title: Ulysses (novel)

text: Bloom's thoughts are peppered with references to food as lunchtime approaches. He meets an old flame, hears news of Mina Purefoy's labour, and helps a blind boy cross the street. He enters the restaurant of the Burton Hotel, where he is revolted by the sight of men eating like animals. He goes instead to Davy Byrne's pub, where he consumes a gorgonzola cheese sandwich and a glass of burgundy, and muses upon the early days of his relationship with Molly and how the marriage has declined: "Me. And me now." Bloom's thoughts touch on what goddesses and gods eat and drink. He ponders whether the statues of Greek goddesses in the National Museum have anuses as do mortals. On leaving the pub Bloom heads toward the museum, but spots Boylan across the street and, panicking, rushes into the gallery across the street from the museum.


title: Ulysses (novel)

text: At the National Library, Stephen explains to some scholars his biographical theory of the works of Shakespeare, especially "Hamlet", which he argues are based largely on the posited adultery of Shakespeare's wife. Buck Mulligan arrives and interrupts to read out the telegram that Stephen had sent him indicating that he would not make their planned rendezvous at The Ship. Bloom enters the National Library to look up an old copy of the ad he has been trying to place. He passes in between Stephen and Mulligan as they exit the library at the end of the episode.


title: Ulysses (novel)

text: In this episode, nineteen short vignettes depict the movements of various characters, major and minor, through the streets of Dublin. The episode begins by following Father Conmee, a Jesuit priest, on his trip north, and ends with an account of the cavalcade of the Lord Lieutenant of Ireland, William Ward, Earl of Dudley, through the streets, which is encountered by several characters from the novel.


title: Ulysses (novel)

text: In this episode, dominated by motifs of music, Bloom has dinner with Stephen's uncle at the Ormond hotel, while Molly's lover, Blazes Boylan, proceeds to his rendezvous with her. While dining, Bloom listens to the singing of Stephen's father and others, watches the seductive barmaids, and composes a reply to Martha Clifford's letter.


title: Ulysses (novel)

text: This chapter is narrated by an unnamed denizen of Dublin who works as a debt collector. The narrator goes to Barney Kiernan's pub where he meets a character referred to only as "The Citizen". This character is believed to be a satirisation of Michael Cusack, a founder member of the Gaelic Athletic Association. When Leopold Bloom enters the pub, he is berated by the Citizen, who is a fierce Fenian and anti-Semite. The episode ends with Bloom reminding the Citizen that his Saviour was a Jew. As Bloom leaves the pub, the Citizen throws a biscuit tin at Bloom's head, but misses. The chapter is marked by extended tangents made in voices other than that of the unnamed narrator; these include streams of legal jargon, a report of a boxing match, Biblical passages, and elements of Irish mythology.


title: Ulysses (novel)

text: All the action of the episode takes place on the rocks of Sandymount Strand, the shoreline that Stephen visited in Episode 3. A young woman, Gerty MacDowell, is seated on the rocks with her two friends, Cissy Caffrey and Edy Boardman. The girls are taking care of three children, a baby, and four-year-old twins named Tommy and Jacky. Gerty contemplates love, marriage and femininity as night falls. The reader is gradually made aware that Bloom is watching her from a distance. Gerty teases the onlooker by exposing her legs and underwear, and Bloom, in turn, masturbates. Bloom's masturbatory climax is echoed by the fireworks at the nearby bazaar. As Gerty leaves, Bloom realises that she has a lame leg, and believes this is the reason she has been "left on the shelf". After several mental digressions he decides to visit Mina Purefoy at the maternity hospital. It is uncertain how much of the episode is Gerty's thoughts, and how much is Bloom's sexual fantasy. Some believe that the episode is divided into two halves: the first half the highly romanticized viewpoint of Gerty, and the other half that of the older and more realistic Bloom. Joyce himself said, however, that "nothing happened between [Gerty and Bloom]. It all took place in Bloom's imagination". "Nausicaa" attracted immense notoriety while the book was being published in serial form. It has also attracted great attention from scholars of disability in literature. The style of the first half of the episode borrows from (and parodies) romance magazines and novelettes.


title: Ulysses (novel)

text: Bloom visits the maternity hospital where Mina Purefoy is giving birth, and finally meets Stephen, who has been drinking with his medical student friends and is awaiting the promised arrival of Buck Mulligan. As the only father in the group of men, Bloom is concerned about Mina Purefoy in her labour. He starts thinking about his wife and the births of his two children. He also thinks about the loss of his only 'heir', Rudy. The young men become boisterous, and start discussing such topics as fertility, contraception and abortion. There is also a suggestion that Milly, Bloom's daughter, is in a relationship with one of the young men, Bannon. They continue on to a pub to continue drinking, following the successful birth of a son to Mina Purefoy. This chapter is remarkable for Joyce's wordplay, which, among other things, recapitulates the entire history of the English language. After a short incantation, the episode starts with latinate prose, Anglo-Saxon alliteration, and moves on through parodies of, among others, Malory, the King James Bible, Bunyan, Pepys, Defoe, Sterne, Walpole, Gibbon, Dickens, and Carlyle, before concluding in a Joycean version of contemporary slang. The development of the English language in the episode is believed to be aligned with the nine-month gestation period of the foetus in the womb.


title: Ulysses (novel)

text: Episode 15 is written as a play script, complete with stage directions. The plot is frequently interrupted by "hallucinations" experienced by Stephen and Bloom—fantastic manifestations of the fears and passions of the two characters. Stephen and his friend Lynch walk into Nighttown, Dublin's red-light district. Bloom pursues them and eventually finds them at Bella Cohen's brothel where, in the company of her workers including Zoe Higgins, Florry Talbot and Kitty Ricketts, he has a series of hallucinations regarding his sexual fetishes, fantasies and transgressions. Bloom is put in the dock to answer charges by a variety of sadistic, accusing women including Mrs Yelverton Barry, Mrs Bellingham and the Hon Mrs Mervyn Talboys. When Bloom witnesses Stephen overpaying in the brothel, he decides to hold onto the rest of Stephen's money for safekeeping. Stephen hallucinates that the rotting cadaver of his mother has risen up from the floor to confront him. Stephen cries "Non serviam!", uses his walking stick to smash a chandelier, and flees the room. Bloom quickly pays Bella for the damage, then runs after Stephen. He finds Stephen engaged in an argument with an English soldier, Private Carr, who, after a perceived insult to the King, punches Stephen. The police arrive and the crowd disperses. As Bloom is tending to Stephen, he has a hallucination of Rudy, his deceased son, as an 11-year-old.


title: Ulysses (novel)

text: Bloom takes Stephen to a cabman's shelter near Butt Bridge to restore him to his senses. There, they encounter a drunken sailor, D. B. Murphy (W. B. Murphy in the 1922 text). The episode is dominated by the motif of confusion and mistaken identity, with Bloom, Stephen and Murphy's identities being repeatedly called into question. The narrative's rambling and laboured style in this episode reflects the protagonists' nervous exhaustion and confusion.


title: Ulysses (novel)

text: Bloom returns home with Stephen, makes him a cup of cocoa, discusses cultural and linguistic differences between them, considers the possibility of publishing Stephen's parable stories, and offers him a place to stay for the night. Stephen refuses Bloom's offer and is ambiguous in response to Bloom's proposal of future meetings. The two men urinate in the backyard, Stephen departs and wanders off into the night, and Bloom goes to bed, where Molly is sleeping. She awakens and questions him about his day. The episode is written in the form of a rigidly organised and "mathematical" catechism of 309 questions and answers, and was reportedly Joyce's favourite episode in the novel. The deep descriptions range from questions of astronomy to the trajectory of urination and include a list of 25 men that purports to be the "preceding series" of Molly's suitors and Bloom's reflections on them. While describing events apparently chosen randomly in ostensibly precise mathematical or scientific terms, the episode is rife with errors made by the undefined narrator, many or most of which are intentional by Joyce.


title: Ulysses (novel)

text: The final episode consists of Molly Bloom's thoughts as she lies in bed next to her husband. The episode uses a stream-of-consciousness technique in eight paragraphs and lacks punctuation. Molly thinks about Boylan and Bloom, her past admirers, including Lieutenant Stanley G. Gardner, the events of the day, her childhood in Gibraltar, and her curtailed singing career. She also hints at a lesbian relationship in her youth, with a childhood friend, Hester Stanhope. These thoughts are occasionally interrupted by distractions, such as a train whistle or the need to urinate. Molly is surprised by the early arrival of her menstrual period, which she ascribes to her vigorous sex with Boylan. The episode concludes with Molly's remembrance of Bloom's marriage proposal, and of her acceptance: "he asked me would I yes to say yes my mountain flower and first I put my arms around him yes and drew him down to me so he could feel my breasts all perfume yes and his heart was going like mad and yes I said yes I will Yes."


title: Ulysses (novel)

text: The publication history of "Ulysses" is complex. There have been at least 18 editions, and variations in different impressions of each edition.


title: Ulysses (novel)

text: According to Joyce scholar Jack Dalton, the first edition of "Ulysses" contained over 2,000 errors. As subsequent editions attempted to correct these mistakes, they would often add more, due in part to the difficulty of separating non-authorial errors from Joyce's deliberate "errors" devised to challenge the reader.


title: Ulysses (novel)

text: Hans Walter Gabler's 1984 edition was the most sustained attempt to produce a corrected text, but it has received much criticism, most notably from John Kidd. Kidd's main theoretical criticism is of Gabler's choice of a patchwork of manuscripts as his copy-text (the base edition with which the editor compares each variant), but this fault stems from an assumption of the Anglo-American tradition of scholarly editing rather than the blend of French and German editorial theories that actually lay behind Gabler's reasoning. The choice of a composite copy-text is seen to be problematic in the eyes of some American editors, who generally favour the first edition of any particular work as copy-text.


title: Ulysses (novel)

text: Less subject to differing national editorial theories, however, is the claim that for hundreds of pages—about half the episodes of "Ulysses"—the extant manuscript is purported to be a "fair copy" that Joyce made for sale to a potential patron. (As it turned out, John Quinn, the Irish-American lawyer and collector, purchased the manuscript.) Diluting this charge somewhat is the fact that the theory of (now lost) final working drafts is Gabler's own. For the suspect episodes, the existing typescript is the last witness. Gabler attempted to reconstruct what he called "the continuous manuscript text", which had never physically existed, by adding together all of Joyce's accretions from the various sources. This allowed Gabler to produce a "synoptic text" indicating the stage at which each addition was inserted. Kidd and even some of Gabler's own advisers believe this method meant losing Joyce's final changes in about two thousand places. Far from being "continuous", the manuscripts seem to be opposite. Jerome McGann describes in detail the editorial principles of Gabler in his article for the journal "Criticism", issue 27, 1985. In the wake of the controversy, still other commentators charged that Gabler's changes were motivated by a desire to secure a fresh copyright and another seventy-five years of royalties beyond a looming expiration date.


