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Talk:4th millennium BC

Susa
Uruk also comes as 'Warka' in some English language texts, but Susa is Susa. A quick googling turns up 2,280 for Susa and 137 for Suse, and the Suse entries are predominantly French-language (or the quotation of French-language titles in English web pages). MichaelTinkler

Uhh - 217.128.36, do you just not believe me that in English we spell the place 'Susa' rather than 'Suse'? Or is it really a different place? I found a map via Google that left me in little doubt. Talk to me here. Don't just change it back. Wikipedia is a collaborative effort. See
 * http://www.umma.lsa.umich.edu/OldWorld/Deh_Luran/IX/Suse_Phase.htmlMichaelTinkler

Sorry, I tough I wrote Susa by mistake. but not that someone else modified it so rapidly

heads of state
How do we know it? 203.162.3.147 05:23, 13 Mar 2005 (UTC)
 * The belief that heads of state represented God on Earth began.

Because as civilizations began to rise that concept came into form. There were no prior states in a previous millennium when that idea was created. Any evidence to the contrary should be submitted. Until then it goes back in. --Richard Cane 02:46, 5 August 2006 (UTC)

 * There must be some more convincing evidence. Can you substantiate what you said above? Wikipeditor 18:23, 7 August 2006 (UTC)
 * Writings from this era have substantiated that heads of state were considered to be divine. As I've said, if you have any evidence that prior to this millennium there were civilizations with a head of state considered divine go ahead and take it out and put it in that millennium. It was a very important event because it influenced and justified the power heads of state had over their people and I think it needs to be mentioned. Richard Cane 09:51, 16 August 2006 (UTC)

Early drainage and sewerage system
Can we change "in India" to "in the Indus Valley Civilization" (which, as it seems, was largely in modern Pakistani territory)? Wikipeditor 18:23, 7 August 2006 (UTC)

Done. douts (talk) 18:07, 5 November 2010 (UTC)

3761 or 3760
A question I myself have been trying to figure out. In Judaism, by the way, the world was created in the fall, so the March date is out. The Hebrew month of Nisan (March-April) being the "first month" only comes as a result of the Exodus. Now seeing as the Hebrew date is currently one full month into the year 5767 and that our common era is counted as a couple of months left in 2006. I think we can say from 5767-2006=3761 that the world was created in 3761 BCE, sometime in September or October assuming the same 12 month calendaring system for the civil calendar and the same lunisolar calendar for the Jewish (as there was obviously no metonic intercalation system in place. I would go for the 3761 date as the civil calendar has always been 2 or 3 months behind the Hebrew calendar in terms of the New Year. The first of tishrei would have been in the Autumn of the year 3761 BCE. Valley2city 05:21, 23 October 2006 (UTC)

A Caveat: Consider that the Christian calendar elides the ordinal number "0" from the count, so the time span from 1 BCE to 1 CE is only 1 year, not 2 as simple arithmetic (1 - (-1) = 2) would suggest. Thus a 5767 year time *span* (cardinal numbers) encompassing the year 2006 CE would have to start in 3762 BCE. Tadchem (talk) 11:57, 10 June 2010 (UTC)

Lack of objectivity
"The term common era is preferred by some as an alternative to the more overtly religious AD and BC, since Common Era does not explicitly make use of religious titles for Jesus, Christ and Lord, that are used in the AD/BC notation." I think that an enciclopedia should be objective, thus BCE instead of BC is preferable.
 * That'd be just fine if we were just starting now, unfortunately we've been using BC/AD for long enough that purposely abandoning them is not objectivity.

Nimrod/Sargon under significant people?
I feel that this should be removed, since there is no citation of this link, and in addition Sargon is from 3000 BC, accoriding to his page.

I will leave it to the experts to do the actual removal, and send a comment to the person that made the original reference. CodeCarpenter 16:27, 1 December 2006 (UTC)
 * this is indeed nonsense. Sargon dates to the late 3rd millennium. dab (𒁳) 16:34, 1 December 2006 (UTC)

Speaking of examples of fine art
I believe that nothing can be compared to Egyptian palettes (Palettes with jackals,lions,Narmer's palette). They are so finely performed comparing to another, rude and primitive art of the same epoch. These probably should be included in the list as examples of "landmarks" in art of the 4th millennium. These palettes are as impressive (considering their age) as the famous (later made) pyramides! QuestPc 13:15, 29 March 2007 (UTC)

oldests
A) Is Ötzi the Iceman the oldest mummified human we've found?

B) Is Tiu, Thesh, Hsekiu, Wazner, Ro, Serket or Narmer the oldest person whose name we know? Is there someone older?

Kingturtle (talk) 06:01, 17 May 2008 (UTC)

*c. 4000 BC - God creates the universe including Adam and Eve according to a literal reading of the Hebrew Bible's Torah.
it was put back in because it is a widely held belief. Widely? And do beliefs really belong in EVENTS? Kingturtle (talk) 02:08, 6 June 2008 (UTC)

 * Good question. There is another "belief" in the article c. 3100 BC – According to the legend, Menes unifies Upper and Lower Egypt, and a new capital is erected at Memphis. Will check 5th millennium BC for comparison. rossnixon 02:14, 6 June 2008 (UTC)

Earliest
Crude oil use (f.e. in mummification)? Fossilic Coal use? Or was it earlier? 80.186.181.23 (talk) 08:47, 19 November 2008 (UTC)

Should add the invention of leather shoes
First Direct Evidence of Chalcolithic Footwear from the Near Eastern Highlands http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010984

...a date range of 3627–3377 Cal BC (95.4% confidence interval) Tadchem (talk) 11:44, 10 June 2010 (UTC)

"Significant Persons" Biblical/Legendary
I keep trying to add Biblical people to the articles, 39th century BC through 26th century BC, according to the Gregorian calender and Ussher Chronology. They keep getting reverted. Why?

Are these people's existence not widely held? Fair enough. Their existence are only held by a few Billion individuals, not to mention hundreds of millions of Muslims, Jews, Mormons, etc. who also acknowledge their existence. As to Ussher Chronology, it is the most widely excepted chronology on creationism. Open any historical text written by a creationist and you can bet money that it starts the world on October 23, 4004 BC. Ask any creationist and he will tell you that civilization is about 4500-5000 years old (which comes directly from James Usshur, who put Noah's Flood at 2348 BC), and time itself is about 6000 years old (James Ussher again).

But why use Ussher Chronology? don't most scientists say that the Universe is much older than 6000 years, thus making James Ussher unreliable? True, but If we were to so strictly follow what "most scientists" say, then why do we mention so much Korean, Hindo, and Chinese mythology, and not the worlds most popular religion? It's beyond bad policy, it's downright discriminatory! Nonetheless, if we are to mention these persons, then I would suggest using Ussher Chronology, which is most widely held.LutherVinci (talk) 17:58, 3 December 2010 (UTC)
 * Because Archbishop Ussher's dates are not consensus even among theologians; much less modern scholarship. There are lots of legendary dates, duly calculated, for personages of ancient tradition: to use a list I've used before: Eurystheus, Busiris, Horus, the antediluvian kings of Kish, Yao and Shun. None of them should be on these pages; Narmer, Sargon, Hezekiah should be: they all have actual contemporary evidence they existed, and it is consensus about when they  did reign. Septentrionalis PMAnderson 23:43, 3 December 2010 (UTC)
 * And that's where you are wrong: There is much consensus. Please make sure you have read my entire discussion above. If you don't believe me so much that I need to actually present you with examples of consensus, I will.

 * But I hope that will not be necessary. The Bible (as well as the Qur'ran, Book of Mormon, etc. which also acknowledge these people) is excepted by Billions of people, so it would be wise to include them simply out of completeness.

