are being conducted to find safer compounds with useful qualities. Another more potent analog, pomalidomide, is now FDA approved. Additionally, apremilast was approved by the FDA in March 2014. These thalidomide analogs can be used to treat different diseases, or used in a regimen to fight two conditions.  Interest turned to pomalidomide, a derivative of thalidomide marketed by Celgene. It is a very active anti-angiogenic agent and also acts as an immunomodulator. Pomalidomide was approved in February 2013 by the U.S. Food and Drug Administration (FDA) as a treatment for relapsed and refractory multiple myeloma. It received a similar approval from the European Commission in August 2013, and is expected to be marketed in Europe under the brand name Imnovid.

Clinical research.

There is no conclusive evidence that thalidomide or lenalidomide is useful to bring about or maintain remission in Crohn's disease.  Thalidomide was studied in a Phase II trial for Kaposi's sarcoma, a rare soft-tissue cancer most commonly seen in the immunocompromised, that is caused by the Kaposi's sarcoma-associated herpesvirus (KSHV).

Thalidomide, sold under the brand name Thalomid among others, is a medication used to treat a number of cancers including multiple myeloma, graft-versus-host disease, and a number of skin conditions including complications of leprosy. While it has been used in a number of HIV associated conditions, such use is associated with increased levels of the virus. It is taken by mouth. Common side effects include sleepiness, rash, and dizziness. Severe side effects include tumor lysis syndrome, blood clots, and peripheral neuropathy. Use in pregnancy may harm the baby, including resulting in malformation of the limbs. In males who are taking the medication, condoms are recommended if their partner could become pregnant. It is an immunomodulatory medication and works by a number of mechanisms including stimulating T cells and decreasing TNF-α production. Thalidomide was first marketed in 1957 in West Germany, where it was available over the counter. When first released, thalidomide was promoted for anxiety, trouble sleeping, "tension", and morning sickness. While initially deemed to be safe in pregnancy, concerns regarding birth defects were noted in 1961 and the medication was removed from the market in Europe that year. The total number of people affected by use during pregnancy is estimated at 10,000, of which about 40% died around the time of birth. Those who survived had limb, eye, urinary tract, and heart problems. Its initial entry into the US market was prevented by Frances Kelsey at the FDA. The birth defects of thalidomide led to the development of greater drug regulation and monitoring in many countries. It was approved for medical use in the United States in 1998. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic medication. In the United Kingdom it costs the NHS about £1,194 per month as of 2018. This amount in the United States costs about US$9,236 as of 2019.

Thalidomid (obchodní název Contergan) je chemická látka, která má léčivé účinky. Zároveň se jedná o teratogen a karcinogen. V Československu se tento lék neprodával.


Anatomy and stimulation.

The abundance of nerve endings in the anal region and rectum can make anal sex pleasurable for men or women. The internal and external sphincter muscles control the opening and closing of the anus; these muscles, which are sensitive membranes made up of many nerve endings, facilitate pleasure or pain during anal sex. "Human Sexuality: An Encyclopedia" states that "the inner third of the anal canal is less sensitive to touch than the outer two-thirds, but is more sensitive to pressure" and that "the rectum is a curved tube about eight or nine inches long and has the capacity, like the anus, to expand".  Research indicates that anal sex occurs significantly less frequently than other sexual behaviors, but its association with dominance and submission, as well as taboo, makes it an appealing stimulus to people of all sexual orientations. In addition to sexual penetration by the penis, people may use sex toys such as a dildo, a butt plug or anal beads, engage in fingering, anilingus, pegging, anal masturbation or fisting for anal sexual activity, and different sex positions may also be included. Fisting is the least practiced of the activities, partly because it is uncommon that people can relax enough to accommodate an object as big as a fist being inserted into the anus.  In a male receptive partner, being anally penetrated can produce a pleasurable sensation due to the inserted penis rubbing or brushing against the prostate through the anal wall. This can result in pleasurable sensations and can lead to an orgasm in some cases. Prostate stimulation can produce a deeper orgasm, sometimes described by men as more widespread and intense, longer-lasting, and allowing for greater feelings of ecstasy than orgasm elicited by penile stimulation only. The prostate is located next to the rectum and is the

Male to female.

Behaviors and views.

The anal sphincters are usually tighter than the pelvic muscles of the vagina, which can enhance the sexual pleasure for the inserting male during male-to-female anal intercourse because of the pressure applied to the penis. Men may also enjoy the penetrative role during anal sex because of its association with dominance, because it is made more alluring by a female partner or society in general insisting that it is forbidden, or because it presents an additional option for penetration.  While some women find being a receptive partner during anal intercourse painful or uncomfortable, or only engage in the act to please a male sexual partner, other women find the activity pleasurable or prefer it to vaginal intercourse.  In a 2010 clinical review article of heterosexual anal sex, "anal intercourse" is used to specifically denote penile-anal penetration, and "anal sex" is used to denote any form of anal sexual

Prevalence.