title: Ulysses (novel)

text: In June 1988 John Kidd published "The Scandal of "Ulysses"" in "The New York Review of Books", charging that not only did Gabler's changes overturn Joyce's last revisions, but in another four hundred places Gabler failed to follow any manuscript whatever, making nonsense of his own premises. Kidd accused Gabler of unnecessarily changing Joyce's spelling, punctuation, use of accents, and all the small details he claimed to have been restoring. Instead, Gabler was actually following printed editions such as that of 1932, not the manuscripts. Gabler was found to have made genuine blunders, such as his changing the name of the real-life Dubliner Harry Thrift to 'Shrift' and cricketer Captain Buller to 'Culler' on the basis of handwriting irregularities in the extant manuscript. (These "corrections" were undone by Gabler in 1986.) Kidd stated that many of Gabler's errors resulted from Gabler's use of facsimiles rather than original manuscripts.


title: Ulysses (novel)

text: In December 1988, Charles Rossman's "The New "Ulysses:" The Hidden Controversy" for "The New York Review" revealed that some of Gabler's own advisers felt too many changes were being made, but that the publishers were pushing for as many alterations as possible. Then Kidd produced a 174-page critique that filled an entire issue of the "Papers of the Bibliographical Society of America", dated the same month. This "Inquiry into "Ulysses": The Corrected Text" was published the next year in book format and on floppy disk by Kidd's James Joyce Research Center at Boston University.


title: Ulysses (novel)

text: Gabler and others, including Michael Groden, have rejected Kidd's critique. In his 1993 afterword to the Gabler edition, Groden writes that Kidd's lists of supposed errors were constructed "with so little demonstrated understanding of Gabler's theoretical assumptions and procedures...that they can point to errors or misjudgments only by accident." The scholarly community remains divided.


title: Ulysses (novel)

text: In 1990, Gabler's American publisher Random House, after consulting a committee of scholars, replaced the Gabler edition with its 1961 version, and in the United Kingdom the Bodley Head press revived its 1960 version (upon which Random House's 1961 version is based). In both the UK and US, Everyman's Library also republished the 1960 "Ulysses". In 1992, Penguin dropped Gabler and reprinted the 1960 text. The Gabler version remained available from Vintage International. Reprints of the 1922 first edition have also become widely available since 1 January 2012, when this edition entered the public domain under U.S. copyright law.


title: Ulysses (novel)

text: In 1992, W. W. Norton announced that it would publish Kidd's much-anticipated edition of "Ulysses" as part of "The Dublin Edition of the Works of James Joyce" series. This book had to be withdrawn when the Joyce estate objected. For a period thereafter the estate refused to authorise any further editions of Joyce's work. This ended when it agreed to allow Wordsworth Editions to bring out a bargain version of the novel (a reprint of the 1932 Odyssey Press edition) in January 2010, ahead of copyright expiration in 2012.


title: Ulysses (novel)

text: Written over a seven-year period from 1914 to 1921, "Ulysses" was serialised in the American journal "The Little Review" from 1918 to 1920, when the publication of the "Nausicaä" episode led to a prosecution for obscenity under the Comstock Act of 1873, which made it illegal to circulate materials deemed obscene in the U.S. mail. In 1919, sections of the novel also appeared in the London literary journal "The Egoist", but the novel itself was banned in the United Kingdom until 1936. Joyce had resolved that the book would be published on his 40th birthday, 2 February 1922, and Sylvia Beach, Joyce's publisher in Paris, received the first three copies from the printer that morning.


title: Ulysses (novel)

text: The 1920 prosecution in the US was brought after "The Little Review" serialised a passage of the book depicting characters masturbating. Three earlier chapters had been banned by the US Post Office, but it was Secretary of the New York Society for the Suppression of Vice John S. Sumner who instigated this legal action. The Post Office did partially suppress the "Nausicaä" edition of "The Little Review". Legal historian Edward de Grazia has argued that few readers would have been fully aware of the masturbation in the text, given the metaphoric language. Irene Gammel extends this argument to suggest that the obscenity allegations brought against "The Little Review" were influenced by the Baroness Elsa von Freytag-Loringhoven's more explicit poetry, which had appeared alongside the serialization of "Ulysses." At the trial in 1921 the magazine was declared obscene and, as a result, "Ulysses" was effectively banned in the United States. Throughout the 1920s, the United States Post Office Department burned copies of the novel.


title: Ulysses (novel)

text: In 1932, Random House and lawyer Morris Ernst arranged to import the French edition and have a copy seized by Customs. Random House contested the seizure, and in "United States v. One Book Called Ulysses", U.S. District Judge John M. Woolsey ruled that the book was not pornographic and therefore could not be obscene, a decision Stuart Gilbert called "epoch-making". The Second Circuit Court of Appeals affirmed the ruling in 1934. The U.S. thus became the first English-speaking country where the book was freely available. Although Ireland's Censorship of Publications Board never banned "Ulysses", a customs loophole prevented it from being allowed into Ireland. It was first openly available in Ireland in the 1960s.


title: Ulysses (novel)

text: In a review in "The Dial", T. S. Eliot said of "Ulysses": "I hold this book to be the most important expression which the present age has found; it is a book to which we are all indebted, and from which none of us can escape." He went on to assert that Joyce was not at fault if people after him did not understand it: "The next generation is responsible for its own soul; a man of genius is responsible to his peers, not to a studio full of uneducated and undisciplined coxcombs."


title: Ulysses (novel)

text: "Ulysses" has been called "the most prominent landmark in modernist literature", a work where life's complexities are depicted with "unprecedented, and unequalled, linguistic and stylistic virtuosity". That style has been called the finest example of stream-of-consciousness in modern fiction, with Joyce going deeper and farther than any other novelist in interior monologue and stream of consciousness. This technique has been praised for its faithful representation of the flow of thought, feeling, and mental reflection, as well as shifts of mood.


title: Ulysses (novel)

text: Literary critic Edmund Wilson noted that "Ulysses" attempts to render "as precisely and as directly as it is possible in words to do, what our participation in life is like—or rather, what it seems to us like as from moment to moment we live." Stuart Gilbert said that the "personages of "Ulysses" are "not" fictitious" but that "these people are as they must be; they act, we see, according to some "lex eterna", an ineluctable condition of their very existence". Through these characters Joyce "achieves a coherent and integral interpretation of life".


title: Ulysses (novel)

text: Joyce uses "metaphors, symbols, ambiguities, and overtones which gradually link themselves together so as to form a network of connections binding the whole" work. This system of connections gives the novel a wide, more universal significance, as "Leopold Bloom becomes a modern Ulysses, an Everyman in a Dublin which becomes a microcosm of the world." Eliot called this system the "mythic method": "a way of controlling, of ordering, of giving a shape and a significance to the immense panorama of futility and anarchy which is contemporary history". Novelist Vladimir Nabokov called "Ulysses" a "divine work of art" and the greatest masterpiece of 20th-century prose, and said that "it towers above the rest of Joyce's writing" with "noble originality, unique lucidity of thought and style". Psychology professor Charles Fernyhough called "Ulysses" "the archetypal stream of consciousness novel".


title: Ulysses (novel)

text: The book had its critics, largely in response to its then-uncommon inclusion of sexual elements. Shane Leslie called "Ulysses" "literary Bolshevism ... experimental, anti-conventional, anti-Christian, chaotic, totally unmoral". Karl Radek called it "a heap of dung, crawling with worms, photographed by a cinema camera through a microscope". Sisley Huddleston, writing for the Observer, wrote: "I confess that I cannot see how the work upon which Mr Joyce spent seven strenuous years, years of wrestling and of agony, can ever be given to the public." Virginia Woolf wrote, ""Ulysses" was a memorable catastrophe—immense in daring, terrific in disaster." One newspaper pundit said it contained "secret sewers of vice ... canalized in its flood of unimaginable thoughts, images, and pornographic words" and "revolting blasphemies" that "debases and perverts and degrades the noble gift of imagination and wit and lordship of language".


title: Ulysses (novel)

text: "Ulysses in Nighttown", based on Episode 15 ("Circe"), premiered off-Broadway in 1958, with Zero Mostel as Bloom; it debuted on Broadway in 1974.


title: Ulysses (novel)

text: In 2006, playwright Sheila Callaghan's "Dead City", a contemporary stage adaptation of the book set in New York City, and featuring the male figures Bloom and Dedalus reimagined as female characters Samantha Blossom and Jewel Jupiter, was produced in Manhattan by New Georges.


title: Ulysses (novel)

text: In 2012, an adaption was staged in Glasgow, written by Dermot Bolger and directed by Andy Arnold. The production first premiered at the Tron Theatre, and later toured in Dublin, Belfast, Cork, made an appearance at the Edinburgh Festival, and was performed in China. In 2017 a revised version of Bolger's adaption, directed and designed by Graham McLaren, premiered at Ireland's National Theatre, The Abbey Theatre in Dublin, as part of the 2017 Dublin Theatre Festival. It was revived in June 2018, and the script was published by Oberon Books.


title: Ulysses (novel)

text: In 2013, a new stage adaptation of the novel, "Gibraltar", was produced in New York by the Irish Repertory Theatre. It was written by and starred Patrick Fitzgerald and directed by Terry Kinney. This two-person play focused on the love story of Bloom and Molly, played by Cara Seymour.


title: Ulysses (novel)

text: In 1967, a film version of the book was directed by Joseph Strick. Starring Milo O'Shea as Bloom, it was nominated for an Academy Award for Best Adapted Screenplay.


title: Ulysses (novel)

text: In 1988, the episode "James Joyce's "Ulysses"" of the documentary series "The Modern World: Ten Great Writers" was shown on Channel 4. Some of the novel's scenes were dramatised. David Suchet played Leopold Bloom.


title: Ulysses (novel)

text: In September 2022, the episode "James Joyce's "Ulysses"" of the documentary series "Arena", was shown on BBC.<ref name="bbc/m001bvp2"></ref><ref name="irishnews/2022/ulysses-documentary"></ref><ref name="lboro.ac.uk/bbc-ulysses"></ref><ref name="independent.ie/arena-ulysses"></ref><ref name="themorgan.org/arena-ulysses"></ref>


title: Ulysses (novel)

text: On Bloomsday 1982, RTÉ, Ireland's national broadcaster, aired a full-cast, unabridged, dramatised radio production of "Ulysses", that ran uninterrupted for 29 hours and 45 minutes.


title: Ulysses (novel)

text: The unabridged text of "Ulysses" has been performed by Jim Norton with Marcella Riordan. Naxos Records released the recording on 22 audio CDs in 2004. It follows an earlier abridged recording with the same actors.