 * If necessary, we could add a separate section, "In classical religion", or some such, for completeness. LutherVinci (talk) 01:04, 4 December 2010 (UTC)
 * The Bible is accepted [sic in English] by billions; no single interpretation of it is - and the good Archbishop's dates are one interpretation among many. I repeat: Erechtheus, Theseus, and Hercules aren't history either. Septentrionalis PMAnderson 17:47, 4 December 2010 (UTC)
 * And one billion Christians are Roman Catholics, who are unlikely to accept the scheme of a Protestant from Northern Ireland in any case. Septentrionalis PMAnderson 19:21, 4 December 2010 (UTC)
 * (Northern Ireland?) There are indeed many versions of the Bible, and many different religions that don't even use the Bible, but my point is that every version and denomination, from Christianity, Islam, and Judaism, and others, all agree that these people existed, and around the same time (Ussher Chronology for Christians, Hebrew Calender for Jews, and the Qur'ran does not specify dates).
 * Armagh, to be precise. Septentrionalis PMAnderson 00:12, 5 December 2010 (UTC)
 * There are just as many Catholics as Protestants, both of which acknowledge Ussher Chronology. LutherVinci (talk) 02:33, 5 December 2010 (UTC)
 * Do you have any evidence for that statement of faith? Septentrionalis PMAnderson 18:51, 5 December 2010 (UTC)
 * And you all are being inconsistent. First you start eliminating every myth from these articles, then you suddenly say that only "disputed chronology" (which magically only applies to the Bible) should be taken out. (Erechtheus, by the way, is indisputably put at 1469 BC to 1375 BC, though mythical, yet you would leave him out too?)LutherVinci (talk) 23:23, 4 December 2010 (UTC)
 * Don't believe everything you read in Wikipedial the chronology of the legendary kings of Athens has been disputed for two millennia. Septentrionalis PMAnderson 00:12, 5 December 2010 (UTC)
 * Actually, I got that from the Wall chart of World History, but I never heard any other date for it. So... doesn't that fit your imaginary definition for a mythical event worthy of Wikipedia?LutherVinci (talk) 02:33, 5 December 2010 (UTC)
 * I think Chronology of the Bible, or a Christian fork of that, would be the best place for those timelines, including alternate dates. I really don't think they should live in the main timeline articles.  — Arthur Rubin  (talk) 16:11, 4 December 2010 (UTC)
 * Eusebius and Ussher should be included in that article. Septentrionalis PMAnderson 17:49, 4 December 2010 (UTC)
 * Before I respond, let me get one thing strait, Mr. Anderson and Mr. Rubin: So we should only include (to these articles on centuries) events with indisputable evidence, and remove all mention of legends, mythology, fiction, or otherwise disputed chronology (even the Bible)?LutherVinci (talk) 18:08, 4 December 2010 (UTC)
 * Actually, I wouldn't go that far. If there is a myth which specifies a particular date, it might be added in an "In fiction" section.  — Arthur Rubin  (talk) 19:09, 4 December 2010 (UTC)
 * Therefore, it is appropriate to include fictional media, mythology, and so forth, so long as it is separate in a specified section (which it is not in some articles), BUT it is not appropriate, even if it is specified, to include Biblical characters, simply on the grounds that nobody can agree on specific dates (and by the way, there is a significant difference between mythical, Biblical, and fictional). Give me enough time and I will show you that these dates are NOT disputed among those who believe. LutherVinci (talk) 22:50, 4 December 2010 (UTC)
 * Few dates are disputed among those who believe them - that's a tautology; but the number that believe Ussher's dates is much less than Christendom - and we do not restrict our sources to Christians; see WP:NPOV. Septentrionalis PMAnderson 00:12, 5 December 2010 (UTC)
 * Neither do we restrict ourselves to the opinion of atheists, for the same reason. Both should be given equal mention. LutherVinci (talk) 02:17, 5 December 2010 (UTC)
 * "Few dates are disputed among those who believe them", what I meant by that is simply that All Creationists adhere to Ussher Chronology, while Atheists don't. I would like to add, by the way, that to ruthlessly remove creationism here is favoring Atheism, which (and I HATE to have to use the Constitution here) is against Freedom of Religion, not to mention freedom of speech. LutherVinci (talk) 02:33, 5 December 2010 (UTC)
 * This, of course, omits most Christians, who do not subscribe to the WP:FRINGE POV being pushed here. Septentrionalis PMAnderson 21:23, 7 December 2010 (UTC)
 * Sit back and think. My edits include both the opinion of Christians, and Atheists, religion and Science. You wish to eliminate all mention of any opinion aside from your own. Thus this POV is being pushed by you, whilst I'm holding it back.LutherVinci (talk) 21:41, 7 December 2010 (UTC)
 * On the contrary, this was a proposal to include both the subjects of Genesis and others under Fictions, on the condition that the legend itself contain a date. Genesis doesn't qualfiy under this condition, since it doesn't actually contain dates: the difference between Eusebius of Caesarea, James Ussher, and the modern Hebrew calendar is largely due to disagreement on how much time passed between Joseph and David. But then I can't think of a legend that does. Septentrionalis PMAnderson 22:59, 4 December 2010 (UTC)
 * Exactly. If you define "true history" as only that which is backed up by contemporary accounts and archeology, then no legend should be mentioned. Yet you do include mythology, and not the Bible. (That is, if I interpret you correctly:"Genesis doesn't qualfiy (qualify?) under this condition, ... But then I can't think of a legend that does.")
 * No, I exclude both - and I said so; three times now. Septentrionalis PMAnderson 00:20, 5 December 2010 (UTC)
 * That's all I wanted to hear. now that you agree that mythology should be removed from these articles, I would like to remind you that you would have to drastically alter the whole of Wikipedia! I will show you, just to name a few:
 * 38th century BC-"Antedeluvian Period" among others
 * 33rd century BC-Any date for Krishna isn't even agreed among by Hindus!
 * 32nd century BC-"Disaperence of Krishma...epic of heroes...retire to the Himalayas"
 * 31st century BC-Methuselah, nuff said.
 * 31st century BC-Why can't we have this section on every article?
 * 30th century BC-Should be self-explanatory.
 * 29th century BC-Hung Vuong?, Three August Ones and Five Emperors? flood stories? are not dates for these events highly disputed? and why are they mentioned parallel with excepted history?
 * 28th century BC-You removed Fu Hsi from deaths (who do expect to be there instead?), but his image remains with the words, "is considered by legend the first ruler of China" under it.
 * 28th century BC-The date for the foundation of Tyre is highly disputed, yet you let it slip by?
 * The most important thing you must understand is that this is just the tip of the ice burg. I offer you a small sample here, not for your benefit, but for the understanding that what you propose is impossible. What is wrong with offering the opinion of someone other than what is "excepted", equally represented along with every belief?LutherVinci (talk) 02:17, 5 December 2010 (UTC)
 * "Disagreement on how much time passed"? The Septuigent and several historians in the Dark ages are the only ones that differ, therefore James Ussher in the Renaissance used the original Hebrew (plus contemporary accounts and archeology), ignoring oral tradition from which the Hebrew calender is derived. LutherVinci (talk) 00:08, 5 December 2010 (UTC)
 * You are entitled to devise arguments; you are not entitled to invent your facts. Septentrionalis PMAnderson 00:20, 5 December 2010 (UTC)
 * My references are pending, but until then you must realize that their as never been any other chronology invented since Ussher; Unlike Josephes, Eusebius, etc. who give different amounts of time between, say, creation and the flood, James Ussher simply gives the amount of time clearly specified in the original Hebrew Bible. Add together the ages of the pre-flood generations in Genesis 5, for instance, and you get 130+105+90+70+65+162+65+187+182=1,056. And since Noah was undeniably 600 years old during the flood (Genesis 7:6), then the amount of time passed from creation to the flood is not indeterminable, but obviously 1,656 year, as told by James Ussher in "Annals of the World", page 19. No possible disputes there. LutherVinci (talk) 15:26, 6 December 2010 (UTC)

The difficulties of totalling up the Biblical account are (mostly) after the Flood. However: The extent of these differences is limited; it is very difficult to claim that the implied date of Adam is later than 3000 BC or earlier than 6000 BC. But even Ussher's Anglican contemporary Lightfoot differed from him by most of a century. Septentrionalis PMAnderson 16:43, 6 December 2010 (UTC)
 * I set aside the entire question whether the seven days of creation were ever intended to be periods of 24 hours; for an evangelical take on that question, read Hugh Miller's The Testimony of the Rocks, now back in print.
 * There are - and have always been - textual variants in the first chapters of Genesis. See the notes to the RSV.
 * The totals of Noah's immediate family suggest the Flood itself is an instant; but forty weeks is most of a year.
 * The time from Joseph to the Exodus is a round number; is it (was it intended to be) an exact figure?
 * The time from Exodus to David is largely a matter of conjecture.
 * Chronicles and Kings are inconsistent (in all of the ancient texts) both with each other and among themselves. Several emendations are possible.
 * The time from Cyrus' conquest of Babylon to the year we call 1 AD (the consulship of Gaius Caesar and L. Aemilius Paullus) is unstated in the Bible (as is the almost certainly false assumption that Jesus was born in that year). Fortunately, this is supplemented by Greek and Persian evidence.
 * From what you say, this is what I observe:
 * The reinterpretation of the literalness of Genesis 1 (or, for that matter, any part of Biblical Chronology) would be to say that the Bible is completely unhistorical. Which is one, completely ignoring the history of Archeology (Hittites, Tiglath Pileasar, Dead sea Scrolls, etc.), and two, restricting ourselves once again to the opinion of Atheists. To those who take the Bible literally (i.e. Christians, but their are others), the date of creation is easily determinable, as Ussher proved.
 * Besides the Septuagint, I have never seen any variation of Genesis so different that they actually give different dates. In fact the only differences between the different versions of the Bible are a rephrasing here, a similar word used there, no version of the Bible ever changes its meaning. And if your going to use the Septuagint against consider this: the Septuagint was written around 200 BC. The oldest complete Old Testament is no later than 320 BC. The dates James Ussher used are exactly the way it is seen in the older document.
 * If you actually read Annals of The World, you might save yourself from looking foolish. No one (not Ussher and no Scientist) even suggests that the Flood happened in an instant. It started on the 17th day of the 2nd month, in Noah's 600th year (Genesis 7:11, and their is no translation that says otherwise); then it rained 40 days and 40 nights (Genesis 7:4, 12, and 17, your "forty weeks" is either false data or plain original research), not just rain, but earthquakes and volcanoes! (Genesis 7:11, and that's just one reference among many) Even after the rain stopped, the waters remained on the Earth 150 days (Genesis 7:24, 8:3), and even when the waters started to subside, the Earth was not "completely dry" until the 27th day of the 2nd month, in Noah's 601st year (Genesis 8:13-14). So the Flood did last more than a year, but I fail to see how this effects Ussher's chronology, being that he actually gives the length of the Flood as such in his Chronology, page 21.
 * This statement appears to be Original Research, being that no one has ever questioned the literalness of the Egyptian Sojourn, particularly because their is archeology to support the date of the Exodus! (The Habru, records of the death of the first-born, the plague of darkness corresponding to the eruption of Santorini, etc.). Besides, your saying that the 430 years from the call of Abraham to the Exodus in Exodus 12:40 is "too round", which is your own POV.
 * Conjecture? are you referring to 1 Kings 6:1, where it says, "...in the 480th year after the Exodus,... in the 4th year of Solomon's reign..." How is that merely "conjecture", unless this is more OR? That 480 years brings us to around 970 for the death of David, which is excepted by historians.
 * It would be quite profound if the Old Testament did indeed give this length of time, being that it was written long before these years came to pass! (no later than 320 BC). Still, you might want to check out the Seventy weeks prophesy by Daniel (Bible). But staying on topic, this is exactly what I meant by saying that James Ussher used contemporary archeology. We know, from "Persian evidence", as you call it, that Jerusalem was destroyed in 588 B.C., the last year in the reign of king Zedekiah of Judah. Thereby it is from that date that scientists convert AM dates to BC.
 * This supposed 2000-year variation is once again Original Research on your part. Thus, in conclusion, everything you have to say, every reason you have against me, is of your own invention or else from your society's prejudice. Biblical Chronology, if any chronology is used, uses that of Ussher as excepted by Historians, Scientists, Journalists, and even the Religious. Your lack of referenced material should be self-convicting.LutherVinci (talk) 20:21, 6 December 2010 (UTC)
 * See the chronological tables of Eusebius of Caesarea and Saint Jerome. Septentrionalis PMAnderson 20:43, 6 December 2010 (UTC)
 * And how would that alter the facts if I do (or did)?
 * It would show you an entirely biblical chronology a millennium longer than Ussher's. Septentrionalis PMAnderson 21:31, 6 December 2010 (UTC)
 * I'm sorry, Pmanderson, but Wikipedia is a place for verifiable information. These people you keep citing (and use the word loosely for you) either did not use an entirely Biblical Chronology, or else they simply did not give a date to creation as you claim they did. On Wikipedia, you can't just say things on faith, you need to provide something that can be verified. I did not just tell you about James Ussher, I gave links to his Chronology, several times. Besides, your entirely missing the point. In the modern day, since the Renaissance, only Ussher Chronology has been used. IF St. Jerome, Eusebius, and who else says otherwise, they are NOT excepted by the modern creationist community. LutherVinci (talk) 21:58, 6 December 2010 (UTC)
 * Kepler, Scaliger, Lightfoot (whose calculation is even mentioned in James Ussher), Sir Isaac Newton (no mean calculator) are all since the Renaissance. No two of them agreed with Ussher - or with each other. Septentrionalis PMAnderson 21:23, 7 December 2010 (UTC)
 * 1) They all lived before Ussher. 2) Kepler's an Astronomer, Scaliger's a writer, Newton was a physicist, I never hears of any of there vast studies of history. Newton, for your sake, I have heard of, and he gives 4000 BC, so round and without further chronology, we all know it was an estimate, the precise number given by Ussher, who was among the great revival of history in the Renaissance. LutherVinci (talk) 21:37, 7 December 2010 (UTC)
 * Lightfoot wrote twenty years after Ussher; Newton was born on Christmas day 1642; Ussher published when he was six. This is before Ussher only in some Pickwickian sense; Newton's two long books on Biblical chronology were published in the 1720's; he spent more time on chronology and alchemy than he did on physics. Septentrionalis PMAnderson 21:58, 7 December 2010 (UTC)
 * I don't care who came first, that has nothing to do with anything. Also I would expect you to provide some sources for the outlandish statement that Newton, the first scientist, inventor of Calculus and physics, spent more time with chronology and alchemy than anything else. LutherVinci (talk) 14:41, 14 December 2010 (UTC)
 * Why do you think Keynes called him "The last of the magicians"? Do I gather you haven't actually read much about Newton's studies of chronology and alchemy? Dougweller (talk) 15:10, 14 December 2010 (UTC)

