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Ricin

Castor beans

The protein ricin (pronounced rye-sin) is a poison manufactured from the castor bean (Ricinus communis). Its name comes from the seed's resemblance to the tick. Ricin can be extracted from castor beans and is known to have an average lethal dose in humans of 0.2 milligrams (1/5,000th of a gram), though some sources give higher figures [1]. It is considered to be twice as deadly as cobra venom.

Toxicity and manufacture

Ricin is poisonous if inhaled, injected, or ingested, acting as a toxin by the inhibition of protein synthesis. There is no known antidote; only symptomatic and supportive treatment is available. Long term organ damage is likely in survivors. In small doses, such as the typical dose contained in a measure of castor oil, ricin causes digestive tract cramps. Ingested in larger doses, ricin causes severe diarrhea and victims can die of shock. (See abrin).

Although the castor bean plant has long been noted for its toxicity, ricin was first isolated and named in 1888 by Hermann Stillmark. Modern feed-making techniques break down the ricin in castor beans by heating at 140 degrees Celsius for 20 minutes, although some studies suggest that residual toxic effects may linger. Although one seed contains enough ricin to kill an adult human, they may pass harmlessly through the digestive system if swallowed whole. [2]. Typically 2.5–20 raw seeds can kill an adult human; 4 a rabbit, 5 a sheep, 6 an ox, 6 a horse, 7 a pig, 11 a dog, but 80 for cocks and ducks.[3]

Ricin consists of two distinct protein chains (almost 30kDa each) that are linked to each other by disulfide bond:

  • Ricin A is toxic to the cell by interfering with Ribosomes, responsible for protein synthesis
  • Ricin B is important in assisting ricin A's entry into a cell by binding with a cell surface component.

Many plants such as barley have the A chain but not the B chain. Since people do not get sick from eating large amounts of such products, ricin A is of extremely low toxicity if and only if the B chain is not present.

Ricin is easily purified from castor-oil manufacturing waste. The seed-pulp left over from pressing for castor oil contains on average about 5% by weight of ricin. Since 0.2 mg of purified Ricin constitutes a fatal dose, this is a considerable amount of ricin.

As little as one castor bean, about 0.5 grams, may be fatal in a child.

In the United states, a person caught manufacturing or possessing ricin may be sentenced up to 30 years in prison.

Potential medicinal use

Ricin may have therapeutic use in the treatment of cancer. Ricin could be linked to a monoclonal antibody to target malignant cells recognized by the antibody. Genetic modification of ricin is believed to be possible to lessen its toxicity to humans, but not to the cancer cells. A promising approach is also to use the non-toxic B subunit as a vehicle for delivering antigens into cells thus greatly increasing their immunogenicity. Use of ricin as an adjuvant has potential implications for developing mucosal vaccines

Use as a chemical/biological warfare agent

The United States investigated ricin for its military potential during the First World War. At that time it was being considered for use either as a toxic dust or coated bullets and shrapnel. The dust cloud concept could not be adequately developed, and researchers believed the coated bullet/shrapnel concept was unethical. The War ended before it was weaponized.

During the Second World War the United States and Canada undertook studying ricin in cluster bombs. Though there were plans for mass production and several field trials with different bomblet concepts, the end conclusion was that it was no more economical than using phosgene. This conclusion was based on comparison of the final weapons rather than ricin's toxicity (LD50 <30 mg.min.m–3). Ricin was given the military symbol W.

The best-known documented use of ricin as an agent of biological warfare was by the Soviet Union's KGB during the Cold War. In 1978, the Bulgarian dissident Georgi Markov was assassinated by Bulgarian secret police who surreptitiously 'shot' him on a London street with a modified umbrella using compressed gas to fire a tiny pellet contaminated with ricin into his leg. He died in hospital a few days later; the pellet was discovered by chance during an autopsy and the poison linked back to the KGB. Earlier, Soviet dissident Aleksandr Solzhenitsyn also suffered (but survived) ricin-like symptoms after a 1971 encounter with KGB agents (D.M. Thomas, Alexander Solzhenitsyn: A Century in His Life, 368-378).

Despite ricin's extreme toxicity and utility as an agent of chemical/biological warfare, it is extremely difficult to limit the production of the toxin. Under both the 1972 Biological Weapons Convention and the 1997 Chemical Weapons Convention, ricin is listed as a schedule 1 controlled substance. Despite this, more than 1 million metric tonnes of castor beans are processed each year, and approximately 5% of the total is rendered into a waste containing high concentrations of ricin toxin [4].

In August of 2002, US officials asserted that the Islamic militant group Ansar al-Islam tested ricin, along with other chemical and biological agents, in northern Iraq.

To put ricin used as weapon into perspective, it is worth noting that as a biological weapon or chemical weapon, ricin may be considered as not very powerful, if only in comparison with other poisons such as botulinum or anthrax. Hence, a military willing to use biological weapons and having advanced resources would rather use either of the latter instead. Ricin is easy to produce, but is not as practical nor likely to cause as high casualities as other agents. Ricin denatures (ie, the protein changes structure and becomes less dangerous) much more readily than anthrax spores, which may remain lethal for decades. (Jan van Aken, an expert on biological weapons explained in an interview with the German magazine Der Spiegel that he judges it rather reassuring that Al Qaeda experimented with ricin as it suggests their inability to produce botulin or anthrax.)