Because most research on anal intercourse addresses men who have sex with men, little data exists on the prevalence of anal intercourse among heterosexual couples. In Kimberly R. McBride's 2010 clinical review on heterosexual anal intercourse and other forms of anal sexual activity, it is suggested that changing norms may affect the frequency of heterosexual anal sex. McBride and her colleagues investigated the prevalence of non-intercourse anal sex behaviors among a sample of men (n=1,299) and women (n=1,919) compared to anal intercourse experience and found that 51% of men and 43% of women had participated in at least one act of oral–anal sex, manual–anal sex, or anal sex toy use. The report states the majority of men (n=631) and women (n=856) who reported heterosexual anal intercourse in the past 12 months were in exclusive, monogamous relationships: 69% and 73%, respectively. The review added that because "relatively little attention [is] given to anal intercourse and other anal sexual behaviors between heterosexual partners", this means that it is "quite rare" to have research "that specifically differentiates the anus as a sexual organ or addresses anal sexual function or dysfunction as legitimate topics.

Male to male.

Behaviors and views.

Historically, anal sex has been commonly associated with male homosexuality. However, many gay men and men who have sex with men in general (those who identify as gay, bisexual, heterosexual or have not identified their sexual identity) do not engage in anal sex. Among men who have anal sex with other men, the insertive partner may be referred to as the "top" and the one being penetrated may be referred to as the "bottom". Those who enjoy either role may be referred to as "versatile".

Prevalence.

Reports regarding the prevalence of anal sex among gay men and other men who have sex with men vary. A survey in "The Advocate" in 1994 indicated that 46% of gay men preferred to penetrate their partners, while 43% preferred to be the receptive partner. Other sources suggest that roughly three-fourths of gay men have had anal sex at one time or another, with an equal percentage participating as tops and bottoms. A 2012 NSSHB sex survey in the U.S. suggests high lifetime participation in anal sex among gay men: 83.3% report ever taking part

Female to male.

Women may sexually stimulate a man's anus by fingering the exterior or interior areas of the anus; they may also stimulate the perineum (which, for males, is between the base of the scrotum and the anus), massage the prostate or engage in anilingus. Sex toys, such as a dildo, may also be used. The practice of a woman penetrating a man's anus

Female to female.

With regard to lesbian sexual practices, anal sex includes fingering, use of a dildo or other sex toys, or anilingus.  There is less research on anal sexual activity among women who have sex with women compared to couples of other sexual orientations. In 1987, a non-scientific study (Munson) was conducted of more than 100 members of a

Health risks.

General risks.

Anal sex can expose its participants to two principal dangers: infections due to the high number of infectious microorganisms not found elsewhere on the body, and physical damage to the anus and rectum due to their fragility. Unprotected penile-anal penetration, colloquially known as "barebacking", carries a higher risk of passing on sexually transmitted infections (STIs) because the anal sphincter is a delicate, easily torn tissue that can provide an entry for pathogens. Use of condoms, ample lubrication to reduce the risk of tearing, and safer sex practices in general, reduce the risk of STI transmission. However, a condom can break or otherwise come off during anal sex, and this is more likely to happen with anal sex than with other

Physical damage and cancer.

Anal sex can exacerbate hemorrhoids and therefore result in bleeding; in other cases, the formation of a hemorrhoid is attributed to anal sex. If bleeding occurs as a result of anal sex, it may also be because of a tear in the anal or rectal tissues (an anal fissure) or perforation (a hole) in the colon, the latter of which being a serious medical issue that should be remedied by immediate medical attention. Because of the rectum's lack of elasticity, the anal mucous membrane being thin, and small blood vessels being present directly beneath the mucous membrane, tiny tears and bleeding in the rectum usually result from penetrative anal sex, though the bleeding is usually minor and therefore usually not visible. By contrast to other anal sexual behaviors, anal fisting poses a more serious danger of damage due to the deliberate stretching of the anal and rectal tissues; anal fisting injuries include anal sphincter lacerations and rectal and sigmoid colon (rectosigmoid) perforation, which might result in death.  Repetitive penetrative anal sex may result in the

Other cultural views.

General.

Different cultures have had different views on anal sex throughout human history, with some cultures more positive about the activity than others. Historically, anal sex has been restricted or condemned, especially with regard to religious beliefs; it has also commonly been used as a form of domination, usually with the active partner (the one who is penetrating) representing masculinity and the passive partner (the one who is being penetrated) representing femininity. A number of cultures have especially recorded the practice of anal sex between males, and anal sex between males has been especially stigmatized or punished. In

Ancient and non-Western cultures.