title: Ulysses (novel)

text: On Bloomsday 2010, author Frank Delaney launched a series of weekly podcasts called "Re:Joyce" that took listeners page by page through "Ulysses", discussing its allusions, historical context and references. The podcast ran until Delaney's death in 2017, at which point it was on the "Wandering Rocks" chapter.


title: Ulysses (novel)

text: BBC Radio 4 aired a new nine-part adaptation dramatised by Robin Brooks and produced/directed by Jeremy Mortimer, and starring Stephen Rea as the Narrator, Henry Goodman as Bloom, Niamh Cusack as Molly and Andrew Scott as Dedalus, for Bloomsday 2012, beginning on 16 June 2012.


title: Ulysses (novel)

text: Comedy/satire recording troupe The Firesign Theatre ends its 1969 album "How Can You Be in Two Places at Once When You're Not Anywhere at All?" with a male voice reciting the final lines of Molly Bloom's soliloquy.


title: Ulysses (novel)

text: The music CD "Classical Ulysses" was launched by the James Joyce Society in Dublin for the Bloomsday100 celebrations in 2004. It contained recorded versions of the classical music mentioned in the book.


title: Ulysses (novel)

text: Kate Bush's song "Flower of the Mountain" (originally the title track on "The Sensual World") sets to music the end of Molly Bloom's soliloquy.


title: Ulysses (novel)

text: "Thema (Omaggio a Joyce)" is an electroacoustic composition for voice and tape by Luciano Berio. Composed between 1958 and 1959, it is based on the interpretative reading of the poem "Sirens" from chapter 11 of the novel. It is sung/voiced by Cathy Berberian. Umberto Eco, a lifelong admirer of Joyce, also contributed to its realisation.


title: Ulysses (novel)

text: Jacob M. Appel's novel "The Biology of Luck" (2013) is a retelling of "Ulysses" set in New York City. It features an inept tour guide, Larry Bloom, whose adventures parallel those of Leopold Bloom through Dublin.


title: Lockheed Martin

text: The Lockheed Martin Corporation is an American aerospace, arms, defense, information security, and technology corporation with worldwide interests. It was formed by the merger of Lockheed Corporation with Martin Marietta in March 1995. It is headquartered in North Bethesda, Maryland, in the Washington, D.C. area. Lockheed Martin employs approximately 115,000 employees worldwide, including about 60,000 engineers and scientists as of January 2022.


title: Lockheed Martin

text: Lockheed Martin is one of the largest companies in the aerospace, military support, security, and technologies industry. It is the world's largest defense contractor by revenue for fiscal year 2014. In 2013, 78% of Lockheed Martin's revenues came from military sales; it topped the list of US federal government contractors and received nearly 10% of the funds paid out by the Pentagon. In 2009, US government contracts accounted for $38.4 billion (85%), foreign government contracts for $5.8 billion (13%), and commercial and other contracts for $900 million (2%).


title: Lockheed Martin

text: Half of the corporation’s annual sales are to the U.S. Department of Defense. Lockheed Martin is also a contractor for the U.S. Department of Energy and the National Aeronautics and Space Administration (NASA).


title: Lockheed Martin

text: Lockheed Martin operates in four business segments: Aeronautics, Missiles and Fire Control (MFC), Rotary and Mission Systems (RMS), and Space. The company has received the Collier Trophy six times, including in 2001 for being part of developing the X-35/F-35B LiftFan Propulsion System and most recently in 2018 for the Automatic Ground Collision Avoidance System (Auto-GCAS). Lockheed Martin is currently developing the F-35 Lightning II and leads the international supply chain, leads the team for the development and implementation of technology solutions for the new USAF Space Fence (AFSSS replacement), and is the primary contractor for the development of the Orion command module. The company also invests in healthcare systems, renewable energy systems, intelligent energy distribution, and compact nuclear fusion.


title: Lockheed Martin

text: Merger talks between Lockheed Corporation and Martin Marietta began in March 1994, with the companies announcing their $10 billion planned merger on August 30, 1994. The headquarters for the combined companies would be at Martin Marietta headquarters in North Bethesda, Maryland. The deal was finalized on March 15, 1995, when the two companies' shareholders approved the merger. The segments of the two companies not retained by the new company formed the basis for L-3 Communications, a mid-size defense contractor in its own right. Lockheed Martin also later spun off the materials company Martin Marietta Materials.


title: Lockheed Martin

text: The company's executives received large bonuses directly from the government as a result of the merger. Norman R. Augustine who was at the time CEO of Martin Marietta received an $8.2 million bonus.


title: Lockheed Martin

text: Both companies contributed important products to the new portfolio. Lockheed products included the Trident missile, P-3 Orion maritime patrol aircraft, U-2 and SR-71 reconnaissance airplanes, F-117 Nighthawk, F-16 Fighting Falcon, F-22 Raptor, C-130 Hercules, A-4AR Fightinghawk and the DSCS-3 satellite. Martin Marietta products included Titan rockets, Sandia National Laboratories (management contract acquired in 1993), Space Shuttle External Tank, Viking 1 and Viking 2 landers, the Transfer Orbit Stage (under subcontract to Orbital Sciences Corporation) and various satellite models.


title: Lockheed Martin

text: On April 22, 1996, Lockheed Martin completed the acquisition of Loral Corporation's defense electronics and system integration businesses for $9.1 billion, the deal having been announced in January. The remainder of Loral became Loral Space & Communications. Lockheed Martin abandoned plans for an $8.3 billion merger with Northrop Grumman on July 16, 1998, due to government concerns over the potential strength of the new group; Lockheed/Northrop would have had control of 25% of the Department of Defense's procurement budget.


title: Lockheed Martin

text: For the Mars Climate Orbiter, Lockheed Martin incorrectly provided NASA with software using measurements in US Customary force units when metric units were expected; this resulted in the loss of the Orbiter at a cost of $125 million. The development of the spacecraft cost $193.1 million.


title: Lockheed Martin

text: In addition to their military products, in the 1990s Lockheed Martin developed the texture mapping chip for the Sega Model 2 arcade system board and the entire graphics system for the Sega Model 3, which were used to power some of the most popular arcade games of the time.


title: Lockheed Martin

text: In May 2001, Lockheed Martin sold Lockheed Martin Control Systems to BAE Systems. On November 27, 2000, Lockheed completed the sale of its Aerospace Electronic Systems business to BAE Systems for $1.67 billion, a deal announced in July 2000. This group encompassed Sanders Associates, Fairchild Systems, and Lockheed Martin Space Electronics & Communications. In 2001, Lockheed Martin won the contract to build the F-35 Lightning II; this was the largest fighter aircraft procurement project since the F-16, with an initial order of 3,000 aircraft. In 2001, Lockheed Martin settled a nine–year investigation conducted by NASA's Office of Inspector General with the assistance of the Defense Contract Audit Agency. The company paid the United States government $7.1 million based on allegations that its predecessor, Lockheed Engineering Science Corporation, submitted false lease costs claims to NASA.


title: Lockheed Martin

text: On May 12, 2006, "The Washington Post" reported that when Robert Stevens took control of Lockheed Martin in 2004, he faced the dilemma that within 10 years, 100,000 of the about 130,000 Lockheed Martin employees – more than three-quarters – would be retiring. On August 31, 2006, Lockheed Martin won a $3.9 billion contract from NASA to design and build the CEV capsule, later named "Orion" for the Ares I rocket in the Constellation Program. In 2009, NASA reduced the capsule crew requirements from the initial six seats to four for transport to the International Space Station.


title: Lockheed Martin

text: In August 2007, Lockheed Martin acquired 3Dsolve, a Cary, North Carolina company that created simulations and training modules for the military and corporate clients. Renamed Lockheed Martin 3D Learning Systems, the company remained in Cary with 3D's founder founder Richard Boyd as director. The name was eventually shortened to Lockheed Martin 3D Solutions.


title: Lockheed Martin

text: On August 13, 2008, Lockheed Martin acquired the government business unit of Nantero, Inc., a company that had developed methods and processes for incorporating carbon nanotubes in next-generation electronic devices. In 2009, Lockheed Martin bought Unitech.


title: Lockheed Martin

text: On November 18, 2010, Lockheed Martin announced that it would be closing its Eagan, Minnesota, location by 2013 to reduce costs and optimize capacity at its locations nationwide. In January 2011, Lockheed Martin agreed to pay the US Government $2 million to settle allegations that the company submitted false claims on a U.S. government contract for that amount. The allegations came from a contract with the Naval Oceanographic Office Major Shared Resource Center in Mississippi. On May 25, 2011, Lockheed Martin bought the first Quantum Computing System from D-Wave Systems. Lockheed Martin and D-Wave will collaborate to realize the benefits of a computing platform based upon a quantum annealing processor, as applied to some of Lockheed Martin's most challenging computation problems. Lockheed Martin established a multi-year contract that includes one system, maintenance and services. Potentially an important milestone for both companies.


title: Lockheed Martin

text: On May 28, 2011, it was reported that a cyberattack using previously stolen EMC files had broken through to sensitive materials at the contractor. It is unclear if the Lockheed incident is the specific prompt whereby on June 1, 2011, the new United States military strategy, makes explicit that a cyberattack is "casus belli" for a traditional act of war.


title: Lockheed Martin

text: On July 10, 2012, Lockheed Martin announced it was cutting its workforce by 740 workers to reduce costs and remain competitive as necessary for future growth. On November 27, 2012, Lockheed Martin announced that Marillyn Hewson will become the corporation's chief executive officer on January 1, 2013.


title: Lockheed Martin

text: On January 7, 2013, Lockheed Martin Canada announced that it will be acquiring the engine maintenance, repair and overhaul assets from Aveos Fleet Performance in Montreal, Quebec, Canada. On July 3, 2013, Lockheed Martin announced that it was partnering with DreamHammer to use the company's software for integrated command and control of its unmanned aerial vehicles. Lockheed Martin teamed up with Bell Helicopter to propose the V-280 Valor tiltrotor for the Future Vertical Lift (FVL) program. In September 2013, Lockheed Martin acquired the Scotland-based tech firm, Amor Group, saying the deal would aid its plans to expand internationally and into non-defense markets. On November 14, 2013, Lockheed announced they would be closing their Akron, Ohio facility laying off 500 employees and transferring other employees to other locations.


title: Lockheed Martin

text: In March 2014, Lockheed Martin acquired Beontra AG, a provider of integrated planning and demand forecasting tools for airport, planning to expand their business in commercial airport information technology solutions. Also in March 2014, Lockheed Martin announced its acquisition of Industrial Defender Inc. On June 2, 2014, Lockheed Martin received a Pentagon contract to build a space fence that would track debris, keeping it from damaging satellites and spacecraft.