Pure ricin could be dispersed through the air, however it would tend to be oxidized and rendered harmless by ozone, nitrogen oxides, and other pollutants in a matter of hours. Since it acts as an enzyme, catalyzing destruction of ribosomes, even a single oxidation is likely to render the ricin molecule harmless. Presumably it could be sealed inside some sort of dust particle that would dissolve in water, but this would be difficult.

The major reason it is dangerous is that there is no specific antidote, and that it is very easy to obtain (the castor bean plant is a common ornamental, and can be grown at home without any special care). Ricin is actually several orders of magnitude less toxic than botulinum or tetanus toxins, but those are more difficult to obtain.

Ricin patent

"Preparation of Toxic Ricin",
patent application.

The process for creating ricin is well-known, in part because a patent was granted for it in 1952. The inventors named in US Patent 3,060,165 (granted October 23, 1962) "Preparation of Toxic Ricin", assigned to the U.S. Secretary of the Army, are Harry L. Craig, O.H. Alderks, Alsoph H. Corwin, Sally H. Dieke, and Charlotte Karel.

The patent was removed from the United States Patent and Trademark Office (USPTO) database sometime in 2004, but is still available online through international patent databases.

Ricin extraction process

The extraction of ricin from castor beans is very similar to the prepartion of soy protein isolates. Modern extraction plants might use membrane filtration to make highly purified ricin isolates

Ricin is initially extracted from defatted castor beans by aquous extraction at pH 3.8 to yield a leachate containing solubilized ricin. The leachate is filtered to remove insoluble matter and the crude ricin then precipitated by the addition of a 12% solution of sodium sulfate with a pH of 7.0-8.0. After precipitation, the crude ricin cake is washed with a 16.7% solution of sodium sulfate to remove extranious nitrogenous substances. The precipitated ricin may be reextracted once to further purify it.

The final ricin precipitate is dried and then purified by floatation in carbon tetrachloride. An aerosol powder may be prepared by spray drying or air grinding the purified ricin using cold air.

Ricin-related arrests in Britain in 2003

It was widely reported in the media that traces of ricin were detected by British police in a flat in Wood Green, North London after a raid on a suspected ring of terrorists on 5 January 2003. Media reports stated that a group was suspected of intending to use the poison in an attack on the London Underground. However at the trial of Kamel Bourgass in 2005 it became apparent that within a few days of the raid the leader of the Biological Weapon Identification Group at the Porton Down Defence Science and Technology Laboratory had concluded that ricin was not present at Wood Green [5] [6]. Some acetone, 22 castor beans, and poor recipes for ricin and other poisons copied from the Internet were found. It appears that an individual conducting amateur research on poisons was found in this raid.

A little later several arrests were made in France and a bottle of something that tested positive for ricin was found. Further analysis identified the material as ground wheat germ. The analytic confusion was caused by the similarity of many plant proteins to one of the ricin components, which suggests that higher quality (better specificity and sensitivity) analytic tests for ricin are needed.

Six more suspects were arrested in Bournemouth in England in connection with the investigation into the alleged ricin incident in London. They were not convicted of any poisons related crime.

Three more suspects were arrested in Manchester in England in connection with the investigation of the alleged ricin found in London, following a raid carried out pursuant to an investigation into immigration issues. A Special Branch policeman, DC Stephen Oake, was fatally stabbed during the arrests, and three other officers were also injured, one seriously.

On January 20, 2003 Finsbury Park mosque was raided by police, apparently as part of the investigation into the alleged discovery of ricin in Wood Green. A number of men who were apparently living at the mosque were arrested.

On February 5, 2003, U.S. Secretary of State Colin Powell presented those arrested as the "UK Poison Cell" of a global terrorist network in making the case for military intervention in Iraq to the UN Security Council [7].

In April 2005 31-year-old Kamel Bourgass was jailed for 17 years after being convicted of conspiracy to commit a public nuisance "by the use of poisons and explosives to cause disruption, fear or injury". He was also jailed for life following a conviction for murdering the Special Branch policeman who went to arrest him. All others accused in connection with the Wood Green flat were acquitted on all counts.

Ricin in Washington, D.C.

Ricin was detected in the mail at the White House in Washington, D.C. in November of 2003. The letter containing it was intercepted at a mail handling facility off the grounds of the White House, and it never reached its intended destination. The letter contained a fine powdery substance that later tested positive for ricin. Investigators said it was low potency and was not considered a health risk. This information was not made public until February 3, 2004, when preliminary tests showed the presence of ricin in an office mailroom of U.S. Senate Majority Leader Bill Frist's office. There were no signs that anyone who was near the contaminated area developed any medical problems. Several Senate office buildings were closed as a precaution.

Ricin in popular culture

Ricin was the poison used in the Agatha Christie Tommy and Tuppence whodunnit The House of Lurking Death in a 1929 collection of short stories called Partners in Crime.

Ricin was used as the poison of choice of the murderer in the 1962 comedy film Kill or Cure.