From the earliest records, the ancient Sumerians had very relaxed attitudes toward sex and did not regard anal sex as taboo. "Entu" priestesses were forbidden from producing offspring and frequently engaged in anal sex as a method of birth control. Anal sex is also obliquely alluded to by a description of an omen in which a man "keeps saying to his wife: 'Bring your backside.'" Other Sumerian texts refer to homosexual anal intercourse. The "gala", a set of priests who worked in the temples of the goddess Inanna, where they performed elegies and lamentations, were especially known for their homosexual proclivities. The Sumerian sign for "gala" was a ligature of the signs for "penis" and "anus". One Sumerian proverb reads: "When the "gala" wiped off his ass [he said], 'I must not arouse that which belongs to my mistress [i.e., Inanna].'"  The term "Greek love" has long been used to refer to anal intercourse, and in modern times, "doing it the Greek way" is sometimes used as slang for anal sex. Male-male anal sex was not a universally accepted practice in Ancient Greece; it was the target of jokes in some Athenian comedies. Aristophanes, for instance, mockingly alludes to the practice, claiming, "Most citizens are "europroktoi" (wide-arsed) now." The terms "kinaidos", "europroktoi", and "katapygon" were used by Greek residents to categorize men who chronically practiced passive anal intercourse. Pederastic practices in ancient Greece (sexual activity between men and adolescent boys), at least in Athens and Sparta, were expected to avoid penetrative sex of any kind. Greek artwork of sexual interaction between men and boys usually depicted fondling or intercrural sex, which was not condemned for violating or feminizing boys, while male-male anal intercourse was usually depicted between males of the same age-group. Intercrural sex was not considered penetrative and two males engaging in it was considered a "clean" act. Some sources explicitly state that anal sex between men and boys was criticized as

Western cultures.

In many Western countries, anal sex has generally been taboo since the Middle Ages, when heretical movements were sometimes attacked by accusations that their members practiced anal sex among themselves. At that time, celibate members of the Christian clergy were accused of engaging in "sins against nature", including anal sex.  The term "buggery" originated in medieval Europe as an insult used to describe the rumored same-sex sexual practices of the heretics from a sect originating in Bulgaria, where its

Religion.

Judaism.

The Mishneh Torah, a text considered authoritative by Orthodox Jewish sects, states "since a man's wife is permitted to him, he may act with her in any manner whatsoever. He may have intercourse with her whenever he so desires and kiss any

Christianity.

Christian texts may sometimes euphemistically refer to anal sex as the "peccatum contra naturam" (the sin against nature, after Thomas

Islam.

"Liwat", or the sin of Lot's people, which has come to be interpreted as referring generally to same-sex sexual activity, is commonly officially prohibited by Islamic sects; there are parts of the Quran which talk about smiting on Sodom and Gomorrah, and this is thought to be a reference to unnatural sex, and so there are hadith and Islamic laws which prohibit it. While, concerning Islamic belief, it is objectionable to use the words "al-Liwat" and "luti" to refer to homosexuality because it is blasphemy toward the prophet of Allah, and therefore the terms "sodomy" and "homosexuality" are preferred, same-sex male practitioners of anal sex are called "luti" or "lutiyin" in plural and are seen as criminals in the same way that a thief is a criminal.

Anal sex or anal intercourse is generally the insertion and thrusting of the erect penis into a person's anus, or anus and rectum, for sexual pleasure. Other forms of anal sex include fingering, the use of sex toys for anal penetration, oral sex performed on the anus (anilingus), and pegging. Although "anal sex" most commonly means penileanal penetration, sources sometimes use "anal intercourse" to exclusively denote penileanal penetration, and "anal sex" to denote any form of anal sexual activity, especially between pairings as opposed to anal masturbation.

Anální sex je sexuální aktivita, při které dochází buď k anální souloži, či k nejrůznějším formám dráždění řitního otvoru (prsty, jazykem, erotickými pomůckami, atp.). Z medicínsko-epidemiologického hlediska se řadí mezi rizikové sexuální praktiky, což je dané zranitelností příslušných orgánů a septickou povahou konečníku. Protože konečník na rozdíl od vaginy postrádá přirozenou vlhkost, je při této praktice obvykle používán lubrikační gel.


Discovery and visibility.