Third opinion

 * That sounds sensible to me. -- Eraserhead1 <talk> 20:17, 6 December 2010 (UTC)
 * I completely agree, I'll do that right-a-way. LutherVinci (talk) 21:13, 6 December 2010 (UTC)
 * Alright, I added a "Bible" section to 39th century BC, with a reference to Ussher Chronology. LutherVinci (talk) 21:21, 6 December 2010 (UTC)
 * Reversing as tendentious pushing of a point of view. Septentrionalis PMAnderson 21:29, 6 December 2010 (UTC)
 * Hwat? My edit was reversed? Is there something you have against the established consensus?
 * My edit, intended to fulfill exactly what we agreed upon (to add a separate section) was reverted by guess who here LutherVinci (talk) 22:03, 6 December 2010 (UTC)
 * I agree. I've moved some of the Hindu stuff into a religion and mythology section as well. -- Eraserhead1 <talk> 22:25, 6 December 2010 (UTC)
 * I changed the "Mythology" section header in this article to "Religion and mythology".
 * Does this entry in the "Calendars and chronology section:
 * 3929 BC—Date of creation according to John Lightfoot based on the Old Testament of the Bible, and often associated with the Ussher chronology.
 * go best there or in the "Religion and mythology" section? It would qualify about as well as the other entries in the "Calendars" section, all of which at present could go equally well under either heading in my view.   Wiki Dao  ☯  (talk)  22:54, 6 December 2010 (UTC)
 * Well given the Bible is "religion and mythology" personally I think that is the appropriate section. -- Eraserhead1 <talk> 23:18, 6 December 2010 (UTC)
 * I adhere to Arthur Rubin's actual and original suggestion: Ussher belongs in the table at Biblical chronology, which now contains two systems: one 240 years shorter than Ussher, one 1500 years longer. If it weren't so much trouble recasting a table which already stretches across a page, I'd do it myself; but those so motivated as to stick this into articles on history should be motivated enough to overcome that. Septentrionalis PMAnderson 00:02, 7 December 2010 (UTC)
 * Like I already said (obviously you're not listening to us), the Septuagint was written in 132 BC (not 200 BC, my apologies), while the Hebrew Bible which James Ussher used was written long before 320 BC; that is the Only difference in Chronology you will find, the only difference in chronology mentioned in the article you cited, and the very resource ignored by not just James Ussher, but every sane creationist in the modern day.
 * This antagonistic user, I think, is seriously stepping out of line.LutherVinci (talk) 02:25, 7 December 2010 (UTC)
 * "240 years shorter"? Which chronology would that be, their are only two in the article you cite: James Ussher and the Septuagint. Remember, you are allowed to continue discussions, not invent or invert facts.LutherVinci (talk) 02:28, 7 December 2010 (UTC)
 * Not so. Only one intrusion is, or refers to, Ussher. For example, the birth of Arphaxad is 1658 AM = 2266 BC. Those who can add will find this is not Ussher's system. Septentrionalis PMAnderson 20:24, 7 December 2010 (UTC)
 *  The first column in Biblical chronology is not Ussher, as it dates the Creation to 3923 BCE, which seems to differ by 81 years.  Ussher should be added as another column, rather than as a note in the "Flood to Babylon" section.  And this "Third opinion" section is improper, as PMA and I have both been opposed to LV's additions.  — Arthur Rubin  (talk) 15:41, 7 December 2010 (UTC)
 * Truth to tell, the article referenced NEVER mentions 3923 BC, first column or otherwise. And a third opinion was not my idea, Eraser Head told me it was necessary.LutherVinci (talk) 18:06, 7 December 2010 (UTC)

I'll bow out and let you folks get back to it, then. Happy editing! :) Wiki Dao  ☯  (talk)  18:13, 7 December 2010 (UTC)
 * To Arthur: What you are saying, by the way, is that if a Comic Book, for instance, gave an exact date for some fictional event, then it deserves a place on Wikipedia's chronology, but anything having to do with the Bible must be removed but whatever means necessary, and restricted to its own article on chronology strictly within itself. That is what you are saying, give outlandish fiction a higher place of interest than Religion. That is what you are suggesting, and that is both paradoxical and outright wrong.LutherVinci (talk) 18:28, 7 December 2010 (UTC)
 * (left) Comic book? Not at all. I take Arthur Rbin to mean legends which have an explicit date as part of the legendary corpus: in the English tradition: the c.800 date of Oliver, Ogier, or Huon; the c. 500 date of the Emperor Arthur or of Beowulf; the c. 850 date of Pope Joan, who began as a chronicle entry; the 1066 date of Taillefer. As far as I can see, none of them are actually listed in the relevant century article; but I would be prepared to discuss the matter. Septentrionalis PMAnderson 19:16, 7 December 2010 (UTC)
 * Ah, so the only difference you would require is to say "c.3850" instead of "3874", I'm okay with that. Although I think you'd be hard pressed to find anyone that gives such a generalization.LutherVinci (talk) 19:25, 7 December 2010 (UTC)
 * No, Sir; Genesis (unlike, say, Geoffrey of Monmouth) gives no date, exact or approximate. And if you do revert again, you will be blocked. Septentrionalis PMAnderson 19:51, 7 December 2010 (UTC)
 * Genesis itself gives no date in BC, that much is true. Neither does any other myth already in these articles.LutherVinci (talk) 21:33, 7 December 2010 (UTC)
 * It gives no dates at all. Septentrionalis PMAnderson 21:58, 7 December 2010 (UTC)
 * You obviously never read the Bible. It obviously gives dates in AM (Anno Mundi), and no Chronology from the Turin Papyrus to Nennius gives dates in BC either. LutherVinci (talk) 14:37, 14 December 2010 (UTC)
 * The Bible gives dates in Anno Mundi? Give me some passages to check. Dougweller (talk) 15:15, 14 December 2010 (UTC)

Ideas for format (as opposed to debate)
I love the look of this "Religion and Mythology" section! Do you think we can extend this from 40th century BC all the way to 26th century BC?LutherVinci (talk) 02:53, 7 December 2010 (UTC)

I added a Religion and Mythology section to Significant persons, including both Hindu and Judeo-Christian beliefs.LutherVinci (talk) 03:06, 7 December 2010 (UTC)

 * I moved those entries to the pre-existing, level-two section. We don't need a "Religion and mythology" subsection for every section; just the one section should do here, don't you think?  Wiki Dao  ☯  (talk)  03:16, 7 December 2010 (UTC)
 * Good idea, although in some circumstances it could get confusing, understanding "persons" from "events", and so forth.LutherVinci (talk) 03:19, 7 December 2010 (UTC)
 * I think it will be clear enough. :) Like I say, too, the date of Creation could go in there, really your preference I suppose because those other "Calendars and chronologies" entries at present also could really go in either place as well. Wiki Dao  ☯  (talk)  03:24, 7 December 2010 (UTC)