Ricin was mentioned in the "call me the prankster" comic at toothpaste for dinner

The Penn and Teller book How To Play With Your Food (ISBN 0679743111) includes a "gimmicks envelope" of small objects related to the tricks inside the book. One of these is a sticker reading "With all-natural ricin!". The book explains that ricin is a poison.


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The book explains that ricin is a poison. Among the controversies where:. One of these is a sticker reading "With all-natural ricin!". The television series prompted some criticism from cultural commentators on both the political left and right. The Penn and Teller book How To Play With Your Food (ISBN 0679743111) includes a "gimmicks envelope" of small objects related to the tricks inside the book. It includes the voices of characters Janice, Gunther and Jack & Judy Geller as hosts. Ricin was mentioned in the "call me the prankster" comic at toothpaste for dinner. A new PS2, PC and Xbox game called "Friends: The One with All the Trivia" was released simultaneously with the Season 10 box set.

Ricin was used as the poison of choice of the murderer in the 1962 comedy film Kill or Cure. The trivia includes questions from all ten seasons. Ricin was the poison used in the Agatha Christie Tommy and Tuppence whodunnit The House of Lurking Death in a 1929 collection of short stories called Partners in Crime. Recently, a Scene It version of Friends was released with actual show clips, trivia questions and other puzzles on screen. Several Senate office buildings were closed as a precaution. There have been two version of a board game relased, one being a carboard box version with fewer question and the other a die cast collector editon with more questions. There were no signs that anyone who was near the contaminated area developed any medical problems. The trivia book spans seasons 1-8.

Senate Majority Leader Bill Frist's office. A few trivia games have been released over the years as well as a trivia book. This information was not made public until February 3, 2004, when preliminary tests showed the presence of ricin in an office mailroom of U.S. But the rumours continued after that, with Kathleen Turner claiming that NBC bosses approached her about reprising her role as Chandler's father within the sitcom: [6]. Investigators said it was low potency and was not considered a health risk. [5]. The letter contained a fine powdery substance that later tested positive for ricin. An NBC spokesperson later indicated that these rumours were untrue.

The letter containing it was intercepted at a mail handling facility off the grounds of the White House, and it never reached its intended destination. [3] [4]. in November of 2003. The cast were apparently receiving $5 million per cast member for their participation in the specials, which were rumoured to air some time in 2007. Ricin was detected in the mail at the White House in Washington, D.C. In January 2006, NBC was reported to have announced that the six stars of Friends, including Jennifer Aniston, would reunite to make four "double episode" special editions of the series. All others accused in connection with the Wood Green flat were acquitted on all counts. Ratings by country for the finale:.

He was also jailed for life following a conviction for murdering the Special Branch policeman who went to arrest him. During the 2001–2002 season, Friends was the highest rated show in America according to the Nielsen Ratings. In April 2005 31-year-old Kamel Bourgass was jailed for 17 years after being convicted of conspiracy to commit a public nuisance "by the use of poisons and explosives to cause disruption, fear or injury". However, it did not surpass the ratings received by series finales for M*A*S*H (106m), Cheers (80.4m) or Seinfeld (76.3m), nor was it the most watched episode of Friends—that accolade remains with the season two episode The One After the Superbowl, which aired on January 28, 1996 and drew 52.9m viewers. Secretary of State Colin Powell presented those arrested as the "UK Poison Cell" of a global terrorist network in making the case for military intervention in Iraq to the UN Security Council [7]. The 66-minute series finale was named by Entertainment Tonight as the biggest US TV moment of the year 2004, and was the second highest rated show in 2004 beaten only by the Super Bowl. On February 5, 2003, U.S. The episode ends with Chandler and Monica moving out of their apartment, and everyone going for one last coffee at Central Perk.

A number of men who were apparently living at the mosque were arrested. As the message ends, she arrives at Ross' apartment, and they kiss. On January 20, 2003 Finsbury Park mosque was raided by police, apparently as part of the investigation into the alleged discovery of ricin in Wood Green. Ross gets back to his apartment and finds a message from Rachel on his answering machine, telling him she does still love him and is trying to get off the plane. A Special Branch policeman, DC Stephen Oake, was fatally stabbed during the arrests, and three other officers were also injured, one seriously. However, she rejects him. Three more suspects were arrested in Manchester in England in connection with the investigation of the alleged ricin found in London, following a raid carried out pursuant to an investigation into immigration issues. In the final episode, Ross realizes he still loves Rachel, and after she leaves for Paris, he goes after her.

They were not convicted of any poisons related crime. They then sleep together. Six more suspects were arrested in Bournemouth in England in connection with the investigation into the alleged ricin incident in London. He is upset about this until Rachel tells him it was too hard to say goodbye to him. The analytic confusion was caused by the similarity of many plant proteins to one of the ricin components, which suggests that higher quality (better specificity and sensitivity) analytic tests for ricin are needed. The group holds a going-away party for her and she says goodbye to each of them in turn, except Ross. Further analysis identified the material as ground wheat germ. Rachel accepts a job in Paris.