title: Lockheed Martin

text: On July 20, 2015, Lockheed Martin announced plans to purchase Sikorsky Aircraft from United Technologies Corporation at a cost of $7.1 billion. The Pentagon has criticized the acquisition as causing a reduction in competition. In November 2015, the acquisition received final approval from the Chinese government, with a total cost of $9 billion. Dan Schulz was named the president of Lockheed Martin's Sikorsky company. Lockheed Martin has shown sketches for a twin-engine, blended wing body strategic airlifter similar in size to the C-5. On March 31, 2015, the US Navy awarded Lockheed Martin a contract worth $362 million for construction of Freedom-class ship LCS 21 and $79 million for advance procurement for LCS 23. The Freedom-class ships are built by Fincantieri Marinette Marine in Marinette, Wisconsin. In December 2015, Lockheed won an $867 million seven-year contract to train Australia’s next generation of military pilots. There is also an option in the deal to extend this contract across 26 years which would greatly increase the deal’s value.


title: Lockheed Martin

text: In August 2016, Canadian Forces Maritime tested an integrated submarine combat system developed by Lockheed Martin. The test marked Canada’s first use of the combat system with the MK 48 heavyweight torpedo, variant 7AT. The same month, a deal to merge Leidos with the entirety of Lockheed Martin's Information Systems & Global Solutions (IS&GS) business came to a close.


title: Lockheed Martin

text: In May 2017, during a visit to Saudi Arabia by President Donald Trump, Saudi Arabia signed business deals worth tens of billions of dollars with U.S. companies, including Lockheed Martin. (See: 2017 United States–Saudi Arabia arms deal)


title: Lockheed Martin

text: On August 13, 2018, Lockheed Martin announced that the company had secured a $480 million contract from the United States Air Force to develop a hypersonic weapon prototype. A hypersonic missile can travel at one mile a second. This is the second contract for hypersonic weapons that Martin has secured; The first was from the Air Force as well and for $928 million which was announced in April 2018.


title: Lockheed Martin

text: On November 29, 2018, Lockheed Martin was awarded a Commercial Lunar Payload Services contract by NASA, which makes it eligible to bid on delivering science and technology payloads to the Moon for NASA, worth $2.6 billion. Lockheed Martin plans to formally propose a lander called "McCandless Lunar Lander", named after the late astronaut and former Lockheed Martin employee Bruce McCandless II, who in 1984 performed the first free-flying spacewalk without a lifeline to the orbiting shuttle, using a jetpack built by the company. This lander would be based on the successful design of the "Phoenix" and "InSight" Mars landers.


title: Lockheed Martin

text: On April 11, 2019, at 6:35 pm EDT, an Arabsat-6A satellite was successfully launched from (LC-39A). This satellite is one of two, the other being SaudiGeoSat-1/HellasSat-4 and they are the "most advanced commercial communications satellites ever built by" Lockheed Martin.


title: Lockheed Martin

text: On September 23, 2019, Lockheed Martin and NASA signed a $4.6–billion contract to build six or more Orion capsules for NASA's Artemis program to send astronauts to the Moon.


title: Lockheed Martin

text: In January 2020, the Naval Sea Systems Command awarded Lockheed Martin with a $138 million contract related with the AEGIS Combat System Engineering Agent (CSEA). The LMT Rotary and Mission Systems (RMS) unit of the company is to develop, integrate, test, and deliver the AEGIS Advanced Capability Build (ACB) 20 integrated combat system. Martin will work on the AEGIS in New Jersey. The project is expected to be completed by December 2020.


title: Lockheed Martin

text: In January 2020, the Pentagon found at least 800 software defects in Lockheed Martin's F-35 fighter jets owned by the US Armed Forces during an annual review. The 2018 and 2019 reviews revealed a large number of defects as well.


title: Lockheed Martin

text: In February 2020, Lockheed Martin acquired Vector Launch Inc's satellite software technology GalacticSky for $4.25 million after a bankruptcy court received no bids by the February 21 deadline.


title: Lockheed Martin

text: On December 20, 2020, it was announced that Lockheed Martin would acquire Aerojet Rocketdyne Holdings for $4.4 billion. The acquisition was expected to close in first quarter of 2022. On February 13, 2022, Lockheed abandoned the deal following regulatory disapproval.


title: Lockheed Martin

text: For the fiscal year 2020, Lockheed Martin reported earnings of $6.833 billion, with an annual revenue of $65.398 billion, an increase of 9.3% over the previous year. Backlog was 144.0 billion at the end of 2019, up from 130.5 billion at the end of the 2018. Firm orders were $94.5 billion at the end of 2019. Its shares traded at over $389 per share. Its market capitalization was valued at US$109.83 billion at the end of 2019. Lockheed Martin ranked No. 60 in the 2019 Fortune 500 list of the largest United States corporations by total revenue (down from No. 59 in 2018).


title: Lockheed Martin

text: Lockheed Martin Corporation reported Total CO2e emissions (Direct + Indirect) for the twelve months ending 31 December 2020 at 919 Kt (-49 /-5.1% y-o-y).


title: Lockheed Martin

text: Lockheed Martin received $36 billion in government contracts in 2008 alone; more than any company in history. It does work for more than two dozen government agencies from the Department of Defense and the Department of Energy to the Department of Agriculture and the Environmental Protection Agency. It is involved in surveillance and information processing for the CIA, the FBI, the Internal Revenue Service (IRS), the National Security Agency (NSA), The Pentagon, the Census Bureau, and the Postal Service.


title: Lockheed Martin

text: In October 2013, Lockheed announced it expected to finalize a $2.2 billion contract with the United States Air Force for two advanced military communications satellites.


title: Lockheed Martin

text: Lockheed Martin has already begun to help the military transition to renewable energy sources with solar photovoltaic powered microgrids and as the military aims to reach 25% renewable energy by 2025 in order to improve national security.


title: Lockheed Martin

text: On March 3, 2012, the U.S. Justice Department said that Lockheed Martin had agreed to settle allegations that the defense contractor had sold overpriced perishable tools used on many contracts. The DoJ said the allegations were based specifically on the subsidiary Tools & Metals Inc's inflation of costs between 1998 and 2005, which Lockheed Martin then passed on to the U.S. government under its contracts. Further, in March 2006, Todd B. Loftis, a former TMI president, was sentenced to 87 months in prison and ordered to pay a fine of $20 million following his guilty plea.


title: Lockheed Martin

text: On February 20, 2013, Lockheed Martin Corp complied with the U.S. District Court in New York, agreeing to pay a $19.5 million lawsuit to conclude a securities fraud class-action legal battle that had accused the company of deceiving shareholders in regards to expectations for the company's information technology division.


title: Lockheed Martin

text: On December 20, 2014, Lockheed Martin Integrated Systems agreed to settle a False Claims Act lawsuit paying $27.5 million to finalize allegations that it had knowingly overbilled taxpayers for work performed by company staff who did not hold the relevant essential qualifications for the contract.


title: Lockheed Martin

text: As of March 2020, Lockheed Martin shares are mainly held by institutional investors (State Street Corporation, Vanguard group, BlackRock, Capital Group Companies, and others).


title: Lockheed Martin

text: Lockheed Martin is listed as the largest U.S. government contractor and ranks first for the number of incidents, and fifth for the size of settlements on the 'contractor misconduct' database maintained by the Project on Government Oversight, a Washington, D.C.-based watchdog group. Since 1995, the company has agreed to pay $676.8 million to settle 88 instances of misconduct.


title: Lockheed Martin

text: In 2013, Lt. Gen. Christopher Bogdan criticized the company's F-35 fighter program. The general said: "I want them both to start behaving like they want to be around for 40 years... I want them to take on some of the risk of this program. I want them to invest in cost reductions. I want them to do the things that will build a better relationship. I'm not getting all that love yet." The criticism came in the wake of previous criticism from former Defense Secretary Robert Gates regarding the same program.


title: Lockheed Martin

text: According to the magazine "Politico", Lockheed Martin has "a political network that is already the envy of its competitors", and its contracts enjoy wide bipartisan support in the U.S. Congress thanks to it having "perfected the strategy of spreading jobs on weapons programs in key states and congressional districts". The company's 2010 lobbying expenditure by the third quarter was $9.9 million (2009 total: $13.7 million).


title: Lockheed Martin

text: Through its political action committee (PAC), the company provides low levels of financial support to candidates who advocate national defense and relevant business issues. It was the largest contributor to the House Armed Services Committee chairman, Republican Buck McKeon of California with over $50,000 donated in the election cycle as of January 2011. It also was the top donor to Sen. Daniel Inouye (D-HI), the chair of the Senate Appropriations Committee before his death in 2012.


title: Lockheed Martin

text: Lockheed Martin Employees Political Action Committee is one of the 50 largest in the country, according to FEC data. With contributions from 3,000 employees, it donates $500,000 a year to about 260 House and Senate candidates.


title: Lockheed Martin

text: Senior management consists of the CEO, CFO, and Executive Vice Presidents (EVPs) of four business areas. The EVPs are responsible for managing major programs.


title: Lockheed Martin

text: On March 16, 2020, Lockheed announced that CEO Marillyn Hewson would become executive chair and be succeeded as CEO by James Taiclet on June 15; Taiclet is currently the head of American Tower, and was previously the president of Honeywell Aerospace and before that a VP at United Technologies. Lockheed also announced that it would create the chief operating officer role, to which current EVP Frank A. St John would be promoted.


title: Lockheed Martin

text: Employees in each program are organized into four tiers: Tier1 –Program Manager/VP, Tier2-Functional Teams (Finance, Chief Engineer, Quality, Operations, etc.), Tier3-Integrated Product Teams (IPTs) (Weapon System Development, Weapon System Integration, etc.), and Tier4-detailed product development. Floor or touch workers belong to component assembly teams. Lockheed Martin manages and maintains its relationship with these touch workers through its supervisors and unions.


title: Lockheed Martin

text: Lockheed Martin manages employees through its Full Spectrum Leadership and LM21 programs. The LM21 program relies on Six Sigma principles, which are techniques to improve efficiency. Senior management constructs leadership councils and assigns managers to facilitate Kaizen events, which target specific processes for improvement. A manager facilitates teams and processes stakeholders and suppliers to streamline process implementation.


title: Lockheed Martin

text: Tier2 Functional Leads and Tier3 IPT Leads report to Tier1. IPT leads are responsible for entire systems or products defined by the contract's Statement of Work.


title: Lockheed Martin

text: To control quality, Lockheed Martin trains and builds IPT teams. and ensures that work is executed correctly through a Technical Performance Measure (TPM) system which emphasizes its Lean and 6 Sigma processes. Middle management uses commitment mechanisms that parallel high commitment and human relations theory.