 * It looks like Arthur Rubin removed the names from the Bible, because no specific source was cited. I don't think that is necessary.  By being in that section, the don't need to be real people with real, hard dates.  Was that your objection?  That they are Biblically placed around this time as a religious belief seems fine for this section to me.  Wiki Dao  ☯  (talk)  04:08, 7 December 2010 (UTC)
 * Besides, no specific source was given for Krishna or Korean mythology, either; probably for the same reason.LutherVinci (talk) 14:21, 7 December 2010 (UTC)
 * I also don't think we should listen to User:Arthur Rubin. He just reverted our Religion and Mythology section in the 39th century here. Right after I undid Pmandersons' revert here .LutherVinci (talk) 14:39, 7 December 2010 (UTC)
 * They don't need to be real people with real, hard dates. They can be unreal people with real, hard dates.  Something we don't have, here.  — Arthur Rubin  (talk) 16:21, 7 December 2010 (UTC)
 * 3874 BC (130 AM) seems pretty real to me, unless you feel yourself entitled to invent the definition. In any case, there is no "hard date" for Krishna either, but I feel that they belong there as well.LutherVinci (talk) 17:58, 7 December 2010 (UTC)
 * That's the birth of Seth? There's no consensus that Seth was a real person; there's no consensus that he was born in 130 AM (the Septuagint disagrees, and it is the oldest text); and there is no consensus that 130 AM = 3874 BC. Septentrionalis PMAnderson 19:03, 7 December 2010 (UTC)
 * 1)Please remember to verify your sources. The Dead sea scrolls predates the Septuagint, by almost 200 years, and copies of them are probably mush older. These documents affirm, as stated in "Annals of the World", that year 1 AM was 4004 BC, thus making the birth of Seth in 3874 BC (Annals of the World, page 18). How many times do I have to tell you this, before you actually start reading my arguments and sources? Unless you are going to once again contradict yourself, there does not have to be any evidence for these people, so long as they are mentioned in a separate "Religion and Mythology" section.LutherVinci (talk) 19:38, 7 December 2010 (UTC)
 * Don't talk nonsense. The Dead Sea Scrolls (which have multiple texts) were written between "150 BCE and 70 CE", as our article says. The Septuagint was made for Ptolemy II Philadelphus, who died in 246 BC (while the other books may well be later, the date of the Torah is what counts here). Septentrionalis PMAnderson 19:47, 7 December 2010 (UTC)
 * The Septuagint article says it was written around 132 BC, (and we must remember that it wasn't published until the Apocrypha was also included, and the Apocrypha wasn't written until 135 BC) while the Dead sea scrolls was written at a time as old as 250 BC, and had to predate Jesus, who was born around 5 BC . But that's all beside the point, as you said, it's the Torah we are talking about. The oldest fragment of the Hebrew Torah (as opposed to the Septuagint, which was in Greek) is as old as 600 BC. As for the Dead Sea scrolls, here is another link which, starting on the eleventh line, puts the Dead Sea scrolls as old as 250 BC, and explaining why 150 BC is too late. LutherVinci (talk) 20:42, 7 December 2010 (UTC)
 * No, our article says it wasn't complete (that is, including both the Protestant OT and the Apocrypha) until 132 BC; but anybody who argues about "publication" has no idea what a manuscript book culture was like. Septentrionalis PMAnderson 21:17, 7 December 2010 (UTC)

I added a Religion and Mythology to the 38th century BC, what do you think?LutherVinci (talk) 18:17, 7 December 2010 (UTC)
 * Please save us all some time and stop inventing facts. It clearly states in the first paragraph of the Septuagint Article that it was completed in 132 BC. Period. LutherVinci (talk) 21:31, 7 December 2010 (UTC)
 * And it also says, and is correct, that the Torah was completed (and quoted) in the middle third century BC. Septentrionalis PMAnderson 21:58, 7 December 2010 (UTC)
 * ", and is correct,"? Who made you the author and finisher of faith?LutherVinci (talk) 14:32, 14 December 2010 (UTC)

If the dates aren't clear then only including them on the Millennial articles seems best. -- Eraserhead1 <talk> 22:20, 7 December 2010 (UTC)
 * The dates were never clear; and the differences can be more than a thousand years. What's wrong with Biblical chronology, which is made to discuss these differences? Septentrionalis PMAnderson 02:58, 8 December 2010 (UTC)

Let's start over
The dates given in the Bible are just as clear as any other event in history. Any other statement otherwise is merely prejudice against the Bible. It should be clear from his above discussions that he does, going off in tangents, starting innumerable sub-arguments, disagreeing with everything I say, (whether relevant or not), he's just trying to find some flaw in my logic. There are many infallible proofs that the birth of Seth is just as well known as the birth of Menes,

But, before I start, I would make one thing clear: PMAnderson, the Only reason you would exclude the Bible from century articles is because no one can agree on the date, correct?LutherVinci (talk) 14:32, 14 December 2010 (UTC)

Let me see where you're coming from. You wish to move all mention of the Bible away from century articles and to the article Biblical Chronology, with an honorable mention in the Millennial article, because the proposed dates supposedly differ by thousands of years, correct?

In that case (although no Biblical Chronology differs more than a century), let me introduce you to another disputed chronology (yes, their is more than mythology): Ancient Egypt. For the rise Menes, I'll just name a few: Wilkinson, 2691 BC; Poole, 2717 ""; Bunsen, 3059 (or 3623, even he can't agree himself); Lespius, 3892; Brugch, 4400, Marriette, 5004, etc. It is traditionally held that Menes existed around c.3000 BC, but that would mean he would only end up in the Millenial article, wouldn't it?

In other words, Egyptian Chronology differs among the finest historians by thousands of years, (the article alone differs by more than 400 years) So, by your made up definition, these reigns of Pharaohs well known to history must be removed from their current state and placed in the Egyptian Chronology, where it will stay.

And that's not enough. There is an article on Mesopotamian Chronology, that also differs by centuries, so the reigns of all rulers in the Sumerian Kinglist should also be moved. (Notice that Menes, also known as Namar, is listed under 31st and 32nd century BCLutherVinci (talk) 14:32, 14 December 2010 (UTC)

 * If the dates given in the Bible as as clear as any other event in history, there should be secular sources for this. Where are they? Are you saying that the date for the Declaration of Independence is no more accurate than dates for biblical stories such as the Exodus, David, etc? Dougweller (talk) 15:19, 14 December 2010 (UTC)
 * Well, if we are excluding all those miraculous archaeological discoveries; including: the Habru, the Moabite stone; the invasions of Seti I and Ramsees II corresponds with "years of oppression" in the Book of Judges; excavation of Noah's Ark; the chariot wheels in the Red Sea; jars from the time of Solomon labeled, 'to the King'; the Hittites; etc.,...
 * If we ignore all that, I would like to point out that comparing to the Declaration of Independence is not fair. The document is only 200 years old, the original draft still exists today. It is incomparable with, say, the rise of Menes, which is 5,000 years old. Besides, that's not my point.

 * Here's my point, this is what I am driving at: I am not saying that the Bible should be treated as historical fact (we know it is, but there's no sense debating that), what I am saying is that a "Religion and Mythology" section in every article on centuries should include the Bible as much as it includes Hinduism, Koren Myth, etc. The suggestion that the dates cannot be agreed upon is no excuse because no one can agree on history either. There is NO Wikipedia Policy that states the following, "If a date for an event cannot be agreed upon, the event should be removed". That statement is entirely made up by PManderson in order to assert his anti-Christian POVLutherVinci (talk) 15:33, 15 December 2010 (UTC)

 * Um, those 'miraculous' discoveries are fictional. No chariot wheels, no Ark found, etc. And as you should know, a lot of Christians would agree, so don't call me anti-Christian. Dougweller (talk) 17:46, 15 December 2010 (UTC)

 * The dates of events in the Bible can be closely tied to secular dates back to 586BC (when Babylon took Jerusalem). Events previous to this have few parallels in reliable secular documents. In many cases though, when secularists have poo-poohed(sp?) the Bible, it has turned out to be correct; e.g. the existence of the Hittite empire. There is a clear case for including traditional dating of events in the Bible as historic events, pending any reliable evidence to the contrary. rossnixon 01:55, 16 December 2010 (UTC)
 * Aside from a few meaningless philosophical differences, That is exactly what I am saying. May I call a consensus to the matter? LutherVinci (talk) 14:33, 16 December 2010 (UTC)
 * I would suggest that we would need evidence that the specific information "turned out to be correct", before including it. For one thing, we would need a WP:RS for the dates attached to this information. HrafnTalkStalk(P) 14:58, 16 December 2010 (UTC)
 * Some say that the Bible has proven so reliable in the areas it can be verified, that we can assume it is reliable in the areas where it cannot be verified. The absence of evidence is not the evidence of absence. The only reason, probably, that there is no contemporary account of the patriarchs in Genesis 5 is that these people were not kings, nor architects, nor did they live in an environment that kept accurate records. Therefore, we should not expect to find any accounts, weather or not they existed.

 * But this is not the point. I am not saying that the Bible should be treated as fact, I am only suggesting that we mention it under a separate section, Religion and Mythology, using traditional dates. LutherVinci (talk) 16:06, 17 December 2010 (UTC)

 * Ok, it's not the point, but absence of evidence can indeed be evidence of absence. I've never understood why people say it can't be. It's actually one of the points made about the alleged Exodus - the lack of evidence in the Sinai, where you would expect the sands to have preserved such evidence as it does other contemporary evidence of human presence, is considered by at least some scholars as evidence of absence, just as more dramatically the lack of a huge crater or radioactivity in the middle of New York City is evidence of the absence of a nuclear explosion there. Dougweller (talk) 17:59, 17 December 2010 (UTC)

 * "Some say" all sorts of strange things. The relevant question is: what do the archaeological experts say? And last I heard, far from claiming "that the Bible has proven so reliable in the areas it can be verified", they have spent the last several decades blowing large holes in its narrative (see Biblical archaeology school). They say, for example, that Genesis contains numerous anachronisms, that, at the time of Exodus, the Egyptians were occupying the Sinai and Canaan, and at the time of Joshua, Jericho was unoccupied. This is quite apart from the "absence of evidence" -- like the Egyptians' strange failure to record the sudden disappearance of what would have been (if we take the numbers in the Bible as reliable) a very significant proportion of the population in Egypt, and of the death-by-drowning of a Pharaoh. Provide a mainstream archaeological source for your claims and we'll look at them. Base your claims on "some say" and then, really, we've got better things to do with our time. HrafnTalkStalk(P) 18:40, 17 December 2010 (UTC)
 * You don't seem to quite understand me, so I will not argue this much further. Their is large amounts of evidence for Biblical events up until the Flood, and i could supply you with them, but that would be irrelevant to a discussion on the 4th Millennium, which is strictly pre-Flood. For that reason, I do not provide you with the post-flood evidence.
 * Why is there little or no Biblical evidence before the Flood? for various reasons:
 * It is entirely likely that there was NO written language before the Flood. If people indeed lived hundreds of years, then written language is necessary. Just ask your grandfather and he'll tell you the beginning of time.
 * The Bible gives very little description of pre-Flood history, so there is NO archeology to look for.
 * All the Bible does give is genealogies. So how can we prove the existence of inconsequential individuals who lived thousands of years ago? it's an impossible task.
 * So if they existed, then we would expect to find the same amount of evidence as if they did not exist.
 * Therefore, my proposition has been, not to treat the Bible as historically proven, but to add a separate section titled, "Religion and Mythology" within every article centennial article. So if you don't believe the entry, you can say to yourself, "Ah, that must be the Mythology". And if you do believe the entry, you can say to yourself, "Ah, that's the Religion". Everyone would be satisfied. You don't have to have the Bible listed among history, and I get to have the Bible mentioned. LutherVinci (talk) 16:06, 18 December 2010 (UTC)