A little later several arrests were made in France and a bottle of something that tested positive for ricin was found. Erica gives birth to twins, a boy and a girl, who are named Jack (after Monica's dad) and Erica (after Erica). It appears that an individual conducting amateur research on poisons was found in this raid. Chandler and Monica apply to adopt the baby of a pregnant woman named Erica and also decide to move out of their apartment into a house in the suburbs. Some acetone, 22 castor beans, and poor recipes for ricin and other poisons copied from the Internet were found. Mike and Phoebe get married, and decide to have a baby. However at the trial of Kamel Bourgass in 2005 it became apparent that within a few days of the raid the leader of the Biological Weapon Identification Group at the Porton Down Defence Science and Technology Laboratory had concluded that ricin was not present at Wood Green [5] [6]. Joey and Rachel's relationship doesn't last and Charlie goes back to an old boyfriend.

Media reports stated that a group was suspected of intending to use the poison in an attack on the London Underground. He kisses Rachel. It was widely reported in the media that traces of ricin were detected by British police in a flat in Wood Green, North London after a raid on a suspected ring of terrorists on 5 January 2003. However, when Joey sees Charlie and Ross kissing he changes his mind. An aerosol powder may be prepared by spray drying or air grinding the purified ricin using cold air. Joey learns Rachel likes him, but refuses her advances. The final ricin precipitate is dried and then purified by floatation in carbon tetrachloride. Joey and Charlie break up.

The precipitated ricin may be reextracted once to further purify it. Mike comes to Barbados and gets engaged to Phoebe. After precipitation, the crude ricin cake is washed with a 16.7% solution of sodium sulfate to remove extranious nitrogenous substances. Monica learns David is planning on proposing to Phoebe, and calls Mike to tell him to get back together with her. The leachate is filtered to remove insoluble matter and the crude ricin then precipitated by the addition of a 12% solution of sodium sulfate with a pH of 7.0-8.0. Phoebe takes her boyfriend David (whom she first met in the first season) and Joey takes his girlfriend Charlie. Ricin is initially extracted from defatted castor beans by aquous extraction at pH 3.8 to yield a leachate containing solubilized ricin. The group goes to Barbados.

Modern extraction plants might use membrane filtration to make highly purified ricin isolates. Rachel begins to develop feelings for Joey. The extraction of ricin from castor beans is very similar to the prepartion of soy protein isolates. They move in together, but when he tells Phoebe he doesn't want to get married they break up. The patent was removed from the United States Patent and Trademark Office (USPTO) database sometime in 2004, but is still available online through international patent databases. Phoebe starts dating Mike Hanigan. Dieke, and Charlotte Karel. Chandler and Monica cannot conceive a baby, so decide to adopt.

Corwin, Sally H. When a female associate comes on to him, he quits and starts a new job in advertising. Alderks, Alsoph H. He puts up with this for a while, but when he finds himself working in Tulsa over Christmas. Craig, O.H. Chandler's job requires him to be in Tulsa. Secretary of the Army, are Harry L. Rachel decides to move back in with Joey and takes Emma with her.

The inventors named in US Patent 3,060,165 (granted October 23, 1962) "Preparation of Toxic Ricin", assigned to the U.S. Rachel finds out that Joey wasn't proposing to her, and neither was Ross. The process for creating ricin is well-known, in part because a patent was granted for it in 1952. Monica and Chandler decide to have a baby. Ricin is actually several orders of magnitude less toxic than botulinum or tetanus toxins, but those are more difficult to obtain. Rachel, seeing Joey on one knee with an engagement ring, thinks that he's proposing to her, and says "yes". The major reason it is dangerous is that there is no specific antidote, and that it is very easy to obtain (the castor bean plant is a common ornamental, and can be grown at home without any special care). He bends down to pick it up.

Presumably it could be sealed inside some sort of dust particle that would dissolve in water, but this would be difficult. After Rachel gives birth to their daughter, Emma, Joey finds the engagement ring. Since it acts as an enzyme, catalyzing destruction of ribosomes, even a single oxidation is likely to render the ricin molecule harmless. Ross keeps the ring in his coat pocket, even though he doesn't want to propose to Rachel. Pure ricin could be dispersed through the air, however it would tend to be oxidized and rendered harmless by ozone, nitrogen oxides, and other pollutants in a matter of hours. Rachel goes into labor, and while she's in the hospital Ross's mother approaches him with a ring to give to Rachel. (Jan van Aken, an expert on biological weapons explained in an interview with the German magazine Der Spiegel that he judges it rather reassuring that Al Qaeda experimented with ricin as it suggests their inability to produce botulin or anthrax.). Joey later reveals his feelings to Rachel, who politely rejects him.

Ricin denatures (ie, the protein changes structure and becomes less dangerous) much more readily than anthrax spores, which may remain lethal for decades. Feeling that Ross is missing out on his fatherly duties, Joey reluctantly suggests that Rachel move in with Ross, and she does so. Ricin is easy to produce, but is not as practical nor likely to cause as high casualities as other agents. As Rachel and Joey continue living together, Joey starts to develop feelings for her. Hence, a military willing to use biological weapons and having advanced resources would rather use either of the latter instead. Ross meets Mona at the wedding and goes out with her for a few months but they break up because of complications arising from his impending fatherhood with Rachel's child. To put ricin used as weapon into perspective, it is worth noting that as a biological weapon or chemical weapon, ricin may be considered as not very powerful, if only in comparison with other poisons such as botulinum or anthrax. They secretly slept together before Chandler and Monica's wedding.