title: Lockheed Martin

text: Floor employees assemble aircraft using Flow-to-takt lean manufacturing process which uses properties from both division of labor and scientific management. By separating tasks based on parts, Lockheed Martin utilizes the division of labor theory, specialization on a specific area creates efficiency.


title: Lockheed Martin

text: The "Double Helix methodology" is a systems development methodology used by Lockheed Martin. It combines experimentation, technology, and a warfighter's concept of operations to create new tactics and weapons.


title: Penicillin

text: Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from "Penicillium" moulds, principally "P. chrysogenum" and "P. rubens". Most penicillins in clinical use are synthesised by P. chrysogenum using deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G (intramuscular or intravenous use) and penicillin V (given by mouth). Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use.


title: Penicillin

text: 10% of the population claims penicillin allergies but because the frequency of positive skin test results decreases by 10% with each year of avoidance, 90% of these patients can tolerate penicillin. Additionally, those with penicillin allergies can usually tolerate cephalosporins (another group of β-lactam) because the Immunoglobulin E (IgE) cross-reactivity is only 3%.


title: Penicillin

text: Penicillin was discovered in 1928 by Scottish scientist Alexander Fleming as a crude extract of "P. rubens". Fleming's student Cecil George Paine was the first to successfully use penicillin to treat eye infection (Ophthalmia neonatorum) in 1930. The purified compound (penicillin F) was isolated in 1940 by a research team led by Howard Florey and Ernst Boris Chain at the University of Oxford. Fleming first used the purified penicillin to treat streptococcal meningitis in 1942. The 1945 Nobel Prize in Physiology or Medicine was shared by Chain, Fleming, and Florey.


title: Penicillin

text: Several semisynthetic penicillins are effective against a broader spectrum of bacteria: these include the antistaphylococcal penicillins, aminopenicillins, and antipseudomonal penicillins.


title: Penicillin

text: The term "penicillin" is defined as the natural product of "Penicillium" mould with antimicrobial activity. It was coined by Alexander Fleming on 7 March 1929 when he discovered the antibacterial property of "Penicillium rubens". Fleming explained in his 1929 paper in the "British Journal of Experimental Pathology" that "to avoid the repetition of the rather cumbersome phrase 'Mould broth filtrate', the name 'penicillin' will be used." The name thus refers to the scientific name of the mould, as described by Fleming in his Nobel lecture in 1945:I have been frequently asked why I invented the name "Penicillin". I simply followed perfectly orthodox lines and coined a word which explained that the substance penicillin was derived from a plant of the genus Penicillium just as many years ago the word "Digitalin" was invented for a substance derived from the plant "Digitalis".In modern usage, the term penicillin is used more broadly to refer to any β-lactam antimicrobial that contains a thiazolidine ring fused to the β-lactam core and may or may not be a natural product. Like most natural products, penicillin is present in "Penicillium" moulds as a mixture of active constituents (gentamicin is another example of a natural product that is an ill-defined mixture of active components). The principal active components of "Penicillium" are listed in the following table:""


title: Penicillin

text: Other minor active components of "Penicillium" include penicillin O, penicillin U1, and penicillin U6. Other named constituents of natural "Penicillium", such as penicillin A, were subsequently found not to have antibiotic activity and are not chemically related to antibiotic penicillins.


title: Penicillin

text: The precise constitution of the penicillin extracted depends on the species of "Penicillium" mould used and on the nutrient media used to culture the mould. Fleming's original strain of "Penicillium rubens" produces principally penicillin F, named after Fleming. But penicillin F is unstable, difficult to isolate, and produced by the mould in small quantities.


title: Penicillin

text: The principal commercial strain of "Penicillium chrysogenum" (the Peoria strain) produces penicillin G as the principal component when corn steep liquor is used as the culture medium. When phenoxyethanol or phenoxyacetic acid are added to the culture medium, the mould produces penicillin V as the main penicillin instead.


title: Penicillin

text: 6-Aminopenicillanic acid (6-APA) is a compound derived from penicillin G. 6-APA contains the beta-lactam core of penicillin G, but with the side chains stripped off; 6-APA is a useful precursor for manufacturing other penicillins. There are many semi-synthetic penicillins derived from 6-APA and these are in three groups: antistaphylococcal penicillins, broad-spectrum penicillins, and antipseudomonal penicillins. The semi-synthetic penicillins are all referred to as penicillins because they are all derived ultimately from penicillin G.


title: Penicillin

text: The use of units to prescribe penicillin is a historical accident and is largely obsolete outside of the US. Since the original penicillin was an ill-defined mixture of active compounds (an amorphous yellow powder), the potency of each batch of penicillin varied from batch to batch. It was therefore impossible to prescribe 1 g of penicillin because the activity of 1 g of penicillin from one batch would be different from the activity from another batch. After manufacture, each batch of penicillin had to be standardised against a known unit of penicillin: each glass vial was then filled with the number of units required. In the 1940s, a vial of 5,000 Oxford units was standard, but the depending on the batch, could contain anything from 15 mg to 20 mg of penicillin. Later, a vial of 1,000,000 international units became standard, and this could contain 2.5 g to 3 g of natural penicillin (a mixture of penicillin I, II, III, and IV and natural impurities). With the advent of pure penicillin G preparations (a white crystalline powder), there is little reason to prescribe penicillin in units.


title: Penicillin

text: The "unit" of penicillin has had three previous definitions, and each definition was chosen as being roughly equivalent to the previous one.


title: Penicillin

text: There is an older unit for penicillin V that is not equivalent to the current penicillin V unit. The reason is that the US FDA incorrectly assumed that the potency of penicillin V is the same mole-for-mole as penicillin G. In fact, penicillin V is less potent than penicillin G, and the current penicillin V unit reflects that fact.


title: Penicillin

text: Penicillin G (benzylpenicillin) was first produced from a penicillium fungus that occurs in nature. The strain of fungus used today for the manufacture of penicillin G was created by genetic engineering to improve the yield in the manufacturing process. None of the other natural penicillins (F, K, N, X, O, U1 or U6) are currently in clinical use.


title: Penicillin

text: Penicillin V (phenoxymethylpenicillin) is produced by adding the precursor phenoxyacetic acid to the medium in which a genetically modified strain of the penicillium fungus is being cultured.


title: Penicillin

text: There are three major groups of other semi-synthetic antibiotics related to the penicillins. They are synthesised by adding various side-chains to the precursor 6-APA, which is isolated from penicillin G. These are the antistaphylococcal antibiotics, broad-spectrum antibiotics, and antipseudomonal antibiotics.


title: Penicillin

text: Antistaphylococcal antibiotics are so-called because they are resistant to being broken down by staphylococcal penicillinase. They are also, therefore, referred to as being penicillinase-resistant.


title: Penicillin

text: This group of antibiotics is called "broad-spectrum" because they are active against a wide range of Gram-negative bacteria such as "Escherichia coli" and "Salmonella typhi", for which penicillin is not suitable. However, resistance in these organisms is now common.


title: Penicillin

text: There are many ampicillin precursors in existence. These are inactive compounds that are broken down in the gut to release ampicillin. None of these pro-drugs of ampicillin are in current use:


title: Penicillin

text: The Gram-negative species, "Pseudomonas aeruginosa," is naturally resistant to many antibiotic classes. There were many efforts in the 1960s and 1970s to develop antibiotics that are active against "Pseudomonas" species. There are two chemical classes within the group: carboxypenicillins and ureidopenicillins. All are given by injection: none can be given by mouth.


title: Penicillin

text: The term "penicillin", when used by itself, may refer to either of two chemical compounds, penicillin G or penicillin V.


title: Penicillin

text: Penicillin G is destroyed by stomach acid, so it cannot be taken by mouth, but doses as high as 2.4 g can be given (much higher than penicillin V). It is given by intravenous or intramuscular injection. It can be formulated as an insoluble salt, and there are two such formulations in current use: procaine penicillin and benzathine benzylpenicillin, which are used only in the treatment of syphilis. When a high concentration in the blood must be maintained, penicillin G must be administered at relatively frequent intervals, because it is eliminated quite rapidly from the bloodstream by the kidney.


title: Penicillin

text: Penicillin G is licensed for use to treat septicaemia, empyema, pneumonia, pericarditis, endocarditis and meningitis caused by susceptible strains of staphylococci and streptococci. It is also licensed for the treatment of anthrax, actinomycosis, cervicofacial disease, thoracic and abdominal disease, clostridial infections, botulism, gas gangrene (with accompanying debridement and/or surgery as indicated), tetanus (as an adjunctive therapy to human tetanus immune globulin), diphtheria (as an adjunctive therapy to antitoxin and for the prevention of the carrier state), erysipelothrix endocarditis, fusospirochetosis (severe infections of the oropharynx, lower respiratory tract and genital area), "Listeria" infections, meningitis, endocarditis, "Pasteurella" infections including bacteraemia and meningitis, Haverhill fever; rat-bite fever and disseminated gonococcal infections, meningococcal meningitis and/or septicaemia caused by penicillin-susceptible organisms and syphilis.


title: Penicillin

text: Penicillin V can be taken by mouth because it is relatively resistant to stomach acid. Doses higher than 500 mg are not fully effective because of poor absorption. It is used for the same bacterial infections as those of penicillin G and is the most widely used form of penicillin. However, it is not used for diseases, such as endocarditis, where high blood levels of penicillin are required.


title: Penicillin

text: Because penicillin resistance is now so common, other antibiotics are now the preferred choice for treatments. For example, penicillin used to be the first-line treatment for infections with "Neisseria gonorrhoeae" and "Neisseria meningitidis", but it is no longer recommended for treatment of these infections.


title: Penicillin

text: Common (≥ 1% of people) adverse drug reactions associated with use of the penicillins include diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including candidiasis). Infrequent adverse effects (0.1–1% of people) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in people with epilepsy), and pseudomembranous colitis. Penicillin can also induce serum sickness or a serum sickness-like reaction in some individuals. Serum sickness is a type III hypersensitivity reaction that occurs one to three weeks after exposure to drugs including penicillin. It is not a true drug allergy, because allergies are type I hypersensitivity reactions, but repeated exposure to the offending agent can result in an anaphylactic reaction. Allergy will occur in 1-10% of people, presenting as a skin rash after exposure. IgE-mediated anaphylaxis will occur in approximately 0.01% of patients.


title: Penicillin

text: Pain and inflammation at the injection site are also common for parenterally administered benzathine benzylpenicillin, benzylpenicillin, and, to a lesser extent, procaine benzylpenicillin. The condition is known as livedoid dermatitis or Nicolau syndrome.