HrafnTalkStalk(P) 16:41, 18 December 2010 (UTC)
 * 1) Given that you argue "Their is large amounts of evidence for Biblical events up until the Flood, ... but that would be irrelevant to a discussion on the 4th Millennium, which is strictly pre-Flood" (my italics), it is hardly surprising that I don't understand you -- you're being incoherent.
 * 2) But then, given that it is a historical and geological fact that the flood did not happen, I really don't care whether you are asserting 'pre-flood' or 'post-flood' -- I just want to see the reliable archaeological sources supporting the information you want to include in the article.
 * 3) The first written language were the Jiahu symbols dated to 6600 BCE.
 * 4) Your "proposition" ignores the fact that significant sections of the Bible have been historically disproven.
 * 5) Even if we agreed to your "proposition", we still run into the problem of finding a reliable secondary source for the dates of Biblical events (see below).

LutherVinci's original contention
Beyond the issues in the thread above, I'd like to dispute LutherVinci's original contention that "The dates given in the Bible are just as clear as any other event in history." To the best of my knowledge, the Bible does not include an explicit chronology referenced to any calendar, and thus does not give "dates". Dates have been inferred from the Bible by various secondary sources -- but the question then is, are these sources reliable? The sources I've seen mentioned to date (the only one being explicitly cited being Ussher), I do not consider to be reliable, and would happily take to WP:RSN if their (lack of) reliability is disputed. HrafnTalkStalk(P) 06:13, 18 December 2010 (UTC)
 * This "inference" you speak of, this "lack of reference to any calendar", is exactly the way any historical date is achieved. Citing the Egyptians as an example, Prof. Rawlinson put it this way,
 * The Egyptians had NO Era from which to date events. (Thus, dates are achieved by simply adding the reigns of the kings which, as we well know, is easily confounded. The Bible gives all its dates according to Anno Mundi, years from creation)
 * They did NOT distinguish between the years of a Single Reign, and those of Joint Reigns of father and son.
 * They NEVER gave the Duration of a Dynasty.
 * They did NOT designate Contemporary Dynasties.
 * "Hence the uncertainty of Dates in Egyptian History... This is the unanimous confession of the Egyptologers."
 * The proposed dates differ by thousands of years, while the Bible hardly differs at all. So if we are to remove religion simply because no one can agree on a date, then Egyptian history must be removed as well.LutherVinci (talk) 16:06, 18 December 2010 (UTC)

 * As (i) I DID NOT ARGUE that "The dates given in [Egyptian records] are just as clear as any other event in history" & (ii) we have numerous reliable WP:SECONDARY sources inferring dates from these records, your 'Egyptian example' is a complete non sequitur.
 * You have provided neither specificity nor substantiation for your claim that "the proposed dates differ by thousands of years".
 * "the Bible hardly differs at all" -- differs from what? Your claim is unintelligible.
 * You still have provided no reliable WP:SECONDARY sources for inferring dates from the Bible.
 * HrafnTalkStalk(P) 16:50, 18 December 2010 (UTC)

Chronology and events sections
Shouldn't the Kali Yuga, Gregorian and Mayan calendar stuff be in the Chronology section, not Events? Dougweller (talk) 08:26, 7 December 2010 (UTC)
 * Yes. Septentrionalis PMAnderson 18:49, 7 December 2010 (UTC)
 * So you agree to place myth in a separate section, rather than removing them entirely? LutherVinci (talk) 14:34, 16 December 2010 (UTC)
 * Non sequitur. — Arthur Rubin (talk) 16:28, 16 December 2010 (UTC)
 * Clarifying, calendars are not myths -- hence Arthur Rubin's comment. HrafnTalkStalk(P) 18:25, 16 December 2010 (UTC)
 * My apologies. LutherVinci (talk) 16:08, 17 December 2010 (UTC)

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title: Talk:4th millennium BC


text:
ATF (disambiguation)

The Bureau of Alcohol, Tobacco, Firearms and Explosives is a federal law enforcement organization within the US Department of Justice.

ATF may also refer to:

Organizations

 * American Type Founders, former dominant American manufacturer of metal type
 * As Trustee For, a legal term for an entity acting as a trustee; see Trust law
 * Asia Task Force, a committee of UK businesses, informing the UK response to globalisation
 * Asian Tennis Federation, a continental body of national tennis associations of Asian countries
 * Atlantic Theatre Festival, a professional theatre company located in Wolfville, Nova Scotia, Canada

Places

 * French Southern and Antarctic Lands (ISO 3166 country code)
 * Chachoan Airport (IATA code), Ambato, Ecuador

Science and technology

 * Anatomical transfer function, the mathematical description of sound wave propagation through the human body
 * Activating transcription factor, a class of DNA-binding proteins that regulate gene transcription
 * Activating transcription factor 2, such a factor encoded by the ATF2 gene in humans
 * Artificial transcription factor, a type of engineered protein used in gene modulation
 * Automatic transmission fluid, the liquid medium used in hydraulic automatic transmission systems
 * Automated Telescope Facility, a robotic telescope built by the University of Iowa
 * Aviation turbine fuel, for jet aircraft

Music

 * After the Fire, a 1970s and 1980s rock band
 * Around the Fur, an album by American rock band Deftones
 * "ATF", a song on the album Feeler by The Toadies
 * "ATF", a rap song on the album It's Dark and Hell Is Hot by DMX

Military

 * Advanced Tactical Fighter, a program undertaken by the United States Air Force to develop a next-generation air superiority fighter
 * A US Navy hull classification symbol: Fleet ocean tug (ATF)
 * ATF Dingo, a German heavily armored military infantry mobility vehicle
 * 1 ATF, the 1st Australian Task Force, which commanded Australian and New Zealand's troops in the Vietnam War

Other uses

 * A.T.F., a 1999 television film produced for the American Broadcasting Company
 * ATF (video game), a computer game released by Digital Integration
 * Acquire the Fire, a Christian youth conference series run by Teen Mania Ministries
 * About The Fit, a fictional startup in the film The Intern (2015 film)

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

title: ATF (disambiguation)


text:
Lead(II) azide

Lead(II) azide  Pb(N3)2 is an inorganic compound. More so than other azides, it is explosive. It is used in detonators to initiate secondary explosives. In a commercially usable form, it is a white to buff powder.

Preparation and handling
Lead(II) azide is prepared by the reaction of sodium azide and lead(II) nitrate in aqueous solution. Lead(II) acetate can also be used.

Thickeners such as dextrin or polyvinyl alcohol are often added to the solution to stabilize the precipitated product. In fact, it is normally shipped in a dextrinated solution that lowers its sensitivity.

Production history
Lead azide in its pure form was first prepared by Theodor Curtius in 1891. Due to sensitivity and stability concerns, the dextrinated form of lead azide (MIL-L-3055) was developed in the 1920s and 1930s with large scale production by DuPont Co beginning in 1932. Detonator development during World War II resulted in the need for a form of lead azide with a more brisant output. RD-1333 lead azide (MIL-DTL-46225), a version of lead azide with sodium carboxymethyl cellulose as a precipitating agent, was developed to meet that need. The Vietnam War saw an accelerated need for lead azide and it was during this time that Special Purpose Lead Azide (MIL-L-14758) was developed; the US government also began stockpiling lead azide in large quantities. After the Vietnam War, the use of lead azide dramatically decreased. Due to the size of the US stockpile, the manufacture of lead azide in the US ceased completely by the early 1990s. In the 2000s, concerns about the age and stability of stockpiled lead azide led the US government to investigate methods to dispose of its stockpiled lead azide and obtain new manufacturers.

Explosive characteristics
Lead azide is highly sensitive and usually handled and stored under water in insulated rubber containers. It will explode after a fall of around 150 mm (6 in) or in the presence of a static discharge of 7 millijoules. Its detonation velocity is around 5180 m/s.

Ammonium acetate and sodium dichromate are used to destroy small quantities of lead azide.

Lead azide has immediate deflagration to detonation transition (DDT), meaning that even small amounts undergo full detonation (after being hit by flame or static electricity).

Lead azide reacts with copper, zinc, cadmium, or alloys containing these metals to form other azides. For example, copper azide is even more explosive and too sensitive to be used commercially.

Lead azide was a component of the six .22 (5.6 mm) caliber Devastator rounds fired from a Röhm RG-14 revolver by John Hinckley, Jr. in his assassination attempt on U.S. President Ronald Reagan on March 30, 1981. The rounds consisted of lead azide centers with lacquer-sealed aluminum tips designed to explode upon impact. A strong probability exists that the bullet which struck White House press secretary James Brady in the head exploded. The remaining bullets that hit people, including the shot that hit President Reagan, did not explode.

title: Lead(II) azide


text:
Botulinum toxin

Botulinum toxin, or botulinum neurotoxin (commonly called botox), is a highly potent neurotoxic protein produced by the bacterium Clostridium botulinum and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction, thus causing flaccid paralysis. The toxin causes the disease botulism. The toxin is also used commercially for medical and cosmetic purposes. Botulinum toxin is an acetylcholine release inhibitor and a neuromuscular blocking agent.

The seven main types of botulinum toxin are named types A to G (A, B, C1, C2, D, E, F and G). New types are occasionally found. Types A and B are capable of causing disease in humans, and are also used commercially and medically. Types C–G are less common; types E and F can cause disease in humans, while the other types cause disease in other animals.