In August of 2002, US officials asserted that the Islamic militant group Ansar al-Islam tested ricin, along with other chemical and biological agents, in northern Iraq. Rachel confirms she is pregnant and Ross is the father. Despite this, more than 1 million metric tonnes of castor beans are processed each year, and approximately 5% of the total is rendered into a waste containing high concentrations of ricin toxin [4]. Chandler and Monica get married, but when Chandler tells Monica he knows about the baby, she says she isn't pregnant, and it wasn't her pregnancy test that Phoebe found. Under both the 1972 Biological Weapons Convention and the 1997 Chemical Weapons Convention, ricin is listed as a schedule 1 controlled substance. He quickly returns on his own, however, deciding that a baby wouldn't be so bad. Despite ricin's extreme toxicity and utility as an agent of chemical/biological warfare, it is extremely difficult to limit the production of the toxin. Phoebe and Ross find Chandler at his office and persuade him to come back, but Chandler overhears Phoebe and Rachel talking about Monica's "pregnancy" and disappears again.

Thomas, Alexander Solzhenitsyn: A Century in His Life, 368-378). While he is gone, Phoebe finds a positive pregnancy test in Monica's bathroom, and assumes Monica is pregnant. Earlier, Soviet dissident Aleksandr Solzhenitsyn also suffered (but survived) ricin-like symptoms after a 1971 encounter with KGB agents (D.M. The night before his wedding, Chandler disappears. He died in hospital a few days later; the pellet was discovered by chance during an autopsy and the poison linked back to the KGB. Joey's new show Mac and Cheese is cancelled and so is his role there but he is able to return to Days of Our Lives. In 1978, the Bulgarian dissident Georgi Markov was assassinated by Bulgarian secret police who surreptitiously 'shot' him on a London street with a modified umbrella using compressed gas to fire a tiny pellet contaminated with ricin into his leg. Phoebe's apartment is repaired, but Rachel likes living with Joey so much she doesn't move back in with Phoebe.

The best-known documented use of ricin as an agent of biological warfare was by the Soviet Union's KGB during the Cold War. They later break up. Ricin was given the military symbol W. Rachel gets a promotion in Ralph Lauren and hires an assistant, Tag, whom she begins dating. This conclusion was based on comparison of the final weapons rather than ricin's toxicity (LD50 <30 mg.min.m–3). Monica and Chandler begin planning their wedding. Though there were plans for mass production and several field trials with different bomblet concepts, the end conclusion was that it was no more economical than using phosgene. Chandler and Monica become engaged.

During the Second World War the United States and Canada undertook studying ricin in cluster bombs. They eventually swap, so Rachel lives with Joey instead. The War ended before it was weaponized. Rachel moves in with Chandler and Monica, Phoebe moves in with Joey. The dust cloud concept could not be adequately developed, and researchers believed the coated bullet/shrapnel concept was unethical. A fire wrecks Phoebe and Rachel's apartment. At that time it was being considered for use either as a toxic dust or coated bullets and shrapnel. Out of a job and desperate for money, Joey gets a job at Central Perk and tries out other acting gigs until he lands a permanent (but short-lived) role as the main star of Mac and Cheese.

The United States investigated ricin for its military potential during the First World War. When Janine reveals she doesn't like Chandler and Monica, Joey breaks up with her. Use of ricin as an adjuvant has potential implications for developing mucosal vaccines. Joey gets a female roommate, Janine, and they start dating. A promising approach is also to use the non-toxic B subunit as a vehicle for delivering antigens into cells thus greatly increasing their immunogenicity. Chandler and Monica move in together, and Rachel moves in with Phoebe. Genetic modification of ricin is believed to be possible to lessen its toxicity to humans, but not to the cancer cells. Ross gets a new job teaching paleontology at New York University, and dates Rachel's sister and one of his students.

Ricin could be linked to a monoclonal antibody to target malignant cells recognized by the antibody. Rachel finds out and forces Ross to go ahead with the annulment, but they are ineligible for one and file for divorce. Ricin may have therapeutic use in the treatment of cancer. After finding out that they are now married, Ross and Rachel agree to get an annulment, but Ross doesn't want to have been divorced three times and lies to Rachel, telling her he has had the marriage annulled when he actually hasn't. In the United states, a person caught manufacturing or possessing ricin may be sentenced up to 30 years in prison. Ross and Rachel get drunk and they get married. As little as one castor bean, about 0.5 grams, may be fatal in a child. Everyone goes to Vegas to see him.

Since 0.2 mg of purified Ricin constitutes a fatal dose, this is a considerable amount of ricin. Joey gets the lead in a movie, but travels to Las Vegas to find production has shut down. The seed-pulp left over from pressing for castor oil contains on average about 5% by weight of ricin. Rachel starts a new job at Ralph Lauren. Ricin is easily purified from castor-oil manufacturing waste. Eventually everybody finds out, and they're all happy about it. Since people do not get sick from eating large amounts of such products, ricin A is of extremely low toxicity if and only if the B chain is not present.. Chandler and Monica continue an intimate relationship in secret.