M13 was discovered by Edmond Halley in 1714, and cataloged by Charles Messier on June 1, 1764 into his list of objects not to mistake for comets; Messier's list, including Messier 13, eventually became known as the Messier Catalog.  About one third of the way from Vega to Arcturus, four bright stars in the constellation of Hercules form the Keystone asterism. M13 can be seen partway between Zeta Herculis and Eta Herculis. Although only telescopes with great light-gathering capability fully resolve the stars of the Cluster, M13 can be visible to the naked eye depending on circumstances. With a low-power telescope, Messier 13 looks like a comet or fuzzy patch. The cluster is visible throughout the year from latitudes greater than 36 degrees north, with the longest visibility during Northern Hemisphere spring and summer.  It is located at right ascension 16 41.7, declination +36° 28'. With an apparent magnitude of 5.8, it is barely visible with the naked eye on clear nights. Its diameter is about 23 arcminutes and it is readily viewable in small telescopes. Nearby is NGC 6207, a 12th-magnitude edge-on galaxy that lies 28 arcminutes directly northeast. A small galaxy, IC 4617, lies halfway between NGC 6207 and M13, north-northeast of the large globular cluster's center.  In traditional binoculars, the Hercules Globular Cluster appears as a round patch of light. At least four inches of telescope aperture will allow resolving the stars in M13's outer extents as small pinpoints of light. However, only larger telescopes allow resolving stars further into the center of the cluster.

Characteristics.

About 145 light-years in diameter, M13 is composed of several hundred thousand stars, the brightest of which is a red giant, the variable star V11, with an apparent visual magnitude of 11.95. M13 is 22,200–25,000 light-years away from Earth.  Single stars in this globular cluster were first resolved in 1779. Compared to the stars in the neighborhood of the Sun, the stars of the M13 population are more than a hundred times denser. They are so densely packed together that they sometimes collide and produce new stars. The newly formed, young stars, so-called "blue stragglers," are particularly interesting to astronomers.  The 1974 Arecibo message, which contained encoded information about the human race, DNA, atomic numbers, Earth's position and other information, was beamed from the Arecibo Observatory radio telescope towards M13 as an experiment in contacting potential extraterrestrial civilizations in the cluster. The cluster will move through space during the transit time; opinions differ as to whether or not the cluster will be in a position to receive the message by the time it arrives.

Messier 13 or M13, also designated NGC 6205 and sometimes called the Great Globular Cluster in Hercules or the Hercules Globular Cluster, is a globular cluster of several hundred thousand stars in the constellation of Hercules.

Messier 13 (také M13 nebo NGC 6205) je kulová hvězdokupa v souhvězdí Herkula. Objevil ji anglický astronom sir Edmund Halley v roce 1714. Hvězdokupa je od Země vzdálena 23 150 světelných let. Skládá se z několika set tisíc hvězd a má průměr 145 světelných let. Patří mezi nejvýraznější a nejznámější kulové hvězdokupy na severní obloze.


Aims.

The Liberal International Constitution (2005) gives its purposes as The principles that unite member parties from Africa, the Americas, Asia and Europe are respect for human rights, free and fair elections and multi-party democracy, social justice, tolerance, market economy, free trade, environmental sustainability and a strong sense of international solidarity.  The aims of Liberal International are also set out in a series of seven manifestos, written between 1946 and 1997, and are furthered by a variety of bodies including a near yearly conference for liberal parties and individuals from around the world.

Bureau.

The bureau of Liberal International is elected every 18 months by the delegates of the congress.  The 14th president of Liberal International is Hakima el Haite of the Mouvement Populaire (Morocco), is former a Minister of Environment, UN climate champion, and climate scientist. Madam El Haite succeeded Dr Juli Minoves, formerly Andorra's foreign minister and representative to the United Nations.  Former Presidents include Hans Van Baalen MEP, Lord John Alderdice, Dutch politician and former European Commissioner Frits Bolkestein, German politician Otto Graf Lambsdorff, and Spain's first democratically elected prime minister after Francoist Spain, Adolfo Suárez.  Other members of the bureau include Deputy President Prof. Karl-Heinz Paque, and Vice Presidents Cellou Dalein Diallo [Guinea]; Kitty Monterrey [Nicaragua]; Abir al-Sahlani [Sweden]; Kiat Sittheamorn [Thailand]; and Robert Woodthorpe Browne MBE [United Kingdom]. There are two elected treasurers, Judith Pallares MP [Andorra] and Minister Omar Youm [Senegal]. The secretary general is Gordon Mackay, a former Member of Parliament from South Africa.

Awards.

Liberal International awards prizes to worthy individuals in the fields of human rights and liberalism.  Prize for Freedom:  The Liberal International Prize for Freedom is LI's most prestigious human rights award. Conveyed annually since 1984 to an individual who of liberal conviction who has made outstanding efforts for the defence of freedom and human rights, recipients include Maria Corina Machado [Venezuela], Senator Leila de Lima [Philippines], Raif Badawi [Saudi Arabia], Waris Dirie [Somalia], and Vaclav Havel [Czechoslovakia/Czech Republic].  Medal of Liberalism:  The Liberal International Medal of Liberalism is awarded to individuals who have worked to advance liberal values on a local, national and international level. Recipients include President Alassane Ouattara [Côte d'Ivoire]; Prime Minister Xavier Bettel [Luxembourg]; President Tsai, Ing-wen [Taiwan]; Sir Graham Watson [United Kingdom].

Publications.