Botulinum toxins are among the most potent toxins known to science. Intoxication can occur naturally as a result of either wound or intestinal infection or by ingesting formed toxin in food. The estimated human median lethal dose of type A toxin is 1.3–2.1ng/kg intravenously or intramuscularly, 10–13ng/kg when inhaled, or 1000ng/kg when taken by mouth.

Medical uses
Botulinum toxin is used to treat a number of therapeutic indications, many of which are not part of the approved drug label.

Muscle spasticity
Botulinum toxin is used to treat a number of disorders characterized by overactive muscle movement, including cerebral palsy, post-stroke spasticity, post-spinal cord injury spasticity, spasms of the head and neck, eyelid, vagina, limbs, jaw, and vocal cords. Similarly, botulinum toxin is used to relax the clenching of muscles, including those of the esophagus, jaw, lower urinary tract and bladder, or clenching of the anus which can exacerbate anal fissure. Botulinum toxin appears to be effective for refractory overactive bladder.

Other muscle disorders
Strabismus, otherwise known as improper eye alignment, is caused by imbalances in the actions of muscles that rotate the eyes. This condition can sometimes be relieved by weakening a muscle that pulls too strongly, or pulls against one that has been weakened by disease or trauma. Muscles weakened by toxin injection recover from paralysis after several months, so injection might seem to need to be repeated, but muscles adapt to the lengths at which they are chronically held, so that if a paralyzed muscle is stretched by its antagonist, it grows longer, while the antagonist shortens, yielding a permanent effect.

In January 2014, botulinum toxin was approved by UK's Medicines and Healthcare products Regulatory Agency for treatment of restricted ankle motion due to lower-limb spasticity associated with stroke in adults.

In July 2016, the US Food and Drug Administration (FDA) approved abobotulinumtoxinA (Dysport) for injection for the treatment of lower-limb spasticity in pediatric patients two years of age and older. AbobotulinumtoxinA is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity. In the US, the FDA approves the text of the labels of prescription medicines and for which medical conditions the drug manufacturer may sell the drug. However, prescribers may freely prescribe them for any condition they wish, also known as off-label use. Botulinum toxins have been used off-label for several pediatric conditions, including infantile esotropia.

Excessive sweating
AbobotulinumtoxinA has been approved for the treatment of axillary hyperhidrosis, which cannot be managed by topical agents.

Migraine
In 2010, the FDA approved intramuscular botulinum toxin injections for prophylactic treatment of chronic migraine headache. However, the use of botulinum toxin injections for episodic migraine has not been approved by the FDA.

Cosmetic uses
In cosmetic applications, botulinum toxin is considered relatively safe and effective for reduction of facial wrinkles, especially in the uppermost third of the face. Commercial forms are marketed under the brand names Botox Cosmetic/Vistabel from Allergan, Dysport/Azzalure from Galderma and Ipsen, Xeomin/Bocouture from Merz, Jeuveau/Nuceiva from Evolus, manufactured by Daewoong in South Korea. The effects of botulinum toxin injections for glabellar lines ('11's lines' between the eyes) typically last two to four months and in some cases, product-dependent, with some patients experiencing a longer duration of effect of up to six months or longer. Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those muscles, resulting in the smoothing of the overlying skin. Smoothing of wrinkles is usually visible three to five days after injection, with maximum effect typically a week following injection. Muscles can be treated repeatedly to maintain the smoothed appearance.

DaxibotulinumtoxinA (Daxxify) was approved for medical use in the United States in September 2022. It is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines (wrinkles between the eyebrows). DaxibotulinumtoxinA is an acetylcholine release inhibitor and neuromuscular blocking agent. The FDA approved daxibotulinumtoxinA based on evidence from two clinical trials (Studies GL-1 and GL-2), of 609 adults with moderate to severe glabellar lines. The trials were conducted at 30 sites in the United States and Canada. Both trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines. Participants received a single intramuscular injection of daxibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows. The most common side effects of daxibotulinumtoxinA are headache, drooping eyelids, and weakness of facial muscles.

LetibotulinumtoxinA (Letybo) was approved for medical use in the United States in February 2024. It is indicated to temporarily improve the appearance of moderate-to-severe glabellar lines. The FDA approved letibotulinumtoxinA based on evidence from three clinical trials (BLESS I [NCT02677298], BLESS II [NCT02677805], and BLESS III [NCT03985982]) of 1,271 participants with moderate to severe wrinkles between the eyebrows for efficacy and safety assessment. These trials were conducted at 31 sites in the United States and the European Union. All three trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines (wrinkles between the eyebrows). Participants received a single intramuscular injection of letibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows. The most common side effects of letibotulinumtoxinA are headache, drooping of eyelid and brow, and twitching of eyelid.

Other
Botulinum toxin is also used to treat disorders of hyperactive nerves including excessive sweating, neuropathic pain, and some allergy symptoms. In addition to these uses, botulinum toxin is being evaluated for use in treating chronic pain. Studies show that botulinum toxin may be injected into arthritic shoulder joints to reduce chronic pain and improve range of motion. The use of botulinum toxin A in children with cerebral palsy is safe in the upper and lower limb muscles.

Side effects
While botulinum toxin is generally considered safe in a clinical setting, serious side effects from its use can occur. Most commonly, botulinum toxin can be injected into the wrong muscle group or with time spread from the injection site, causing temporary paralysis of unintended muscles.

Side effects from cosmetic use generally result from unintended paralysis of facial muscles. These include partial facial paralysis, muscle weakness, and trouble swallowing. Side effects are not limited to direct paralysis, however, and can also include headaches, flu-like symptoms, and allergic reactions. Just as cosmetic treatments only last a number of months, paralysis side effects can have the same durations. At least in some cases, these effects are reported to dissipate in the weeks after treatment. Bruising at the site of injection is not a side effect of the toxin, but rather of the mode of administration, and is reported as preventable if the clinician applies pressure to the injection site; when it occurs, it is reported in specific cases to last 7–11 days. When injecting the masseter muscle of the jaw, loss of muscle function can result in a loss or reduction of power to chew solid foods. With continued high doses, the muscles can atrophy or lose strength; research has shown that those muscles rebuild after a break from Botox.

Side effects from therapeutic use can be much more varied depending on the location of injection and the dose of toxin injected. In general, side effects from therapeutic use can be more serious than those that arise during cosmetic use. These can arise from paralysis of critical muscle groups and can include arrhythmia, heart attack, and in some cases, seizures, respiratory arrest, and death. Additionally, side effects common in cosmetic use are also common in therapeutic use, including trouble swallowing, muscle weakness, allergic reactions, and flu-like syndromes.

In response to the occurrence of these side effects, in 2008, the FDA notified the public of the potential dangers of the botulinum toxin as a therapeutic. Namely, the toxin can spread to areas distant from the site of injection and paralyze unintended muscle groups, especially when used for treating muscle spasticity in children treated for cerebral palsy. In 2009, the FDA announced that boxed warnings would be added to available botulinum toxin products, warning of their ability to spread from the injection site. However, the clinical use of botulinum toxin A in cerebral palsy children has been proven to be safe with minimal side effects. Additionally, the FDA announced name changes to several botulinum toxin products, to emphasize that the products are not interchangeable and require different doses for proper use. Botox and Botox Cosmetic were given the generic name of onabotulinumtoxinA, Myobloc as rimabotulinumtoxinB, and Dysport retained its generic name of abobotulinumtoxinA. In conjunction with this, the FDA issued a communication to health care professionals reiterating the new drug names and the approved uses for each. A similar warning was issued by Health Canada in 2009, warning that botulinum toxin products can spread to other parts of the body.

Role in disease
Botulinum toxin produced by Clostridium botulinum (an anaerobic, gram-positive bacterium) is the cause of botulism. Humans most commonly ingest the toxin from eating improperly canned foods in which C. botulinum has grown. However, the toxin can also be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin within the intestine and can cause a condition known as floppy baby syndrome. In all cases, the toxin can then spread, blocking nerves and muscle function. In severe cases, the toxin can block nerves controlling the respiratory system or heart, resulting in death.

Botulism can be difficult to diagnose, as it may appear similar to diseases such as Guillain–Barré syndrome, myasthenia gravis, and stroke. Other tests, such as brain scan and spinal fluid examination, may help to rule out other causes. If the symptoms of botulism are diagnosed early, various treatments can be administered. In an effort to remove contaminated food that remains in the gut, enemas or induced vomiting may be used. For wound infections, infected material may be removed surgically. Botulinum antitoxin is available and may be used to prevent the worsening of symptoms, though it will not reverse existing nerve damage. In severe cases, mechanical respiration may be used to support people with respiratory failure. The nerve damage heals over time, generally over weeks to months. With proper treatment, the case fatality rate for botulinum poisoning can be greatly reduced.

Two preparations of botulinum antitoxins are available for treatment of botulism. Trivalent (serotypes A, B, E) botulinum antitoxin is derived from equine sources using whole antibodies. The second antitoxin is heptavalent botulinum antitoxin (serotypes A, B, C, D, E, F, G), which is derived from equine antibodies that have been altered to make them less immunogenic. This antitoxin is effective against all main strains of botulism.

Mechanism of action

Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically to presynaptic surface of neurons that use the neurotransmitter acetylcholine. Once bound to the nerve terminal, the neuron takes up the toxin into a vesicle by receptor-mediated endocytosis. As the vesicle moves farther into the cell, it acidifies, activating a portion of the toxin that triggers it to push across the vesicle membrane and into the cell cytoplasm. Botulinum neurotoxins recognize distinct classes of receptors simultaneously (gangliosides, synaptotagmin and SV2). Once inside the cytoplasm, the toxin cleaves SNARE proteins (proteins that mediate vesicle fusion, with their target membrane bound compartments) meaning that the acetylcholine vesicles cannot bind to the intracellular cell membrane, preventing the cell from releasing vesicles of neurotransmitter. This stops nerve signaling, leading to flaccid paralysis.