title: Penicillin

text: The term "penam" is used to describe the common core skeleton of a member of the penicillins. This core has the molecular formula R-CHNOS, where R is the variable side chain that differentiates the penicillins from one another. The penam core has a molar mass of 243 g/mol, with larger penicillins having molar mass near 450—for example, cloxacillin has a molar mass of 436 g/mol. 6-APA (CHNOS) forms the basic structure of penicillins. It is made up of an enclosed dipeptide formed by the condensation of L-cystein and D-valine. This results in the formations of β-lactam and thiazolidinic rings.


title: Penicillin

text: The key structural feature of the penicillins is the four-membered β-lactam ring; this structural moiety is essential for penicillin's antibacterial activity. The β-lactam ring is itself fused to a five-membered thiazolidine ring. The fusion of these two rings causes the β-lactam ring to be more reactive than monocyclic β-lactams because the two fused rings distort the β-lactam amide bond and therefore remove the resonance stabilisation normally found in these chemical bonds. An acyl side side chain attached to the β-lactam ring.


title: Penicillin

text: A variety of β-lactam antibiotics have been produced following chemical modification from the 6-APA structure during synthesis, specifically by making chemical substitutions in the acyl side chain. For example, the first chemically altered penicillin, methicillin, had substitutions by methoxy groups at positions 2’ and 6’ of the 6-APA benzene ring from penicillin G. This difference makes methicillin resistant to the activity of β-lactamase, an enzyme by which many bacteria are naturally unsusceptible to penicillins.


title: Penicillin

text: Penicillin can easily enter bacterial cell in case of Gram-positive species. This is because Gram-positive bacteria do not have an outer cell membrane and are simply enclosed in a thick cell wall. Penicillin molecules are small enough to pass through the spaces of glycoproteins in the cell wall. For this reason Gram-positive bacteria are very susceptible to penicillin (as first evidenced by the discovery of penicillin in 1928).


title: Penicillin

text: Penicillin, or any other molecule, enters Gram-negative bacteria in a different manner. The bacteria have thinner cell walls but the external surface is coated with an additional cell membrane, called the outer membrane. The outer membrane is a lipid layer (lipopolysaccharide chain) that blocks passage of water-soluble (hydrophilic) molecules like penicillin. It thus acts as the first line of defence against any toxic substance, which is the reason for relative resistance to antibiotics compared to Gram-positive species But penicillin can still enter Gram-negative species by diffusing through aqueous channels called porins (outer membrane proteins), which are dispersed among the fatty molecules and can transport nutrients and antibiotics into the bacteria. Porins are large enough to allow diffusion of most penicillins, but the rate of diffusion through them is determined by the specific size of the drug molecules. For instance, penicillin G is large and enters through porins slowly; while smaller ampicillin and amoxicillin diffuse much faster. In contrast, large vancomycin can not pass through porins and is thus ineffective for Gram-negative bacteria. The size and number of porins are different in different bacteria. As a result of the two factors—size of penicillin and porin—Gram-negative bacteria can be unsusceptible or have varying degree of susceptibility to specific penicillin.


title: Penicillin

text: The chemical structure of penicillin is triggered with a very precise, pH-dependent directed mechanism, affected by a unique spatial assembly of molecular components, which can activate by protonation. It can travel through bodily fluids, targeting and inactivating enzymes responsible for cell-wall synthesis in gram-positive bacteria, meanwhile avoiding the surrounding non-targets. Penicillin can protect itself from spontaneous hydrolysis in the body in its anionic form while storing its potential as a strong acylating agent, activated only upon approach to the target transpeptidase enzyme and protonated in the active centre. This targeted protonation neutralizes the carboxylic acid moiety, which is weakening of the β-lactam ring N–C(=O) bond, resulting in a self-activation. Specific structural requirements are equated to constructing the perfect mousetrap for catching targeted prey.


title: Penicillin

text: Penicillin kills bacteria by inhibiting the completion of the synthesis of peptidoglycans, the structural component of bacterial cell wall. It specifically inhibits the activity of enzymes that are needed for the cross-linking of peptidoglycans during the final step in cell wall biosynthesis. It does this by binding to penicillin binding proteins with the β-lactam ring, a structure found on penicillin molecules. This causes the cell wall to weaken due to fewer cross-links and means water uncontrollably flows into the cell because it cannot maintain the correct osmotic gradient. This results in cell lysis and death.


title: Penicillin

text: Bacteria constantly remodel their peptidoglycan cell walls, simultaneously building and breaking down portions of the cell wall as they grow and divide. During the last stages of peptidoglycan biosynthesis, uridine diphosphate-"N"-acetylmuramic acid pentapeptide (UDP-MurNAc) is formed in which the fourth and fifth amino acids are both -alanyl--alanine. The transfer of D-alanine is done (catalysed) by the enzyme DD-transpeptidase (penicillin-binding proteins are such type). The structural integrity of bacterial cell wall depends on the cross linking of UDP-MurNAc and "N"-acetyl glucosamine. Penicillin and other β-lactam antibiotics act as an analogue of -alanine--alanine (the dipeptide) in UDP-MurNAc owing to conformational similarities. The DD-transpeptidase then binds the four-membered β-lactam ring of penicillin instead of UDP-MurNAc. As a consequence, DD-transpeptidase is inactivated, the formation of cross-links between UDP-MurNAc and "N"-acetyl glucosamine is blocked so that an imbalance between cell wall production and degradation develops, causing the cell to rapidly die.


title: Penicillin

text: The enzymes that hydrolyze the peptidoglycan cross-links continue to function, even while those that form such cross-links do not. This weakens the cell wall of the bacterium, and osmotic pressure becomes increasingly uncompensated—eventually causing cell death (cytolysis). In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and autolysins, which further digest the cell wall's peptidoglycans. The small size of the penicillins increases their potency, by allowing them to penetrate the entire depth of the cell wall. This is in contrast to the glycopeptide antibiotics vancomycin and teicoplanin, which are both much larger than the penicillins.


title: Penicillin

text: Gram-positive bacteria are called protoplasts when they lose their cell walls. Gram-negative bacteria do not lose their cell walls completely and are called spheroplasts after treatment with penicillin.


title: Penicillin

text: Penicillin shows a synergistic effect with aminoglycosides, since the inhibition of peptidoglycan synthesis allows aminoglycosides to penetrate the bacterial cell wall more easily, allowing their disruption of bacterial protein synthesis within the cell. This results in a lowered MBC for susceptible organisms.


title: Penicillin

text: Penicillins, like other "β"-lactam antibiotics, block not only the division of bacteria, including cyanobacteria, but also the division of cyanelles, the photosynthetic organelles of the glaucophytes, and the division of chloroplasts of bryophytes. In contrast, they have no effect on the plastids of the highly developed vascular plants. This supports the endosymbiotic theory of the evolution of plastid division in land plants.


title: Penicillin

text: Some bacteria produce enzymes that break down the β-lactam ring, called β-lactamases, which make the bacteria resistant to penicillin. Therefore, some penicillins are modified or given with other drugs for use against antibiotic-resistant bacteria or in immunocompromised patients. The use of clavulanic acid or tazobactam, β-lactamase inhibitors, alongside penicillin gives penicillin activity against β-lactamase-producing bacteria. β-Lactamase inhibitors irreversibly bind to β-lactamase preventing it from breaking down the beta-lactam rings on the antibiotic molecule. Alternatively, flucloxacillin is a modified penicillin that has activity against β-lactamase-producing bacteria due to an acyl side chain that protects the beta-lactam ring from β-lactamase.


title: Penicillin

text: Penicillin has low protein binding in plasma. The bioavailability of penicillin depends on the type: penicillin G has low bioavailability, below 30%, whereas penicillin V has higher bioavailability, between 60 and 70%.


title: Penicillin

text: Penicillin has a short half-life and is excreted via the kidneys. This means it must be dosed at least four times a day to maintain adequate levels of penicillin in the blood. Early manuals on the use of penicillin, therefore, recommended injections of penicillin as frequently as every three hours, and dosing penicillin has been described as being similar to trying to fill a bath with the plug out. This is no longer required since much larger doses of penicillin are cheaply and easily available; however, some authorities recommend the use of continuous penicillin infusions for this reason.


title: Penicillin

text: When Alexander Fleming discovered the crude penicillin in 1928, one important observation he made was that many bacteria were not affected by penicillin. This phenomenon was realised by Ernst Chain and Edward Abraham while trying to identify the exact of penicillin. In 1940, they discovered that unsusceptible bacteria like "Escherichia coli" produced specific enzymes that can break down penicillin molecules, thus making them resistant to the antibiotic. They named the enzyme penicillinase. Penicillinase is now classified as member of enzymes called β-lactamases. These β-lactamases are naturally present in many other bacteria, and many bacteria produce them upon constant exposure to antibiotics. In most bacteria, resistance can be through three different mechanisms: reduced permeability in bacteria, reduced binding affinity of the penicillin-binding proteins (PBPs) or destruction of the antibiotic through the expression of β-lactamase. Using any of these, bacteria commonly develop resistance to different antibiotics, a phenomenon called multi-drug resistance.


title: Penicillin

text: The actual process of resistance mechanism can be very complex. In case of reduced permeability in bacteria, the mechanisms are different between Gram-positive and Gram-negative bacteria. In Gram-positive bacteria, blockage of penicillin is due to changes in the cell wall. For example, resistance to vancomycin in "S. aureus" is due to additional peptidoglycan synthesis that makes the cell wall much thicker preventing effective penicillin entry. Resistance in Gram-negative bacteria is due to mutational variations in the structure and number of porins. In bacteria like "Pseudomonas aeruginosa", there is reduced number of porins; whereas in bacteria like "Enterobacter" species, "Escherichia" "coli" and "Klebsiella pneumoniae", there are modified porins such as non-specific porins (such as OmpC and OmpF groups) that cannot transport penicillin.


title: Penicillin

text: Resistance due to PBP alterations is highly varied. A common case is found in "Streptococcus pneumoniae" where there is mutation in the gene for PBP, and the mutant PBPs have decreased binding affinity for penicillins. There are six mutant PBPs in "S. pneumoniae", of which PBP1a, PBP2b, PBP2x and sometimes PBP2a are responsible for reduced binding affinity. "S. aureus" can activate a hidden gene that produces a different PBP, PBD2, which has low binding affinity for penicillins. There is a different strain of "S. aureus" named methicillin-resistant "S. aureus" (MRSA) which is resistant not only to penicllin and other β-lactams, but also to most antibiotics. The bacterial strain developed after introduction of methicillin in 1959. In MRSA, mutations in the genes ("mec" system) for PBP produce a variant protein called PBP2a (also termed PBP2'), while making four normal PBPs. PBP2a has poor binding affinity for penicillin and also lacks glycosyltransferase activity required for complete peptidoglycan synthesis (which is carried out by the four normal PBPs). In "Helicobacter cinaedi", there are multiple mutations in different genes that make PBP variants.