The "LI Human Rights Bulletin" is published three times per year and consists of opinion articles, video interviews and digest of the work of the LI human rights committee.  "Thematic publications" are published online and in print on an "ad hoc" basis. Recent texts have offered a liberal perspective on issues ranging from freedom of belief to the responsibility to protect. ʒ

Oxford Manifesto.

The Oxford Manifesto, drawn up in April 1947 at Wadham College in Oxford by representatives from 19 liberal political parties, led by Salvador de Madariaga, is a document describing the basic political principles of the Liberal International.  The Oxford Manifesto was inspired by the ideas of William Beveridge and is regarded as one of the defining political documents of the 20 century.  Fifty years on, in 1997, Liberal International returned to Oxford and issued a supplement to the original manifesto, "The Liberal Agenda for the 21st century", describing Liberal policies in greater detail. The second Oxford Manifesto was adopted by the 48th Congress of Liberal International, which was held on 27–30 November 1997 in the Oxford Town Hall. In 2017, the global federation marked its 70th anniversary with the adoption of the Andorra Liberal Manifesto for the twenty-first century (ALM). A three-year project across numerous continents initiated by then president Juli Minoves, the ALM embodied the widest consultation of views undertaken by Liberal International in order to compile a policy document.

Cooperating organizations.

Cooperating and regional organisations are groups with a recognised status in the constitution of Liberal International as bodies that share the values and objectives of LI but do not operate as a political party. Co-operating organisations have the right of representation but in no case the right to vote at statutory events.

Liberal think tanks and foundations.

The International is also in a loose association with the following organisations:

Liberal International (LI) is the political international federation for liberal political parties. It was founded in Oxford in 1947, and has become the pre-eminent network for liberal parties and for the strengthening of liberalism around the world. Its headquarters are at 1 Whitehall Place, London, SW1A 2HD within the National Liberal Club. The Oxford Manifesto describes the basic political principles of the Liberal International.

Liberální internacionála (LI) je mezinárodní svaz liberálních stran, založený roku 1947 se sídlem v Londýně. Sdružuje více než 100 politických stran z různých zemí Evropy, Afriky, Asie a obojí Ameriky, které souhlasí s manifestem LI. Politické zaměření je spíše sociálně liberální s důrazem na lidská práva, svobodu podnikání i solidaritu. Žádná strana z ČR není členem Liberální internacionály.


Life.

Early years.

La Fontaine was born at Château-Thierry in France. His father was Charles de La Fontaine, – a kind of deputy-ranger – of the Duchy of Château-Thierry; his mother was Françoise Pidoux. Both sides of his family were of the highest provincial middle class; though they were not noble, his father was fairly wealthy.  Jean, the eldest child, was educated at the collège (grammar school) of Château-Thierry, and at the end of his school days he entered the Oratory in May 1641, and the seminary of Saint-Magloire in October of the same year; but a very short sojourn proved to him that he had mistaken his vocation. He then apparently studied law, and is said to have been admitted as "avocat"/lawyer.

Family life.

He was, however, settled in life, or at least might have been so, somewhat early. In 1647 his father resigned his rangership in his favor, and arranged a marriage for him with Marie Héricart, a girl of fourteen, who brought him 20,000 livres, and expectations. She seems to have been both beautiful and intelligent, but the two did not get along well together. There appears to be absolutely no ground for the vague scandal as to her conduct, which was, for the most part, raised long afterwards by gossip or personal enemies of La Fontaine. All that can be positively said against her is that she was a negligent housewife and an inveterate novel reader; La Fontaine himself was constantly away from home, was certainly not strict in point of conjugal fidelity, and was so bad a man of business that his affairs became involved in hopeless difficulty, and a financial separation of property ("separation de biens") had to take place in 1658. This was a perfectly amicable transaction for the benefit of the family; by degrees, however, the pair, still without any actual quarrel, ceased to live together, and for the greater part of the last forty years of de la Fontaine's life he lived in Paris while his wife remained in Chateau Thierry which, however, he frequently visited. One son was born to them in 1653, and was educated and taken care of wholly by his mother.

Paris.