The toxin itself is released from the bacterium as a single chain, then becomes activated when cleaved by its own proteases. The active form consists of a two-chain protein composed of a 100-kDa heavy chain polypeptide joined via disulfide bond to a 50-kDa light chain polypeptide. The heavy chain contains domains with several functions; it has the domain responsible for binding specifically to presynaptic nerve terminals, as well as the domain responsible for mediating translocation of the light chain into the cell cytoplasm as the vacuole acidifies. The light chain is a M27-family zinc metalloprotease and is the active part of the toxin. It is translocated into the host cell cytoplasm where it cleaves the host protein SNAP-25, a member of the SNARE protein family, which is responsible for fusion. The cleaved SNAP-25 cannot mediate fusion of vesicles with the host cell membrane, thus preventing the release of the neurotransmitter acetylcholine from axon endings. This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by the affected cell.

The seven toxin serotypes (A–G) are traditionally separated by their antigenicity. They have different tertiary structures and sequence differences. While the different toxin types all target members of the SNARE family, different toxin types target different SNARE family members. The A, B, and E serotypes cause human botulism, with the activities of types A and B enduring longest in vivo (from several weeks to months). Existing toxin types can recombine to create "hybrid" (mosaic, chimeric) types. Examples include BoNT/CD, BoNT/DC, and BoNT/FA, with the first letter indicating the light chain type and the latter indicating the heavy chain type. BoNT/FA received considerable attention under the name "BoNT/H", as it was mistakenly thought it could not be neutralized by any existing antitoxin.

Botulinum toxins are AB toxins and closely related to Anthrax toxin, Diphtheria toxin, and in particular tetanus toxin. The two are collectively known as Clostridium neurotoxins and the light chain is classified by MEROPS as family M27. Nonclassical types include BoNT/X, which is toxic in mice and possibly in humans; a BoNT/J found in cow Enterococcus; and a BoNT/Wo  found in the rice-colonizing Weissella oryzae.

Initial descriptions and discovery of Clostridium botulinum
One of the earliest recorded outbreaks of foodborne botulism occurred in 1793 in the village of Wildbad in what is now Baden-Württemberg, Germany. Thirteen people became sick and six died after eating pork stomach filled with blood sausage, a local delicacy. Additional cases of fatal food poisoning in Württemberg led the authorities to issue a public warning against consuming smoked blood sausages in 1802 and to collect case reports of "sausage poisoning". Between 1817 and 1822, the German physician Justinus Kerner published the first complete description of the symptoms of botulism, based on extensive clinical observations and animal experiments. He concluded that the toxin develops in bad sausages under anaerobic conditions, is a biological substance, acts on the nervous system, and is lethal even in small amounts. Kerner hypothesized that this "sausage toxin" could be used to treat a variety of diseases caused by an overactive nervous system, making him the first to suggest that it could be used therapeutically. In 1870, the German physician Müller coined the term botulism to describe the disease caused by sausage poisoning, from the Latin word botulus, meaning 'sausage'.

In 1895 Émile van Ermengem, a Belgian microbiologist, discovered what is now called Clostridium botulinum and confirmed that a toxin produced by the bacteria causes botulism. On 14 December 1895, there was a large outbreak of botulism in the Belgian village of Ellezelles that occurred at a funeral where people ate pickled and smoked ham; three of them died. By examining the contaminated ham and performing autopsies on the people who died after eating it, van Ermengem isolated an anaerobic microorganism that he called Bacillus botulinus. He also performed experiments on animals with ham extracts, isolated bacterial cultures, and toxins extracts from the bacteria. From these he concluded that the bacteria themselves do not cause foodborne botulism, but rather produce a toxin that causes the disease after it is ingested. As a result of Kerner's and van Ermengem's research, it was thought that only contaminated meat or fish could cause botulism. This idea was refuted in 1904 when a botulism outbreak occurred in Darmstadt, Germany, because of canned white beans. In 1910, the German microbiologist J. Leuchs published a paper showing that the outbreaks in Ellezelles and Darmstadt were caused by different strains of Bacillus botulinus and that the toxins were serologically distinct. In 1917, Bacillus botulinus was renamed Clostridium botulinum, as it was decided that term Bacillus should only refer to a group of aerobic microorganisms, while Clostridium would be only used to describe a group of anaerobic microorganisms. In 1919, Georgina Burke used toxin-antitoxin reactions to identify two strains of Clostridium botulinum, which she designated A and B.

Food canning
Over the next three decades, 1895–1925, as food canning was approaching a billion-dollar-a-year industry, botulism was becoming a public health hazard. Karl Friedrich Meyer, a Swiss-American veterinary scientist, created a center at the Hooper Foundation in San Francisco, where he developed techniques for growing the organism and extracting the toxin, and conversely, for preventing organism growth and toxin production, and inactivating the toxin by heating. The California canning industry was thereby preserved.

World War II
With the outbreak of World War II, weaponization of botulinum toxin was investigated at Fort Detrick in Maryland. Carl Lamanna and James Duff developed the concentration and crystallization techniques that Edward J. Schantz used to create the first clinical product. When the Army's Chemical Corps was disbanded, Schantz moved to the Food Research Institute in Wisconsin, where he manufactured toxin for experimental use and provided it to the academic community.

The mechanism of botulinum toxin action – blocking the release of the neurotransmitter acetylcholine from nerve endings – was elucidated in the mid-20th century, and remains an important research topic. Nearly all toxin treatments are based on this effect in various body tissues.

Strabismus
Ophthalmologists specializing in eye muscle disorders (strabismus) had developed the method of EMG-guided injection (using the electromyogram, the electrical signal from an activated muscle, to guide injection) of local anesthetics as a diagnostic technique for evaluating an individual muscle's contribution to an eye movement. Because strabismus surgery frequently needed repeating, a search was undertaken for non-surgical, injection treatments using various anesthetics, alcohols, enzymes, enzyme blockers, and snake neurotoxins. Finally, inspired by Daniel B. Drachman's work with chicks at Johns Hopkins, Alan B. Scott and colleagues injected botulinum toxin into monkey extraocular muscles. The result was remarkable; a few picograms induced paralysis that was confined to the target muscle, long in duration, and without side effects.

After working out techniques for freeze-drying, buffering with albumin, and assuring sterility, potency, and safety, Scott applied to the FDA for investigational drug use, and began manufacturing botulinum type A neurotoxin in his San Francisco lab. He injected the first strabismus patients in 1977, reported its clinical utility in 1980, and had soon trained hundreds of ophthalmologists in EMG-guided injection of the drug he named Oculinum ("eye aligner").

In 1986, Oculinum Inc, Scott's micromanufacturer and distributor of botulinum toxin, was unable to obtain product liability insurance, and could no longer supply the drug. As supplies became exhausted, people who had come to rely on periodic injections became desperate. For four months, as liability issues were resolved, American blepharospasm patients traveled to Canadian eye centers for their injections.

Based on data from thousands of people collected by 240 investigators, Oculinum Inc (which was soon acquired by Allergan) received FDA approval in 1989 to market Oculinum for clinical use in the United States to treat adult strabismus and blepharospasm. Allergan then began using the trademark Botox. This original approval was granted under the 1983 US Orphan Drug Act.

Cosmetics
The effect of botulinum toxin type-A on reducing and eliminating forehead wrinkles was first described and published by Richard Clark, MD, a plastic surgeon from Sacramento, California. In 1987 Clark was challenged with eliminating the disfigurement caused by only the right side of the forehead muscles functioning after the left side of the forehead was paralyzed during a facelift procedure. This patient had desired to look better from her facelift, but was experiencing bizarre unilateral right forehead eyebrow elevation while the left eyebrow drooped, and she constantly demonstrated deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. Clark was aware that Botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with Botulinum toxin to paralyze the moving and wrinkling normal functioning right forehead muscles to make both sides of the forehead appear the same. This study and case report of the cosmetic use of Botulinum toxin to treat a cosmetic complication of a cosmetic surgery was the first report on the specific treatment of wrinkles and was published in the journal Plastic and Reconstructive Surgery in 1989. Editors of the journal of the American Society of Plastic Surgeons have clearly stated "the first described use of the toxin in aesthetic circumstances was by Clark and Berris in 1989."

Also in 1987, Jean and Alastair Carruthers, both doctors in Vancouver, British Columbia, observed that blepharospasm patients who received injections around the eyes and upper face also enjoyed diminished facial glabellar lines ("frown lines" between the eyebrows). Alastair Carruthers reported that others at the time also noticed these effects and discussed the cosmetic potential of botulinum toxin. Unlike other investigators, the Carruthers did more than just talk about the possibility of using botulinum toxin cosmetically. They conducted a clinical study on otherwise normal individuals whose only concern was their eyebrow furrow. They performed their study between 1987 and 1989 and presented their results at the 1990 annual meeting of the American Society for Dermatologic Surgery. Their findings were subsequently published in 1992.

Chronic pain
William J. Binder reported in 2000 that people who had cosmetic injections around the face reported relief from chronic headache. This was initially thought to be an indirect effect of reduced muscle tension, but the toxin is now known to inhibit release of peripheral nociceptive neurotransmitters, suppressing the central pain processing systems responsible for migraine headache.

Economics
, botulinum toxin injections are the most common cosmetic operation, with 7.4 million procedures in the United States, according to the American Society of Plastic Surgeons.

The global market for botulinum toxin products, driven by their cosmetic applications, was forecast to reach $2.9 billion by 2018. The facial aesthetics market, of which they are a component, was forecast to reach $4.7 billion ($2 billion in the US) in the same timeframe.

US market
In 2020, 4,401,536 botulinum toxin Type A procedures were administered. In 2019 the botulinum toxin market made US$3.19 billion.

Botox cost
Botox cost is generally determined by the number of units administered (avg. $10–30 per unit) or by the area ($200–1000) and depends on expertise of a physician, clinic location, number of units, and treatment complexity.

Insurance
In the US, botox for medical purposes is usually covered by insurance if deemed medically necessary by a doctor and covers a plethora of medical problems including overactive bladder (OAB), urinary incontinence due to neurologic conditions, headaches and migraines, TMJ, spasticity in adults, cervical dystonia in adults, severe axillary hyperhidrosis (or other areas of the body), blepharospasm, upper or lower limb spasticity.

Hyperhidrosis
Botox for excessive sweating is FDA approved.

Cosmetic
Standard areas for aesthetics botox injections include facial and other areas that can form fine lines and wrinkles due to every day muscle contractions and/or facial expressions such as smiling, frowning, squinting, and raising eyebrows. These areas include the glabellar region between the eyebrows, horizontal lines on the forehead, crow's feet around the eyes, and even circular bands that form around the neck secondary to platysmal hyperactivity.