title: Penicillin

text: Enzymatic destruction by β-lactamases is the most important mechanism of penicillin resistance, and is described as "the greatest threat to the usage [of penicillins]". It was the first discovered mechanism of penicillin resistance. During the experiments when purification and biological activity tests of penicillin were performed in 1940, it was found that "E. coli" was unsusceptible. The reason was discovered as production of an enzyme penicillinase (hence, the first β-lactamase known) in "E. coli" that easily degraded penicillin. There are over 2,000 types of β-lactamases each of which has unique amino acid sequence, and thus, enzymatic activity. All of them are able to hydrolyse β-lactam rings but their exact target sites are different. They are secreted on the bacterial surface in large quantities in Gram-positive bacteria but less so in Gram-negative species. Therefore, in a mixed bacterial infection, the Gram-positive bacteria can protect the otherwise penicillin-susceptible Gram-negative cells.


title: Penicillin

text: There are unusual mechanisms in "P. aeruginosa", in which there can be biofilm-mediated resistance and formation of multidrug-tolerant persister cells.


title: Penicillin

text: Starting in the late 19th century there had been reports of the antibacterial properties of "Penicillium" mould, but scientists were unable to discern what process was causing the effect. Scottish physician Alexander Fleming at St. Mary's Hospital in London (now part of Imperial College) was the first to show that "Penicillium rubens" had antibacterial properties. On 3 September 1928 he observed that fungal contamination of a bacterial culture ("Staphylococcus aureus") appeared to kill the bacteria. He confirmed this observation with a new experiment on 28 September 1928. He published his experiment in 1929, and called the antibacterial substance (the fungal extract) penicillin.


title: Penicillin

text: C. J. La Touche identified the fungus as "Penicillium rubrum" (later reclassified by Charles Thom as "P. notatum" and "P. chrysogenum", but later corrected as "P. rubens"). Fleming expressed initial optimism that penicillin would be a useful antiseptic, because of its high potency and minimal toxicity in comparison to other antiseptics of the day, and noted its laboratory value in the isolation of "Bacillus influenzae" (now called "Haemophilus influenzae").


title: Penicillin

text: Fleming did not convince anyone that his discovery was important. This was largely because penicillin was so difficult to isolate that its development as a drug seemed impossible. It is speculated that had Fleming been more successful at making other scientists interested in his work, penicillin would possibly have been developed years earlier.


title: Penicillin

text: The importance of his work has been recognized by the placement of an International Historic Chemical Landmark at the Alexander Fleming Laboratory Museum in London on 19 November 1999.


title: Penicillin

text: In 1930, Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, successfully treated ophthalmia neonatorum, a gonococcal infection in infants, with penicillin (fungal extract) on November 25, 1930.


title: Penicillin

text: In 1940, Australian scientist Howard Florey (later Baron Florey) and a team of researchers (Ernst Chain, Edward Abraham, Arthur Duncan Gardner, Norman Heatley, Margaret Jennings, Jean Orr-Ewing and Arthur Gordon Sanders) at the Sir William Dunn School of Pathology, University of Oxford made progress in making concentrated penicillin from fungal culture broth that showed both "in vitro" and "in vivo" bactericidal action. In 1941, they treated a policeman, Albert Alexander, with a severe face infection; his condition improved, but then supplies of penicillin ran out and he died. Subsequently, several other patients were treated successfully. In December 1942, survivors of the Cocoanut Grove fire in Boston were the first burn patients to be successfully treated with penicillin.


title: Penicillin

text: The first successful use of pure penicillin was when Fleming treated Harry Lambert of fatal infection of the nervous system (streptococcal meningitis) in 1942. By that time the Oxford team could produce only a small amount. Florey willingly gave the only available sample to Fleming. Lambert showed improvement from the very next day of the treatment, and was completely cured within a week. Fleming published his clinical trial in "The Lancet" in 1943. Following the medical breakthrough the British War Cabinet set up the Penicillin Committee on 5 April 1943 that led to projects for mass production.


title: Penicillin

text: As the medical application was established, the Oxford team found that it was impossible to produce usable amounts in their laboratory. Failing to persuade the British government, Florey and Heatley travelled to the US in June 1941 with their mould samples in order to interest the US government for large-scale production. They approached the USDA Northern Regional Research Laboratory (NRRL, now the National Center for Agricultural Utilization Research) at Peoria, Illinois, where facilities for large-scale fermentations were established. Mass culture of the mould and search for better moulds immediately followed.


title: Penicillin

text: On March 14, 1942, the first patient was treated for streptococcal sepsis with US-made penicillin produced by Merck & Co. Half of the total supply produced at the time was used on that one patient, Anne Miller. By June 1942, just enough US penicillin was available to treat ten patients. In July 1943, the War Production Board drew up a plan for the mass distribution of penicillin stocks to Allied troops fighting in Europe. The results of fermentation research on corn steep liquor at the NRRL allowed the United States to produce 2.3 million doses in time for the invasion of Normandy in the spring of 1944. After a worldwide search in 1943, a mouldy cantaloupe in a Peoria, Illinois market was found to contain the best strain of mould for production using the corn steep liquor process. Pfizer scientist Jasper H. Kane suggested using a deep-tank fermentation method for producing large quantities of pharmaceutical-grade penicillin. Large-scale production resulted from the development of a deep-tank fermentation plant by chemical engineer Margaret Hutchinson Rousseau. As a direct result of the war and the War Production Board, by June 1945, over 646 billion units per year were being produced.


title: Penicillin

text: G. Raymond Rettew made a significant contribution to the American war effort by his techniques to produce commercial quantities of penicillin, wherein he combined his knowledge of mushroom spawn with the function of the Sharples Cream Separator.


title: Penicillin

text: By 1943, Rettew's lab was producing most of the world's penicillin. During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds among Allied forces, saving an estimated 12%–15% of lives. Availability was severely limited, however, by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance of the drug, necessitating frequent dosing. Methods for mass production of penicillin were patented by Andrew Jackson Moyer in 1945. Florey had not patented penicillin, having been advised by Sir Henry Dale that doing so would be unethical.


title: Penicillin

text: Penicillin is actively excreted, and about 80% of a penicillin dose is cleared from the body within three to four hours of administration. Indeed, during the early penicillin era, the drug was so scarce and so highly valued that it became common to collect the urine from patients being treated, so that the penicillin in the urine could be isolated and reused. This was not a satisfactory solution, so researchers looked for a way to slow penicillin excretion. They hoped to find a molecule that could compete with penicillin for the organic acid transporter responsible for excretion, such that the transporter would preferentially excrete the competing molecule and the penicillin would be retained. The uricosuric agent probenecid proved to be suitable. When probenecid and penicillin are administered together, probenecid competitively inhibits the excretion of penicillin, increasing penicillin's concentration and prolonging its activity. Eventually, the advent of mass-production techniques and semi-synthetic penicillins resolved the supply issues, so this use of probenecid declined. Probenecid is still useful, however, for certain infections requiring particularly high concentrations of penicillins.


title: Penicillin

text: After World War II, Australia was the first country to make the drug available for civilian use. In the U.S., penicillin was made available to the general public on March 15, 1945.


title: Penicillin

text: Fleming, Florey, and Chain shared the 1945 Nobel Prize in Physiology or Medicine for the development of penicillin.


title: Penicillin

text: The chemical structure of penicillin was first proposed by Edward Abraham in 1942 and was later confirmed in 1945 using X-ray crystallography by Dorothy Crowfoot Hodgkin, who was also working at Oxford. She later in 1964 received the Nobel Prize for Chemistry for this and other structure determinations.


title: Penicillin

text: Chemist John C. Sheehan at the Massachusetts Institute of Technology (MIT) completed the first chemical synthesis of penicillin in 1957. Sheehan had started his studies into penicillin synthesis in 1948, and during these investigations developed new methods for the synthesis of peptides, as well as new protecting groups—groups that mask the reactivity of certain functional groups. Although the initial synthesis developed by Sheehan was not appropriate for mass production of penicillins, one of the intermediate compounds in Sheehan's synthesis was 6-aminopenicillanic acid (6-APA), the nucleus of penicillin.


title: Penicillin

text: 6-APA was discovered by researchers at the Beecham Research Laboratories (later the Beecham Group) in Surrey in 1957 (published in 1959). Attaching different groups to the 6-APA 'nucleus' of penicillin allowed the creation of new forms of penicillins which are more versatile and better in activity.


title: Penicillin

text: The narrow range of treatable diseases or "spectrum of activity" of the penicillins, along with the poor activity of the orally active phenoxymethylpenicillin, led to the search for derivatives of penicillin that could treat a wider range of infections. The isolation of 6-APA, the nucleus of penicillin, allowed for the preparation of semisynthetic penicillins, with various improvements over benzylpenicillin (bioavailability, spectrum, stability, tolerance).


title: Penicillin

text: The first major development was ampicillin in 1961. It offered a broader spectrum of activity than either of the original penicillins. Further development yielded β-lactamase-resistant penicillins, including flucloxacillin, dicloxacillin, and methicillin. These were significant for their activity against β-lactamase-producing bacterial species, but were ineffective against the methicillin-resistant "Staphylococcus aureus" (MRSA) strains that subsequently emerged.


title: Penicillin

text: Another development of the line of true penicillins was the antipseudomonal penicillins, such as carbenicillin, ticarcillin, and piperacillin, useful for their activity against Gram-negative bacteria. However, the usefulness of the β-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems, and, most important, the cephalosporins, still retain it at the center of their structures.


title: Penicillin

text: Penicillin is produced by the fermentation of various types of sugar by the fungus "Penicillium rubens". The fermentation process produces penicillin as a secondary metabolite when the growth of the fungus is inhibited by stress. The biosynthetic pathway outlined below experiences feedback inhibition involving the by-product -lysine inhibiting the enzyme homocitrate synthase.


title: Penicillin

text: The "Penicillium" cells are grown using a technique called fed-batch culture, in which the cells are constantly subjected to stress, which is required for induction of penicillin production. While the usage of glucose as a carbon source represses penicillin biosynthesis enzymes, lactose does not exert any effect and alkaline pH levels override this regulation. Excess phosphate, available oxygen, and usage of ammonium as a nitrogen source represses penicillin production, while methionine can act as a sole nitrogen/sulfur source with stimulating effects.


title: Penicillin

text: The biotechnological method of directed evolution has been applied to produce by mutation a large number of "Penicillium" strains. These techniques include error-prone PCR, DNA shuffling, ITCHY, and strand-overlap PCR.


title: Penicillin

text: Overall, there are three main and important steps to the biosynthesis of penicillin G (benzylpenicillin).