Even in the earlier years of his marriage, La Fontaine seems to have been much in Paris, but it was not until about 1656 that he became a regular visitor to the capital. The duties of his office, which were only occasional, were compatible with this non-residence. It was not until he was past thirty that his literary career began. The reading of Malherbe, it is said, first awoke poetical fancies in him, but for some time he attempted nothing but trifles in the fashion of the time – epigrams, ballades, rondeaux, etc.  His first serious work was a translation or adaptation of the "Eunuchus" of Terence (1654). At this time the patron of French writing was the Superintendent Fouquet, to whom La Fontaine was introduced by Jacques Jannart, a connection of his wife's. Few people who paid their court to Fouquet went away empty-handed, and La Fontaine soon received a pension of 1000 livres (1659), on the easy terms of a copy of verses for each quarters receipt. He also began a medley of prose and poetry, entitled "Le Songe de Vaux", on Fouquet's famous country house.  It was about this time that his wife's property had to be separately secured to her, and he seems by degrees to have had to sell everything that he owned; but, as he never lacked powerful and generous patrons, this was of small importance to him. In the same year he wrote a ballad, "Les Rieurs du Beau-Richard", and this was followed by many small pieces of occasional poetry addressed to various personages from the king downwards. Fouquet fell out of favour with the king and was arrested. La Fontaine, like most of Fouquet's literary protégés, showed some fidelity to him by writing the elegy "Pleurez, Nymphes de Vaux".  Just at this time his affairs did not look promising. His father and he had assumed the title of esquire, to which they were not strictly entitled, and, some old edicts on the subject having been put in force, an informer procured a sentence against the poet fining him 2000 livres. He found, however, a new protector in the duke and still more in the Duchess of Bouillon, his feudal superiors at Château-Thierry, and nothing more is heard of the fine.  Some of La Fontaine's liveliest verses are addressed to the duchess Marie Anne Mancini, the youngest of Mazarin's nieces, and it is even probable that the taste of the duke and duchess for Ariosto had something to do with the writing of his first work of real importance, the first book of the "Contes", which appeared in 1664. He was then forty-three years old, and his previous printed productions had been comparatively trivial, though much of his work was handed about in manuscript long before it was regularly published.

Fame.

It was about this time that the quartet of the Rue du Vieux Colombier, so famous in French literary history, was formed. It consisted of La Fontaine, Racine, Boileau and Molière, the last of whom was almost of the same age as La Fontaine, the other two considerably younger. Chapelain was also a kind of outsider in the coterie. There are many anecdotes, some pretty obviously apocryphal, about these meetings. The most characteristic is perhaps that which asserts that a copy of Chapelain's unlucky "Pucelle" always lay on the table, a certain number of lines of which was the appointed punishment for offences against the company. The coterie furnished under feigned names the personages of La Fontaine's version of the "Cupid and Psyche" story, which, however, with "Adonis", was not printed till 1669. Meanwhile, the poet continued to find friends. In 1664 he was regularly commissioned and sworn in as gentleman to the duchess dowager of Orléans, and was installed in the Luxembourg. He still retained his rangership, and in 1666 we have something like a reprimand from Colbert suggesting that he should look into some malpractices at Chateau Thierry. In the same year appeared the second book of the "Contes", and in 1668 the first six books of the "Fables", with more of both kinds in 1671. In this latter year a curious instance of the docility with which the poet lent himself to any influence was afforded by his officiating, at the instance of the Port-Royalists, as editor of a volume of sacred poetry dedicated to the Prince of Conti.  A year afterwards his situation, which had for some time been decidedly flourishing, showed signs of changing very much for the worse. The duchess of Orléans died, and he apparently had to give up his rangership, probably selling it to pay debts. But there was always a providence for La Fontaine. Madame de la Sablière, a woman of great beauty, of considerable intellectual power and of high character, invited him to make his home in her house, where he lived for some twenty years. He seems to have had no trouble whatever about his affairs thenceforward; and could devote himself to his two different lines of poetry, as well as to that of theatrical composition.

Academy.