Bioterrorism
Botulinum toxin has been recognized as a potential agent for use in bioterrorism. It can be absorbed through the eyes, mucous membranes, respiratory tract, and non-intact skin. The effects of botulinum toxin are different from those of nerve agents involved insofar in that botulism symptoms develop relatively slowly (over several days), while nerve agent effects are generally much more rapid. Evidence suggests that nerve exposure (simulated by injection of atropine and pralidoxime) will increase mortality by enhancing botulinum toxin's mechanism of toxicity. With regard to detection, protocols using NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when samples containing botulinum toxin are tested. To confirm a diagnosis of botulinum toxin poisoning, therapeutically or to provide evidence in death investigations, botulinum toxin may be quantitated by immunoassay of human biological fluids; serum levels of 12–24 mouse LD50 units per milliliter have been detected in poisoned people.

During the early 1980s, German and French newspapers reported that the police had raided a Baader-Meinhof gang safe house in Paris and had found a makeshift laboratory that contained flasks full of Clostridium botulinum, which makes botulinum toxin. Their reports were later found to be incorrect; no such lab was ever found.

Brand names
Commercial forms are marketed under the brand names DAXXIFY® (daxibotulinumtoxinA-lanm), Botox (onabotulinumtoxinA), Dysport/Azzalure (abobotulinumtoxinA), Letybo (letibotulinumtoxinA), Myobloc (rimabotulinumtoxinB), Xeomin/Bocouture (incobotulinumtoxinA), and Jeuveau (prabotulinumtoxinA).

Botulinum toxin A is sold under the brand names Jeuveau, Botox, and Xeomin. Botulinum toxin B is sold under the brand name Myobloc.

In the United States, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and cosmetic use. A US supplier reported in its company materials in 2011 that it could "supply the world's requirements for 25 indications approved by Government agencies around the world" with less than one gram of raw botulinum toxin. Myobloc or Neurobloc, a botulinum toxin type B product, is produced by Solstice Neurosciences, a subsidiary of US WorldMeds. AbobotulinumtoxinA), a therapeutic formulation of the type A toxin manufactured by Galderma in the United Kingdom, is licensed for the treatment of focal dystonias and certain cosmetic uses in the US and other countries. LetibotulinumtoxinA (Letybo) was approved for medical use in the United States in February 2024.

Besides the three primary US manufacturers, numerous other botulinum toxin producers are known. Xeomin, manufactured in Germany by Merz, is also available for both therapeutic and cosmetic use in the US. Lanzhou Institute of Biological Products in China manufactures a botulinum toxin type-A product; as of 2014, it was the only botulinum toxin type-A approved in China. Botulinum toxin type-A is also sold as Lantox and Prosigne on the global market. Neuronox, a botulinum toxin type-A product, was introduced by Medy-Tox of South Korea in 2009.

Toxin production
Botulism toxins are produced by bacteria of the genus Clostridium, namely C. botulinum, C. butyricum, C. baratii and C. argentinense, which are widely distributed, including in soil and dust. Also, the bacteria can be found inside homes on floors, carpet, and countertops even after cleaning. Complicating the problem is that the taxonomy for C. botulinum remains chaotic. The toxin has likely been horizontally transferred across lineages, contributing to the multi-species patten seen today.

Food-borne botulism results, indirectly, from ingestion of food contaminated with Clostridium spores, where exposure to an anaerobic environment allows the spores to germinate, after which the bacteria can multiply and produce toxin. Critically, ingestion of toxin rather than spores or vegetative bacteria causes botulism. Botulism is nevertheless known to be transmitted through canned foods not cooked correctly before canning or after can opening, so is preventable. Infant botulism arising from consumption of honey or any other food that can carry these spores can be prevented by eliminating these foods from diets of children less than 12 months old.

Organism and toxin susceptibilities
Proper refrigeration at temperatures below 4.4 C slows the growth of C. botulinum. The organism is also susceptible to high salt, high oxygen, and low pH levels. The toxin itself is rapidly destroyed by heat, such as in thorough cooking. The spores that produce the toxin are heat-tolerant and will survive boiling water for an extended period of time.

The botulinum toxin is denatured and thus deactivated at temperatures greater than 85 C for five minutes. As a zinc metalloprotease (see below), the toxin's activity is also susceptible, post-exposure, to inhibition by protease inhibitors, e.g., zinc-coordinating hydroxamates.

Blepharospasm and strabismus
University-based ophthalmologists in the US and Canada further refined the use of botulinum toxin as a therapeutic agent. By 1985, a scientific protocol of injection sites and dosage had been empirically determined for treatment of blepharospasm and strabismus. Side effects in treatment of this condition were deemed to be rare, mild and treatable. The beneficial effects of the injection lasted only four to six months. Thus, blepharospasm patients required re-injection two or three times a year.

In 1986, Scott's micromanufacturer and distributor of Botox was no longer able to supply the drug because of an inability to obtain product liability insurance. People became desperate, as supplies of Botox were gradually consumed, forcing him to abandon people who would have been due for their next injection. For a period of four months, American blepharospasm patients had to arrange to have their injections performed by participating doctors at Canadian eye centers until the liability issues could be resolved.

In December 1989, Botox was approved by the US FDA for the treatment of strabismus, blepharospasm, and hemifacial spasm in people over 12 years old.

In the case of treatment of infantile esotropia in people younger than 12 years of age, several studies have yielded differing results.

Cosmetic
The effect of botulinum toxin type-A on reducing and eliminating forehead wrinkles was first described and published by Richard Clark, MD, a plastic surgeon from Sacramento, California. In 1987 Clark was challenged with eliminating the disfigurement caused by only the right side of the forehead muscles functioning after the left side of the forehead was paralyzed during a facelift procedure. This patient had desired to look better from her facelift, but was experiencing bizarre unilateral right forehead eyebrow elevation while the left eyebrow drooped and she emoted with deep expressive right forehead wrinkles while the left side was perfectly smooth due to the paralysis. Clark was aware that botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with botulinum toxin to paralyze the moving and wrinkling normal functioning right forehead muscles to make both sides of the forehead appear the same. This study and case report on the cosmetic use of botulinum toxin to treat a cosmetic complication of a cosmetic surgery was the first report on the specific treatment of wrinkles and was published in the journal Plastic and Reconstructive Surgery in 1989. Editors of the journal of the American Society of Plastic Surgeons have clearly stated "the first described use of the toxin in aesthetic circumstances was by Clark and Berris in 1989."

J. D. and J. A. Carruthers also studied and reported in 1992 the use of botulinum toxin type-A as a cosmetic treatment.[78] They conducted a study of participants whose only concern was their glabellar forehead wrinkle or furrow. Study participants were otherwise normal. Sixteen of seventeen participants available for follow-up demonstrated a cosmetic improvement. This study was reported at a meeting in 1991. The study for the treatment of glabellar frown lines was published in 1992. This result was subsequently confirmed by other groups (Brin, and the Columbia University group under Monte Keen ). The FDA announced regulatory approval of botulinum toxin type A (Botox Cosmetic) to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines) in 2002 after extensive clinical trials. Well before this, the cosmetic use of botulinum toxin type A became widespread. The results of Botox Cosmetic can last up to four months and may vary with each patient. The US Food and Drug Administration (FDA) approved an alternative product-safety testing method in response to increasing public concern that LD50 testing was required for each batch sold in the market.

Botulinum toxin type-A has also been used in the treatment of gummy smiles; the material is injected into the hyperactive muscles of upper lip, which causes a reduction in the upward movement of lip thus resulting in a smile with a less exposure of gingiva. Botox is usually injected in the three lip elevator muscles that converge on the lateral side of the ala of the nose; the levator labii superioris (LLS), the levator labii superioris alaeque nasi muscle (LLSAN), and the zygomaticus minor (ZMi).

Upper motor neuron syndrome
Botulinum toxin type-A is now a common treatment for muscles affected by the upper motor neuron syndrome (UMNS), such as cerebral palsy, for muscles with an impaired ability to effectively lengthen. Muscles affected by UMNS frequently are limited by weakness, loss of reciprocal inhibition, decreased movement control, and hypertonicity (including spasticity). In January 2014, Botulinum toxin was approved by UK's Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of ankle disability due to lower limb spasticity associated with stroke in adults. Joint motion may be restricted by severe muscle imbalance related to the syndrome, when some muscles are markedly hypertonic, and lack effective active lengthening. Injecting an overactive muscle to decrease its level of contraction can allow improved reciprocal motion, so improved ability to move and exercise.

Sialorrhea
Sialorrhea is a condition where oral secretions are unable to be eliminated, causing pooling of saliva in the mouth. This condition can be caused by various neurological syndromes such as Bell's palsy, intellectual disability, and cerebral palsy. Injection of botulinum toxin type-A into salivary glands is useful in reducing the secretions.

Cervical dystonia
Botulinum toxin type-A is used to treat cervical dystonia, but it can become ineffective after a time. Botulinum toxin type B received FDA approval for treatment of cervical dystonia in December 2000. Brand names for botulinum toxin type-B include Myobloc in the United States and Neurobloc in the European Union.

Chronic migraine
Onabotulinumtoxin A (trade name Botox) received FDA approval for treatment of chronic migraines on 15 October 2010. The toxin is injected into the head and neck to treat these chronic headaches. Approval followed evidence presented to the agency from two studies funded by Allergan showing a very slight improvement in incidence of chronic migraines for those with migraines undergoing the Botox treatment.

Since then, several randomized control trials have shown botulinum toxin type A to improve headache symptoms and quality of life when used prophylactically for participants with chronic migraine who exhibit headache characteristics consistent with: pressure perceived from outside source, shorter total duration of chronic migraines (<30 years), "detoxification" of participants with coexisting chronic daily headache due to medication overuse, and no current history of other preventive headache medications.

Depression
A few small trials have found benefits in people with depression. Research is based on the facial feedback hypothesis.

Premature ejaculation
The drug for the treatment of premature ejaculation has been under development since August 2013, and is in Phase II trials.

title: Botulinum toxin