Many plants such as barley have the A chain but not the B chain. She tries to keep one after becoming attached to them, but finds out that Frank and Alice are unwilling to give up a child. Ricin consists of two distinct protein chains (almost 30kDa each) that are linked to each other by disulfide bond:. Phoebe gives birth to triplets. Typically 2.5–20 raw seeds can kill an adult human; 4 a rabbit, 5 a sheep, 6 an ox, 6 a horse, 7 a pig, 11 a dog, but 80 for cocks and ducks.[3]. Ross moves into Ugly Naked Guy's apartment when he leaves. [2]. Ross agrees, but Emily continues to make unreasonable demands and they divorce.

Although one seed contains enough ricin to kill an adult human, they may pass harmlessly through the digestive system if swallowed whole. The group goes back to New York where Emily calls Ross and tells him that she will only stay married if he promises he will never see Rachel again. Modern feed-making techniques break down the ricin in castor beans by heating at 140 degrees Celsius for 20 minutes, although some studies suggest that residual toxic effects may linger. Ross and Emily's wedding continues despite Ross' faux pas and they are married, but Emily disappears at the reception. Although the castor bean plant has long been noted for its toxicity, ricin was first isolated and named in 1888 by Hermann Stillmark. The wedding goes ahead, but comes to an abrupt halt when Ross says "I take thee, Rachel" instead of "I take thee, Emily". (See abrin). When she gets there, she sees him with Emily and decides it wouldn't be right to ruin the wedding.

Ingested in larger doses, ricin causes severe diarrhea and victims can die of shock. Rachel realizes she still loves Ross and goes to London to tell him. In small doses, such as the typical dose contained in a measure of castor oil, ricin causes digestive tract cramps. Chandler comforts her and they end up sleeping together. Long term organ damage is likely in survivors. At the wedding rehearsal dinner, Monica becomes depressed because she's not married. There is no known antidote; only symptomatic and supportive treatment is available. The group travels to London for the wedding, except Phoebe, who is in her last trimester, and Rachel, who doesn't want to see Ross get married.

Ricin is poisonous if inhaled, injected, or ingested, acting as a toxin by the inhibition of protein synthesis. Ross dates a British woman, Emily, and they become engaged. . The girls hate their new apartment, so Joey and Chandler agree to switch apartments when Monica and Rachel make out. It is considered to be twice as deadly as cobra venom. Monica and Rachel switch apartments with Joey and Chandler after losing a bet. Ricin can be extracted from castor beans and is known to have an average lethal dose in humans of 0.2 milligrams (1/5,000th of a gram), though some sources give higher figures [1]. She does sleep with him, and they break up.

Its name comes from the seed's resemblance to the tick. Chandler suspects that Kathy is sleeping with a fellow cast member after watching one of her plays. The protein ricin (pronounced rye-sin) is a poison manufactured from the castor bean (Ricinus communis). Joey is angry, but forgives Chandler when he sees that Chandler and Kathy love each other. Ricin B is important in assisting ricin A's entry into a cell by binding with a cell surface component. Joey and Kathy break up after Kathy kisses Chandler. Ricin A is toxic to the cell by interfering with Ribosomes, responsible for protein synthesis. Joey begins dating Kathy, but Chandler likes her too.

She becomes pregnant with triplets. Phoebe agrees to be a surrogate mother for her half brother Frank and his wife Alice. Phoebe tells her twin sister Ursula, who knew all along. Phoebe learns the older Phoebe is her real mother.

However, when Ross insists that they were on a break, they break up again. Ross decides to get back together with Rachel, and breaks up with Bonnie. Ross must decide between Rachel and Bonnie. Ross and Rachel argue about this and start to feel like they still love each other.

Rachel is unhappy and persuades Bonnie to shave her head so Ross will be less attracted to her. Rachel becomes upset when Ross starts dating Bonnie, who unexpectedly comes to the beach. She invites the group to go with her to the beach. Phoebe finds a woman who knew her parents.

Joey's acting career continues to fail. Joey and Chandler buy a chick and a duck as pets. He tries to resume his relationship with Rachel without telling her, but she finds out and they break up. Feeling depressed, he sleeps with another woman.

After hearing a phone call between Rachel and her boss, he assumes Rachel is dating him. Tension between Ross and Rachel culminates on their anniversary, and Rachel suggests they take a break. Ross becomes convinced her new boss wants to date her, and becomes increasingly jealous. Rachel quits her job at Central Perk for a job at Bloomingdale's.

Monica dates Richard Burke, a friend of her parents who is significantly older than her, but break up when Richard tells her he doesn't want to have children. Phoebe finds she has a half brother called Frank and they start building a relationship. With no income Joey moves back into Chandler's apartment and Eddie leaves. When Joey states in an interview that he writes his own lines, the show's writers kill off his character.

Left on his own, Chandler gets a new roommate, Eddie, who is insane. Drake Ramoray on the soap Days of our Lives, and earns enough money to move into his own apartment. Joey gets an acting job as Dr. They later get back together when Rachel sees how sincere Ross is.