In 1682 he was, at more than sixty years of age, recognized as one of the foremost men of letters of France. Madame de Sévigné, one of the soundest literary critics of the time, and by no means given to praise mere novelties, had spoken of his second collection of "Fables" published in the winter of 1678 as divine; and it is pretty certain that this was the general opinion. It was not unreasonable, therefore, that he should present himself to the Académie française, and, though the subjects of his "Contes" were scarcely calculated to propitiate that decorous assembly, while his attachment to Fouquet and to more than one representative of the old Frondeur party made him suspect to Colbert and the king, most of the members were his personal friends.  He was first proposed in 1682, but was rejected for Marquis de Dangeau. The next year Colbert died and La Fontaine was again nominated. Boileau was also a candidate, but the first ballot gave the fabulist sixteen votes against seven only for the critic. The king, whose assent was necessary, not merely for election but for a second ballot in case of the failure of an absolute majority, was ill-pleased, and the election was left pending. Another vacancy occurred, however, some months later, and to this Boileau was elected. The king hastened to approve the choice effusively, adding, "Vous pouvez incessamment recevoir La Fontaine, il a promis d'etre sage".  His admission was indirectly the cause of the only serious literary quarrel of his life. A dispute took place between the Academy and one of its members, Antoine Furetière, on the subject of the latter's French dictionary, which was decided to be a breach of the Academy's corporate privileges. Furetière, a man of no small ability, bitterly assailed those whom he considered to be his enemies, and among them La Fontaine, whose unlucky "Contes" made him peculiarly vulnerable, his second collection of these tales having been the subject of a police condemnation. The death of the author of the "Roman Bourgeois", however, put an end to this quarrel.  Shortly afterwards La Fontaine had a share in a still more famous affair, the celebrated Ancient-and-Modern squabble in which Boileau and Charles Perrault were the chiefs, and in which La Fontaine (though he had been specially singled out by Perrault for better comparison with Aesop and Phaedrus) took the Ancient side. About the same time (1685–1687) he made the acquaintance of the last of his many hosts and protectors, Monsieur and Madame d'Hervart, and fell in love with a certain Madame Ulrich, a lady of some position but of doubtful character. This acquaintance was accompanied by a great familiarity with Vendôme, Chaulieu and the rest of the libertine coterie of the Temple; but, though Madame de la Sablière had long given herself up almost entirely to good works and religious exercises, La Fontaine continued an inmate of her house until her death in 1693. What followed is told in one of the best known of the many stories bearing on his childlike nature. Hervart on hearing of the death, had set out at once to find La Fontaine. He met him in the street in great sorrow, and begged him to make his home at his house. "J'y allais" was La Fontaine's answer. In 1692, the writer had published a revised edition of the "Contes", although he suffered a severe illness. In that same year, La Fontaine converted to Christianity. A young priest, M. Poucet, tried to persuade him about the impropriety of the "Contes" and it is said that the destruction of a new play was demanded and submitted to as a proof of repentance. La Fontaine received the Viaticum, and the following years he continued to write poems and fables.  A story is told of the young duke of Burgundy, Fénelon's pupil, who was then only eleven years old, sending 50 louis to La Fontaine as a present of his own motion. But, though La Fontaine recovered for the time, he was broken by age and infirmity, and his new hosts had to nurse rather than to entertain him, which they did very carefully and kindly. He did a little more work, completing his "Fables" among other things; but he did not survive Madame de la Sablière much more than two years, dying on 13 April 1695 in Paris, at the age of seventy-three. When the Père Lachaise Cemetery opened in Paris, La Fontaine's remains were moved there. His wife survived him nearly fifteen years.

Anecdotes.

The curious personal character of La Fontaine, like that of some other men of letters, has been enshrined in a kind of legend by literary tradition. At an early age his absence of mind and indifference to business gave a subject to Gédéon Tallemant des Réaux. His later contemporaries helped to swell the tale, and the 18th century finally accepted it, including the anecdotes of his meeting his son, being told who he was, and remarking, "Ah, yes, I thought I had seen him somewhere!", of his insisting on fighting a duel with a supposed admirer of his wife, and then imploring him to visit at his house just as before; of his going into company with his stockings wrong side out, &c., with, for a contrast, those of his awkwardness and silence, if not positive rudeness in company.  It ought to be remembered, as a comment on the unfavourable description by Jean de La Bruyère, that La Fontaine was a special friend and ally of Benserade, La Bruyere's chief literary enemy. But after all deductions much will remain, especially when it is remembered that one of the chief authorities for these anecdotes is Louis Racine, a man who possessed intelligence and moral worth, and who received them from his father, La Fontaine's attached friend for more than thirty years. Perhaps the best worth recording of all these stories is one of the Vieux Colombier quartet, which tells how Molière, while Racine and Boileau were exercising their wits upon "le bonhomme" or "le bon" (by both which titles La Fontaine was familiarly known), remarked to a bystander, "Nos beaux esprits ont beau faire, ils n'effaceront pas le bonhomme". They have not.

Works.

The numerous works of La Fontaine fall into three traditional divisions: the Fables, the Tales and the miscellaneous (including dramatic) works. He is best known for the first of these, in which a tradition of fable collecting in French verse reaching back to the Middle Ages was brought to a peak. Although these earlier works refer to Aesop in their title, they collected many fables from more recent sources. Among the foremost were Marie de France's "Ysopet" (1190) and Gilles Corrozet’s "Les Fables du très ancien Esope, mises en rithme françoise" (1542).  The publication of the twelve books of La Fontaine's "Fables" extended from 1668 to 1694. The stories in the first six of these derive for the most part from Aesop and Horace and are pithily told in free verse. Those in the later editions are often taken from more recent sources or from translations of Eastern stories and are told at greater length. The deceptively simple verses are easily memorised, yet display deep insights into human nature. Many of the lines have entered the French language as standard phrases, often proverbial. The fables are also distinguished by their occasionally ironical ambivalence. The fable of "The Sculptor and the Statue of Jupiter" (IX.6), for example, reads like a satire on superstition, but its moralising conclusion that "All men, as far as in them lies,/Create realities of dreams" might equally be applied to religion as a whole.  The second division of his work, the tales ("Contes et nouvelles en vers"), were at one time almost equally as popular and their writing extended over a longer period. The first were published in 1664 and the last appeared posthumously. They were particularly marked by their archly licentious tone.