title: Alfred Molina

text: Alfred Molina (born Alfredo Molina; 24 May 1953) is a British actor residing in America who is known for his work on the stage and screen. He first rose to prominence in the West End, earning a nomination for the Laurence Olivier Award for Best Newcomer in a Play for his performance in the production of "Oklahoma!" in 1980. He made his film debut as Satipo in "Raiders of the Lost Ark" and his Broadway debut as Yvan in a production of "Art" from 1998 to 1999. His other Broadway roles include Tevye in the musical "Fiddler on the Roof" from 2004 to 2005 and Mark Rothko in the play "Red" from 2009 to 2010.


title: Alfred Molina

text: On screen, his best known roles include Kenneth Halliwell in "Prick Up Your Ears" (1987), Sayyed Bozorg Mahmoody in "Not Without My Daughter", (1991), Mellersh Wilkins in "Enchanted April" (1992), Rahad Jackson in "Boogie Nights" (1997), Comte de Reynaud in "Chocolat" (2000), Diego Rivera in "Frida" (2002), Johann Tetzel in "Luther" (2003), Bishop Aringarosa in "The Da Vinci Code" (2006), Jack Mellor in "An Education" (2009), and George in "Love Is Strange" (2014). He has voiced characters in "Rango" (2011), "Monsters University" (2013), "Ralph Breaks the Internet" (2018), "Frozen II" (2019), and "DC League of Super-Pets" (2022). He is also known for his portrayal of Otto Octavius / Doctor Octopus in Sam Raimi's "Spider-Man 2" (2004) and the Marvel Cinematic Universe film "" (2021).


title: Alfred Molina

text: Molina's work has brought him widespread acclaim. For his portrayal of Robert Aldrich in the miniseries "Feud" (2017), he was nominated for a Golden Globe Award and a Primetime Emmy Award. He received a BAFTA Award nomination for Best Supporting Actor for his performance in "Frida", and has also been nominated for an Independent Spirit Award, a British Independent Film Award, five Screen Actors Guild Awards, and three Tony Awards.


title: Alfred Molina

text: He was born Alfredo Molina on 24 May 1953 in Paddington, London. His father, Esteban J. Molina, was a Spanish immigrant from Murcia, who came to England in 1939, and worked as a waiter and chauffeur. His mother, Giovanna (née Bonelli), was an Italian immigrant who moved to Britain after World War II, and who cleaned rooms in a hotel, and worked as a cook and housekeeper. Molina grew up in a working-class district in Notting Hill that was inhabited by many other immigrant families. He attended a Roman Catholic secondary school there. He decided to become an actor after seeing "Spartacus" at the age of nine, and attended the Guildhall School of Music and Drama, as well as auditioning for and becoming a member of the National Youth Theatre. At the age of 21, he changed his name to Alfred, at the urging of his first agent.


title: Alfred Molina

text: Molina appeared with Leonard Rossiter in the sitcom "The Losers" (1978). He made his film debut with a minor role alongside Harrison Ford in Steven Spielberg's adventure film "Raiders of the Lost Ark" (1981) as Indiana Jones' ill-fated guide, Satipo, during its iconic opening sequence. Molina stated in an interview in 2013 that he owes his stage and film career to the "Indiana Jones" series. "I'm very, very proud of that, I have to admit I didn't think at the time, 'Oh, this is going to go down in movie history.' I'd never been in front of a camera before," Molina said about his short but memorable appearance in "Raiders of the Lost Ark". He recalled getting the job as a "gift from God" and said, "I've publicly thanked Steven many, many times. That job saved my bacon, in more ways than one." About his now-famous line in the film, Molina stated that "I've never had a problem with people coming up to me about it. They'll shout that line to me, 'Throw me the idol, I'll throw you the whip!' I'm delighted that people still remember it."


title: Alfred Molina

text: However, his big break came with "Letter to Brezhnev" (1985), which he followed with a starring role in "Prick Up Your Ears" (1987), playing Joe Orton's lover (and eventual murderer) Kenneth Halliwell. He was originally cast as Arnold Rimmer in the TV sitcom "Red Dwarf", but was replaced by Chris Barrie.


title: Alfred Molina

text: In the early 1990s, Molina was a ubiquitous presence on British television, with his highest profile role being the lead in the first two series of "El C.I.D.". He appeared in the critically acclaimed films such as Mike Newell's costume drama "Enchanted April" (1992), Richard Donner's western comedy "Maverick" (1994), and Jim Jarmusch's western "Dead Man" (1995). Subsequent film roles include the drama "Not Without My Daughter" (1991), the science fiction horror film "Species" (1995), the broad comedy "Dudley Do-Right" (1999). With a midwestern American accent, Molina starred alongside Betty White in the US television series "Ladies Man", which ran from 1999–2001. In 1993 he appeared in the BBC miniseries adaptation of "A Year in Provence", playing the annoying Tony, along with John Thaw and Lindsay Duncan. In 1995, Molina starred with Marisa Tomei in "The Perez Family", playing Cuban refugees who pretend to be married so they can more easily stay in America. Marjorie Baumgarten praised Molina as attaining "the right mixture of gentle honor and baffled stupefaction" to portray his character, although Peter Rainer of "Los Angeles Times" called Molina "so intensely sodden that he’s like a great big scowling dark cloud." Molina has worked twice with Paul Thomas Anderson, first in "Boogie Nights" (1997) and then in "Magnolia" (1999).


title: Alfred Molina

text: In 2000, Molina appeared in Lasse Hallström's "Chocolat" which received critical acclaim and an Academy Award for Best Picture nomination. He gained wide recognition for his portrayal of Diego Rivera alongside Salma Hayek in the biopic "Frida" (2002), a role for which he gained BAFTA and SAG award nominations. He played himself alongside Steve Coogan in Jarmusch's "Coffee and Cigarettes" (2003) and gained further commercial recognition when he portrayed Johann Tetzel in "Luther" (2003) and Otto Octavius / Doctor Octopus in "Spider-Man 2" (2004), which became one of the highest-grossing films of that year. For the latter, Molina was nominated for a Satellite Award as Best Supporting Actor. He reprised his role in the video game adaptation. In 2006, Molina portrayed Touchstone in Kenneth Branagh's film version of Shakespeare's "As You Like It" and appeared in Ron Howard's adaptation of "The Da Vinci Code". Molina provided the voice of the villain Ares in the 2009 animated film "Wonder Woman".


title: Alfred Molina

text: Molina's stage work has included two major Royal National Theatre productions, Tennessee Williams' "The Night of the Iguana" (as Shannon) and David Mamet's "Speed-the-Plow" (as Fox). In his Broadway debut, Molina performed in Yasmina Reza's Tony Award-winning play "'Art'", for which he received a Tony nomination in 1998. In 2004, Molina returned to the stage, starring as Tevye in the Broadway production of "Fiddler on the Roof". For his performance he once again received a Tony Award nomination, this time for Best Actor in a Musical. He received his third Tony Award nomination for "Red" in 2010, for Best Performance by a Leading Actor in a Play.


title: Alfred Molina

text: In 2007, Molina narrated a 17-part original audiobook for Audible.com called "The Chopin Manuscript". This serialized novel was written by a team of 15 best-selling thriller writers, including Jeffery Deaver, Lee Child, Joseph Finder and Lisa Scottoline. The novel won the 2008 Audiobook of the Year Award form Audio Publishers Association.


title: Alfred Molina

text: On 1 April 2010, Molina opened at Broadway's John Golden Theatre in the role of artist Mark Rothko in John Logan's drama "Red" opposite Eddie Redmayne for a limited engagement through 27 June. He had played the role to much critical success at the Donmar Warehouse in London in December 2009 and revisited that role at the Wyndham's Theatre in the West End in 2018.


title: Alfred Molina

text: In 2010, Molina starred opposite Dawn French in the six-part BBC sitcom "Roger & Val Have Just Got In", with a second series in 2012.


title: Alfred Molina

text: Molina has three Lego Minifigures modelled after him, namely Doctor Octopus from "Spider-Man 2", Satipo from "Raiders of the Lost Ark" and Sheik Amar from "".


title: Alfred Molina

text: In July 2010, it was announced that Molina had joined the cast of "" as Deputy District Attorney Morales. He previously guest-starred in a two-part crossover in 2005 in two other "Law & Order" franchise shows, "" and "".


title: Alfred Molina

text: Molina is a patron of the performing arts group Theatretrain. He is also a longtime member of the Los Angeles theatre company The New American Theatre, formerly known as Circus Theatricals, where he often teaches Shakespeare and Scene Study along with the company's artistic director Jack Stehlin.


title: Alfred Molina

text: In 2017 he portrayed film director Robert Aldrich in Ryan Murphy's FX limited series "Feud: Bette & Joan". The series revolved around the filming of "What Ever Happened to Baby Jane?" in 1962 and the relationship between actresses Bette Davis and Joan Crawford played by Susan Sarandon and Jessica Lange respectively. Molina received critical praise for the film as well as awards attention received nominations from the Primetime Emmy Awards, and Golden Globe Awards for his performance.


title: Alfred Molina

text: In 2020, Molina appeared in David Oyelowo's drama "The Water Man", and Emerald Fennell's black comedy thriller "Promising Young Woman". On 8 December 2020 it was announced that he would be returning as Doctor Octopus for "" in the Marvel Cinematic Universe, set to premiere on 17 December 2021. Molina later confirmed that he would actually be reprising his role as the "Spider-Man 2" incarnation of Doctor Octopus in "No Way Home", retconning his character's apparent death at the end of the former film. He was digitally de-aged to his 2004 self.


title: Alfred Molina

text: On September 2, 2021, it was announced that Alfred Molina is set to star in Amazon Prime police drama series "Three Pines," which comes from "The Crown" producer Left Bank Pictures. Molina will play Chief Inspector Armand Gamache of the Sûreté du Québec, the lead character from Louise Penny’s book series, he also serves as executive producer for the show. The trailer came out in October 2022 and announced the show's premiere in December 2022.


title: Alfred Molina

text: Molina married actress Jill Gascoine in Tower Hamlets, London. They were married from 1986 until her death on 28 April 2020 in Los Angeles from Alzheimer's disease.


title: Alfred Molina

text: Molina resides in Los Angeles, California. In 2004, he announced that he had become a U.S. citizen. He is fluent in English, Spanish, and Italian. In 2017, he moved to La Cañada Flintridge.


title: Alfred Molina

text: In addition to acting, Molina is an advocate for people with Acquired Immune Deficiency Syndrome (AIDS). He donates towards AIDS research, participates in the Los Angeles AIDS Walk and appeared as himself in a documentary produced by Joseph Kibler (who has been HIV+ and paraplegic since his birth, c. 1989) about Kibler's life titled "Walk On", first screened in 2013.