Unfortunately, Rachel discovers this list, becomes angry, and rejects Ross. He decides he loves Rachel, and breaks up with Julie. Ross is unable to choose between Rachel and Julie and decides to make a list of the advantages and disadvantages of both women. He and Rachel kiss.

Ross hears the message and becomes confused over his own feelings. While drunk, Rachel leaves a message on Ross's answer machine saying she is over him. Unaware that Rachel likes him, Ross starts a relationship with Julie, whom he met in China. Rachel decides she would like to start a romantic relationship with Ross, and goes to meet him at the airport when he returns from China, unaware that he is getting off the plane with another woman..

While he is gone, Chandler accidentally reveals to Rachel that Ross is in love with her. On Rachel's birthday, Ross leaves for a paleontological trip to China. Throughout the season he fails to make his feelings known to her, and eventually Chandler and Joey persuade him to move on. Ross reveals he had a crush on Rachel in high school (unbeknownst to Rachel), and he still has feelings for her.

and she gives birth to a boy, named Ben, who is subsequently raised by Carol and her partner, Susan. Ross discovers his ex-wife Carol is pregnant. She moves in with Monica, gets a job as a waitress at Central Perk, and struggles to work for a living, having previously lived a rich life. Monica's old school friend, Rachel, enters Central Perk wearing a wedding dress, having just run away from her wedding to Barry Farber.

Monica, Phoebe and Ross all live alone, while Chandler and Joey live together. Phoebe, Monica, Chandler, Joey, and Ross meet up in Central Perk shortly after Ross's wife Carol realizes she is a lesbian and divorces him. However, NBC has not yet confirmed this rumour, but has said that "Negotiations on future projects are going on all the time." [2]. It has been rumoured that NBC will produce a pilot for another spin-off from the series entitled It's a Guy Thing featuring Joey, Chandler and Ross.

The spinoff debuted to strong ratings, but its numbers have sunk since then, and there is speculation that it will not be renewed after its second season, ending in spring 2006. It has been hinted at that Matthew Perry will be the first to, however. Past Friends cast members are expected to have cameo appearances on the show from time to time, though as of December 2005, none have, and none have been asked. It centres on the Friends character Joey Tribbiani, still played by LeBlanc, who moved to Los Angeles to advance his career as an actor.

Joey premiered September 9, 2004 on NBC. The show also inspired the cultural meme of the laminated list. Along with this, Joey Tribbiani's catchphrase, “How you doin'?” has become a popular part of American slang, often used as a pick-up line or when greeting friends. Jennifer Aniston, in particular, had her hair-style copied by many women.

[1] Also commonly said by the characters, particularly Monica, was the loud “I know!” The series has also been noted for its impact on everyday-fashion and hair-styles. The use of “so” to mean “very” or “really” was not invented by any Friends writer, but it is quite arguable that the extensive use of the phrase in the series encouraged its use in everyday life. Friends has, in some areas, made a notable contribution to language, fashion, and (to a lesser extent) women's attitudes. For a full list of gags, see Running gags in Friends..

Some of the most famous include:. Friends had many running gags throughout the span of the show. See also: List of significant others of Friends and List of guest stars on Friends. The band's record label required them to write additional material and re-record the track as a full-length song, which peaked on the Billboard Hot 100 chart at #17.

The show's theme song, "I'll Be There For You" by The Rembrandts, became a major hit after a Tennessee disc jockey looped it into a full length track and played it on the radio. A constant story line throughout the series was the on-again/off-again romance between Ross and Rachel, and later in the series, the developing relationship between Chandler and Monica. Phoebe makes out a living as a singer-songwriter and a masseuse. Paleontologist Ross eventually becomes a college professor.

After on-and-off success as a soap opera actor Joey's career eventually stabilized with a regular part on a soap opera from which he was initially fired earlier in the series' run. Chandler eventually switched to a career in advertising by the last few seasons. Monica struggled for the first several seasons for success, and later became head chef at a well-respected restaurant. After cutting herself off from her father's money, Rachel got her first job as a waitress in the coffee shop and later becomes a personal shopper at Bloomingdale's, then a buyer for Ralph Lauren.

The settings for the show include Monica's apartment, Chandler and Joey's apartment and the coffee shop downstairs, Central Perk. They hang out with Monica's brother, Ross – who recently divorced his lesbian wife – and Phoebe, the "free spirit" of the bunch and Monica's old roommate. The pair live across the hall from Chandler and Joey. As the pilot begins, Rachel has just left her fiancé Barry at the altar and moves in with her childhood best friend, Monica.

The show focused on the lives of a group of six friends living in a state of arrested development: spoiled Daddy's girl Rachel Green; compulsively clean chef Monica Geller; wise-cracking, perennially unlucky-in-love, underconfident office drone Chandler Bing; oversexed, clueless actor Joey Tribbiani; divorced paleontologist nerd Ross Geller; and flaky, positive, masseuse, and aspiring folk singer-songwriter Phoebe Buffay. The last episode was released on DVD 5 days after its broadcast. Advertisements during the series finale, which attracted an audience of over 52 million viewers, cost $2,000,000 for a 30-second spot in the United States and CAD$190,000 in Canada. By the end of the series the six main cast members were each paid US$1,000,000 per episode.