Depictions and legacy.

While the Fables have an international reputation, celebration of their author has largely been confined to France. Even in his own lifetime, such was his renown, he was painted by three leading portraitists. It was at the age of 63, on the occasion of his reception into the Académie française in 1684, that he was portrayed by Hyacinthe Rigaud. Nicolas de Largillière painted him at the age of 73, and a third portrait is attributed to François de Troy (see below). Two contemporary sculptors made head and shoulders busts of La Fontaine. Jean-Jacques Caffieri’s was exhibited at the 1779 Salon and then given to the Comédie Française; Jean-Antoine Houdon’s dates from 1782. There are in fact two versions by Houdon, one now at the Philadelphia Museum of Art, and another at the castle of his former patron Fouquet at Vaux-le-Vicomte (see below).  In Paris there is a full length marble statue by Pierre Julien, now in the Louvre, that was commissioned in 1781 and exhibited at the 1785 Salon. The writer is represented in an ample cloak, sitting in contemplation on a gnarled tree on which a vine with grapes is climbing. On his knee is the manuscript of the fable of the fox and the grapes, while at his feet a fox is seated on his hat with its paw on a leather-bound volume, looking up at him. Small scale porcelain models were made of this by the Sèvres pottery and in polychrome porcelain by the Frankenthal pottery. In the following century small models were made of the bronze statue by Etienne Marin Melingue, exhibited in Paris in 1840 and in London in 1881. In this the poet is leaning thoughtfully against a rock, hat in hand. Also in the Cour Napoléon of the Louvre is the 1857 standing stone statue by Jean-Louis Jaley.  Another commemorative monument to La Fontaine was set up at the head of the Parisian Jardin du Ranelagh in 1891. The bronze bust designed by Achille Dumilâtre was exhibited at the Exposition Universelle (1889) before being placed on a high stone pedestal surrounded by various figures from the fables. The work was melted down, like many others during World War II, but was replaced in 1983 by Charles Correia's standing statue of the fabulist looking down at the fox and the crow on the steps and plinth below him. There are more statues in Château-Thierry, the town of the poet's birth. The most prominent is the standing statue by Charles-René Laitié, which was ordered by command of Louis XVIII as a gift to the town. It was officially set in place in a square overlooking the Marne in 1824. During the Second Battle of the Marne it was damaged and was then moved about the town. Repaired now, its present position is in the square fronting the poet's former house. At his feet the race between the Tortoise and the Hare is taking place. The house itself has now been converted into a museum, outside which stands the life-sized statue created by Bernard Seurre. Inside the museum is Louis-Pierre Deseine’s head and shoulders clay bust of La Fontaine.  Further evidence of La Fontaine's enduring popularity is his appearance on a playing card from the second year of the French Revolution. In this pack royalty is displaced by the rationalist free-thinkers known as Philosophes, and the ironical fabulist figures as the King of Spades. He was no less popular at the Bourbon Restoration, as is evidenced by the royal commission of his statue. Besides that, there was the 1816 bronze commemorative medal depicting the poet's head, designed by Jacques-Édouard Gatteaux, in the Great Men of France series. More recently there has been a sideways seated view of him in the "Histoire de France series". The head of La Fontaine also appeared on a 100 franc coin to commemorate the 300th anniversary of his death, on the reverse of which the fable of the fox and the crow is depicted. Another commemoration that year included the strip of 2.80 euro fable stamps, in the composite folder of which appeared a detachable portrait without currency. In 1995 equally, the asteroid 5780 Lafontaine was named in his honour.  Other appearances on postage stamps include the 55 centimes issue of 1938, with a medallion of the fable of The Wolf and the Lamb below him; and the Monaco 50-cent stamp commemorating the 350th anniversary of La Fontaine's birth in 1971, in which the head and shoulders of the fabulist appear below some the more famous characters about which he wrote. Another coin series on which he appears is the annual"Fables de La Fontaine" celebration of the (Chinese) lunar new year. Issued since 2006, these bullion coins have had his portrait on the reverse and on the face each year's particular zodiac animal.  Fictional depictions have followed the fashionable view of La Fontaine at their period. As a minor character in Alexandre Dumas's novel "The Vicomte of Bragelonne", he appears as a bumbling and scatterbrained courtier of Nicolas Fouquet. In the 2007 film "Jean de La Fontaine – le défi", however, the poet resists the absolutist rule of Louis XVI after the fall of Fouquet.

Jean de La Fontaine (,, ; 8 July 162113 April 1695) was a French fabulist and one of the most widely read French poets of the 17th century. He is known above all for his "Fables", which provided a model for subsequent fabulists across Europe and numerous alternative versions in France, as well as in French regional languages.

Jean de La Fontaine (8. července 1621, Château-Thierry – 13. dubna 1695, Paříž) byl francouzský spisovatel – bajkař a básník.