Friends is one of the most successful sitcoms in the US. . In the US, its first episode was aired on September 22, 1994, the last on May 6, 2004. Television for NBC in the US, first broadcast on that network and followed by other broadcast networks in numerous countries throughout the world.

The program was produced by Bright/Kauffman/Crane Productions in association with Warner Bros. Friends was a long-running American television sitcom centered on the lives of a group of six twenty-somethings (eventually thirty-somethings) consisting of three men and three women living in New York City. Social conservatives were upset when Friends became the first network show on American television to feature a lesbian wedding ceremony, and social liberals often felt that the lesbian characters in the show were unfairly sidelined. At the end of the series, the show addressed this quip, with the joke that the characters were able to afford the nice apartments through rent control.

The characters lived in upper-middle class apartments, despite the fact that throughout the series the characters had jobs that could never afford such an apartment. The fact that the show is suppose to take place in New York City even though persons of color almost never appeared in the series and that only two non-white characters were given temporary guest-starring roles in the series, reportedly at the demand of actor David Schwimmer. The actors became such close friends that at least one guest star, Tom Selleck, reported sometimes feeling left out. This included requesting that all actors on the show be nominated either for the same category (mostly "Supporting Actor") or not at all, and entering collective instead of individual salary negotiations.

The six main actors made deliberate and conscious efforts, from early on, to keep the show's ensemble format and to not allow any one of them to dominate. Behind the scenes, the show was known for its unusually cohesive and unified cast. Courtney Cox was originally approached for the role of Rachel, but convinced the producers that her personality was more suited for the character of Monica—which, amusingly, is the role producers first approached Jennifer Aniston for. Shortly after production began, it was decided that the apartment building where much of the show takes place was too big to have upper apartments with numbers as low as 4 and 5, so the numbers were changed to 19 and 20, respectively.

In the first six episodes of Season 1, Chandler and Joey's apartment number was 4, and Monica and Rachel's was 5. Alternate titles were "Six Of One", "Across The Hall", "Insomnia Cafe" and "Friends Like Us". Most episodes were filmed with a laugh track, particularly those featuring Ursula and Phoebe together. Not all episodes were filmed in front of a studio audience.

55 people were paid to come to the studio and watch the first four episodes of "The Six of Us"; the title was thereafter changed to "Friends.". The producers liked the look and decided not to replace the mirror. The picture frame around the peep hole in Monica and Rachel's apartment originally was a framed mirror, but a crew member accidentally broke it. The exterior shot of the Friends' apartment building is actually located at Grove and Bedford streets in the Village.

Although the show was filmed in California, it took place in the West Village in Manhattan, New York City. Central Perk, the coffee shop on the show, is based on Chomondley's (pronounced Chumley's), a coffee shop/lounge in Usen Castle at Brandeis University, the alma mater of the show's creators. He was hired because he was the only extra on the set of the pilot who knew how to operate an espresso machine. He can be seen as an extra throughout the first season, and when given a line in the second, the directors were adequately impressed that they created a full-time part for him.

James Michael Tyler's character (Gunther) came into the series by accident. Phoebe was not originally envisioned as having a twin, but the show's creators added the fact to explain why Kudrow was appearing on two different shows, at one point on the same night. Lisa Kudrow played Ursula on both Mad About You and Friends. The character of Ursula (Phoebe's twin sister) first appeared in the sitcom Mad About You as a waitress.

Australia: 2.54m (OZTAM). United Kingdom: 8.6m (BARB). Canada: 5.159m (BBM Canada). United States: 52.5m (Nielsen).

This was first referred to in the episode 'The One With The Baby In The Bus'. The Grandma Killer: In several episodes, usually when one of the cast was reading a newspaper or watching TV, someone refers to a serial killer who strangles grandmas and shoves them in ovens. They also wrote respectful slogans to the 9/11 victims after the September 11 attacks. The Magna Doodle: The Fisher-Price Magna Doodle almost always had something humorously written or drawn on it.

How You Doin'?: This is Joey's pick-up line. One exaggerated example, where Ross was mocking Chandler's speech pattern: "The hills are alive with the sound (pause) OF music". Chandler's speech: Chandler has a strange way of speaking, in which he emphasizes the wrong word in his sentences. Oh...My...God!: Janice's catchphrase; used as her introductory line in her later guest appearances.

Phoebe's music: Phoebe was often a musician at Central Perk and was known for her rather unusual, original songs. Ross' tendency to marry: Ross marries a total of three times throughout the course of the show, all of which end in divorce. Gunther likes Rachel: When Gunther appeared in an episode it usually involved his anything-but-secret crush on Rachel, who however remains oblivious to his feelings throughout most of the show's run. Gay Chandler: Chandler was often painted with the possibility of being gay, despite his determination to prove himself as the heterosexual he actually was.

Fat Monica: Monica, now slim and attractive, was obese as a child. The One With/Where [episode name]: Almost every episode name starts with these three words.

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